DIABETES MELLITUS
Certificate Course on Diabeto(ogy Distance Learning Project
Distance Learning Project
Diabetic Association of Bangladesh
DIABETES MElliTUS Certificate Course on Diabetology Distance Learning Project Diabetic Association of Bangladesh First published 2005
Second edition
July, 2007
Cover design
Sucharoo,8624178
Published by
Diabetic Association of Bangladesh
Copy right
All rights reserved. No part of this publicatlon may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or othelWise, without prior permission of the Distance Learning Project of Diabetic Association of Bangladesh.
ISBN
984 - 32 - 2552 - X
Foreward The Diabetic Association of Bangladesh (DAB) plays a unique role in diabetes healthcare delivery in Bangladesh. The association has been involved in creating appropriately trained manpower for the modern management of diabetic persons. BIRDEM has been running postgraduate courses in collaboration with the Dhaka University since 1986 in medical sciences including endocrinology and metabolic disorders. Other institutions of DAB, namely, National Institute of Health Science and Ibrahim Medical College are involved in development of laboratory experts and doctors. DAB has a large network of affiliated associations, and NHN and HCDP satellite clinics in addition to BIRD EM, distributed all over the country. We have now designed a Certificate Course on Diabetology utilizing the DAB set up. The doctors can simultaneously continue
their routine work and
participate in the course during the weekends. The course was designed in collaboration with two experts namely Prof. Janet Grant, Director of Medical Education and Prof. Mike Stewart, Prof. of Neuroscience from the Open University, UK. They initially conducted a feasibility study and then a Training of Tutors programme. The curriculum was subsequently developed with the contributions of experts from BIRDEM and NHN who are diabetologists and endocrinologists. It is a tutor-based modular course consisting of ten modules. Each module consists of its well-defined objectives, text and in-text activities, end-module tutor marked assignments and practical projects on the management of diabetic persons. This book is written in the style of distance learning technique for the course. It provides in text reading and also serves as a further reading guide. Such a text is a combined effort of experts on diabetology and distance learning methods. This course can be adapted for other public health related problems, such as hypertension, malaria or tuberculosis. It may be appropriate for other countries in this region and we intend to develop more advanced courses in the same style in future. We are pleased to present this book for the training of doctors and also to help our people across the country. We are grateful to Prof Janet Grant and Prof Mike Stewart for their keen interest and commendable role in the development of the project. We are thankful to the experts / tutors from BIRDEM and NHN for their contribution in developing the text of the book.
This second edition has been thoroughly revised and updated. We hope, this will be very much beneficial to the doctors participating in the course.
� Azad Khan
Prof AK
Chairman of the Project
7-1 C!.f ?J-
f-LeJJ:J Mahtab
Prof Hajera
Chairman of the Course
Editorial Board Prof AK Azad Khan, Bangladesh Prof Hajera Mahtab, Bangladesh Prof Janet Grant, UK Prof Mike Stewart, UK Dr Tofail Ahmed, Bangladesh Dr J Asraful Haq, Bangladesh
Financial contributor Novo-Nordisk Stakeholders Relation
Contents -
--- ---_.
Page Introduction Distance Learning Chapter 1: Epidemiology
17
Chapter 2: Definition, presentation, diagnosis & classification
27
Chapter 3: Aetiopathology
39
Chapter 4: Management: Lifestyle modification
55
Chapter 5: Management: Drug therapy
73
Chapter 6: Acute complications
91
Chapter 7: Microvascular complications
103
Chapter 8: Macrovascular complications
125
Chapter 9: Prevention
145
Chapter 10: Special situations
155
Objectives •
To understand what distance learning is and how the Certificate Course on Diabetology is delivered through Distance Learning Proj ect.
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Introduction Diabetes mellitus in people of all ages is reaching epidemic proportions in Bangladesh. In some sectors of society, more than 10% of people have diabetes. The good news is that secondary and tertiary preventions are now highly effective. Secondary prevention includes screening, modification of diet, adopting a healthy lifestyle and increased physical activity. Tertiary prevention
includes proper clinical management of the patient's condition, for
example, to prevent blindness in diabetic retinopathy. To a large extent, even primary prevention is possible and includes stich measures as dietary and exercise advice. All these preventive measures require the correct educational approach towards the patient to encourage self-care.
This means that there is a great need to educate our doctors as
efficiently and effectively as possible in this aspect. The Diabetic Association of Bangladesh has designed and produced this distance-learning course to provide appropriate education to all the doctors in Bangladesh who need to learn about the prevention and treatment of diabetes. Many of the doctors have helped to write this course and we shall be using our extensive network to deliver the course across the country. We shall offer individual study of specially prepared modules, local tutorials, supervised clinical experience and local and national assessments to assure the progress and achievement of the doctors studying the certificate course. Distance learning is an ideal educational method in Bangladesh where doctors are committed to their heavy clinical workloads, and live in geographically dispersed areas, unable to travel frequently to study centers or to take leave to study a course at another location. The entire project has been guided by experts in distance learning in science and medicine from the UK Open University. Professor Michael Stewart,
Head
of Biology and Professor
Neuroscience, and Professor. Janet Grant, Director of the Open University Center
!.b01IlcaQ4:>n in Medicine first conducted a feasibility study for distaace BugJadesh. Then they wu-keci cloeely -witJl
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leamiDg iA mediciae
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This certificate course in diabetology also offers possibilities for other public health related problems, such as malaria, hypertension or tuberculosis. The course can be adapted for use in other countries in this region and we intend to develop more advanced courses in the same style in future. We are happy to introduce this course for the education of doctors and to help our people across the country.
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Distance Learning
What is Distance Learning? Individual study of specially prepared learning materials (usually printed). The procedure uses integrated learning resources, learning experiences, feedback on learning and student support service.
Characteristics of Distance Learning •
Specially designed materials to ensure active learning
•
Rich integrated learning materials
•
Learning from student-to-student and tutor-to-student
•
Feedback on learning
•
Appropriate workload and time scale Quality assurance
11
Certificate Cou rse on Dia betology
General information •
Printed learning materials will be provided to each student in modular form.
•
There will be 1 0 modules in this course.
•
Each module will contain text and in-text activities for active learning by the student.
•
Tutorial and an 'End-module Tutor Marked Assignment' will complete each module.
•
Two ISOO-word assignments will be marked by the tutor at the end of Sth and 10th modules. [Tutor Marked Assignments - TMAs]. Each TMA will cover all topics studied so far. TMAs may comprise a combination of patient management problems, MCQs, interpretation of data, tests and investigations, short answer questions and patient orientated essay questions.
•
One end-of-course assessment will be made by the tutor [Tutor Marked Rating TMR]. Rating scale is to rate the· student on: •
End-Module Tutor Marked Assignment
•
Clinical learning
•
Attendance
•
Participation/team-work
•
Global judgment of overall performance
•
Time-keeping
One written and clinical final 'End Course Examination' [EeE] will be conducted centrally.
12
Standard setting of the course •
Students must pass all assessment components with a pass mark of at least 50%. If students fail in TMA, they will be able to reappear in the assessment within a month for the first TMA and within two weeks for the second TMA. The repeat assessment(s) will be marked centrally.
•
If students fail in any end of module assignment, the tutor may offer a remedial tutorial session.
Student must successfully complete TMAs and their TMRS prior to the final ECE [End Course Examination]. If any student fails to pass the ECE, he/she can reappear in the ECE in subsequent session.
The assessment system of the course Purposes •
Ensures that the learners reach a mInImUm standard of competence and performance. This will be done by setting assessments at a standard agreed by the project team at 3 points during the course.
•
Provides feedback to learners on their progress and attainments. This will be done by giving students the results of their assessments and discussing these with them.
•
Offers opportunities for remedial learning. This will be done by offering special tutorial advice to students who fail to achieve the required standard in any assessment.
•
Provides information about the effectiveness of the course. The results of assessments will reflect the course evaluation.
Quality assurance of the assessment system • •
Assessments will cover all chapters of the course and the overall course objectives. Students will be informed of the course assessment policy. Assessments will be clearly presented to students, along with the �'�'61 schedule.
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Course evaluation strategy and quality assurance The evaluation strategy It will comprise of 3 components:
o
Tutor feedback in weeks 12 and 24
Tutors in weeks
12
and 24 will complete a Course Evaluation Form or interview covering:
•
Strengths and weaknesses
•
Workload
•
Suggestions for improvement
•
Implementation of the course
•
Quality of administrative support Relevance of different cour se components
•
Course evaluation forms will be returned to the Central Office in Dhaka where they will be analyzed, impending actions decided, and report will be distributed to tutors. •
Student evaluation of the course in week 24
Students will complete an Evaluation Questionnaire or interview in week 24 covering: • Quality of tuition •
Support
•
Relevance of content
•
Changes in practice
•
Level of content
•
Workload including assessments
•
Project work and clinical components
•
Strengths and weaknesses Suggested improvements
Again, evaluation forms will be returned to the Central Office in Dhaka where they will be analyzed, impending actions decided, and report will be distributed to learners and tutors.
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Central or peer review visits to each centre at least once every 6 months
Peer review visits will involve review of administration records, observation of tuition, and open discussions with tutors and students.
Quality assurance Review of facilities and periodic programme review by outside experts in diabetes and distance teaching will also form part of the quality assurance process. Other essential components of quality assurance are: •
Reviewing the course in draft
•
Training and supporting tutors
•
Monitoring tutor p erformance
•
Monitoring assessments
•
Progress and outcome data
-
� 1� � dUle 10
odule 9
I 1
�
odule 8
1
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odule 7
1
TMR �
--=--'
End Course Exami nati on
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�
MOdUle
e
�
OdUle 6
1
Chapter
1
Epidemiology
/
Objectives •
To understand what is meant by prevalence rate of diabetes mellitus and how it is estimated.
•
To explain why there are differences in prevalence rate of diabetes mellitus in different places and in the same place at different times.
•
To explain how to assess the risk factors for diabetes mellitus in a population.
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Epidemiology
Diabetes mellitus, a chronic and debilitating disease, is associated with a range of severe complications namely cardiovascular disease, renal disease and blindness. Epidemiological evidences suggest that the incidence of diabetes is increasing worldwide. The management of diabetes mellitus and the managemegt and pr�vention of the complications are important challenges of the present time. There are ample evidences from applied clinical research that morbidity and mortality risks associated with diabetes are preventable. This section of the chapter will help you to understand the meaning of prevalence rate of diabetes mellitus, why there are differences mellitus in different places and in the same place at different times. You will also learn how to estimate it.
Defin ition of prevalence of d iabetes mel litus /revalence of diabetes mellitus in a defined population at a certain time is the number of . persons suffering from dla6etes mellitUs per 1 00 persons at that given time. yjc-JI"
V7Number of affected persons X
revaIence
____-=: z::s �
=
Total number of populatIon .
1 00
1.
.
In a survey in 2003 among city dwellers' of Dhaka, aged 20 years and above, documented a prevalence of diabetes mellitus as 1 1 .2%. This means 1 1 .2 per 1 00 . Prevalence people aged 20 years and above of Dhaka city in the year 2003 were • Tenn is used to express the magnitude of a disease suffering from diabetes mellitus. • It infonns the number of diseased person Here, the population defined was city dwellers of Dhaka aged 20 years, and • It is expressed as rate per hundred at given time above and the time defined was 2003 1-------"",...._--1. -
�
.
'.
- " '-
•
19
-
..
_-M----wM-
W_WMi.'"
____w__________
--0
Global trend More than 85% of diabetic patients in the world have type2liiabetes. Type2 diabetes has now reached epidemic proportions and is predicted to increase to 300 million cases worldwide in 2025, from 1 54 million in 2000. Because of the nature of the disease, alm� st all type 1 diabetics are diagnosed compared to only approximately half of type2 diabetics. The 'presept prevalence rate of diabetes in the world among the people of20-79 y'ears of age is 5 .9� ....
.�
Type1 diabetes: The worldwide incidence varies greatly, from 2 per 1 00,000 per
year in Japan to 35 per 1 00,000 per year in some Scandinavian countries. In Europe, a Denmark, Norway and the UK, compared with higher incidence is seen in Finlans1, <;�"'('\ (r�,, cO.J",-\v,,) ' Franc�y.- r
Type2 diabetes: There is a great variation in prevalence of type2 diabetes amongst
different ethnic populations. It is less than 2% in Mapuche Indians (Chile) and Chinese (China), and 40-50% in Pima Indians (USA) and Micronesians (Nauru). This variation in prevalence rate may be due to ge]5Sic susceptibili!y and environmental risk fact?rs, �uch as change in diet, .2besity and physical inactivity. Prevalen�e rate of impaired g!ticose tolerance (IGT) throughout the world is about 7.5% in people of 20-79 year� of age . .. �
----
.
. '
=
----
-
299.1,
300 • World
• SEAR
150
o
�
,
153.9 79.5
1995
2000
the year 2025 the world will have approximately
2025
300 million diabetic cases of which
79.5 million will be in South East Asia Region (SEAR)
20
Regional estimates for diabetes and impaired glucose tolerance (20-79 years age group), 2003 and 2025 are given below. 2003
--------------
Population
AFR
(20-.79) (millions) 295
No. of people with diabetes (millions)
Diabetes
(%)
prevalence
No. of people with
IGT (millions)
IGT
prevalence
7. 1
2.4
2 1 .4
7.3
EMME
276
19.2
7.0
1 8.7
6.8
EUR
62 1
48.4
7.8
63.2
1 0.2
NA
290
23.0
7.9
20.3
7.0
SACA
252
14.2
5.6
1 8.5
7.3
SEA
705
39.3
5.6
93.4
1 3.2
WP
1 ,3 84
43.0
3.1
78.5
5.7
Total
3,823
194
5.1
314
8.2
(%)
2025 Population
Diabetes
No. of people with
(%)
No.of people with
IGT
(20-79) 54 1
diabetes (millions)
1 5.0
2.8
39.4
7.3
EMME
494
39.4
8.0
36.5
7.4
EUR
646
58.6
9.1
70.6
1 0.9
NA
374
36.2
9.7
29.6
7.9
SACA·
364
26.2
7.2
29.5
8. 1
SEA
1 ,08 1
8 1 .6
7.5
1 46.3
1 3.5
WP
1 ,75 1
75.8
4.3
1 20.2
6.9
Total
5,25 1
333
6.3
472
9.0
AFR
prevalence
IGT (millions)
prevalence
(%)
j
I
.r ' t J'
I!
[AFR- Africa; EMME- Eastern Mediterranean & Middle East; EUR- Europe; NA- North America; SACA South & Central America; SEA- South East Asia; WP- Western Pacific.]
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Bangladesh trend Magnitude of diabetes mellitus in Bangladesh is increasing. Such a comment requires appropriate data on this issue. The next figure has summarized findings of 1 0 screening studies carried out from 1 966 to 2003 where any blood glucose >7.8 mmol/L after 2 hours of 75 gram glucose was considered as an abnormal glucose tolerance. Observe that in mid 60s, the prevalence rate was around l .5%, which has increased to more than 1 5% in recent years.
20 � 0
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A �
10
....
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fr �11
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A
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) .8
"-....oL
II: �
.8
1966 1983 1985 1992 1993 1995 1996 2001 2002 2003 Time(Yrs.)
Abnormal glucose tolerance (2hBG >7.8mmoVI) among Bangladeshi people In Bangladesh the current pre,: alence rate of dia�etes (amoeg the people of20-7�years of a.,ge) iit:8�. It is supposed to rise to 6.)% in 2025. Almost all are oftype�M; weI is rare. The prevalence onGT in Bangla&sh is 8.�, which will rise to 8.8% in 2025., -¥
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Diabetes mellitus is a chronic, debilitating disease that is associated with a range of severe complications. Complications due to diabetes increase with its duration. So with time, a diabetic person is prone to develop complication(s) and thereby prevalence of complications of diabetes within a population will also increase with time. Let us study the following table; it has summarized the prevalence of some complications in a diabetic population when duration of diabetes was 5 years or less, 6 to 1 0 years, 1 1 to 1 5 years and over 1 5 years in a follow-up study.
Complication
h Retinopathy lNephropathy
I
'
' '�. :":�}: '. ' ' Oura fion of OM '-
'
II up to 5,years i
6·10 years
1 5.3%
34.4%
4 1 .2%
48.5%
1 0.7%
24%
3 1.5%
39.2%
1 .6%
3.4%
3.9%
4.7%
v
/Stroke
I
II 11·15 years
>15 years
Complications of diabetes increase with duration of the disease
// valence increased �
=
(Present prevalence - Previous prevalence) X 100
-..:.---=------:--:-----"-�---'--
PrevioUS prevale
nce
,
,
Perform the activity 1.3 i n'the module 1 to understand how to calculate
prevalence of complication i n a particular population i n a particular time. '------.
------ ..-' --�� --
23
......
6 ti me s highe r ri sk for paralysis (stroke )
Le adi ng cause of ne w case s of bli ndne ss;
25 ti me s more prone to e ye proble ms
2-3 ti me s hi ghe r ri sk for he art attack �.
5 ti me s more prone to ki dne y fai lure
20 ti me s more prone to lowe r li mb
p
am utati on �
,,"
Diabetes mellitus is a serious disease
24
Epidemiological study can help us to find out the possible factors associated with a particular disease. Let us study the following report. There was a survey in Azimpur colony in Dhaka city in 1 992. Out of a total of 1 247 persons living in 1 3 5 families 23 1 of them were under 20 years. Among the remaining 1 0 1 6 persons - the mean age was 37.5 years, 503 (49.5%) were male, 1 58 ( 1 5 .6%) were obese, 20 1 ( 1 9.8%) had regular physical activity, 306 (30. l %) had hypertension, 7 1 (6.9%) were diabetic and 2 1 9 (2 l.6%) persons had known diabetes in their first-degree relatives. The total population studied for diabetes mellitus ( 1 0 1 6) was then divided into 2 groups namely diabetic (7 1 ) and non-diabetic (945) to compare the parameters between the 2 groups. The result is summarized in the table bellow.
! Total population
Parameters
Number Mean age (years) -��------
Sex (M: F) -
=i
-----
Obese
Physical activity -Familynistory ofDM Hypertension
I
Diabetic
71
1016
i
Non-diabetic
945
�--�---
51
36.5
37:34
466:479
4 1(57.7%)
1 1 7 ( 1 2.4%)
20 1 ( 1 9.8%)
23 (32.4%)
1 78 ( 1 8.8%)
2 1 912 1 �6%)
4
37.5 -------
503: 5 1 3 --
---
1 58 ( 1 5.6%) -
--
j06 (30. 1 %)
-
.Wo)
2711L8.
0
Epidemiological study to find out the risk factors of diabetes
.
•
Mean indicates 'average'
•
Frequency indicates 'number per hundred'
Perform the activity 1.4 in the module 1 to learn how to u nderstand risk
factors for diabetes i n a particular population fro", epidemiological study.
25
Chapter2
Definition Presentation Diagnosis Classification
Objectives •
To define diabetes mellitus.
•
To discuss about the aetiological factors and types of diabetes mellitus.
•
To make distinction between type 1 DM and type2 DM by observing clinical presentation.
•
To supervise the procedures for OGTT.
•
To interpret blood glucose values at fasting, at random or during OGTT for diagnosis of diabetes, IGT and IFG.
·.-t----MM--
+e+IMf4--
e+§
_M_W____+M_*.'
Definition, presentation, diagnosis and classification of diabetes mellitus Diabetes mellitus, a chronic, debilitating disease, is associated with a range of severe complications which include cardiovascular disease, renal disease and blindness. Demographic and epidemiological evidences suggest that the incidence of diabetes is increasing worldwide. The management of diabetes mellitus and the management and prevention of its complications are major challenges for the future. There is ample evidence from applied clinical research that morbidity and mortality risks associated with diabetes can be reduced by strict glycemic control.
This, module will provide you with the opportunity of memorizing the different cutoff values for raised blood glucose at different investigation settings. The activities will develop your skill to label individuals suffering from diabetes. It will also familiarize you with clinical differentiation of different classes of diabetes, particularly typelDM vs type2DM.
�----
Definition
Diabetes mellitus is a metabolic disorder resulting in raised blood glucose (hyperglycemia) from defects in insulin secretion, insulin action or both that arise from genetic as well as enVironmental factors. It i s Diabetes mellitus . defined b y documenting raised ."i:;«1__� in fastillg state • Blood glucose goes up • Symptomatic or asymptomatic • High risk of complications (acute/chronic)
29
-
Perform the activity 2.1 in the module 2 to u nderstand hyperglycemia and it's cutoff values for diabet.
Clinical presentation The spectrum of presentation ranges from asymptomatic to typical features.
Asymptomatic cases are diagnosed by biochemical test only. Type! DM is always symptomatic and shows classical features of glycemia.
A vast maj ority types
remain
of type2 DM and other asymptomatic
for a
prolonged period, until blood glucose persistently remains above the renal threshold.
Presentation of OM
hyper
Routine or annual health
•
Asymptomatic (no symptoms)
•
Typical (classical symptoms)
•
Atypical (unusual symptoms)
•
With micro/macro-angiopathy
check-up usually picks up this form of presentation of diabetes.
Typical features of diabetes mellitus : Typical features start with 'glycosuria', which means loss of glucose in urine, that begins after the blood glucose level has gone above the individual's 'renal threshold' for glucose. Features include: •
Polyuria, means increased urination
•
Polydipsia, means increased thirst
•
Polyphagia, means increased hunger
•
Weight loss
•
General weakness
30
In type l DM, where there is total lack of insulin from the beginning of disease, presentation is always a typical one. In type2 DM and other forms of diabetes mellitus, presentations may remain asymptomatic for quite a long period after the onset of diabetes. In practice, about 20% cases of type2 diabetes present with one or more features related to diabetic complications such as rnicro and macro-angiopathies.
Microangiopathies
Macroangiopathies
•
Diabetic retinopathy
•
Cardiovascular disease
•
Diabetic nephropathy
•
Cerebrovascular disease
•
Diabetic neuropathy
•
Peripheral vascular disease
31
Diagnosis Diagnosis is based on documentation of glucose intolerance in the subject. Procedures for documenting glucose intolerance •
Oral glucose tolerance test (OGTT), or
•
Random (un-standardized) blood glucose level, or
•
Fasting blood glucose level
Oral glucose tolerance test,
-
,
(OGTT)
.
This is the standard procedure where 2 blood glucose levels - at fasting and at 120th minute after 75 grams of oral glucose drink classify a person as a diabetic, IGT (impaired glucose tolerance) or non-diabetic (normal).
• •
Test: OGTT
FBG � 7.0 mmollL
=
OM
At 120 minute � 1 1. 1 mmollL = OM
Random blood glucose (RBG) RBG can suspect diabetes only by inferring whether diabetes is likely or unlikely; but often falls in uncertain range. So such test result, should be interpreted along with the clinical background and very often demands OGTT for subjects falling in uncertain range.
Test: RBG •
BG � 1 1. 1 mmollL
•
BG < 5.5 mmollL =
OM is likely OM is unlikely
=
Fasting blood glucose (FBG) By fasting blood glucose level a person can be labeled as a diabetic on�y if it is above a set , value (7.0 mmollL in venous plasma); and as normal fasting glucose (NFG) if it is below another set value (6.0 mmoIIL). If it lies in
32
Test: FBG •
BO � 7.0
•
BO � 6.1 to
mmollL = DM < 7.0 mmo l lL
=
IFO
Inferences of glucose levels in different diagnostic set up are given below as per WHO diagnostic criteria of 1999.
: I
Inference
.
.
Diabetes mellitus (DM)
0 min glucose level (venous plasma)
.
120 min glucose level (venous plasma)
� 7.0 mmoVL
�1 1 . 1 mmoVL
Impaired glucose tolerance (IGT)
< 7.0 mmollL
� 7.8 to < 1 1 . 1 mmoVL
Impaired fasting glycemia (IFG)
� 6. 1-< 7.0 mmollL
< 7.8 mmoVL (if measured)
Normal
< 6. 1 mmoVL
< 7. 8 mmoVL
----- ------�----
Or al glucose tolerance test (OGTT)
Inference
Random glucose level (venous plasma)
Diabetes mellitus likely
� 1 1 . 1 mmoVL
Diabetes mellitus uncertain
5.5 to < 1 1 . 1 mmoVL
Diabetes mellitus unlikely
< 5.5 mmoVL
[ Cases of uncertain group should under go OGTT. It is useful when a person is suspected to have diabetes mellitus on clinical ground.]
Random (unstandardized) blood glucose level
Inference
Glucose level (venous plasma)
Diabetes mellitus (DM)
�7.0 mmoVL
Impaired fasting glycemia (IFG)
� 6. 1 to < 7.0 mmoVL
Normal
< 6. 1 mmoVL
All IFG cases should undergo OGTI. A person of either NFG or IFG if subjected to oorr may become i.diaI»etic or IGT.]
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OGTT procedure Fasting state:
fast.
The test should begin in the morning after a 8-1 4 hours of overnight -
Carbohydrate in meals prior to the test:
Person should take unrestricted diet containing at least 1 50 grams of carbohydrate daily for at least previous 3 days. First blood sample:
A fasting blood sample prior to glucose drink is collected.
Glucose drink: An
oral glucose load of 75 gm for adult, 1 .75 gmlkg body weight up to maximum 75 gm for child, is given in 250-300 ml of water. The drink must be completed within 5 minutes: A blood sample is collected at 1 20th minute after the glucose drink. If glucose is not estimated immediately then the blood sample may be preserved with sodium fluoride (6 mg/ml whole blood). Blood should be centrifuged, and plasma separated and frozen until estimation. Smoking, tea or physical stress is not allowed during the test.
Second blood sample:
Glucose in urine and diabetes mellitus Sometimes you may wonder �hether urine examination for glucose can be used as a diagnostic tool for diabetes. Glucose in urine (glycosuria) informs us that blood glucose . the person has crossed above hislher renal threshold for glucose sometime or all the during the formation of urine. Therefore, it is not a diagnostic parameter of diabetes.
34
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Classification
Diabetes mellitus is usually divided into 4 distinct types of which first 2 are the major classes: 1.
Typel Diabetes Mellitus (TIDM)
2. 3. 4.
Type2 Diabetes Mellitus (T2DM)
Other specific types Gestational Diabetes Mellitus (GDM) Type! diabetes mellitus tends to occur in the young, although it can occur at any age, and usually in people who are lean. Onset of symptom is usually rapid. It is caused by 'autoimmune destruction of the beta-cells in the pancreas, resulting in no insulin production. Although there does not appear to be a strong genetic link, there may be a genetic susceptibility to the disease. Environmental factors and viral infections have also been implicated. Patients with typel diabetes are dependent on insulin to survive, so previously they were called insulin dependent diabetes mellitus (IDDM). Type2 diabetes mellitus
occurs more often in older people who are obese and lead sedentary lifestyles . Onset of symptoms is slower and the disease may. remain undiagnosed for many years. It is associated with both impairment of insulin secretion and resistance to insulin action (insulin resistance). Type2 diabetes is often associated with a strong genetic predisposition, more so than type 1 diabetes. Once diagnosed, an improvement may result from weight reduction, dietary modification and increased exercise . Oral hypoglycemic agents and, in advanced cases, insulin, may be required. Type10M
Type2 OM
Present
Absent
Age of onset*
< 30 years
> 30 years
Body habitus*
Normal to wasted
Obese/over-weight
Insulin reserve
Low or absent
Normal or high
Ketoacidosis (DKA)
HONK
Responsive
Responsive
Unresponsive
Responsive
Symptoms
Sudden, classical
Gradual, atypical
Genetic correlation
Less; HLA-linked
Markers of � -cell destruction
Acute complications* Insulin therapy* Sulfonylurea therapy*
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Although the 2 major classes can be characterized by defective carbohydrate metabolism resulting in hyperglycemia, they are clinically different in many ways. cover a group of diabetes where the cause of hyperglycemia can be attributed to factors such as drug, disease or genetic syndrome, etc. Clinically these groups of cases will posses_ features of both diabetes and the underlying causal factor(s). For elaborate classification of this group consult text books of diabetes. Other specific types of diabetes mellitus
Some examples of other specific types of diabetes mellitus: Endocrinopathy
Drugs
&
•
Cushings syndrome
•
Glucocorticoids
•
Acromegaly
•
ACTH
•
Thyrotoxicosis
•
Diazoxides
•
Hyperaldosteronism
•
Diuretics
•
Pheochromocytoma
•
Phenytoin
•
Pentamidine
•
Vacor
[ FCPD= Fibro-Calcific Pancreatic Diabetes]
Gestational diabetes mellitus (GDM)
Pancreatic disease
toxins
I
•
•
FCPD Chronic or recurrent pancreatitis
•
Hemochromatosis
is glucose intolerance of any severity (lF G/I GT/DM ) detected in a pregnant woman who was not known to have these abnormalities prior to conception. This definition is valid even if there is a chance that some of them. might have had this abnormality earlier. A significant portion of the GDM cases become normal after delivery. Once the GDM woman becomes normal, she has increased risk of developing GDM in subsequent pregnancies. She will also have increased risk of becoming a diabetic later in life.
36
Glucose concentration, mmol/l (mg/dl) Whole blood Plasma Venous Capillary Venous
-------
Diabetes Mellitus:
Fasting or
� 6. 1 (� i 10)
� 6. 1 ( � 110)
� 7.0 (� 1 26)
2-h post glucose load
� 10.0 (� 1 80)
<
� 1 1 . 1 (� 200)
Fasting (if measured) and
<
� 1 1 . 1 (�200)
2-h post glucose load
� 6.7 (� 1 20)
� 7.8 (� 1 40)
� 7.8 (� 1 40)
<
� 5.6 (� 100) and
<
� 6. 1 (�J 1 0) and
Impaired Glucose Tolerance (IGT):
Impaired Fasting Glycemia (IFG):
Fasting
6. 1 « 1 10) and
� 5.6 (� 100) and
and (if measured)
<
2-h post glucose load
6. ' 6.7 «
1 20)
<
6. 1 « 1 10) and
6. 1 « 1 10) 7.8 «
1 40)
<
7.0 «
1 26) and
<
7.0 « 1 26)
<
7.8 «
1 40)
Values for diagnosis of diabetes mellitus and other categories of hyperglycemia (as per WHO Expert Committee 1 999) Unstandardized (casual. random) blood glucose values Whole blood Venous
Capillary
Venous
mmol/litre (mg/dl)
I
10.0 (lS0)
I
4.4 (SO)
Plasma
Glucose concentration
11.1 (200)
4.4 (SO)
15 (270)
14 13 12 11 10
(1ao)
9 8 7 6 5190) 4 3 2
I I I
11.1 (200)
5.5
37
Capillary
(100)
12.2 (220)
5.5
(100)
I �
Diabetes mellitus likely
Diabetes mellitus . uncertain
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Reference and further reading
l. 2.
Report of WHO Consultation -Part 1 , 1 999, WHO, Geneva. Text Book of Diabetes-3rd Edition -Vol 1, edited by John C. Pickup and G. Williams, Blackwell Science, 2003, p 2. 1 to 2. l3.
3.
Clinical Practice Recommendations, 2007, ADA.
38
Chapter3
Aetiopathology
Objectives •
To describe the relationship between blood glucose and insulin in healthy people.
•
To discuss insulin actions.
•
To discuss consequences of insulin lack and insulin resistance in diabetes.
•
To identify the factors (modifiable & non-modifiable) associated in a diabetic person.
•
To describe pathogenesis of diabetes mellitus.
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Aetiopathology Diabetes mellitus primarily affects the carbohydrate metabolism; but it also affects protein and fat metabolism. The disturbed metabolism is due to defects in insulin secretion or insulin action or both. Although the metabolic derangement of diabetes is related primarily to the failure of efficient glucose uptake by insulin dependent cells but it also produces an altered scenario of protein and fat metabolism of the whole body. The causes and events related to defects of insulin production and action rest on genetic susceptibility and are aggravated by some modifiable and un-modifiable risk factors. Understanding both physiological and pathological events are fundamental to the understanding of the disorder for appropriate management strategies. This chapter will provide you with the opportunity of understanding how blood glucose level is maintained after taking food and in between meals, and how biochemical abnormalities set in by the abnormalities (pathology) of secretion and action of insulin in diabetes mellitus along with factor(s) responsible for doing so.
Normal glucose homeostasis
Our body cells/tissues can be divided in to 2 groups on the basis of their dependency on insulin for uptake of blood glucose: 1.
Insulin independent
2.
Insulin dependent
blood glucose can enter into the cell without the help of insulin. blood glucose cannot enter into the cell without the help of insulin. 41
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Gl ucose homeostasis d u ring fasting state
Pancreas Insulin
Liver
Glucose homeostasis during fasting state In between meals and throughout the night when there is no glucose supply to blood from the gut our body mechanism is adjusted to ensure glucose supply to the vital tissues by the following three processes: ". Insulin secretion goes down ( 1 ) Increased hepatic glucose output (2) and • • Glucose uptake by insulin independent cells (Brain, RBC etc) (3). Insulin independent cell •
• •
•
•
42
Brain cells Gut epithelium Cells of nephron Red blood cells �- cell of pancreas
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Gl ucose homeostasis after food i ntake Pancreas
Liver
Glucose homeostasis after food intake Following ingestion of meal, when there is excess glucose supply to blood from the gut our body mechanism is adj usted to ensure euglycemia by the following three processes: \.
• •
Insulin secreti on increases ( 1 ) Suppression of hepati c glucose output (2) and
Glucose uptake by insulin " dependent cells (muscle, fats) (3).
The meal/glucose-induced hyperglycemia can independently enhance muscle glucose uptake (mass effect) and suppress hepatic glucose output, but these effects are modest compared to those of insulin. Abnormalities at any of these sites, namely the �ell (insulin secretion), muscle and/or liver (insulin action) can lead to development of glucose intolerance. Consequences of such alteration are immense; fuel economy of the total body needs to be altered. Insulin dependent cells increase their fat and Rrotein expenditure for energy while the others also need some adaptation to face the excess glucose that enters into the blood; as a result there is rearrangement in the whole metabolic system.
43
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I ns u l i n secretion i n healthy subjects
I nsulin
Time
Insulin secretion in healthy subjects Blood glucose is the principal stimulator of � -cells of the pancreas to secrete insulin. There is a continuous 10'Y-level secretion of insulin (approximately 1 unit per hour) between meals and· throughout night. It is called basal insulin. So about 24 units of insulin is secreted as basal secretion.
•
•
.
Following meals there is sharp rise, which is called prandial or bolus insulin. . release . The rate and amount of secretion is influenced by amount and composition of meals . dn an average there is also another 24 units of insulin secretion per day as meal related bolus.
Total lack of endogenous insulin results in type l DM; while two abnonnalities - insulin .secretary defect and insulin resistance take part in the development oftype2 DM. There is a lot of debate on 'which one is primary?' Currently a large body of evidence and consensus is available to show that for the full-blown disease process in the syndrome of type2 DM, --.a..._ �......_...;_ both the defects are obligatory. ;.. �__________' -..
_ _ _
44
-
�-cell stimulation by glucose Ca+ Channel
Ca2
II
ATP ADP
Insulin secretory granule
�-cell stimulation by glucose
1.
2. 3. 4. 5. 6.
7.
Blood glucose molecules enter into the cell through the glucose transporter 2 (GLUT2) of cell membrane. This does not require insulin because this is an insulin independent cell. Within the cell ATP/ADP ratio goes up due to glycolysis Potassium channel gets blocked Membrane becomes depolarized Voltage-gated calcium channel gets opened Calcium gets in and Insulin is released by exocytosis I N
1st Phase
S U L I N
Basal o min
O=======:J
10 min
Patem of insulin secretion after meals Basal insulin release becomes bolus in response to a raised blood glucose level as in the piandial state. A bolus release shows 2 phases- 1 st phase is a sharp and transient rise for less than 10 minutes; that is followed by 2nd sustaihe!ttpllase which persists tiD the blood glucose goes bact Be8t to basal s1ate.
45
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Effect of insulin
Action of insulin
• Increased glycogen synthesis
• Stimulation of glycogen synthase
Liver
S
• Decreased glycogen breakdown
• Inhibition of glycogenolytic
• Inhibition of neoglucogenesis
enzymes • Inhibition of neoglucogenetic
enzymes • Increased glucose transporter
Fat
• Increased entry of glucose into fat cells
activity
• Reduced TG levels
• Increased lipogenesis
•
• Reduced availability in plasma of
Decreased lipolysis
neoglucogenic substrates
• Reduction in number of LDL particles
Skeletal muscle
• Increased glucose transporter
• Increased entry of glucose into muscle
• Increased protein synthesis
• Increased muscle mass
• Increased glycogen synthesis
• Build-up of reserve stores of energy in
activity
cells
muscle
• Decreased glycogen breakdown
• Prolonged endurance
Actions of insulin and its effects at different tissues
-'
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Pttrform the activity·3:1 nn�the moq�le 3 to understand- utilization of blood glucose by cells and its relationshlp,with insulin-secretion' in non-diabetic. ,
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Pathophysiology Hyperglycemia, the biochemical hallmark of the state of diabetes mellitus, is the reflection of different pathophysiological mechanisms playing differently in different classes of diabetes. Environmental factors trigger the diabetogenic process in a genetically susceptible individual. Impaired insulin production and/or hinderance to action of insulin are the ultimate mechanisms of hyperglycemia. The complications in diabetic state are most likely secondary to hyperglycemia.
Pathway to the development of d iabetes
Healthy people with genetic -susceptibility
Diabetogenic insult(s) (environmental)
Diabetogenesis ..
i
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_
47
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Pathogenesis of type1 DM
Some key points
lack is the key defect in typel DM.
•
Absolute insulin
•
Hyperglycemia starts abruptly.
•
If not treated with insulin,
acute complications cost the life within a short period.
Insulin lack is present at the time of clinical onset of the disease and throughout the entire clinical course. Though some residual beta cell function may be seen (as demonstrated by C-peptide levels) and transient periods of remission can occur producing the so-called 'honeymoon' phase of the disease. The decrease in insulin secretory capacity is due to actual loss of immunological mechanism of
�
�
-cell mass. An
-cell destruction is initiated and maintained by
interplay of genetic and environmental factors. The precise nature of the genetic influence in the pathogenesis of type l DM is still unclear. Identical twins show only about 5 0% concordance. HLA DR3 and DR4 are associated with a 3 to 5
_
folds increase in risk for type l DM, and the risk of the disease in the double heterozygote individual with DR3 and D� increases almost 1 0 folds. HLA B s and B 1 5 also show similar associations. Increasingly HLA BsIDR3 are associated with a persistence of islet cell antibodies in patients with type l DM, whereas HLA B 1 5 IDR4 are associated with development of high titer of insulin auto-antibodies .
/
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48
6
-_-M----w·--
_W@
+_WI_.4"
_.'-,WMM_W__W_
Genetic susceptibility _�>------=;:==-_ Environmental factors (Virus, toxins etc.) (HLA linked) I mmune response T Lymphocytes
B
Lymphocytes
Absolute lack of insulin
r------�---�� r/---�--��-----. Hyperglycemia
+ other metabolic abnormalities Pathogenesis of type 1 DM
0 :.= c
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120 100 80 60 40 20 0
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Time (years)
49
2
3
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Pathogenesis of type2 D M Some key poi nts Type2 DM is more heterogenous than type ! DM
in respect to aeti opathogenesis
.
•
The basis of metabolic impairment i.e. hyperglycemia is a defective insulin response to glucose and insulin sensitivity.
•
The impact of the two components varies over a broad scale.
•
A few patients may exhibit severe impairment of insulin release and normal sensitivity.
•
Another small group of patients demonstrate exaggerated insulin release.
•
Inheritance of the disease is multifactorial.
•
Complete concordance in monozygotic twin for type2 DM has proven the strong genetic basis of the disease.
I nsulin release ' Basal insulin secretion is normal in non-obese and high in obese type2 DM patients. But there is impairment of the capacity of � -cell to release insulin when stimulated by glucose or carbohydrate-rich meal. Dynamic assay of insulin release - documents: • •
suppressed first phase of insulin release second phase/may be low, normal or high
In all type2 DM cases the first phase insulin release is blunted or absent even before they develop glucose intolerance. This state, which interpolates between birth and appearance of glucose intolerance is now termed as pre-diabetic state.
50
I nsulin resitance This is also an early finding in type2 DM especially in obese and some non-obese patients. The molecular basis of the resistance seems to reside both at the receptor as well as post receptor levels. Observations like higher basal insulin level, decreased effect of exogenous insulin, glucose clamp with insulin infusion study, low insulin receptor concentration etc. provide ample support to this component of type2 DM. Causes
PCOS Typ e2 DM Hyp ertension Effects
Insulin resitance - causes and effects
Metabolic syndrome or insulin resistance syndrome It is combination of 3 or more of the following features : •
• • •
Waist circumference � 90 cm in male and �
80 cm in female
BP � 130/85 HDL < 40 mgldl in male and < 50 mgldl in female TO � 150 mgldl FBG � 5.6 mmoIIL
51
M-.-M____--
... _.M...
.Mij
---M:--------__
The natural history of the type 2DM disease spectrum It starts by breakdown of healthy status of a genetically susceptible individual. Earliest abnormality is low insulin response without any glucose intolerance. Glucose intolerance begins with the appearance of IFG or IGT. Ultimately it reaches the severe diabetic level.
l Aging
Genetic susceptibility
Environmental factors (physical inactivity, obesity etc.)
(Insulin secretion nonnal; sensitivity.Ji-) with nonnal glucose tolerance
....
Earliest stage
....
IFG f lGT state
�
Diabetic state
•
(Insulin secretion .Ji- ; sensitivity ,J,.) with mild glucose intoleran�e
• (Insulin secretion '!" '!" ; sensitivity'!") with moderate to severe glucose intolerance
.-
�
Asymptomatic Symptomatic Complications
---
Pathogenesis of type2 DM 250 g 200 U c: 150 .2
16 100 E � 50 '*
0 -10
-5
o
5 ·
10
Time (years)
52
15
20
25
30
Reference and further reading 1.
Text Book of Diabetes _3rd Edition vol 1, edited by John C. . Blac:kweIl Science, 2003 , p 20. 1 to 3 1 . 14.
53
Pickup aad O. WdilillllllJ
Chapter4
Management: Lifestyle modification
. Objectives •
To discuss the issue regarding adj ustment of one's daily life by planning of meal, daily activities including exercise with specific targets that will enable living healthy inspite of diabetes.
•
To acquire the skill to provide hands-on training of self monitoring of blood glucose (SMBG), urinary glucose, protein and ketone body tests, etc.
•
To discuss the basic principles of dietary modifications in diabetes and to teach healthy eating.
•
To make recommendations for intensity, duration and frequency of exercise for individual patient.
56
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1-\ 1
Lifestyle modification Management of diabetes mellitus, till date, is aimed at supporting people to live with diabetes with minimum or no risk of complication(s) and there is ample evidence that such an aim is achievable by achieving some specific targets of blood glucose, lipids and body weight etc.
This chapter will help you to understand the role of diet, physical activity and self monitoring of blood glucose in achieving the targets of diabetes management.
Diabetes mellitus is a life long disorder. The type ! DM is a deficiency disorder from the onset and its management is 'efficient replacement of the deficiency' and life style needs to be synchronized with insulin administration. But type2 DM is more complex disorder and here lifestyle modifications / inter ventions has the potentiality to ,,,..,.......,,� some of factors which are only proven as risk factors deve� .diabetes but also --
detelioratioa
Blood Glucose
•
•
•
HbAl c
•
Lipid
•
• •
in
lk mdividaal .
57
<< 7.0
Fasting < 6. 1 mmollL [ 1 1 0 mgldl] Post-prandial 8.0 mmollL { 145mgldl] mmollL [ 1 25 mg/dl] Bed time
< 7.0%
<
LDL Cholesterol
< 100
mg/dl HDL Cholesterol > 40 mgldl Triglyceride 1 50 mgldl
---
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A significant portion of these type2 DM patients can achieve and maintain the targets set for management for quite a long period (if diagnosed early). Drug therapy, particularly secretagogues are added along with the lifestyle changes when the treatment target falls below that is to be achieved. Insulin may be combined with drugs (combination therapy) or replace the drugs (specially when it is contra daptation to regular physical activity . indicated or fails), and the lifestyle modification becomes more important ke part in monitoring treatment outcome as because that needs to be synchronized with drug/insulin administrations.
�
ya
The important issues of lifestyle of a diabetic include their dietary habit, p�ysical activity and exercise, foot care and footwear habit and involvement in monitoring blood glucose such as self monitoring of blood glucose (SMBG) etc.
J-8ss stringent control of diabetes .r Less strict control of blood glucose is appropriate for ,
'--...
:
\.r;Very young children � . Older people � Persons with history of severe or repeated hypoglycemia v-e Limited life expectancy Y Presence of comorbid conditions ,
HbA1 c Glycated haemoglobins are formed by non-enzymatic condensation of glucose with globin component of haemoglobin. They generally reflect glycemic status over the preceding 2-3 months. HbAlc estimation is to be done at least twice a year in stable controlled diabetes. It is to be preformed quarterly in uncontrolled diabetes or in .case of change in therapy. It is not yet approved as screening test for diabetes.
58
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---
Medical n utrition thera py ( M NT) A proper diet is a fundamental element of therapy in all diabetic individuals. A diet recommended for a diabetic patient is, in fact, a 'balanced diet' for anyone. A balanced meal is a combination of carbohydrates, fats, proteins and fibers appropriate for the individual. A diet plan should be individualized according to his/her needs; it must be simple to understand and easy to follow.
Goals of dietary modification •
To eat a balanced meal
•
To have regular meal
•
To attain and maintain desirable body weight
•
To provide adequate nutrition for health and growth in pregnant and lactating mothers, and children
•
To preserve th� pleasure of eating
Carbohydrate
Fat
Protein
50-60% of DCI
30% of DCI
1 0-20% of DC I
Fibre 20-35 gm
Saturated fat < 7% Cholesterol < 200 mg
, A recommendation of daily calorie intake (DCI) for � diabetic by WHO
Carbohydrates Refined or simple carbohydrates e.g. sugar, glucose, soft drinks, jam, honey, mannalade, sweets, Cakes, chocolate etc. should be avoided because they are quickly � in the. body aOO"caUse sudden·rise in blOOd sugar level.
59
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Unr@ned or cQffiPlex carbohydrates such as bread, cereals, potatoes, rice are more suitable, . �s they are digested more slowly in the body and cause less rapid rise in blood sugar levels.
Fats and oils A reduced intake of fat (particularly saturated) i s recommended. Foods high i n saturated fat are butter, margarine, fried foods, cakes, chocolate, dairy products etc. Fatty foods have high calorie which lead to weight gain and increase the risk of heart disease.
How to cut down fat in food? •
Adopt cooking methods other than frying e.g. boiling, roasting, stewing, grilling etc.
• Trim any visible fat from meat (fats solid at room temperature are high in saturated fat). •
Choose poultry and fish (avoid chicken skins).
•
Avoid high fat containing foods such as cream, ice cream, chips, sausages, roast potato, processed meat.
Proteins Protein is essential in meal. A diabetic should receive adequate protein. Animal source : provides better quality protein. Egg, milk, meat, fish, Poultry are protein rich foods from
animal source. Plant source : individually provides less good quality
u.. v ._.... u
but when two Complimentary types of plant proteins are
itolp� a"aaality iaJptoves. PoIses. cereals" nuts are the sources of l*llUI
60
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Simplified guideline for calorie allowance
� To
r persons over the age of 50 years, with light to moderate activity, total daily calorie . allowance can roughly be calculated by the following formula: Daily calorie allowance (Kcal)
=
Ideal body weight (lEW) X 30.
=-;:..
This allowance is proportionately reduced in sedentary, elderly and over-waightlobese; it is proportionately increased in higher physical activity, younger age group, under-weight, pregnancy and lactation. IBW can be obtained from standard height-weight charts. It can roughly be...calculated by subtracting 1 00 from height (in centimeters). -"
61
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MNT in type1 diabetes A meal plan based on the individual 's usual food intake should be determined and used as the basis for integrating insulin therapy into the usual eating and exercise patterns. It is recommended that individuals using insulin therapy eat at times synchronized with the time of action of the insulin preparation used. They also need to monitor their blood glucose regularly, -.@d adjust the insulin dose against the food and activitx level. It is recommended that carbohydrate is to be evenly distributed over the day, to eat meals and snacks at regular intervals and maintain a regular eating schedule from day to day. The timing and type of insulin regimen should ideally be based on the eating and exercise ofthe person and blood glucose levels.It is geperally easier to adjust insulin dosage
ha�
and timing instead of changing eating habits. Intensive insulin therapy requiring multiple
insulrn doses especially wIth new analogues or insulin infusion pump allows more flexibility in food and exercise regimen. Individuals on intensified insulin regimens can make adjustments in rapid or short acting insulin to �over the carbohydrate content of their
�
meals, and for deviations from usual eating and exer se habits. It is important to space the meals (spreading nutrient intake, particularly carbohydrate, throughout the day). Intake of complex carbohydrates with low glycemic index and high fibre is recommended. According to life style, distribution of calories may vary. Total daily food intake should be distributed consistently throughout the day, especially for carbohydrate intake. •
3 main meals - breakfast, lunch and dinner
•
2-3 snacks - mid morning snack, afternoon snack etc
•
, bed-time snack is important to avoid nocturnal hypoglycemia
i'i!Y, life style and
Tin;ililg and amount of food will depend on type of insulinJlhysical act .
result� of blood glucose monitoring.
62
,
-�-----
."
•
Sancks 1 5%
•
Dinner 30%
0
N
•
Breakfast 20%
•
Lunch 35%
Distribution of meals . What is important to remember is to synchronize the meal and insulin peak times. Different insulins have different peak times and this needs to be taken into consideration, when planning the meals. It may now be possible to choose the right pre-meal insulin to suit the different food habits.
MNT in type2 diabetes The main aim for individuals with type2 diabetes is to ac�ve and maintain glucpse� and body weight goals. Distribute and space calories and carbohydrates evenly over the day. If overweight they are advised to go on to a low caloric diet. A moderate caloric restriction (250-500 calories less than qverage daily intake as calculated fr� a food history) and a mftritionally adequate meal plan witlia red �ction of total fat, especially satur� along with an increase in h sical activity should be recommended. A� calonc diet (independent of weight loss) is associ�ed with increased sensitivit to insulin and improvement in blood glucose level. Mederate weight loss (5-9 kg), irrespective of initial wei.ght, has been shown to reduce hyperglycemia, dyslipidemia, and even " hypertension if exists. Regular. exerci�� �d making healthy lifestyle changes help in managing the type2 diabetes better. However; if individuals with diabetes after having made all the lifestyle changes are . unable to improve their metabolic control, they should consider the need to add an oral glucose·;lowering agent and/or insu� for th�ir treatment.
63
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Meals should be uniformly distributed throughout the day.
-./.
3 main meals - breakfast, lunch and dinner
/�nacks should not be encouraged in over-weight persons J. The obese should be on appropriate calorie restriction to favour a (
gradual weight correction programme
Timing and amount of food will depend on type of drug/insulin, physical activity, life style _ """and�esuifs of blood glucose monitoring. =-
..,;;;;
Special diet counseling and monitoring by dietitian
It is necessary in children, adolescent, pregnant women and other medical conditions where dietetics are of direct concern. All diabetics should be referred to a dietitian for counseling at diagnosis of diabetes and also subsequently if they have problem with their diet adjustment.
T1 OM
Strategy
T2 OM Obese
T2 OM Non-obese
Regular meal timing
H
M
M
Consistency of day-to- day intake
H
M
M
Meal spacing
M
H
M
Sucrose limitation
M
M
M
Exercise
M
H
H
Calorie restriction
L
H
L
Blood glucose monitoring
H
H
H
[H-High priority, M-Moderate priority, L-Low priority]
Strategies for medical nutrition therapy in diabetes
64
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Meal planning approach The diet remains the biggest problem in diabetes care. The health professionals typically blame the patient as being non-compliant, while the patients feel the health professionals do not approach the problem in a more realistic and practical manner. One of the main reasons for this 'non-compliance' is lack of nutritional self-management training. Depending on the individual patient's learning capabilities, clinical needs, level of motivation, activity level and lifestyle, different methods of teaching can be used. . In the initial stages basic information needs to be given:
�asic nutrition guidelines
�
,
- ',
,
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ealthY food choices (signal s stem, which classifies foods based on a traffic light system: green - , healthy, yellow. - less healthy and red - least healthy food s)
�
�iabetes diet pyramid
In the second stage, individual meal plan is made using individually determined goals. This can be accomplished using any of the three methods or a combination of all: -<
• • •
Food exchange system
-
'
Carbohydrate counting '"
Glycemic index
Fats, Oils & Sweets Sparingly Milk & Milk Products 2-3 Servings
Meat, Fish, Egg, Nuts & Dry beans 2-3 Servings
Fruits 2-4 Servings
Vegetables 3-4 Servings
Cereals, Rice & BTeM 6-1 1 Servings _,
' ,.
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Diabetes diet � 65
____�_____"""""
Dietary assessment The purpose of the dietary assessment is to identify a person' s eating habits and to estimate the average daily nutrient intake. Through a variety of methods, information can be obtained on the amount and type of food eaten.
24-Hour recall
•
trained interviewer asks an individual to recall all foods
.
consumed in the past 24 hours.
Food records
•
-
individuals are asked to record food intake over a specified
period of time. Example of food record sheet is given below. This can be used as recall sheet also.
Meal
Time
Be d te a
Food items
Amount
0
_1__ i -- --- +-------t--- ---Ir---- -t-- ----- -+-I-�· , L� __ _
B re akfast M id morni ng snack Lu nch Eve ning te a P re- dinne r dri nk D inne r
I
t=�-
,
-
- -+ -----
Be d time snack
•
Weighed food records
•
the dietary history method of assessment is used to evaluate usual intake in an individual over a long period of time .
•
the subject is instructed to weigh and record all ingredients and foods consumed.
Dietary history
. ,
-
-
Food frequency questionnaire a food frequency questionnaire (FFQ) is used -
to determine the frequency of consumption of certain foods.
Alternative sweeteners
Sweetening agents which provide sweetness but little calories are now approved for use. Non-nutritive sweeteners include a&Partame, neota.I!!e, saccharin, acesulfame and sucralose. \ ' ...... . 01, etc. It s mclude sorbitol, , 66
Alcohol
Alcohol has various adverse effects in diabetes. Daily intake should be limited to one dink ( 1 5 gm alcohol) or less in females and two drinks (30 gm) or less in males. Alcohol should be avoided in pregnancy, liver disease, pancreatitis, advanced neuropathy and severe hypertriglyceridemia.
Anthropometric measurements Nutritional anthropometry helps to determine nutritional status of an individual. Anthropometric measurements used commonly are: •
Body mass index: Weight and height measurements help to determine body
mass index (BMI). It is calculated by the formula: BMI Weight in kg / (Height x Height) in meter. BMI helps diagnose and grade obesity using standard normograms. = -
�
8MI (kg/m2 )
Category
< 1 8.5
Under - weight
1 8.5-24.9
Normal
25.0-29.9
1--------- -
30.0-39.9
- -
/---------- -- -
> 40.0
•
------
-
Over-weight Obese Morbidly obese
Waist hip ratio: Waist and hip circumference measurements help to calculate
the waist hip ratio (WHR) or the abdominal-gluteal ratio (or android-gynoid ratio). WHR is the abdominal (waist) circumference divided by the hip circumference .
Waist or abdominal circumference is measured at midway between the costal margin and iliac crest; it is the s�est circumference at the waist.
Hip or gluteal circumference is taken as the largest circumference at the posterior eXtension of the buttocks measured over the greater tmchanters. 67
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Central adiposity, rather than total adiposity, is considered an important risk marker, for various/cardiovascular and metabolic diseases. The higher the waist hip ratio, the greater is the risk. Based on fat distribution, body shape is referred to as, being 'pear' or 'apple'. The pear Shape is preferable to an apple shape. Persons with an apple shape, have a higher WHR, and are at a greater risk for cardiovascular complications, than persons with pear shaped bodies. Men may be considered to have higher risk, if the WHR is > 0.9 and women if it is > 0.8. Waist circumference of <90 cm in male & <80 cm in female is desirable. ( -
.....
-
,
-
r
Benefits of weight loss
Loss of body weight in over-weight/obesity is associated with: . •
Fall in mortality Fall in blood glucose Fall in blood pressure Inprovement in blood lipids (all components) Fall in cancer-deaths
68
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_ _ _ _
�Exercise i n diabetes mell itus Exercise is an important component of treatment plan of diabetes. In addition to physical fitness exercise helps in � -, ' Aims of exercise · controlling blood glucose, lip� a'itd blood pressure. ! �To achieve good metabolic control of diabetes It helps to E1��ntain ideal o reduce excess weight i . weight. It prevents atheroTo increase physical capacity sclerosis and thereby I improve sense of well-being and quality of life macroangiopathic To improve cardiovascular function complIcatIons In dIabetics. EercTse improves insulin sensitivity of muscles. It afso improves blood supply to different vital organs.
Jr
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An exercise plan should be individualized according to his/her physical status, meals, drugs, profession, interest, etc. To start with exercise one should be gradual in increasing the duration and intensity. There should be ultimate target of doing aerobic exercise of moderate intensity for at least 150 minutes/week or vigorous intensity for at least 90 minutes/week, distributed over a! ka;i 3 qays a week, with no�ore than 2 consecutive .,.
t*
Prior to recommending any exercise programme one should be careful of coronary heart disease, �liferative retinopathy, advanced renal failure, osteoarthritIs, hypoglycemi a unawm-eness, neuropathy. etc.
69
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Aerobic and anaerobic exercise Aerobic exercise uses large group of muscles, can be maintained continuously, and is rhythmic in nature. It is a fype of exercise th�t overloads the heart. -=---
Examples of aerobic exercise: aerobic dance, bicycling, running, treadmill, stair climbing, swimming, walking, jogging, etc. ---
--
----
Benef.its of aerobic exerc..i se
.:f:- �
•
Increases maximal oxygen consumption
•
Improves in cardiovascular / cardio-respiratory function
• •
Increases blood supply to muscles and their ability to use oxygen Lowers resting systolic and diastolic blood pressure in people with high blood pressure
•
Increases HDL cholesterol
•
Decreases blood triglycerides
•
Reduces body fat and improves weight control
•
Improves glucose toleran.se and reduces i..nsulin resistance
aerobic exercise is of short duration that ca!l be supported by the energy sources stored in � the muscles arid that does not require oxygen. Examples of anaerobic ex.ercises are strength training, weight lifting, and sprinting at very fast speed .
Benefits of anaerobic exercise Increases muscular strength Increases strength of tendons and ligament� Potentially improves flexibility (range of motion of joints) Reduces body fat and increased lean body mass (muscle mass) Improves glucose tolerance and insulin sensitivity Improves strength, balance, and functional ability in older adults
70
I
Some practical points on exercise Exercise recommendation for persons with diabetes is the same, as for persons without diabetes, where in an exercise programme includes a proper warm-up and cool-down period. A warm-up should consist of 5- �0 minutes of aerobic activity (eg. walking) at a low-intensity level. After a short warm-up, muscles should be gently stretched for anoJher 5-1 0 minu�s. A cool down period of 5- 1 0 minutes should follow the main activity session. It gradually brings the heart rate down to its pre-exercise level. ..,,- --
Persons with type l diabetes who do not have complications and are in good blood glucose control can do all levels of exercise, including leisure activities, recreational sports, and competitive professional performances. The emphasis must be given on adjusting the therapeutic regimen with the level of exercise and the diet and avoiding hypoglycemia. In children, extra attention needs to be paid to balance glycemic control with the normalcy of play, and for this the support of parents, teachers and athletic coaches may be necessary. Their meal and activity in school are important. Persons with type2 diabetes must view exercise as a vital component for the management. Exercise along with a reduced calorie intake may enhance weight loss. The combination of diet, exercise and behaviour modification is the most effective approach to weight control. Normally low intensity long duration exercise is recommended for weight loss. The diabetic patient �ith �riphera�uropathy and loss of protective sensation should not engage in repetitive weight bearing exercises, such as prolonged walking, treadmill, jogging, as these activities may result in blistering, ulceration, and fracture. Non-weight bearing exercises such as swimming, bicycling, !owing, chair exercises, arm exercises, ' yoga, etc. may be better. .
-
-----�--.
. -
-
...."
Persons with severe Charcot's joint should avoid weight-bearing exercises, as it can result in multiple fractures and dislocation of the bones of the arikIes and feet without even the patient being aware. In patients who have proliferative diabetic retinopathy (PDR) and moderate to severe non proliferative diabetic retinopathy, strenuous · actIvity may preCIpItate VItreous haemorrhage ' or trac�flO=-=n=aI re:..:t:;:. m a� l ...;:;det ; =a= chm , ent. These individuals should avoid anaerobic d . : � =-:---=:- � � ;; physiCal activity that involves straining, jarring, or Valsalva-like manoeuvres (eg. weight lifting, boxing, heavy competitive s�rts, etc. ). In these person's low impact exercises like swimng (but not diving), walking, stationary cycling maybe recommellded.
�an
71
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Platients with stabl� c.oronary heart disease should perform excrise of moderate intensity. ." Persons with uncontrolled hypertension should avoid exercise. One should not do exercise during any significant acute illness or uncompensated major chronic illnesses. -- ---- - - _ .
-=
\
-
During pregnancy moderate exercise (eg. walking at moderate speed for 20 minutes twice a day) is advised. " ,
---7
Reference and further reading
1.
2.
3.
Patient's' Guide Book - published by DAB. Text book of Diabetes _3rd Edition vol 1 , edited by John C. Pickup and G. Williams, Blackwell Science, 2003, p 36. 1 to 38. 1 3. Davidson's Diabetes Mellitus- Diagnosis and Treatment - 5 th edition, A.P. Harmel and R. Mathur, Saunders, 2004, p 49 to 69.
4.
Current Medical Diagnosis and Treatment -44th edition, Lange Medical Books, 2005, p . 1 2 1 0 to 1 242.
5.
Chinical Practice Recomrnedation, 2007, ADA.
6.
GIQbal Guideline for Type2 Diabetes, 2005, IDF.
72
Chapter
5
,
I f
Management: Drug therapy
Objectives •
•
• •
To describe the mechanism of action and maximum dose of secretagogues, metformin, thiazolidinediones and alpha-glucosidase inhibitors in treatment of T2DM. To identify appropriate time to commence drug treatment and type of drug to be used in different clinical situations. To identify secondary).
OAD
failures (primary &
To explain different insulin regimens and understand the principles of insulin dose adjustment.
•
To identify appropriate regimen of insulin to be used in different clinical situations.
•
To provide hands-on training on insulin administration to the patients and their family members.
__-M---MM--
--0
+.MIMt. ...
Drug therapy Diabetes mellitus is a serious disorder in respect to its potentiality of complications alone. With the availability of insulin and other drugs having different modes of action has brightened the management of diabetes mellitus. Prevention of complications of diabetes is now more realistic than ever before.
This chapter will help you to understand the use of different oral agents and insulin regimen to achieve the targets of diabetes management.
� of treatment • • • • • •
To make the patient symptom-free when he/she is symptomatic . . To maintain nonnal blood glucose level round the clock. To prevent acute metabolic derangements, such as hypoglycaemia, ketoacidosis etc . To prevent or delay complications of diabetes, such as nephropai:4y, retinopathy, etc . To ensure proper growth and development in young subjects. To support a productive and socially respectful life. HbA 1 c
< 7.0 %
Fasting BG
< 6. l mmollL [ 1 1 0 mg/dl]
Post-prandial BG
< 8.0 mmollL [ 1 45 mg/dl]
Bed time BG
< 7.0 mmoliL [ 1 25 mg/dl]
Targets of glycemic control
-� � ---�
.
75
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_-M---__--
._§
-_M.Mra ..
._._�_._.__.M••
Treatment modes Various treatment modes are needed in dealing diabetes, which can be divided into non ifications described in Cpapter 4) and p�arrnacological (oral �nts pharmac and insulIn). Non-pharmacological approach initially can be sufficient for some cases of type2 OM;
_
but all type l . _--
OM and mosiOfilie type2 OM require both of these together.
---.--�-----
----�---->,,',,�-�
Pharmacological agents are of 2 types: .----- �----
1. Oral anti-diabetic drugs (OAD)
2. Insulin
Ora l anti-d iabectic d rugs (OAD) OAD are d�gs, . which can be administered orally, and help to reduce plasma glucose concentrations if there is some insulin reserve that is the �-c�lls have the ability to secrete endo.zenous insulin. They are not useful in type1 diabetes and in those patients witiity pe2 diabetes who have advanceo �-cell exhaustion and failure. .
�.---.-.
�
-
--....: :-
----
A number of oral agents are used in the treatment of diabetes. These can be classified on the basis of mechanism of action into: 1. Insulin secretagogues --'
2. Insulin sensitizers -
3. Alpha-glucosidase inhibitors
�)
76
I ns u l i n secretagogues These drugs increase endogenous insulin secretion and thereby reduce plasma glucose levels in diabetic as well as non-diabetic persons. Two classes are available: • •
Sulfonylurea�
C""
Non-sulfonylur��s
I Strength j
Drugs
I
sulfonylureas
Chlorpropamide
(mg)
I
- ---_. _j
Gliclazide Glipizide Glimepiride
- --
II 1
I
!
Nateglinide
500
:
f----�------
20
1 -2
80
320
1 -2
5
40
1 -2
1 , 2 3, 4
8
Mode of excretion
Duration of ' action (hrs)
24 - 36
Kidney 1 00%
I
5
-- -1 - - --� I
l
-t
Kidney 50%, bile 50% I
Kidney 60-70%
i Kidney 80%, bile 20%
I
I I
1 2- 1 8 8- 1 2 8- 1 2
! Kidney 60% bile 40%
24
,
,
Non-sulfonylureas 1
Repaglinide
I
1 00, 250
i Second generation I . sulfonylureas
Glibenclamide
<
Max. dose/ Frequency/ ! day day (mg)
0.5, 1 , 2 1 20
I
8
1 -3
Bile (mostly)
2-- 4
360
1 -3
Bile (mostly)
2- 4
Phannacology of secretagogues
,
77
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Sulfonylureas (SUS)
SUS increase the release of insulin from pancreatic B-cells and thus exert a hypoglycemic effect in diabetic as well is non-diabetic persons. First introducedm 1 956, these are the oldest oral agents and still in predominant use in type2 DM. Their primary mechanism of action is on p-cells to enhance insulin secretion. This action is initiated by binding to a specific sulfonylurea receptor on the pancreati& p-cell leading to closure of potassium -dependent ATP (K-ATP) channel. With the closure of K-ATP channel, there is increase in calcium influx and translocation of secretory granules on the cell surface and extrusion of insulin by exocytosis. Extra-pancreatic effects of sulphonylureas ( ostulated): In liver - reduce hepatic glucose output In muscle - improve insulin stimulated glucose uptake In adipose tissue - stimulate lipogenesis Glibenclamide (also known as glyburide)
Readily absorbed from gastro-intestinal tract, having extensive plasma protein binding, metabolised almost completely in the liver, principal metabolite is only weakly active. The usual initialdose is 2 . 5-5 mg before breakfast, increment of 2.5 mg every 7 days till maintenance dose is achieved. Dose more than 1 0 mg is given in two divided doses. Gliclazide
Readily absorbed from gastro-intestinal tract, having extensive plasma protein binding, extensivelt..,metabolized in the liver to mostly inactive metabolites Usual initial dose is 4080 mg/day, before breakfast. Increase by 40-80 mg every week. Dose above 1 60 mg is given in two divided doses. Glipizide
Rapid and complete absorption from gastro-intestinal tract, having extensive plasma protein binding, metabolized in the liver, to inactive metabolites. Usual initial dose is 2 . 5-5 mg before brea.kfast; increment of 2.5-5 mg per week; no more than two doses per day.
78
Glimepiride
This drug shows rapid and complete absorption from gastro-intestinal tract, with extensive plasma protein binding. Usual initial dose is 1 mg before breakfast; increment of 1 mg per week. Non-sulfonhylurea secretagogues (/repaglinide, nateglinide)
Mechanism of action is similar to the sulfonylureas. But because of their slight different binding site, pharmacokinetic profile is also different. These have a quicker onset and shorter duration of action and can be administered just before or with a meal. These have a lower risk of producing hypoglycemia. Hence these are also called< 'prandial glucose regulator. ' Further more, its hypoglycemic action is glucose-dependent and hence it works better in the presence of hyperglycemia and Its effect wears off as the plasma glucose --- --�� concentration-retUrns to the normal range. . .
79
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I ns u l i n sensitizers These drugs improve insulin sensitivity. Two classes are currently available: ,-
��ides, e.g. metformin �iazolidinediones, e.g. rosiglitazone, pi6glitazone etc. Drugs •
", .
.
.
'1
j
I
Strength {mg}
fI
Max. dose " /day{mg}
Biguanides Metformin
500, 850
I Dur�tion '
I[ Frequency I · Mode of ' /day ! excretion With meal
2500
;_ ••__••. _ •••_____ ...__ ... . . .!.. . .._.. __. .. _.__ ._ .l.. __.....___._.. ..__ __.. l..
Q-3)
'
-["
_ .. _ ... ..
.
··· ' Kidney 50""%
_._
I
{hrs}
·· · ,..
··· 8� i 2·.... · -
. .. .
Faeces 30%
......... .._ ..
Thiazolidinediones Rosiglitazone
2,4
1 2
8
-
Bile 1 00%
Pioglitazone
15, 30
45
24
_--
.j._-- . _--
Bile 100%
24
._.. .
_
Pharmacology of sensitizers
Metformin
� It does not cause gain in weight. It has low-E:, risk of hypoglycemia; can be combined with a �
wide range of oth� anti-diabetic drugs including insulin and is considered as the first line treatment Jor obese diabetics. ' Produces nausea, flatulence and loss of appetite. Does not ' alter blood glucose levels in non-diabeticjiersQns, but produce an anti-hyperglycemic effect " in persons with diabetes. Metformin is well absorbed on oral administration, not bouiid to ' plasma protcins, not metabolized, and is excreted unchanged in urine. Precise mechanism of action is not known, but possibilities include delay in absorption of glucose, increase in insulin sensitivity and inhibition of hepatic neoglucogenesis.
80
l '
"ct
Thiazolidinediones Thiazolidinediones are a class of drugs that improve insulin sensitivity and are useful in type2 diab.@s where insulin insensitivity is a majo�'omponent in the pathogenesis. These drugs reduce hepatic glucose output and increase peripheral lucose utilization by improving insulin sensitivity. They re-uce Clrcu atmg levels of free fatty acids, increase peripheral clearance and reduce hepatic s�hesis o f triglycerides. They i�a� JyrOSfne kinaseactfvity, a���t�tQ L signaling._-Pfu1ci DS and enhance insulin-stimulated translocation dtglucose transporter molecule (GLUT-4) into plasma membrane. They have low risk of hypoglycemia; cause only a modest weight gain.
--
--
-
D rug
-
--
I I
-
Acarbose
-
�
-
�
- -
Stren g th ! Max. dose (mg) I /day(mg) , '
!
50
:
300
--
- ---
Frequency /day _
With meal
(1-3)
,
Modo of , excretIOn
D uration
Faeces 100%
2-4
(Ius)
Pharmacology of alpha-glucosidase inhibitors
Acarbose Blocks the action of the intestinal enzyme a-glucosidase which breaks down starch, and so inhibits th�_��mplete digestion. It is administered orally with meals. Usual initial dose is thrice a,day, if required increased gradually. Flatulence and diarrhoea are the most co on side 'effects and are probably caused by formation of gases due to unabsorbed carbohydrate in the colon. Acarbose is poorly absorbed from the gut, extensively metabolized in the intestinal wall and excreted.
50&!
I
81
M-M---WM--
-_W'Mr.--
'-0
.M__;W••__._••
Some key points: OAD in type2 DM
Usually an DAD is the drug of first choice in type2 DM. nsulin secretagogues are preferred as first line treatment in young, or middle aged non-obese patients. -J Insulin action enhancers - biguanides, such as metformin or thiazolidinediones (glitazone), such as rosiglitazone or pioglitazone are preferred as initial therapy in tients with evidence of insulin resistance. -glucosidase inhibitors, repaglinide or nateglinide are useful and relatively safer in the elderly patients. mbination of insulin releasing and insulin action enhancing drugs may be used when single agent does not work alone. most OAD to have any significant effect, the presence of sufficient amount of insulin or the ability of the �-cells to secrete endogenous insulin is a must. �AD may be replaced by or used in combination with insulin after carefully considering all aspects of the disease and features of therapy.
y
? Je � � �
Y-ction issues of an oral agent : Metformin :
Favorable points
Obesity i Dyslipidemia
:
I
Potent
i
- -- ,--+I�,
II
l
Sulfonylurea I Repaglinideo ThiazolidinediOne ! a- glucosidase i i · i inhibitor Flexible meal I schedule i Elderly
i
Unfavorable Lactic acidosis Hypoglycemia Weight gain Hypoxia points Sulfur allergy , I CHF Gastro-intestinal : upset
, Hypoglycemia i Weig ht again
:
Insulin resistance ; Dyslipidemia
I
1 : Gastro-intestinal
I
___
�o
I Heart disease
i Liver disease
I
Post meal hyperglycemia Elderly
Oedema Weight gain ,::}\ n � ) { ..,..
I
,
<J>.rf' �
""� "'(
upset
1 I
��\ v: "\: , '1.l\�
Favorable and unfavorable points of oral agents
o
Perform the activity 5.1 in the module 5 to recall the memory on maximum dose, duration of action and fn!quency/day of commonly used secretagogues in type2 OM. ��__,,�_._��1a82
Failure of oral agents Failure is said to occur when an orally administered anti-diabetic agent does not produce the required fall in blood glucose level adequately in type2 diabetes. The failure of a drug may be one of two types : • •
Primary i.e. occurring from initiation of treatm�nt.or Secondary i.e. after a few years of successful control of hyperglycemia with that drug.
Primary OAD failure
Primary OAD failure is said to occur when maximal dose of the OAD does not produce any reduction il!...l.P asma glucose concentration . It is found to occur in approximately 1 0% of newly.:.diagnosed type2 diabetes patients. These are mostly those who have been diagnosed late in the course of the disease, and have suffered �-cell exhaustion. Secondary OAD failure
Secondary OAD failure is said to occur when maximal dose of the OAD fails to control plasma glucose concentrations adequately enough to meet the target plasma glucose value, though it had been effectIve earher. The approximate rate of development of secondary failure of OAD as reported in various studies is around 5- 1 0% per year. Before defining failure of any particular agent, it is important to consider that the agent has been used with maximum dose for adequate time to produce its full effect, and other components of treatment (eg. diet, exercise) have been practiced properly.
,
83
�ations
I nsu l i n thera py
*
.
All patients of type 1 DM
•
Pregnancy and diabetes Acute metabolic decompensated states in type2 DM, ego DKA, HONK, lactic acidosis
• • • • •
Type2 DM with OAD failure Acute stressful conditions, ego infection, trauma, MI, etc. During major surgery Advanced complications of DM, ego nephropathy, retinopathy etc.
-
Insulin
I I
-
-
-
-
A Chain �
I
-
;
-
-
-
--
B Chain
,
A2 1
--
B28
B 29
� _
-
_ _
B30
A8
AlO
Human
Threonine
Isoleucine
Threonine
Bovine
Alanine
Valine
Alanine
Porcine
Threonine
Isoleucine
Alanine
Insulin analogues Lispro
Lysine
Aspart
Aspertic acid
Glargine
Proline
+Arg 32
Glycine
+Arg33 + 1 4C � FA
Detemir
Structure of different molecules of insulin
84
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I nsulin preparations
�rt acting insulin
Regular and semilente insulin are the rapid-onset ( 1 5-30 minutes), short acting insulin of 6-8 hours duration. This can be used by intravenous route as ll as by other routes.
7 JIntermediate acting insulin
,
o 2 4 6 8 1 0 1 2 1 4 1 6 1 8 20 22 24
' f-
,..--------------, There are two formulations: • NPH (Neutral protamine hagedorn) or Isophane • IZS (Insulin zinc suspension) or lente This insulin has duration of action of about 1 8-24 hours. NPH have a quicker onset than IZS (2-4 o 2 4 6 8 1 0 1 2 1 4 1 6 1 8 20 22 24 hours).
�g acting insulin
It has long duration of action of about 24-36 hours ans} slower onset of action (4-6 hours).
�
Blood level of different insulin preparations after subcutaneous injection
PhasiC (premixed insulin)
These insulins contain a combination of short-acting and intermediate-acting insulin in a standard proportion. Example - premixed 30170 contains 30% of short acting and 70% of intermediate acting insulin. Insulin analogues
.:::I<. . -*
�
Rapid acting a alogues •
Lispro Aspart
-
duration of action 3-4 hrs.
.J; � Long acting analogues - duration of action 24 hrs.
--{
•
Glargine Detemir
\! ��)p� \O �:k ��A"'+ (Wo. Gtc , ....w-')
Premlxeel analogues
Side e • •
L�
ts of insulin:
0
_)
.
Hypoglycemia Allergy InsUlin oedema and lipodystrophy
85
.
l o �{ '"
)
.
I nsulin administration
Insulin secretion pattern in a healthy person is continuous basal and bolus secretion in response to rising blood glucose after each meal. Ideal insulin therapy in diabetic should mimic normal secretion pattern.
0 N
60 .s :;
40
en
E 20
Time of day
Normal insulin secretion In type l DM total insulin replacement is required. Different types of insulin are required intermediate or long acting (for basal levels) and short acting (for food related bolus). Number of injections may range from 2 to 7 injections a day depending on frequency of eating. In type2 DM, usually supplementation of insulin is required but total insulin replacement or excess (to overcome resistance) may be required. Commonly 1 or 2 injections daily are needed, because the patient may have some insulin reserve to maintain basal secretion. Insulin may be combined with OAD.
I nsulin reg i mens
The appropriate regimen of insulin therapy must be individualized. Usual regimens are : • • • •
One injection a day Two injections a day 3 to 7 injections a day Insulin pump
86
One injection a day
One injection of intennediate or long acting insulin is given either in morning or evening. It serves as supplement/basal secretion. It may be effective in type2 DM as monotherapy or in combination with OAD. Two injections a day • • •
Most commonly used regimen. Can be used in type l DM and type2 DM. Injections are given before breakfast and dinner. Any of the following . insulins can be used: • Intennediate insulin • Biphasic insulin including analogue Split and mixed regimen • .
c: :J en c:
Short & intennediate acting insulins are mixed in proportions that are adjusted by trial. Multiple injections •
Three to
7 . inj ections per day are used
where there is difficulty in achieving optimal
control
with
prevlOus
reglmens. • •
A dose of short acting insulin is given
before each meal as bolus dose.
Intermediate acting insulin before bedtime
and
sometimes
before
breakfast as basal dose. •
Various insulin regimens
This is very flexible and ideal for those who
are
very active and cannot comply with the rigid meal plan or in
diabetes control is difficult with the above regimens.
,
87
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Site of injection Absorption of insulin differs at different sites; it is the fastest and highest at the abdominal region, slower at the brachial or gluteal areas and still slower at the femoral region. These .r�gional differences are related to differences in tissue perfusion. It is important that day after day the injection should be pushed into predefined areas and not randomly. Within the region, injection site is to be rotated. Injection into lipoatrophic sites must be avoided, as it is likely to be highly unreliable.
Sub-cutaneous insulin injection
I nsulin pump Insulin pumps are available i n two fonns: i ) open loop system and ii) closed loop (artificial pancreas) system. The open loop system is composed of two parts- a. battery-operated pump and b. computer preprogrammed system for insulin delivery. The closed loop consists of three parts -
a.
battery-operated pump, b. computer-controlled insulin delivery system and c. glucose sensor giving feedback to the computer. These are portable and designed to deliver basal amount of insulin throughout the day as well as meal-related boluses. Some newer agents are now in use; important one being inhaled insulin.
Perform the activity 5 . 3 . in the rnodule 5 to develop skill in adjusting doso(; ) of Insuli n in a diabetic person.
88
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stn;lified guideline of
A.
initiation of diabetes management
Type2 DM
If fasting blood glucose is
<
•
If fasting blood glucose is
1 l . 1 - 1 6.7 mmollL: start OAD
•
I f fasting blood glucose is > 1 6.7 mmollL:
•
1 1 . 1 mmol/L:
lifestyle measures start insulin
."I\ v � . � I"\vo · (S Ol \'...
,
fJ � '),
Lifestyle measures are essential components in all stages of management. Each component should be given sufficient time to see changes in blood glucose as well as HbA l c levels. If target is not achieved, next step is to be tried; combination of various regimens may also be requried. Some other guidelines suggest to start with metformin if the patient is not under-weight, then to move to combination. B. Type1 DM
Intensive insulin therapy (4 or more injections daily) is the standard treatment.
Diabetes education Diabetes self management education (DSME) or simply diabetes education is an integral component of effective diabetes management. The dibetic patients should be trained in self management skills. Otherwise there will be no co-ordination among the other components of management, notably MNT, exercise, drugs, monitoring, etc.
10
The patints are to be educated immediately after detection of diabetes. At least hours of initial education is required in multiple sessions over 3 months. The curriculum of diabetes education should include idea about the mechanism of diabetes, dietary measures, physical activity, drug therapy, monitoring, detection, prevention and management of acute and chronic camplications, sick day's management, care of pregnancy, psychological coping, etc. Physicianldiabetologist, diabetes specialist nurse, nutritionist, psychologist and some other health care professionals are members of diabetes education team.
,
89
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+_MI_4-
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_·MM£___iW_-+M".
Reference and further reading l. 2.
Davidson's Principles and Practice of Medicine-20th edition, Churchill Livingstone, 2006, p 83 1 to 836. Harrison's Principles of lntemal Medicine- 1 6th edition vol 2, McGraw-Hill, 2005, p 2 1 72 to 2 1 78.
3. 4. 5. 6. 7.
Basic and Clinical Endocrinology- ih edition, edited by F.S. Greenspan and D.G. Gardner, Lange Medical Books, 2004, p 689 to 7 1 1 . Current Medical Diagnosis and Treatment - 46th edition, Lange Medical Books, 2007, p 1 23 1 to 1 246. d Text book of Diabetes _3r Edition vol 1 , edited by John C. Pickup and G. Williams, B lackwell Science, 2003, p 42. 1 to 45 . 1 8. th Davidson' s Diabetes Mellitus- Diagnosis and Treatment - 5 edition, A.P. Harmel and R. Mathur, Saunders, 2004, p 7 1 to 1 45. Clinical Practice Recommendation, 2007, ADA.
90
Chapter
6
Acute complications
Objectives •
To i dentify a case of DKA along with its cause and/or precipitating factor(s); thereby to initiate its treatment and hospitalization.
•
To identify a case of HONK along with its cause and/or precipitating factor(s); thereby to initiate its treatment and hosp italization.
•
To diagnose and treat cases of hypoglycemia and
teach
the
hypoglycemia.
patient
how
to
prevent
•
•
•
•
•
Acute complications
The complications of diabetes mellitus may be acute or chronic. The acute compli:..ations are related to immedia�S-i.n-metabo-'ysm that _ arise within a shorqime (hours or days):
� Diabetic ketoacidosis (DKA)
fHyperosmolar non-ketotic coma (HONK) --YLactic acidosis �ypoglycemia
(�
.•
�.JI O-z, (
< 4"4
...
v SY'..... I ""'-l
. )
Z ;
The chronic complications occur after a long period (usually in terms of years) of uncontrolled diabetes. ' Main ch;OIii c complIcatiOns are retinopathy, �europathy, nephr�athy and macro-vascular dIseases. DKA occurs far more often in individual with insulin dependent diabetes. The acute complications are to some extent preventable and require immediate medical attention.
This chapter will help you to identify DKA and HONK in persons known to have diabetes or even at the time of detection of their diabetes. You will be able develop your skill of identifying and managing hypoglycemia in diabetic patients. Consult standard text book for detailed management of acute complications.
93
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Diabetic ketoacidosis (DKA) Diabetic ketoacidosis (DKA) is a medical emergency in diabetic patients. It is commonly found in !)'pe l DM. But it also occurs in other types of diabetes during stressful s �ation. It results from lack of insulin and rise in counter-regulatory hormones, that lead to hyperglycemia and subsequent lipolysis.
JJ(s
es
UndIagnosed diabetes Omission of insulin dose Injudicious reduction of insulin dose Intercurrent illness, especially acute infection Trauma Pregnancy
•
• • • • •
Y
Diagnosis Of DKA •
Blood glucose > 14 mmol/L
•
Acidosis - arterial pH < 7.3; plasma bicarbonate < 15 meq/L
•
Ketone bodies in blood & urine greatly increased
Clinical features .
•
•
• •
�
Ketoacidosis usually develops rapidly (hours to days) Symptoms of uncontrolled diabetes precedes Weakness, vomiting, impairment of level of consciousness, acute abdomen Dehydration is the most obvious clinical feature with dry skin and tongue, low BP, rapid weak pulse Acidotic breathing is characteristic; there may be acetone smell in breath
agement
•
Hospitalization
•
Clinical assessment
•
Determination of blood
•
•
gluc ose ,
urea, electrolytes, arterial blood
osmolality, complete blood picture
gas with pH,
Send blood and urine for culture Blood/urine for ketone body
Treatment institution is to be done immediately without waiting for laboratory reports.
94
Fluid replacement
;-
Infuse initially normal saline (0.9% NaCI), then 0.9% or 0.45% NaCl calculating against clinical and biochemical status. When blood glucose comes A\ ' down to 1 4.0 mmollL, 5% dextrose is started. .
.vt<=- -\
Short acting insulin
•
lit \I )L '-.J\ �' , ,(, (J •
I
_
0"..)
•
If infusion pump is available, infuse at a rate of)-6 units per hour; otherwise 1 0-20 unitsj.m. is given, followed by 5- 1 0 units i.m. hourly.
•
Hourly fall of blood sugar should be in the range of 3-4 mmoliL.
•
Usual sub-cutaneous regimen of insulin may be started when the patient is stable clinically and biochemically and able to take oral food.
,��
-�------
Potassium Replacement depends on blood level of K+.
<3.3.5-55mmollL � � om�OlJhr mmolJhr . 5 mmollL Do not >5.5 mmollL Blood level of K+
K+
-
-
-
I
•
• •
20
infusion rate
-------
give
Sodium bicarbonate In severely acidotic patient (PH < 7.0 infuse sodium bicarbonate slowly. Proper nursing care Monitoring •
Clinical condition
•
Blood glucose, electrolytes, arterial blood gas, urea 2-4 hourly until stable.
•
Blood/urine ketone
•
Other tests as required
Complications •
Cerebral oedema
•
Thromboembolism
•
Ole, etc.
Circulatory failure
�v I
95
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-_M.Mr.--
_W§
_._w;__________
Hyperosmolar nonketotic coma ( H O N K)
(Now termed as hyperglycemic hyperosmolar state) A severe degree of hyperglycemia, dehydration a�hyperosmillality, without significant ketonuria, usually seen as cOmplication of elderly type2 DM patients. Here residual insulin reserve p�nts ketosis. --
�;w ses
-
Diagnosis of HONK
,j/ yLack of proper treatment of diabetes
YAny acute stress ego infection, stroke, . myocardial infarction, trauma Y .5Pmpromised fluid intake Vu.etc.rugs ego glucocorticiods, diuretics,
• Blood glucose >33 mmollL • Hyperosmolality
(effective serum osmolality >320 mOsm/kg)
• No acidosis - arterial pH >7.3; plasma
bicarbonate > 1 5 meq/L
• Absence of significant ketonemia/ketonuria
�al features Develops slowly (days to weeks) / Symptoms of uncontrolled diabetes c
� •
• •.
precede Dehydration is profound Impairment of consciousness is common
Management (very similar to that of DKA) •
Hospitalization
•
Clinical assessment
•
Determination of blood glucose, osmolality, urea, electrolytes, arteriat blood gas with pH, complete blood picture
•
Send blood and urine for culture
Treatment institution is to be done immediately without waiting for laboratory reports. •
Fluid replacement Similar to that of DKA. Rapid change in plasma o�lality should be checked.
96
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•
Insulin Similar to that of OKA. Usually less insulin than DKA is required. 7Jh � -r-I
•
Potassium Similar to that of OKA
•
Sodium bicarbonate Not required Proper nursing care
• •
Monitoring Similar to that of OKA
Complications
Similar to that of OKA
97
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Hypog l ycem i a It is defined biochemically with blood glucose level below 45 mg/dl (2.5 mmol/L) with clinical teatures of neuroglycopenia and adrenal over activity. However, some diabetics may develo clinica features (particularly of adrenal over activity) of hypog ycemla at a igher blood glucose level due to relative hypoglycemia. Clinical features
�nergic features (also called warning symptoms) to low blood glucose. v-D'ue to excess adrenaline secretion in response . A
�Sweating �Palpitation
/ Tremor
J Jrritability ¥ Hunger
Jeuroglycopenic features
Due to disturbance of central nervous system from low glucose availability. � Headache J Confusion '/ Visual disturbances :/" Behavioural abnonnality � Drowsiness Convulsion J Coma
�/
Clinical features vary according to severity I types of hypoglycemia
Mild hrpoglycem'a ,.
8drenergic symptoms, like tremor, palpitation, sweating and hunger are common.
98
Moderate hypog lycemia Neuroglycopenic symptoms, such as, headache, confusion, anxieties are present along with adrenergic symptoms. ·
Severe hypoglycemia Only severe neuroglycopenic features, like unresponsiveness or unconsciousness or coma or convulsi On are present. Severity
Types
�
renergiC symptoms
�
eurOglYCOpenic symptoms
Mild
Moderate
Severe
Present
Present
Absent
Absent
Headache Confusion Visual disturbance Behavioural abnormality
Drowsiness Convulsion Coma
Various hypoglycemic features
Unaware hypog lycemia Long-standing diabetes with autonomic neuropathy or persons on medication, like non selective beta-blockers, or presons under very strict glycemic control may not have adrenergic symptoms.
Nocturnal hypog lycemia •
Night-time hypoglycemia usually occurs between 2 a.m. and 4 a.m.
•
Patient or their relative may be awakened due to trembling or sweating.
•
,
'
�.
&, ,,+i ��?" f .
"'-0 "'....... .......
Sometimes the pati ent may have morning headache, dizziness, forgetfulness and confusion. t
Confirmation of the suspected condition is made by blood test at appropriate time.
99
'7/V '
Causes
�
mmon causes of hypoglycemia in a diabetic are:
� Doing more exercise than usual /' Delay or omission of a snack or meal .r
Administration of too much insulin
J
Over indulgence in alcohol
Y Excess intake of insulin secretagogues 'i Severe impairment of renal or hepatic function
Treatment of hypoglycemia Mild to moderate hypoglycemia Most cases are treated by the patient himlherself or by a family member. � \" s.f �'1>\11\�
�i"�o ,_tv
•
It is usually relieved by 1 5 gm glucose, ego equivalent food, ego a glass of soft drink, or fruit juice, or snacks, or meal (if it is due). These measures are usually adequate to raise blood glucose to reasonably safe limit (5.5 mmoVL).
•
If the symptoms reappear within half an hour, repeat the treatment.
•
Patient on insulin responds secretago�es doeGot .
•
to
such treatment jYell, but the patient on -. -. ..
If recurrent hypoglycemia follows, hospitalization is to be considered as in a case of severe hypogiycemia......... -
•
Make necessary modification in treatment.
Severe hypoglycemia • •
Confinn diagnosis with a fmger prick. For type l DM, injection glucagon l mg i.m. If recovery is satisfactory consider .another shot.
•
If recovery is unsatisfactory - hospitalization.
•
•
In type2 DM, immediately administer 1 Q;25 ml of intravenous 50� dextrose, which may require hospitalization. 1 �W\ �i�"","'-t � f)-II 9A If recovery does not occur search for additional causes.
•
Make � modification mtrtatmeat,
100
-.------MM-
_•••Mt•.,.
1M
Nocturnal hypoglycemia • •
Reduction of dose of insulin ... Changing the time of evening insulin dose with dinner time
These adjustments are made in conjunction with blood glucose monitoring
Hypoglycemia unawareness Frequent blood glucose monitoring to prevent severe hypoglycemia Each patient with hypoglycemia should be evaluated education to prevent and manage future episodes.
and provided with appropriate
Reference and further reading 1
Davidson's Principles and Practice of Medicine-20th edition, Churchill Livingstone, 2006, p 820 to 826.
2
Harrison's Principles of Internal Medicine-16th edition vol 2, McGraw-Hill, 2005, p 2158 to 2161 and 2180 to 2185.
9
Current Medical Diagnosis and Treatment - 46th edition, Lange Medical Books, 2007, p 1253 to 1265. Basic and CIinitaJ. Endocrinology-7th edition , edited by F.S. Greenspan and D.O. Gwdner, Lange Medical Books, 2004, P 711 to 723.
10 1
Chapter
7
Micro-vascular complications
Objectives •
To enumerate the micro-vascular complications of diabetes mellitus and discuss their pathogenesis.
•
To discuss various types of diabetic retinopathies.
•
To perform clinical examinations to detect and manage nephropathy.
•
To perform clinical examinations to detect and manage peripheral diabetes.
and
autonomic
neuropathies
due
to
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Micro-vascular complications Diabetes mellitus is a chronic, debilitating disease, which is associated with a range of severe complications including renal disease, cardiovascular disease and blindness. Early
detection and meticulous management to prevent comPlications is the major challenge of diabetic care.
Diabetes mellitus as a disease has earned its importance by its complications. Magnitude and pattern of complications are changing with time.
Complications of diabetes mellitus Duration as well as degree of hyperglycemia i s associated with both macro- and micro angiopathies in diabetic individual. Both lesions �ay re�ult in organ and tissue dysfunctions
which are designated as chronic complications of diabetes. During pre-insulin era, life expectancy was very short as a result of acute metabolic complications, like ketoacidosis. However, with the discovery of insulin and subsequently oral hypoglycaemic agents, lives of diabetic patients have been prolonged. Now it has become clear that diabetes mellitus is not just an acute metabolic threat to life, but also causes chronic complications, some of which may lead to premature death or considerable morbidity.
This chapter will help you to understand the retinopathy, nephropathy and neuropathy in diabetes mellitus.
105
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Chronic complications of diabetes mellitus • •
Micro-vascular complications (when smaller vessels are affected) Macro-vl�lar complications (when bigger vessels are affected) --------_.
,-_.
-
.-
Micro-vascular complications may be present at detection of diabetes. Sometimes, routine/annual health check-up identifies subjects who were not known to be a diabetic. " Micro-angiopathies Classical examples of micro-angiopathy '�Diabetic retinopathy include diabetic retinopathy, nephropathy, I? iabetic nephropathy neuropathy, dermopathy, etc. �
.--
-
,
Diabetic neuropathy
Results from many studies namely DCCT (in L .I type l DM) and UKPDS (in type2 DM), have shown that the morbidity as well as mortality risks associated with diabe�es can be reduced by strict blood pressure and intensive glycaernic control. ___
______________
Factors affecting complications Factors associated with complicatjons-are : • Duration of diabetes • Control of diabetes • Other factors
Duration of diabetes Chronic complications vary markedly in individuals, but generally increase with duration of diabetes. In type l DM chronic complications are rarely seen before 5-7 years. It-occurs .--usually after 10-20 years. Patients with t��2 DM often have a long undiagnosed period after the onset of the disease. A significant number of cases present with chronic. complications, like retingpathy, cases often have _ macroneuropathy or foot ulcer �the't1me of detection ofdia6etes:IQT w;
vascJI1ar complications mu�� earlier than tyPpl or type2 pM. In le�oung DM cases, complications like neuropathy, nep1!!.opa tllY peat" much earlier than in other types of DM. t== _____ ,:;::::a .
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Control of diabetes Status of glycaemic control as indicated by blood glucose or by HbA 1 c are strongly related . ,-
.
" --' -_.-
,
-..
. __
to chronic complications of diabetes. Numerous studIes have proved that good control of blood glucose reduces the rate of development of complications. Some diabetics do not /----
.
seem to be affected by complications regardless of their duration or metabolic control of diabetes.
Other factors •
Genetic susceptibility to certain complications may be present.
•
Hypertensi��. �� a common risk factor for devel �ping retinopathy�nephropathy, ' coronary and cerebro-vascular diseases.
•
Smoking, hypertension, dyslipidemia, obesity and lack of exercise are risk factors > for coronary heart disease and cerebro-vascular disease.
•
Hypertension is associated with the development of nepropathy, leading to renal ---..----failure.
•
c=
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Leading cause of new cases of blindness '_
c�
25 times more prone fa eye problems
ti�es more prone to kidne� failu�: . .
Micro-vascular complicationg of diabetes
�------�.--
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Diabetic micro-angiopathy: proposed mechanisms H lperglycemia may c�use • •
Increased glycation lea�ing to accumulation of basement membrane collagen and membrane leakiness Stimulation of intracellular polyol pathway leading to basement membrane and capillary endothelial cell damage --
-
Overall effects include •
capil�ary basement membrane thickening
•
protein leakage
•
microthrombus formation
•
tissue ischaemia
Disease of small blood vessels thus in •
kidneys, leads to nephropathy
•
eyes, leads to retinopathy
•
vasa nervorum of peripheral nerves, leads to neuropathy
,....
---
�
108
Diabetic retinopathy It is a specific form of micro-angiopathy of �e!�� wJth one or m9fe of the following _ _ lesions: � •
M!croaneurysm
•
Hemorrhage
•
Exudate
•
New vessel formation
Early changes may be ��y�ptomatic, but later may even lead to blin<Jness. , Structure of eyeball
Diagnosis Diagnosis and classification is done on the basis of findings of: •
Fundoscopy
•
Stereoscopic colour fundus �hotography
•
Fluorescein angio�raphy
Normal eye
109
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Classification 1.
Early non-proliferative diabetic retinopathy (NPDR)
Early NPDR Documenting one or more of the following intraretinal lesions makes diagnosis: • •
�Microaneurysm: sma�red dots, often in punctate pattern Dot and blot haemorrhage: red round or blot shaped in the inner nuclear layer;""Of flame shaped in nerve fiber la¥er Hard eJ.'udates: yellowish specks or patches of lipid-protein mixture W'
•
2. Moderate to severe non-p roliferative diabetic retinopathy (NPDR)
Moderate to severe NPDR
Diagnosis is done by documenting one or more of the following intraretinal lesions: •
/J� wool
!)pOts: soft exudates - white spots Of patches composed ofi
axoplasm and o�elles of nerv.JUi� indicative of localized retinal ischemia
• •
Vetiij,i!abnor ......,. . he!.ds and loops of retinal v-Sins I In1raretinal microV8leUlar abnomuilities - loops of fine vessels arising ftom _•.�or_ :
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Proliferative diabetic retinopathy (PDR)
Diagnosis is done by documenting one or more of the following lesions:
PDR •
Neovascularization of the disc: NVD - larger-- bun4t�s of new vessels on the optic nerve head Neovascularization elsewhere: NVE - large bundles of new vessels on the periphery of the reti.na Vitreous haemorrhage: vitreous is cloudy or opaque and often has a reddish hue Tractional-retinal detachment: loss of vision if macula is detached ___ _
• • •
4. Maculopathy
It is diagnosed by documenting retinal o�
Evaluation • •
Visual aCl! should be checked routinely. . Associated ocular lesions like cataract also need to he noted during visual acuity check up. Fundoscopy at least on detection of diabetes . and once a year if not indicat�d otherwise. Direct ophthalmoscopy routinely. Indirect ophthalmoscopy if media is hazy due to cataract or vitrous • haemorrhage and when peripheral lesjonsare anticipated. Fundus drawing to doCument haenl(;rrhage, exudate, oedema and new vessels. Colour fundus photography. .
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Fluorescein angiogram t2. evaluate •
Ischemic retinal leakage Neovascularization
•
Unexplained reduction of vision
•
Treatment •
Metaholic control: Good metabolic control reduces incidence of diabetic retinopathy and dela� its progression significantly.
•
Control of hyperten�ion: It is very important because uncontrolled hypertension causes rapid progression of diabetic retinopathy.
•
Panretinal photocoagulation '(pRP): Patient with proliferative diabetic retinopathy are now-a-days treated by panretinal photocoagulation with argon laser. In this procedure a series of 1 200 to 1 600 laser burns of 500 micrometers ofd iameter are applied in the mid - peripheral retina, avoiding macular region. This procedure reduces the rate of progression to blindness by about 50%.
•
Vitrectomy: It is done in cases with advanced proliferative diabetic retinopathy. It can often restore useful vision of eyes that would otherwise be blind.
•
Pharmacotherapy: Drugs, such as, aldose reductase inhibitors are being tried to reduce the progress of diabetic retinopathy with variable success. .
.
Other changes in eye •
Cataract: Similar to senile catract; but changes are accelerated and occurs prematurely. Very rarely, diabetes specific snow-flake cataract occurs in young . subjects. -
•
Glaucoma: SecondaIY. (angl�-closure) --g laucoma develops due to blockage of aqueous flow by new vessels on �terior surface hl'iris (rubeosis iridis ).. �
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Epidemiological aspect • • •
•
Leading cause of blindness Strongly related to duration of diabetes Some degree of retinopathy is evident after 15 to 20 years in nearly all type 1 diabetics and in more than 60% of type2 diabetics Early detection is essential
Decision making path Diabetic person
Eye examination
(Ophthalmoscopy of dilated eye)
Evidence of retinopathy r �----� �------� --
Establish and maintain HbA1c < 7% Look for other micro-angiopathies Treat hypertension if present
,
.
Referral to ophthalmologist
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Diabetic nephropathy It is a specific form of micro-angiopathy of kidney with the characteristic hallmarks of : •
Persistent loss of albumin in urine and
•
Progressive renal insufficiency with or without
•
Hypertension =------
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Structure of normal kidney Early changes may be asymptomatic, but later may lead t,Q renal failure. A diabetic person with persistent albumin loss in urine and progressive renal insufficiency (dec1ining J]ER Glumerolar Filtration Ratel CCR_- Creatinine Clearence Rate) with or without hypertension is said to have diabetic nephropathy. BUt it ideally depends on docume ntation of diabetic specific chan ges in kidney biopsy in aterial. ..
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Urinary Albumin Excretion (UAEL<2Q_pg/minute is co�_ no!!!!al; a UAE rate of 20 to 200 J.lgJmin is called microalbuminuria,-while UAE rate >200 J.lgImin or<jOO mg/day is the Overt proteinuria. :=:;s::z �
Microalbuminuria may be •
Intermittent microalbuminuria . Pe�stent microalbuminuria • Progressive renal insuffi�cy is documented by decline in gluomerular filtration rate (GFR) and! or creatiiieiri clearance rateiCCR). ' Development of diabetic nephropathy follows a stage fashion. Development of proteinuria . � is followed by progressive decline in GFR and CCR. -
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End-stage renal failure
Stages of diabetic nephropathy (adapted from Mogensen 1 999)
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Mon i toring
.� Full clinical check-up during each visit ; Monitoring of glycaemic control YJ Blood urea, serum creatinine, serum protein, electrolytes estimation (once in every .
two-four months)
VUAER (Urinary albumin excretion rate), GFR (Glomerular filtration rate) and CCR (Creatinine clearance rate) estimation
� Monitoring of other urinary complications such as, UTI (including asymptomatic),
bladder dysfunction (autonomic bladder) • /Renal biopsy is indicated in nephropathy in absence of retinopathy, RBC casts in 0. �rine, heavy proteinuria, rapid deterioration of renal function in absence of renal illary necrosis
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-.Y ��nitoring by sonography - kidney size, progressive increase in echogenicity of cortex
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Treatment •
Metabolic control: Good metabolic control reduces incidence of diabetic nephfopathy and-aelays Its progression signi1i cantfY:
•
Control of hypertension: It is very important because uncontrolled hypertension causes rapid progression of diabetic ne hr�athy. Nephropathy itself makes hypertension refractory to anti-hypertensive drugs, thus necessitate intensive and combination regimens. -=.
Target of blood pressure in diabetetes If AER < Ig /day < 130/80 mm of Hg If AER > Ig /day < 120170 mm of Hg �R Albumin Excretion Rate =
Drugs used for control of hypertension: •
ACE Inhibit.ors, ARB,Lnon-dihydropyridine calcium channel antagonists are <2: drugs of first choice to reduce albuminuria .
•
Alpha-adrenergic antagonists : Minimal side effect.
•
Beta-adrenergic antagonists : Alternative to drugs of first choice. May mask hypoglycemic symptoms.
-
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.,
•
Dietary protein restriction: D� low in protein reduces glomerular hyperperfusion and albuminuria. Limit protein intake up to 0.8 �g of ideal bodJ' weight (ADA recommendation).
•
Treatment of anemia: Iron supplementation often fails to correct anemia in renal failure. Iron along with erythropoietin provide optimum response.
•
Renal replacement therapy: Renal replacement therapy should start earlier (GFR is 10-15 ml/�in unlike 5 mlImin in non-diabetic) because •
•
Most patient with ESRD have severe organ involvement
•
Hypertension and fluid overload are often difficult to treat
Methods of renal replacement therapy: •
Dialysis •
Hemodialysis (HD)
•
Continuous ambulatory peritoneal dialyasis (CAPD) .
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Transplantation •
Renal transplant (RT)
•
Dual transplant (DT): Pancreas transplantation (PT) along with RT in typel DM cases only.
Epidemiological aspect •
A leading cause of end-stage renal failure in the world.
•
Approximately nephropathy.
•
Nephropathy is less common in type2 diabetes than typel but due to the greater number oftype2 diabetics, the majority of patients Wit h ESRD will have type2 diabetes.
�%
of type'l diabetics will eventually . develop diabetic � "
Decision making path
Screening t e s t s
(Albuninuria and creatinine)
]
c;e of �ep�thY
Eviden
Establish and maintain HbA1c
<
7%
Look for other micro-angiopathies Treat hypertension if present (preferably with ACE inhibtor or ARB)
I:
Referral to nephrologist
1 18
Diabetic neuropathy Diabetic neuropathy is a descriptive term that denotes demonstrable (either clinical or sub clinical) evidence of peripheral or autonomic neuropathy in a diabetic individual.
Classification A. Diab�tic peripheral neuropathy (DPN) B. Diabetic autonomic neuropathy (DAl�J)
A. DPN presentations 1.
Chronic/insidious sensory neuropathy •
Progressive development of unpleasant sensations
•
Pain and hyperaesthesia in legs and feet
•
Associated muscle wasting and autonomic dysfunctions are cO.!!!Ilol n
2.
- -------�--
Acute painful neuropathy and diabetic amyotrophy --
----
Sudden onset of pain in legs and/or thighs
•
.�-
---- ...
.---
•
Usually unilateral amyotrophy
•
Severe muscle wasting may lead to severe weight loss
No sensory loss These often begin during hyperglycemia; may improve on strict control of blood glucose •
•
Diffuse motor neuropathy
3.
Severe, generalized muscle wasting and weakness
• �
(r------
No pain oi senso
---= -
loss
Recovery is poor � 4.
Focal neuropathies
Occurs due to press�
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Pressure Damage such as that of median nerve, common peroneal nerve
•
Vascular damage such as JIlt- IV, VI, VII nerve palsies, phrenic and thoracic nerve palsies
--
..
-
--
----
----
�.-
B. Diabetic autonomic neuropathy (DAN) 1.
Gastroparesis
Delayed emptying or retention of gastric contents may lead to nausea, vomiting, abdominal discomfort. Treatment : Metoclopramide 1 0-20 mg 3-4 times a day, or Domperidone 1 0-20 mg 4-6 times a day
2. Diabetic diarrhoea Bacterial overgrowth from stasis in small intestine may lead to passage of large volume of watery stool even in bed at night. Treatment : Codeine phosphate 30 mg 3-4 times a day, or Loperamide 2 mg 3-4 times a day can relieve the symptoms. Antibiotics, like erythromycin, ciprofioxacin, tetracycline for bacterial over-growth. 3.
Impotence (in male)
Deabetes is responsible for about 15% cases of total number of impotence. It may be a combination of neuropathy and vasculopathy. Treatment consists of medical, surgical and mechanical means. 4.
Gustatory sweating
Profuse sweating of face during eating. 5.
Neurogenic bladder
Gradual loss of ability to void urine is the cli!lical hall mark of neurogenic bladder. Diagnostic confIrmation is done by cystometric abnormality and residual urine volume. Surgical intervention is necessary if medical therapy fails, because chronic retention may lead to*repeated infectior and renal failure. 6.
Impaired cardiovascular reflexes
9rthostatic
hypotension and persistent tachycardia result from autonomic neuropathy affecting cardiovascular reflexes. Symptoms of hypotension may be relieved by using compression stockings, abdominal binder and use of oral mineralocorticoids ( fludrocortisone).
120
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Clinical evaluation Systematic assesment of neuropathic symptoms and signs include: • Thorough neurological examination • Confounding disordersLumbar root disease • • Peripheral vascular disease • Non-diabetic neuropathies
Electrodiagnosis •
Nerve action potential amplitude measurement represents total number of active fibres.
•
Motor and sensory nerve conduction study reflects functional status of large myelinated fibres.
•
EMG done on intrinsic foot muscle may reveal partial degeneration as an early sign of diabetic neuropathy.
•
Electrodiagnostic studies are usually done on ulnar and/or median nerve (upper limb) and peroneal nerve (lower limb) for motor function; ulriar and/or median nerve (upper limb) and medial plantar/sural nerve (lower limb) for sensory function.
121
Quantitative sensory testing (QST) •
Measures somatosensory dysfunction
•
Non-invasive, reproducible and highly sensitive vibration thresholds are measured by biothesiometer
•
Thermoreceptive and pain thresholds are measured by contact thermoses
Autonomic nerve function (ANF) tests (Classical cardiovascular tests of ANF) 1.
Tests reflecting parasympathetic function
(a) Heart rate change during Valsalva maneuver (Valsalva ratio) Valsalva ratio
Normal
Borderline
Abnormal
Preliminary heart rate
>1.21
1.11-1.20
<1.10
Heart rate during Valsalva
(b) Heart rate change during deep breathing Heart rate variation during deep breathing
Maximum - Minimum HR (Beats/min)
Normal
Borderline
Abnormal
>15
11-14
<10
(c) Immediate heart rate response to standing •
ECG recording after standing
- ,Nor�al'" .
Borderline
HR at 30th beat! HR at 15th beat
>1.04
1.01- 1.03
�.
1 22
.
Abnormaf
<1.00
.
2. Tests reflecting sympathetic function (a) Blood pressure response to standing Blood pressure after
Normal
Borderline
Abnormal
standing
Fall in systolic BP (mm of Hg)
<10
>30
11-29
(b) Blood pressure response to sustained handgrip Blood pressure after sustained handgrip
Normal
Rise in diastolic BP (mm of Hg)
>16
Borderline
Abnormal
11-15
<10
Treatment •
Painful diabetic peripheral neuropathy:
..
•
Optimum glycemic control
•
Pain may be relieved by simple analgesic as aspirin or codeine
•
For burning pain tricyclic antidepressants, such as imipramine or amitriptyline with or without fluphenazine
•
For lancinating pain - gabapentin, carbamazepine, phenytoin or valproate
•
For restless legs - clonazepam
•
For painful cramps - quinine sulfate
•
Use of aldose reductase inhibitor is still in the experimental stage
•
Exclude or treat other contributing factors: such as alcohol, cord lesions, vitamin deficiency, renal failure etc.
1 23
Decision making path
I
I
Diabetic person
� Clinical examination
-
I
I
Evidence of neuropathy
�
Establish and maintain HbAlc < 7% Provide specific treatment Look for other microangiopathies
I
Referral to neurologist if needed
I ,
Perform the activity 7.6 in the module 7 to understand diabetic neuropathy and its management. Reference and further reading 1
Davidson's Principles and Practice of Medicine-20th edition, Churchill Livingstone, 2006, 836 to 844.
124
Chapter8
Macro-vascular complications
Objectives •
To enumerate the macro-vascular complications of diabetes mellitus and discuss their pathogenesis.
•
To discuss on management of hypertension and dyslipidemias of a diabetic person.
•
To perform clinical examinations of foot
to detect
'high risk foot' and advise diabetics for appropriate foot care practice.
o
N
Macro-vascular complications Diabetes mellitus is a disease associated with several macro-vascular complications including coronary artery disease, cerebrovascular disease and peripheral vascular disease. Hyperte!!�ion and dyslipidemia are the two prominent modifi able factors 10 the development of these forms of complication in a diabetic person.
Macro-angiopathies •
C;:oronary artery disease
•
Cerebrovascular disease
•
Peripheral vascuJ¥ disease "'
People with diabetes have more chance of heart attack (-2-3 times), stroke (-6 tirveJ») and lower limb amputations (- 20 times) ---- ====_ than non�iabetics due to increased macro-vascular abnormalities. ""
..
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__
This chapter will cover identification and treatment of macro-vascular complications of diabetes mellitus. This chapter will help you to understand why and how to screen for hypertension and dyslipidemia in diabetic person for prevention of macro-vascular complications. It will also help you to learn how to screen for 'high risk foot' and provide appropriate care of foot in diabetics.
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Factors affecting complications of diabetes Factors associated with complications are: •
Duration of diabetes
•
Diabetic control
•
Other factors - hy�ertension, d);:slipidemia,
obesity, lack of
exercis� and genetic factors are important
6 times higher risk for paralysis (stroke)
2-3 times higher risk for heart attack
20 times more prone to lower limb amputation
Macro-vascular complications of diabetes
rJlacro-vascular disease in diabetes •
•
Coron� artery disease is the most common cause of death in persons with type2 .
diaoeres.
.
-
StrQ@ (cerebrovascular disease) is th$ second most common vascular problem in
diabetes. Both of the above are also important causes of premature mortality in
di��. •
"
-
Peripheral vascular disease (PVD) affecting the large arteries supplying bl<>?d to the litnbs particularly the lower limbs is also common in diabetes and adds considerably to the morbidity related to foot problems leading to lower extremity amputations.Atherosclerosis is �ral-fold more �t in persons with diabetes. In diabetic people athtiOmatuos lesions
are
more
1 28
severe
and widespread
Vascular disease is more common in diabetes •
•
High blood glucose level damages the endothelial cells lini� theJ?lood vessels making t�tm tillaZ,- �rd and les ; elastic. This make� difficult for the b 199d to .. , flg,w thr�h. People with diabetes have h�her levels of fat in the blood. Again high blood glucose contributes to this. The fats.,9r lipids in �els-may clog the vessels and restrict the flow of blood. --------
•
High blood glucose affects the RBCs and makes them less pliable.
•
There is increase in the factors that favour blood clotting.
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Hypertension High blood pressure causes damage to large and small blood vessels in the body. The higher the blood pressure the greater is the risk. The adverse effect of hypertension mainly involves the blood vessels of the central nervous system, the retina, the heart and the kid�s. <
Changes in blood vessels due to hypertension •
In larger ar1erie�e internal elastic lamina is thickened, smooth muscle is hypertrophied and fibrous tIssue IS deposIted.
•
In smaller arteries hyaline arteriosclerosis occurs in the wall, the lumen narrows and ane urysm may develop.
-
-------
Some key points on hypertension in diabetes mellitus •
• •
Widespread atheroma may develop leading to coronary or cardiovascular disease particularly if oth� Esk factors �, dysli idemia are resent. _ Hypertension increases the risk to heart attacks. ---
,.......-
Stroke is a common complication of hypertension and mE be due to cerebral haemorrhage or cerebral infarction. -----
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-
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.
_.__
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-
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-
•
Depending on the severity of hypertension, the optic fundi reveal a series of changes (hype�ensive retinopathy). Fundoscopy can provide an indication of the arteriolar damage occurring elsewhere. Hypertension is also asso�ed with centraLretinal vein thrombosis. Hypertension enhances the already existing retinal damage due to diabetes, accelerates the progression as well as increases the severity of existing diabetic retinopathy.
•
Severe hypertension can causz left ventricular failure in the absence of coronary artery disease, especialltif renal function js impaired .
•
Hypertension may cause proteinuria and progressive renal faihIre by damaging " the renal vasculature. Diabetics ar e already at risk of kidney disease and added hypertenSio� incr: ases the �k �ey dis��_sever.&fokls.
...".--
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.-
- --
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Hypertension contributes to the development and j!!"ogression...J,lf chronic complicajjon of diabe��s. In patients with type! diabetes, persistent hypertension is often a manifestation of diabetic nephropathy, as seen by elevated levels of .
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urinary albumin and, in later stages, by a decrease in the glomerular filtration rate (GFR). In patients with type2 diabetes, hypertension often is a part of a syndrome that includes glucose intolerance, insulin resistance, obesity, dyslipidemia, and coronary artery dise ase.
' Perform the activity 8.3 in the module 8 to understand the changes in macrovasculature system in diabetes with hypertension.
Target of blood pressure for people with diabetes Many prospective studies with hypertensive diabetic persons have documented that reduction ,of blood pressure is the single most important factor that reduces both renal disease progressIon and card}ovascular ev�nts . ......
"
-
•
B.P. <
•
B.P.
<
130/80 mm of Hg 120/70 mm of Hg in renal diseases
On the basis of those evidences now it is advised to lower the blood pressure of patients with diabetes to <130/80 mm Hg even finther down to <120nO mm Hg if there is renal involvement �Ii � prote�uria.�
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Screening for hypertension Blood pressure should be measured at the initial visit and subsequently at every follow-up visit. Incidence of hypertension in diabetes varies greatly and is influenced by many factors like duration, type of diabetes, glycemic control status, etc.
Some key points on treatment of hypertension in diabetics Treatment is aimed to achieve pre-defined systolic and diastolic targets:
•
•
BP �130/80 mm Hg and
•
If protinuria or chronic renal failure is present then, BP <120170 mm Hg
•
For mild hypertension, first line management is always non-pharmacological one.
•
Drug Therapy •
Antihypertensive regimens should include f\CE inhibitors or angiotensinII receptor blockers (ARB) in order to provid� maximum car� reno protecti on in these patients. This will help reduce the cardiovascular risk to a 7 greater extent than can be achieved with other agents.
•
In virtually all patients with type2 diabetes, combination antihypertensive medication� mayJ>e needed t�sired blood pressure target.
•
Physicians must make every effort to decrease the blood pressure to as close as possible to the target by the leasJ intrusive means possible. This will minimize drug-related side effects, improve� patient adheren� and reduce cardiovascular .. '\::" and renal events. . -.
�--- .
.-. -
Ensure targets of glycemic control (HbAl c <7.0%, blood glucose- fasting <6.1 mmollL and post-meal <8.0 mmollL).
•
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drug: Perform the acti�ity 8.4 i-Ii the' m��uie 8, to �nd�e-r�tand�how to initiate . therapy for hypertension in a 'diabetic patient. .
132
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Decision making path: hypertension in a diabetic person
I
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BP > 130/80 mm Hg
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Non-pharmacological interventions
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Pharmacological approach
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-- --
+ Diuretics
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ARB Add
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a-blockers
I
--
Non-pharmacological interventions •
Weight loss for obese
•
Regular exercise
•
Medical nutrition therapy
•
Restriction of salt intake ( < 6 g/day)
133
Ivasodilators
-
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--'
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--,
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Pharmacological interventions Groups
ACE inhibitors(Angiotensin converting enzyme inhibitors)
•
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• • •
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•
-
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•
(Angiotensin II receptor blockers)
• • •
•
Diuretics
•
�-adrenergic
• •
receptor blockers
• •
\
Captopril Enalapril Benazepril Lisinopril Ramipril Cilazapril
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Losartan Valsartan Candesartan Irbesartan
Hydrochlorthiazide Indapamide Atenolol Metoprolol Propranolol Carvedilol
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Ca channel blockers
-
•
,
!
• • •
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Others
• • •
Remarks
Dose
Drugs
Nifedipine . . Amlodipme Lercanidipine Diltiazem Verapamil
i I
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Prazosin oc-methyldopa
Anti-hypertensive drugs Fill up the column of do� mentioning from the lowest to the highest range. Fill up the column of remarks mentiomng side effects and special notes.
134
Dyslipidemia " Dyslipidemia is defined as an ab�orma�vel of one or more blood lipids, which most typically are total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (H�), and/or triglyceride(TG). There is strong e�idence that elevated LDL and decreased HDL levels directly contribute to the formation of atherosflerotic plaque§, in turn, increase the patient's risk of cardiovascular disease.
Key features of diabetic dyslipidemia • • •
Hypertriglyceridemia A reduction in high-density lipoprotein cholesterol (HDL) A rise in low-density lipoprotein cholesterol (LDL)
Prevalence of dyslipidemia in type2 diabetes The most common pattern of dyslipidemia in type2 diabetic patients is elevated triglyceride level and decreased HDL cholesterol level. Though the concentration of total and LDL . ������====� cholesterol in type2 diabetic patients is usually not significantly different from non-diabetic individuals, the diabetics may have elevated levels of non-HDL cholesterol (LDL and VLDL). However, type2 diabetic patients typically have a preponderance of small and dense LDL particles, which possibly . increase atherogenicity even if the absolute concentration of cholesterol is not significantly increased.
Lipid fractions The main lipid.s in blood are carried in lipoproteins, which are globular packages that also .... contain proteins known as a�roteins. 1 . Cholesterol Cholesterol is an essential element of all animal cell membranes and forms the backbone of steroid hormones and bile acids. Although dietary cholesterol found in foods of animal origin, contributes to the plasma cholesterol level, endogenous 'production is believed to account for most plasma cholesterol.
,.
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2. Triglycerides
Triglycerides � simple lipid§.jerived from fatty_acids. Vegetable oils, dairy product and animal fats contain triglycerides. VLDL, a precursor of LDL, is involved in the transport of endogenous triglyceride from the liver to the peripheral tissues. 3.
High-density lipoprotein (HDL)
The ma�r production of HDL occurs in the liver. Studies have reported that the HDL has a closer inverse association with atherosclerosis. HDL shows an inverse relationship with plasma LDL and triglyceride levels. Insulin treatment in typel DM restores HDL to normal range. In type2 DM, HDL cQ!!.cen�tion is favourably associated with female sex, weight loss, cessation of smoking, exercise and low intake of alcohol. 4.
Low-density lipoprotein (LDL)
The rate of LDL secretion from the liver is influenced by many factors, such as diet, .�ulin level, g�cagon, time jJf the day, and degree of adiposity; therefore, a wide variability in its levels· is 'common. High level of plasma LDL has been shown to be associated with atherosclerosis and macro-vascular complications. Target of blood lipids for people with diabetes mellitus
Prospective studies with diabetic persons have documented that reduction of blood lipids particularly TG and LDL cholesterol reduces ��itJa.(ge��� �r bIO�d lipids their cardiovascular events. On the basis of .. , � ' ' " .' :-<;::, �iri diabetes that evidences now it is advised to lower the ;!......,i �""t.. <.!: (Air;:'�� triglyceride and LDL cholesterol and to raise • LDL cholesterol < 100 mg/dl HDL cholesterol. • HDL cholesterol > 40 m..g/dl ..
..�.
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.
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<
.•
•
.
------
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•
.
Triglyceride < 150 mg/dl
.
Perform the activity 8.5 in the module 8 to memorize some key features of �yslipidemia in diabetes mellitus. .
136
Screening for dyslipidemia Dyslipidemia, characteristically low HDL and high TO, and also high LDL, is a frequent accompaniment of the diabetic state. Correction of dyslipidemia helps to reduce the risk of developing CAD in persons with diabetes. Corrective treatments e.g. diet and lifestyle modification, cessation of smoking and lipid lowering treatments can alleviate the dyslipidemia of diabetes and improve long-term prognosis. A lipid profile examination at baseline and annually thereafter is therefore recommended in all adults with diabetes.
Decision making path: dyslipidemias in a diabetic person
LDL cholesterol > 100 mg/dl ,HDL < 40 mg/dl
TG > 150 mg/dl �------� r-----------�
Review the blood glucose profile . Non-pharmacological interv�ntions
Pharmacological approach
Statins
p.---.--�---'
Fibrates
J il
L__ __ __ _
Cholestyramine
Nicotinic acids
•
Weight loss for obese
•
Regular exercise
•
Medical nutrition therapy for dyslipideroia
137
-'1
_' '- ____ _ __ ----' '--__ __ _ __
'-----' � ""__ __
Non-pharmacological i nterventions
Ezetimibe
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Pharmacological interventions Groups
Drugs •
Statins (inhibit HMG-Co A reductase activity) -
•
.
=
•
�
• •
,
Remarks
Dose
Fluvastatin Rosuvastatin� c.- re"c.\4� f'ft>-+<:,,,, �". . Lovastatin Atorvastatin Simvastatin -=.>3+ >�,,� I.e "!/Y\. +o � n.- l t-.. < £> 1-
Lower LDL and triglycerides Raise HDL
e�\c e.. ve V\{
tJ ·
Lower triglycerides Raise HDL
Fibrates (stimulate lipoprotein lipase attivity; increase VLDL breakdown)
•
NicQtinic acid (inhibits productiol!.. of VLDL)
•
Cholestyramine (prevents �absoption of b�le acid)
•
Cholestyramine
Lowers LDL
Ezetimibe (prevents intestinal absorption of ch
•
Ezetimibe
Lowers LDL
Bezafibrate • Fenofibrate • Gemfibrozil
,
Lowers LDL and
Nicotinic acid
triglycerides Raise HDL
---
___ __ ____ • __�.w
--
Lipid lowering drugs Fill up the column of dose mentioning from the lowest to the highest range.
Aspirin in diabetes •
•
•
Aspirin (75-162 mg/day) is to be used as secondary prevention strategy of CVD in those wiJh history· of�CVD. ...
Aspirin (75-162 mg/day) is to be used as primary prevention of CVD in those with --age >40 years, hypertension, dyslipidem ia, family history of CVD, _ � _��� � i--�� rubu�una andsmo�ng. __ __
-�
--
It can ruso be considered in 30-40 years age grOUp in presence of �ardiovascular risk factors. Use under 30 years orage has not been !tudied.
138
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Diabetic foot There are several reasons why foot of a diabetic person is vulnerable to lesion. These include: • Loss..2,f sensation (neuropathy) • Poor ci!culation (perip��ral vascular disease) • Higher likelihood of developing infections Diabetic foot ulcers are the most common cause for prolonged hospitalization. Also, diabetes is the most important cause of non-traumatic foot amputations.
Sensory & motor neuropathy
,1
Autonomic neuropathy
Peripheral vascular disease
Callus
Ischaemia
-
Pressure++
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Foot ulcer
Gangrene
Amputation
Pathway to amputation
Wagner's classification of diabetic foot lesions Grade
� ��
Description of lesion
No ulcer but high risk foot : ,
Su =r _u..lce �!!'!"Ilc_ial """ ..pe GradeJ �_---=== Grade 2 rrs
___ _
----.
--Deep- ulcer but no bony involvement, no abscess ...
-----
� -
-- -- ._-- - --
Deep ulcer with abscess or bony involvement
-- ---�
Loc@!ed gangrene (at toe; Ileet) <:nmne of whole fOQt
.�;'-:"':"':':ioi!!! :'::"" �_.� !!'! �;,L...�c... ... .::::
_ _ ___ _ _ _
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Screening for high-risk foot in diabetic person Check foot at initial visit and then once every 3 month. � -
What is a high risk foot? A foot is labeled as 'High risk' if one or more of the 6 factors of the box is/are present. Foot deformities that can make a foot hIgh nsk are:· claw toes, prominent heads, callus, bunion, ' buni;nnette, Char�ot joint and bdny prominence.
High risk foot
1 . Loss of protective sensation 2. Absent pedal pulses 3. Severe foot deformity 4. Hi�tory of foot ulcer 5 . Previous amputation 6. Limited joint mobility '=0
,
==
Foot lesions
Clinical assessment •
Raised vibration perception threshold using biothesiometer or graduated tuning fork.
•
Impairment of fine touch using Semmes-Weinstein nylon monofilament.
•
Impaired thermal sensation using hot and cold test tubes separately.
./
-
140
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•
Peripheral vascular disease by examining peripheral pulses and the doppler test.
•
Evidence of infection or increased pressure e.g. erythema, heat, callus formation, haemorrhage under a callus.
•
Presence of thic� nails, limitedjoint mobility and/or bone deformity. ,-
•
Previous history of ulcer or amputation.
. . ---7"
How to avoid heat injury to the foot? Because of the associated nerve damage a person with diabetes cannot sense temperature changes. So to avoid heat injury,.the following precautions must be made known to them: •
Do not have very hot baths.
•
Avoid sitting too close to the heater or fire.
•
Do not use hot fomentations.
•
Do not use hot water bottles or electric blankets in the bed at night.
The diabetics should have to avoid all possible injuries.
How to inspect feet? •
Inspect feet regularly (preferably daily) the toes, between the toes and the sole, and look and feel for breaks in th� cuts, scratChes, bruises, blisters, sores, and c=, ....... (, . discolouration. .
_
•
-
J
Use a mirror or friend/relative to aid better vIewmg.
How should a person with diabetes cut nails? •
Cut nails after ' a bath, when these are soft and pliable. . Cut nails straight, not too deep on the sides. Do not use a sharp instrument to clean under the nail, or in the grooves. In case of pain or difficulty in cutting, consult your nurse or doctor. "
• • •
Inspection of the sole of foot
141
How to choose shoes for a person with diabetes? •
Shoes must provide proper support to the foot. They must be of the correct shape and size for the feet. It is important to draw the outline of the feet by placing them on paper. Cut this outline and carry it when buying shoes. The cut paper must fit the inside of the shoe properly without crimping or folding anywhere. This would be the correct and comfortable shoe size.
•
Always shop for shoes in the evening when the feet are the largest.
•
Check the size of the shoes wearing the thickest socks.
•
Always choose flat shoes.
'.
Thick, sturdy soles protect the feet from sharp objects.
•
Rounded toes give more space to the feet.
•
Leather shoes help the feet breathe freely.
•
Slippers and sandals do not provide adequate support to the feet and should be avoided for full-day-wear. They should be used only for short periods like night wear.
142
Checking shoes
Treatment of foot lesion •
Minor non-infected wound is treated with non-irritant antiseptic solution, dressing'ind foot rest.
•
Infected lesions and more severe lesions need intensive therapy at hospital, use ' of appropriate and adequate antibiotics, surgical drainage �nd debribement of devitalized tissue, amputation if necessary.
-------
�
•
Pressure off-Ioadillg by various means.
•
Tight metabolic control of diabetes.
•
Consider vascular surgery in appropriate cases .
--------
.-
-----
Therapeutic shoe for ulcer in the front part of foot
Reference' and further reading 1. 2. 3. 4.
Davidson's Principles and Practice of Medicine-20th edition, Churchill Livingstone, 2006, p 443 to 45; 608 to 615 and 844 to 845. Harrison's Principles of Internal Medicine-16th e4ition vol 2, McGraw-Hill, 2005, p 1463 to 1481; 2166 to 2169 and 2286 to 2298. Current Medical Diagnosis and Treatment - 46th edition, Lange Medical Books, 2007, p 429 to 459; 1267 to 1278 and 1250 to125 l . Text book -of Diabetes - 3ed edition vol I, edited by John C. Pickup and G. Williams, Blackwell Science, 2003, � 54.1 to 57.19.
143
Chapter
9
Prevention
145
Objectives •
To enumerate the types of prevention applicable for diabetes mellitus.
•
To discuss on primary,
secondary
and tertiary
preventions of diabetes mellitus. •
To identify individuals with ' high risk of developing diabetes and help them to do
appropriate lifestyle
adj ustment to prevent or delay the development of diabetes.
146
'_-M----.--
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Prevention of diabetes mellitus Diabetes mellitus, a chronic debilitating disease which is associated with a range of severe complications. Prevention of the disease and or its complications is a challenge for diabetic health care delivery providers. ' Primary prevention refers to avoiding the onset of the dis�se. Secondary prevention means '\ > earl}' detection of diabetes and prompt initiation of treatment Tefliary prevention aims to delay andlor prevent further progression of�dia6etic complications. There is now substantial evidence that type2 DM can be Types of prevenention of prevented and its complications can also be diabetes mellitus prevented or delayed. Identification of individuals at risk of developing diabetes can be done • Primary prevention effectively. Diabetes prevention programmes focus » '" • Secondary prevention on lifest))e mo
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\
--..
This chapter will help you to understand what are the different types ofprevention strategies of diabetes. It will also help you to learn why early detection & achievement of targets of treatment are important in secondary & tertiary preventions of diabetes respectively. .'
147
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Primary prevention
Primary prevention refers to prevention of the onset of the disease. It can be achieved ----::-:-:::h �c:t:es : =p=r:::ap through two basic -:oa c--
•
Population approach
•
High-risk group approach
""-
Strategies of prinary prevention
Population approach of primary
•
Po�lation approach
•
High risk group approach ==
prevention includes:
A. Creation of mass awareness can be done through strategies like : •
Incorporation of basic information in school text book curriculums
•
Use of mass medias, such as news papers, radio, television, etc
•
Use of social organizations, such as religious institutes, voluntary organizations,
etc.
B. Care of risk factors for diabetes through public health approach: •
Creating facilities for performing physical activities like sports, gym, etc.
•
Promoting healthy eating habits like campaign against 'fast food culture' etc.
H igh-risk group approach of pril!l�ryJrevention is in fact a clinical approach where physicians perform the following activities: A. Detect the presence of established risk factors in an individual. B. Reinforce lifestyle changes by ensuring regular physical activity and practice of
medical nutrition therapy and may even prescribe drug(s) to modify the risk factors. Type2 diabetes is the commonest form of diabetes. Althou,gh a heteragenemls disordex; insulin to IGT, then to diabetes is now clearly understood. It people at increased risk of progrsssion based on is possible to identifY -------.BMI, waist hip ratio (WHR), family history, etc. ,
148
Specific strategies for high-risk group •
Individuals with risk factors for diabetes need to undergo screening to detect I FG or IGT.
•
Cases with lEG or IGT and/Jrr- .pas-t- history of GDM may even be treated for -a-r'e, -'g"r hT:" taz-e'" )-)nlITlQtrton to bo�son interventi �n with drugs llike metfor�� lifestyle modification if scope of regular monitoring is available.
The risk factors for type2 diabetes are also the risk factors for other non-communicable diseases like ischemic heart disease, higl!- blood pressure, strokes, etc. By creating awaren.e.-ss-about the bad effects of such lifestyle, it maybe possible not only to slow down the rising tide of diabetes but also to have beneficial effects on some of these associated diseases. F or type I diabetes genetic and imm�"llOlog1cal markers are available but coilly. It is not feasible to use them for population-based identi fication, but specific high-risk groups can be screened. The cost effectiveness, social and moral issues of such screening activities remain unclear.
Individual at hig h risk of type2 diabetes mellitus •
Age � 45 years
•
Positive family history of DM
•
Habitual physical inactivity
•
BMI above normal ( � 25 kg/m2)
•
Waist hip ratio above normal
• History GDM or delivery of baby > 9 lbs Other suggested strategies include • Previousl� identified as I EG/IGT encouraging . breast-feeding, use of antioxidants and �-cell rest by • Hypertension giving insulin to individuals with • Dy.§lipidemi� identified genetic and immunological markers have been tried but have not worked. As yet there is no evidence to suggest that type 1 diabetes can be prevented, none-the-Iess efforts continue, as it is a goal worth pursuing.
149
•M
-.ew:-_---_.__•
Secondary prevention Prevention of micro- and macro-angiopathies in a diabetic person is termed secondary prev�fi(ili. Studies documented that appr�ximately 20% of type2 diabetic patients already have these complicatIons at detection of their diabetes. Early detection --of diabetes to- initiate - -. - --"'-its treatment thereby to llaI t or delay these complications is the aim of secon�ary prevention. -
Diabetes awareness in the community and amongst physicians to enhance the routine screening of population at risk is important. Screening should be considered in all individuals �45 years of age, and if normal should be repeated every 3-year. Screening should be done at a younger age
Early detection of diabetes mell itus • D i abetes screening for high risk ...
individuals for type2 D M
• Screening o f a l l pregnant women at 24 to 28 weeks of pregnancy
• Screening for type 1 DM
and/or more frequently in those with BMI �25 kgim:lPlus one or more additional risk --factors.
•
Fasting < 6 . 1 mmolfL [ n O mg/dlJ
•
Post-prandial < 8 .0 mmolfL [ 1 45 mg/dlJ
•
Bed time <
HbA l c
•
<
Lipid
• • •
•
7.0 mmolfL
[ 1 25 mg/dlJ
7.0%
100 mg/dl HDL Cholesterol > 40 mg/dl LDL Cholesterol <
Triglyceride < 1 5 0 mg/dl
Teaching, training and empowerment to take part in treatment
Some targets of diabetes management ; 1IpPll.�· oost effective, as costs of treating complications resulting from diabetes ,are ...... Several factolJ. have been ideatifted as
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risk factors that are associated with deterioration of multiple organ function in a diabetic person. In addition to �ycemic control , strict control of Qlood pressure delays/prevents development of retinopathy & nephropathy; further control of lipid abnormalities improves cardiovascular, cerebrovascular and e�i heral vascular -·Complications. Cessation of smoking, weig t control and physical activity are beneficia .
�----
151
Tertiary prevention Interventions designed to minimize consequences of diabetes and help rehabilitation fall under this category. Here attempts are directed to contain damage R1 aggressiye therapy to ar:rest or Qelay progression of complications. Each complication may be addressed with special objectives and strategies reducing morbidity, disability and mortality.
Screening for complications •
Type! DM: -a:::::::S ::::r
At diagnosis; then after 5 years; then every year (in absence of complications) •
Ty�
At diagnosis; then 'every year (in absence of complications) �
Effective $trategies of tertiary prevention ----
----
A. A� utation
J/ Improved self care 7' Appropriate footwear use '
�
-�
Reduction of risk factors Control o( hyperglycemIa
B. Cardiovascular disease
� Control of hypertension
� Control of dyslipidemia
�
y C.
cessation of smoking
Control of hyperglycemia
R.,.. disease � CoQtrol of hypertension
�
necessary) low protein diet
1 52
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Economic analysis from the different studies have shown that prevention programmes are cost effective. Other studies also have shown that simple measures, like education and awareness also help. Comprehensive care of diabetes with patient education and awareness about complications can bring about a remarkable reduction in blindness, end-stage renal diseases (ESRD) and lower extremity amputation (LEA).
Computer modeling predicts substantial reduction in complications as a result of comprehensive care
Reference and further reading 1.
WHO Technical Report Series 844; Prevention of Diabetes Mellitus - 1 994, WHO, Geneva.
2.
Development Programme for the prevention and care of Diabetes in Finland- 200 1 ; Finish Diabetes Association.
3.
Clinical Practice Recommendations, 2007, ADA.
1 53
Chapter
10
S p ecial situations
Objectives •
To enumerate the basic principles of management of diabetes mellitus in children.
•
To enumerate the basic principles of management of diabetes mellitus during pregnancy.
•
To enumerate the basic principles of management of diabetes mellitus during surgery.
•
To highlight the special care during days of sickness and fasting (Ramadan).
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Diabetes mellitus in special situations Diabetes mellitus in childhood and adolescence is most often type l DM but type2 or secondary diabetes mayalso occur. There is Increasmg trend of diabetes in children globally. Diabetes care m chIldren requires inJensive individualized education of the '"'" children and the members of their family. _
Pregna!1cy in women with d.iabetes is a high risk one. Care must be given with an aim to make pregnancy as safe as in a non-diabetic state for both the expectant mother and the baby. Such a goal is feasible if blood glucose can be maintained to a non-diabetic level ' throughout the pregnancy. Surgery in diabetic petsons has associations with increased risk of per-operative and postoperative complic�tions compared to that of non-diabetic persons. Surgery can be done safely with optimal care of diabetes mellitus. Necessary surgical procedures should never be avoided due to diabetic status. Diabetes control may be difficult during days of sickness and fasting (Ramadan). So special care is required during this time.
This chapter will help you to understand the management principles of diabetes in children, during pregnancy, surgery, sick days andfasting (Ramadan).
157
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N
Diabetes mellitus in children Diabetes mel!itus in chjJd�
Type2 d�ab�tes mellitus in children is relatively less common than type l . But now-a-days, it is being reported more frequently in many countries in association with rising rate of obesity. In many tropical countries, including Bangladesh, there is a substantial number of young lean diabetic cases with or without pancreatic calcification that cannot be included into sp� class. pLdiabetes; previously they were called 'malnutrition related diabetes r , mellitus (MRDM) . __
Whatever may be the class of diabetes - management of the disease in children needs special attentions on several specific aspects to achieve some targets - of glycemic control, growth and diabetic e
:
Targets of glycem ic control
Blood Glucose
• • • •
HbA l c
Patient & Parents
•
•
Pre-meal 5.0 - 10.0 mmollL Post-meal 5.5 - 11.1 mmollL Bed time 5.5 - 10.0 mmollL No hvtllol!lvcemia <
8.0%
Teaching, training and empowerment ' to take part in treatment such as blood glucose testing and insulin
1 58
-------
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Childhood diabetes mellitus may be of any of the following two forms :
1 . Type} DM (majority) 2 . Early onset type2 DM or �her types of diabetes Whatever may be the form, all need special attention because of some special problems in management issue.
Some key points •
Educator (doctors, nurses, dietitian and other health care providers) should have access to continuing specialized training in diabetes education.
•
The priorities for health care professionals in diabetes education may not match those of the child and family. Thus diabetes
Principles of diabetes -;management
education
, in cttLId.���d
should be based on a thorough of
the
beliefs , attitude s , learning style, ability and readiness to learn, existing
knowledge
and goal. •
Diabetes
Children, adolescents, their parents and other
assessment person ' s
_ -"'-d�Js.:;'-L'< ')r- ',
care providers should all have easy access to
I
and be included in the educational process.
•
D iabetes education should be delivered by health
care
professionals
with
a
clear
understanding of the special and changing needs of young people and their families as
education
they grow through the different stages of life.
needs to be adaptable
Train them for home monitoring of blood
and personalized
glucose and insulin inj ection techniques.
so
that it is appropriate to each individual' s age, stage of maturity,
I
diabetes, lifestyle,
Monitor physical growth and development. Provide emotional support, etc.
culture and at a pace to suit individual needs. Diabetes education needs to be a continuous process and repeated for it to be effective. •
Diabetes education should be plarined, documented, monitored and evaluated regularly by the diabetes care team.
1 59
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Diabetes education according to age group
Infants and toddlers •
They are totally dependent on parents and care providers for injections, food and monitoring; educate them.
•
Advise to stop or minimize erratic eating and activity.
•
Educate on prevention, recognition and management of hypoglycemia because it is very common complication in this age group.
School going children •
Teach them insulin injections and blood glucose monitoring.
•
Train them on recognizing hypoglycemic symptoms and understanding selfmanagement.
•
Teach them to adapt to school programs, school meals, exercise and sports.
•
Involve teacher/ school authority.
•
Advise the parents on the gradual development of the child's independence and progressive hand-over of responsibility.
Adolescents •
Promote independent, responsible self-management appropriate to the level of maturity and understanding.
•
Teach strategies for dealing with dietary indiscretions, illness, hypoglycemia, sports, etc.
•
Negotiate targets, goals and priorities and ensure that the tasks taken are understood and accepted.
•
Develop strategies to manage transition to adulthood.
1 60
,------
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Medical nutrition therapy (M NT) •
' A meal plan based on the individual s usual food intake should be determined and used as the basis for integrating insulin therapy into the usual eating and exercise patte:ns.
•
Timing and amount of food will depend on type of insulin, physical activity, life style and results of blood glucose monitoring.
•
Special diet counseling and monitoring by dietician. All children with diabetics should be referred to a dietitian for counseling at diagnosis of diabetes and also subsequently if they have problem with their diet adjustment. General principle will be similar to that described in chapter 4.
Sports and exercise •
Children with type l diabetes with good blood glucose control can do all levels of exercise, including leisure activities, recreational sports, and competitive professional performance. The emphasis must be on adjusting the therapeutic regimen with the level of exercise and the diet and avoiding hypoglycemia.
•
Extra attention needs to be paid to glycemic control with the normalcy of play, and for this the support of parents, teachers, and athletic coaches may be necessary.
•
Children between 3-5 years of age may take part in free pia , walking, running, throwing, catching, tumbling, etc. but shou � avoid competitive sports. ,.
�
•
Children between 6-9 years of age may take part in running, swimmjng, gymnastics, and start learning to pIa team sPJ)rts -.Such a! lootball or cnc et.
•
Children between l O- l 2years of ue and adolescents may be able to take part in all complex and contact sports like wrestling, basketball, football, tennis, hockey, � etc.
•
the case of adolescents, hormonal changes can contribute to the difficulty in controlling blood glucose levels. So extra care is required for exercise at this age group. Iii
161
P regancy and diabetes mellitus Pregnancy in women with diabetes is a high risk one and care must be given with an aim that both expectant mother and the baby must be as safe as in a non-diabetic person. A woman may encounter either of the following two forms of diabetes:
(Pre-pregnancy -
•
Woman is a known diabetic before she becomes pregnant
•
Glucose intolerance detected afteL the woman becomes pregnant
diabete�)
diabetes mellItus
-
-=
GDM)
----_.-'
.
Some key points •
•
•
Diabetes in pregnancy has associations with acute as well as chronic maternal-- andf etal -. complic' ���
A.
• Other problems like, pre-eclampsia, eclampsia,
E
�
PolY yd�_amnios
With optimum diabetes control prfo;- io.-and during pregnancy, complication rates approach those seen in normal pregnancies.
• Difficulties in diabetes control • Deterioration of pre-existing compications, ego retinopathy, nephropathy
B. Baby • Congenital malformations • Neonatal problems
Good qiabetic control throughout pregnancy as well as improved neonatal management has lead to a reduction in the incidence of morbidity associated with pregnancy in diabetic women. Spontaneous abortions and babies born with congenital anomalies are seen much less when good diabetic control has been established prior to conception and maintained during the first 6-8 weeks of pregnancy. -
Women with high HbA l c level at ear JLprenatal visit shoul.!,be studied with ultI'a§onogram for malfol])1ation. Maternal serum alpha fetoprotein sho�ld be tested for neural tube defects . .-
•
Mother
• Pregnancy loss: abortion/intrauterine death
-
•
Problems of
diabetes mel litus in pregnancy
------
•
(Gestational
.
Maietv.v of nonnoglycemia (blood glucose
6.0 IIIIIlGIJL and HbA l c < 6.S%) from the time of c onception is the: main tool fot.� __ dd such pregI1IIlcles .
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<
� Plications of baby due to maternal hyperglycemia •
Macr�omia (birth weight above 90th percentile for gestational age) caused by chronic maternal hyperglycemia causing fetal hyper-insulinism that results in excessive fat deposition and organomegaly.
•
Neonatal h�cemia is due to sudden withdrawal of maternal glucose at birth --- - -in presence of fetal hyper-msuhmsm.
•
Erythremia and hyperbilirubinemia partly due to response to relative hypoxia in utero.
•
Neonatal hypocalcemia due to functional hypoparathyroidism.
•
Respirat�ry distress syndrome due to delayed maturation of the enzyme machimiry for synthesis of lung phospholipids.
•
Congenital J!!,alformations, ego cardiac or renal anomaly, caudal regression, CNS . defects, etc; there is also intra-uterine growth retardation. (�----
Pre-pregnancy diabetes Pregnancy in all women with known diabetes must be pre-planned. Diabetic women of . .child bearing age and desirous of pregnancy, must ; be thoroughly counselled. This counseling must include intensive education about:
.,!/' Importance of tight glycemic control before and during pregnancy;
/�edical nutrition therapy;
Jskill on �nsulin injection techniques, home monitoring of blood glucose, and �eed for a close and regular follow-up. OraL agents must be discontinued. The women are managed with lifestyle modification and insulin (if necessary) to achieve tight metabolic control, which is defmed by HbA l c and blood glucose values. At all times they should be within the target If the control is not within this target range, pregnancy should be postponed until these target values are \ maintained.
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Gestational diabetes mellitus (GDM)
�
n:r degree of glucose intolerance [i.e �lood glucose values during oral glucose tolerance � test satisfy criteria of impaired fasting glucose (IF G) or impaired glucose tolerance (IGT) or d�s mellitus (DM.)lJletected in pregnant women for the first time is called GOM
)
It affects 2-8% of all pregnancies. Placental homones are responsible for the development of GDM.
Screening of GDM by glucose challenge test (GeT) If no risk factor for GDM is present perform screening at 24-28 weeks of gestation. If there is o�e or more risk factor(s) present, perform earlier ( 1 2- 1 4 weeks) and for" negative cases ...... - " repeat at 24-28 weeks of gestatIOn. •
•
•
•
A 50 gm oral glucose load is given regardless of the last meal.
Venous plasma glucose level at 60 minutes � 7.8 mmollL is consrdere� . GeT (Glucose challenge test) posi!i.ve. OGTT �th 75 gm of glucose is done m all GeT positive cases. GDM is confirmed if blood glucose at 0 minute � 6. 1 mmollL orland atl20th minute '" � 7.8 mmollL during..OGTT.
Individual at high risk of - - - - -----
gestational diabetes mellitus
-- -- -- - -
-
--
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• Bad obstetric history, like abortion, infertility, unexplained stillbirth, etc. ..,..
• Age
� 25 years
• Positive family history of DM <-
• Habitual physical inactivity • BMI above normal -
• Waist hip ratio above normal • History of GDM or delivery of baby > 9 lbs.
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• • •
HbA l c
•
F.asting < 6.0 mmollL Post-prandial < 6.0 mmollL Bed time < 6.0 mmollL <
6.5%
No hypoglycemia or ketonuria
Patient
�
•
Teaching, training and empowerment to take part in treatment such as blood glucose testing and insulin injection.
Targets of diabetes management in pregnancy
tment
•
Medical nutrition therapy (MNT) of pregnancy in diabetics.
•
Frequent home monitoring of blood glucose and urine ketones. Follow up at clinic - once every two weeks upto 30th gestational week and thereafter once every week.
•
•
Office treatment should comprise of a team of specialists: diabetologists, obstetricians and nutritionists.
•
Proper and timely change in insulin dose.
•
HbA l c determination initially and once in each trimester.
Medical nutrition therapy Daily total calories intake is to be 30 kcal/kg of ideal body weight in first trimester and 38 kcal/kg of ideal body weight thereafter ....
:. y"
Carbohydlate : S()..6()OIo Fat
f Protein
30% 1 0 -20%; may be increased in exchange of carbohydrate
L_J!�����lementation of iro
folic acid and calcium. 1 65
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Meal plan Major Meals: Breakfast, lunch, dinner. Snacks : Mid-morning, mid-afternoon and bedtime. Bedtime snack is essential to prevent fasting ketonuria.
"PhYsical activitY should be encouraged .
.-----::---
I nsulin therapy in pregnancy GDM Insulin therapy should be instituted
.JfIf dietary co�pliance fails to maintain glycemic target, or .:vif fasting ketonuria is present, or A sub-optimal weight gain is seen.
Pre-pregnancy diabetes Do not Jl�e oral antidiabetic agents. Start or adjust insulin to achieve glycemic target. Monitor blood glucose (preferably by home monitoring) to adjust the dose. Dose requiremerrt' ;ilfshow increasing trend with duration of pregnancy. Spjjt resimenof insulin therapy can better attain target of blood glucose levels.
Timing of labour and delivery Term delivery is feasible in most diabetic pregnancies by<
-
.
� Meticulous control of diabetes .
�Modern .obstetric technology
�",/ Monitoring of fetal well-being ( by studying fetal heart rate) and lung m��ity Jby testing_a.rrmiotic fluid). ,/
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Diabetes management during labour and delivery Blood �se should be between 4-5.5 mmoVL in order to prevent neonatal hypoglycemia. It is bestachIeved by continuous insulin infusion coupled with g ucose m SlOn, because it is essential to meet the energy expenditure of active labour:-Blood glucose should . be monitored hOJldy. The infusion is stopped immediately after the delivery of the baby. During this time regular insulin in ;�all dose �s given before meals ii1pre=pfegnancy diabetics; pre-pregnancy regular schedule of insulin may be started within a week. In almost all GDM cases insulin is not at all required after delivery; th�ecome eugl�emic. In aU GDM cases OGTT should bej?ne 6 weeks after delivery; if it is normal, OGTT is to be repeated every year, as these group of individuals are at risk of future diabetes. =
Hypoglycemia in the newborn
All newborns of diabetic mother have risk to develop �oglycemia . .
----
•
Blood glucose levels must be checked by heel prick within 30-60 minutes of birth and continued at regular intervals until one is sure that there is'llonsk for hypoglycemia.
•
Neonatal hypoglycemia is defined as blood glucose level less than 40 mg/dL in full term baby and less than 30 mg/dL in premature babieS. � -------
•
Management: •
If th� glucometer readings are between .,25 an2 45 mWl!.L, give gastric or oral feedings of 1 01 5 ml of 1 0% glucose; repeat if necessary, and start feeding as • soon as possible .
•
If the glucometer readings are less than - 25 mg/dL, i.v. 1 0% de�trose at the rate of 6 mglkglminut;-iUtarted.
•
Bolus doses are to be avoided as this may stimulate the already pancreas to secrete more insulin and add to the problem.
- 2------
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nVII'1"!lI1'1tnTP!
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Surgery and diabetes mellitus Surgery i n diabetic persons has associations with increased risk of per-operative and post oper'}jiv� complications compared to that in non-diabetic person ;-This i Sdue to-tIie involvement of their vital organs including the autonomic nervous system in the natural cours� ofthe disease. With optimal care, a surgery can be made safe in diabetics. Necessary surgical procedures should never be avoided due to one's diabetic --status. --. --� . -----�
.-
Some key points
J" Poor metabolic control results in dangerous acute metabolic complications due to ;urgical �tress. � The infection if develops, tends to become virulent which further worsens the metabolic state, thus establishing a vicious cycle.
/ Hyperglycemia
leads to impaired wound healing, deficient formation of granulation tissue, with poor tensile strength of collagen. The fibroblast formation takes longer time than non-diabetics and there is a deficient capillary growth into the wound. The chemotactic, phagocytic and bactericidal activity of the neutrophil is deficient. There is impaired humoral host defense mechanism and abnormal complement function.
Pre-operative assessment •
Pre-operative assessment must be done in close consultation with the physician, surgeon and anaesthetist.
•
It should include assessment of any diabetic complication, or associated conditions, which may increase surgical risk, e.g. cardiac autonomic neuropathy. � ===--
Aim should be to have optimal control of diabetes in all diabetic� undergoing surgery. This may not be always feasible, especially in an· emergency situation.
Factors nee� to be considered during planning surgery
¥ Type of diabetes mellitus
Treatment - diet, oral antidiabetic drugs, insulin .. Metabolic status "" Vascular status - cardiac, renal, cerebral Neurological status - specially autonomic nervous system '\A S!JfgClY : � or elective JY
..e;:.
�E
.,.
lI .JW1l . 1lOI' «:Jr. •-.or procedure
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General principles of treatment strategies
Day prior to surge ry , •
Avoi.QlQng acting secretagogues and biguanides prior to and during surgery.
•
Long acting insulin should be avoided on the night prior to surgery.
•
For major surgeries, the patient may be kept_ nil_�y mouth (NBM) over-night prior to surgery; in patients with gastroparesis, the duration of NBM should be around 1 0- 1 2 hours.
Day of surgery • • •
Anti-diabetic medications are omitted on the morning of the operation. - ---Schedule surgery as early as possible in the morning. In major surgery start glucose-insulin infusion. There is no standard formula for the amount of insulin that will need to be added to the dextrose infusion. The unit of insulin to be added to 5% dextrose (5% DA) or 5% dextrose saline (5% DNS) is arbitrary, n��ds to be individualized and adjusted as per the results of the glucometer readings. Blood glucosesfiould be monitored 1 to 2 hourly; it should be in the range of 6.Q-l1 .0 rwno/L. Glucose-insulin infusion may also be required in uncontrolled diabetes during minor surgery. But in case of minor surgery where blood glucose is well controlled, this infusion may be avoided.
Management during surgery •
The choice of the anaesthetic is best left to the anaesthetist; there is no preferred choice of anaesthetic agent for diabetics.
•
Cardiovascular status should be closely monitored during surgery.
•
The glucose-insulin administration is continued where it is required; it is guided by blood glucose monitoring.
Post-operative care •
The glucose-insulin administration is continued (where required) till the patient is able to take oral food.
•
At this time, if the bloo
•
Once patient is back on his routine diet and is stable, he can be managed with the regimen he was on prior to .surgery.
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Specific treatment strategies Minor surgery in well controlled diabetes •
If patient is on short acting secretagogues and/or insulin omit _breakfast and the mo�nggpse; restart regimen once patient is back on routine diet.
•
If patient is on long acti �ecretagogues, replace it with shorter acting . secretagogues 5 days pr�ior-to- surgery.
•
Per-operative glucose-insulin drip may be avoided. -
-
Major surgery (requiring overnight nothing by mouth) in well controlled diabetes -
•
Diabetes should be controlled by insulin.
•
Per-operatiye gluc.s>se-insulin � js eJsential.
•
In the post-operative period, once diet is resumed, patients usually do better with short acting insulin therapy.
•
Restarting of the patent' s previous regimen can be done once the patient is fully stable.
Type1 D� al!d poorly controlled type2 DM •
Always use insulin to control diabetes in major as well as minor surgeries .
•
Hospitallze the patient at least 3 days before operation.
•
Short acting insulin may be preferrable.
• . -
.
--
Emergency surgery .'
Hospitali�e the patient.
•
Start insulin infusion and frequent monitoring of blood glucose.
•
Check electrolytes, acid base status and urinary ketone levels.
•
Try to avoid surgery till blood glucose goes below 20 mmollL and ketonuria
disappears. •
If not possible, allow operation with intensive management of diabetic s�te in conjunction with the surgical procedure.
\i,\,.. ..,, �, ��
monitorias·
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It is important to emphasize that with optimal care, surgery in a diabetic is as safe as in a person without diabetes. For more elaborate idea about surgery in diabetes, consult text book of diabetes.
Perform the activity 1 0.5 in the module 1 0 to recall the memory on surgery in diabetes mellitus.
Sick day's management Period of illnesses �. fever, vomiting or diarrhoea, usua�ly cause hyperglycaemia and subse�nt ketosis rather- than hypoglycemia; certain management principles need to be followed are: •
The person needs to test hislher blood for glucose and ketones. If it is not possible, testing urine for glucose and ketones is very important.
•
Fluid balance needs to be maintained; so sufficient intake is necessary. If the blood glucose is low, sweetened fluids, ego fruit juice is to be given to avoid hypoglycaemia. If blood glucose is elevated, this is to be maintained by low calorie soft drinks, soup or broth:
.•
If the person is on insulin, continue intermediate or long acting insulin; the dose may need to be reduced. Shorter acting insulin should be adjusted according to blood glucose values and food intake.
•
If the person is on OAD the dose is to be readjusted; sometimes the longer acting OADs may need to be replaced by shorter acting ones or insulin.
•
Never stop the anti-diabetic agents altogether; its dose may be reduced.
•
These principles are to be followed until the blood glucose is < 1 2 mmollL and th ketones diminish or disappear.
.•
In situations with high fever, treat the infective focus. Treatment for. vomiting/diarrhoea may also be required.
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Be alert if •
Vomiting or diarrhoea persists for longer than 6 hours
•
Sick for 2 days and not getting better
•
Blood glucose remains above ! 4 mmollL (250 mg/dl)
•
Moderate ketonuria persists despite treatment
•
Very young individual
•
Abdominal pain
•
Hyperventilation
•
Co-existing serious diseases �
(Ramadan) Fasting and diabetes mellitus Forbid fastingj!l •
All bJjttle type ! Q!.abetic .atients�') tlYl"'-l
•
Poorly controlled type ! or type2 diabetic patients
•
Diabetics non-compliant to diet, daily activity and �imens
'.
.
�
. ¢ � -
•
Diabetics with serious
•
Patients with a history of diabetic ketoacidosis
•
Pregnant diaQ9ics
•
Diabetics with inter-current infections
•
Eloerly patients with any degree of alertness problems
• �
-------
Two or more episodes of hypogl�mia and/or hyperglycemia during fasting � � --�
Recommendation during fasting Nutrition
Dietary indiscretion during the non-fasting period with excessive gorging, or compensatory eating, of carbohydrate and fatty fOods contributes to the tendency towards hyperglycemia and weight gain. Diabetics must abstain from the high-calorie and highly refined foods prepared during this month.
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Physical activity Several studie.s:.indicate that light to moderate regu�r �x�rcise !during Ramadan fasting is harmless for type2 patients.
Drug regimens Type1 patients: Some experienced physicians conclude that Ramadan fasting is safe for type l patients with proper self-monitoring and close supervision. Two insulin regimens, have been studied successfully. l Three-dose insulin regimen: two doses before meals (sunset and dawn ot short acting insUlin and one dose in the late evening of intermediate-acting insulin. . .
-
-
- -
2. Two-dose insulin regimen: Evening J..nsulin of combined short�acting and intermediate-acting insulin equivalent to the previous morning dosage, and a pre dawn insulin consisting only of a short-acting i�sulin.
Type2 patients: Available reports indicate that there are no major problems encountered with type2 overweight patients who observe fasting in Ramadan.
The usu��ose of anti-diabetic agent (OAD o! insulin) is taken at sun-set; the evening d�e is reduced to 50% an..d t¥en at dawn. Conversion of longer acting medication to shorter acting ones (specially at dawn) canals.o be considered� -
-
--
.
.
'-
Reference and further reading
2.
Text book of Diabetes _3rd edition vol 1, edited by John C. Pickup and G. Williams, Blackwell Science, 2003 p 41.1 to 41.10 and vol-2, 65.1 to 66.25. Davidson's Diabetes Mellitus- Diagnosis and Treatment - 5th edition, A.P. Harmel and R.
3.
ChinicaI Practice Recommendation, 2007, ADA.
1.
Mathur, Saunders 2004, p 275 to 277; 283 to 289 and 323 to 364 .
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