DIABETES MELLITUS
Certificate Course on Diabeto(ogy Distance Learning Project
Distance Learning Project
Diabetic Ass...
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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
9
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
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odule 8
1
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odule 7
1
TMR �
--=--'
End Course Exami nati on
15
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MOdUle
e
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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, 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.
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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., -¥
22
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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.
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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)
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. .
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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
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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\�
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•
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-
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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
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neuropathies
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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 . ,-
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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.
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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
,....
---
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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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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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Abnormal
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Review the blood glucose profile . Non-pharmacological interv�ntions
Pharmacological approach
Statins
p.---.--�---'
Fibrates
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Cholestyramine
Nicotinic acids
•
Weight loss for obese
•
Regular exercise
•
Medical nutrition therapy for dyslipideroia
137
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Non-pharmacological i nterventions
Ezetimibe
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Pharmacological interventions Groups
Drugs •
Statins (inhibit HMG-Co A reductase activity) -
•
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Remarks
Dose
Fluvastatin Rosuvastatin� c.- re"c.\4� f'ft>-+ 1-
Lower LDL and triglycerides Raise HDL
e�\c e.. ve V\{
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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