1. Etiopathology of Diabetes
Dr Shahjada Selim Assistant Professor Department of Endocrinology Bangabandhu Sheikh Mujib Medical University, Dhaka

2. Diabetes: A global emergency

3. Diabetes around the world

4. Diabetes around the world

5. Diabetes around the world

6. South-East Asia At a glance 2015 2040 Adult population (20-79 years)
926 million
1.31 billion
Diabetes (20-79 years)
Regional prevalence
8.5% ( %‡)
10.7% ( %‡)
Age-adjusted comparative prevalence
9.1% ( %‡)
9.9% ( %‡)
Number of people with diabetes
78 million
( million‡)
140 million
( million‡)
Number of deaths due to diabetes
1.2 million -
Health expenditure due to diabetes (20-79 years)
Total health expenditure, R=2*, USD
7.3 billion
12.9 billion
Impaired glucose tolerance (20-79 years)
Regional prevalence
4.6% ( %‡)
5.6% ( %‡)
Age-adjusted comparative prevalence
4.7% ( %‡)
5.4% ( %‡)
Number of people with impaired glucose tolerance
42.2 million
( million‡)
73.9 million
( million‡)
Type 1 diabetes (0-14 years)
Number of children with type 1 diabetes
81,400 -
Number of newly diagnosed children each year
13,100 -
* See Glossar y
‡ Uncertainty inter val
IDF Diabetes Atlas · Seventh Edition

7. Health expenditure Data sources Mortality
Mauritius has one of the highest adult diabetes
prevalence rates in the world (22.3% age-
adjusted comparative prevalence, 24.3% raw
prevalence). The Maldives (9.2% age-adjusted,
7.5% raw) has the second-highest prevalence
rate in the region. India is home to the second
largest number of adults living with diabetes
worldwide, after China. People with diabetes in
India, Bangladesh, and Sri Lanka make up 99.0%
of the region’s total adult diabetes population.
Health expenditure
A total of USD7.3 billion (R=2*) to USD12.4 billion
(R=3*) (ID24.9 billion to ID42.4 billion) was spent
on the 78 million people living with diabetes in
2015, 12% of the health budget of the region. This
accounts for 1% of the global health spending on
diabetes. Compared to the other IDF regions, the
South-East Asia Region had the lowest health
expenditure per person with diabetes (USD93 to
USD158, ID319 to ID542).
A further 42.2 million people have impaired
glucose tolerance and are at increased risk of
developing type 2 diabetes in the future. The
number of people with diabetes in the region is
predicted to be 140 million by 2040 – 10.7% of
the adult population aged This increase is
largely a consequence of ongoing urbanisation
and increasing life expectancy.
Data sources
All countries except Bhutan had primary data
sources that were used to generate estimates for
diabetes in adults in the region. A total of 13 data
sources from six countries were used. Diabetes
prevalence estimates for India, Nepal, Sri Lanka
and Bhutan were based, in part, on data sources
that were more than five years old and may be
underestimates.
There are an estimated 81,400 children under the
age of 15 living with type 1 diabetes in the South-
East Asia Region. Approximately 13,100 children
developed type 1 diabetes in the region during
2015.
Estimates for type 1 diabetes in children were
largely based on data from India, the Maldives
and Mauritius. 91
India is home to the second largest number
of children with type 1 diabetes in the world
(70,200), after the USA, and accounts for the
majority of the children with type 1 diabetes in
the region. The incidence rate for type 1 diabetes
in India was used to extrapolate figures for other
similar countries, and therefore plays a pivotal
role in the regional and global estimates.
Mortality
With 1.2 million deaths in 2015, the region had
the second highest number of deaths attributable
to diabetes of any of the seven IDF regions, after
the Western Pacific Region. More than half
(53.2%) of these deaths occurred in people under
60 years of age. India was the largest contributor
to regional mortality, with one million deaths
attributable to diabetes.
Chapter 4 – Diabetes by region

8. Map 4.6 Prevalence* (%) estimates of diabetes (20-79 years), 2015
Pr di (2 20 15 10 5 Pr
evalence (%) estimates of
Male
Female
diabetes by age
(20-79 years) and sex
< 7
7 - 8
9 - 10
> 10
* comparative prevalence
Figure 4.6 Mortality due to diabetes, South-East Asia Region, 2015 93
Percentage of all-cause mortality due to diabetes by age (20-79 years) and sex
Male
Female 35 30 25 20 15 10 5
20-29
30-39
40-49
50-59
60-69
70-79
Death due to diabetes by age 3% 8%
15%
27%
25%
22%
50-59 years
60-69 years
70-79 years
20-29 years
30-39 years
40-49 years
53% under the age of 60
1,188,465 total deaths due to diabetes
(664,071 women, 524,394 men)
Chapter 4 – Diabetes by region

9. Pathogenesis of Type 1 diabetes.
Autoimmune Type 1 Diabetes
Beta cells destroyed via autoimmune mechanism.
Genetically predisposed people:triggering factor = production of islet cell Ab.
Islet cell Ab destroy Beta cells.
Insulin production decreases.
3 August 2018
Etiopathogenesis of diabetes by Dr Shahjada Selim

10. Pathogenesis of Type 1 diabetes.
Autoimmune Type 1 Diabetes
Viruses + other environmental agents have been shown to be triggering factors.
Viruses can damage beta cells by:
1.Direct invasion.
2.Triggering an auto immune response.
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Etiopathogenesis of diabetes by Dr Shahjada Selim

11. Pathogenesis of Type 1 diabetes.
Autoimmune Type 1 Diabetes
Implicated viruses:
mumps, intrauterine rubella, coxsackie B virus, echo virus, gytomegalo virus and herpes virus.
Chemical substances that reduce diabetes:
alloxan, streptozotosin and dietary nitroamides.
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Etiopathogenesis of diabetes by Dr Shahjada Selim

12. Pathogenesis of Type 1 diabetes.
Idiopathic Type 1 Diabetes
No known aetiology.
Permanent insulinopaenia.
This form is strongly inherited.
Not HLA associated.
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Etiopathogenesis of diabetes by Dr Shahjada Selim

13. Clinical features of Type 1 diabetes.
Presents acutely. Symptoms due to hyperglycaemia (thirst, polyuria, tiredness,weight loss).
Ketone production - abdominal pain, nausea and vomiting.
Other symptoms: blurred vision, repeated infections.
No chronic complications at diagnosis, may only be apparent 5-10 years post diagnosis.
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Etiopathogenesis of diabetes by Dr Shahjada Selim

14. Incidence of Type 1 diabetes.
Incidence peaks at years.
Seasonal variation: lowest rates in spring and summer.
Geographical variation: Japan has a very low incidence.
10% of Type 1 diabetics are over 65 years of age.
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15. Etiopathogenesis of diabetes by Dr Shahjada Selim
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16. Etiopathogenesis of diabetes by Dr Shahjada Selim
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Etiopathogenesis of diabetes by Dr Shahjada Selim

17. Etiopathogenesis of diabetes by Dr Shahjada Selim
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18. Etiopathogenesis of diabetes by Dr Shahjada Selim
Natural history of patients with type 2 diabetes...Problems before you see them
Content Points:
People with type 2 diabetes are at high risk for atherosclerosis and consequent CVD. Part of this risk is thought to be due to insulin resistance and resultant hyperinsulinemia as the pancreas secretes extra insulin to overcome the resistance of muscle and fat to insulin.
There is evidence that hyperglycemia is one factor that may cause oxidation of compounds and contribute to endothelial dysfunction and, subsequently, CVD.36
Many individuals who are insulin resistant or who have type 2 diabetes are not diagnosed until they have sustained cardiovascular damage from hyperglycemia and hyperinsulinemia. Prediabetics (people with impaired glucose tolerance or IGT), without chronic hyperglycemia, have a 2-fold increase in risk of coronary artery disease compared with normal subjects. By the time a person has developed full-blown type 2 diabetes, their risk has increased to 3-fold greater than normal.37
In an effort to decrease the high level of morbidity and mortality and to facilitate early diagnosis, the American Diabetes Association has recently revised their guidelines by lowering the fasting plasma glucose level at which diabetes is diagnosed from 140 mg/L to 126 mg/L.38
Physicians need to be aggressive in diagnosing and treating type 2 diabetes to reduce risk of cardiovascular events.
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Etiopathogenesis of diabetes by Dr Shahjada Selim

19. Pathophysiology of type 2 diabetes
Skeletal
Muscle
GI tract
Pancreas
Adipocyte
Muscle
α cells
 cells
Incretin deficiency
Altered fat metabolism
Hyperglucagonaemia
↑ hepatic sensitivity to glucagon
INSULIN RESISTANCE
INADEQUATE INSULIN SECRETION
↑ HEPATIC GLUCOSE PRODUCTION
CNS
Kidney
↑ BLOOD GLUCOSE
Enhanced glucose reabsorption
CNS, central nervous system; GI, gastrointestinal; T2DM, type 2 diabetes mellitus
Cernea S & Raz I. Diabetes Care 2011;34(suppl 2):S264–S271

20. Etiopathogenesis of diabetes by Dr Shahjada Selim
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Etiopathogenesis of diabetes by Dr Shahjada Selim

21. Etiopathogenesis of diabetes by Dr Shahjada Selim
Type 2 diabetes
Patients frequently undiagnosed for many years.
May present with hyperglycemia symptoms.
Coma is rare in type 2 diabetes.
May progress to an absolute state of insulin deficiency.
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Etiopathogenesis of diabetes by Dr Shahjada Selim

22. Pathogenesis of Type 2 diabetes.
Cause: insulin secretory failure on the background of insulin resistance.
Impaired insulin secretion due to beta cell malfunction can be associated with:
Incorrect secretion pattern.
Ratio of proinsulin to insulin.
Amyloid deposits.
Slow destruction of beta cells
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Etiopathogenesis of diabetes by Dr Shahjada Selim

23. Mechanisms for insulin resistance.
Receptor numbers are decreased. (Often seen in obese and aged patients.)
Receptor structure is abnormal.
Insulin resistance at post receptor events.
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Etiopathogenesis of diabetes by Dr Shahjada Selim

24. Clinical features of Type 2 diabetes.
Diagnosis due to presence of complications.
(At least 30% patients have complications at diagnosis).
Symptoms are mild, gradual onset : classic diabetic symptoms may be present.
Type 2 diabetics are usually: usually occurs in young or elderly, in fat (“apple obesity”).
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Etiopathogenesis of diabetes by Dr Shahjada Selim

25. Etiopathogenesis of diabetes by Dr Shahjada Selim
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Etiopathogenesis of diabetes by Dr Shahjada Selim

26. Etiopathogenesis of diabetes by Dr Shahjada Selim
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Etiopathogenesis of diabetes by Dr Shahjada Selim

27. Insulin Secretion in Non-Diabetics
and Type 2 Diabetics
Clock Time (Hours)
06:00
Normal
Type 2 DM
10:00
14:00
18:00
22:00
02:00
800
700
600
500
400
300
200
100
Insulin Secretion (pmol/min)
O'MEARA et al. Am. J. Medicine, 1990;89
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28. Glucose Contributions to HbA1c+
Postprandial Glucose,
Influenced by:
Preprandial glucose
Glucose load from meal
Insulin secretion
Insulin sensitivity in peripheral tissues and liver
Fasting Glucose,
Hepatic glucose production
Hepatic sensitivity to insulin
HbA1c =
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Etiopathogenesis of diabetes by Dr Shahjada Selim

29. Etiopathogenesis of diabetes by Dr Shahjada Selim
Postprandial glucose
Most of the day may be postprandial
HbA1c = FPG + PPG
Postprandial from the time glucose starts to rise until it comes down again
Time period up to 2.5 h after a meal – normal individuals 1.5 h
Testing of PPG recommended 2h after the start of a meal
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Etiopathogenesis of diabetes by Dr Shahjada Selim

30. Possible Pathogenesis of Diabetic Complications
Overall Glycemic Control (HbA1c)
Hyperglycemic "Peaks"
Fasting/Preprandial glucose elevations
Acute toxicity
Chronic toxicity
Tissue lesion
Complications
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Etiopathogenesis of diabetes by Dr Shahjada Selim

31. Which glucose variable?
Fasting plasma glucose (FPG), postprandial plasma glucose (PPG) and HbA1c all have pros and cons
Where feasible, HbA1c should be the standard measurement by which to gauge risk and treatment efficacy
FPG and PPG are useful
to adjust daily treatment
to monitor for hypoglycaemia
for confirmation as haemoglobin metabolism problems may mask true HbA1c levels
if there is a lack of resources for HbA1c measurement
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Etiopathogenesis of diabetes by Dr Shahjada Selim

32. Link Between Obesity and Type 2 Diabetes: Nurses’ Health Study
Colditz GA, et al. Ann Intern Med. 1995;122:
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33. Lessons from UKPDS: Better control means fewer complications
EVERY 1%
reduction in HBA1C
REDUCED RISK* 1%
-21%
Deaths from diabetes
-14%
Heart attacks
Lessons from UKPDS: better control means fewer complications
The UKPDS has proven beyond doubt that intensive glycaemic control is strongly associated with significant clinical benefits for patients with type 2 diabetes. In an epidemiological analysis of the UKPDS cohort every 1% decrease in HbA1C was associated with clinically important reductions in the incidence of
diabetes-related death ( 21%)
myocardial infarction ( 14%)
microvascular complications ( 37%)
peripheral vascular disease ( 43%)
There is no lower limit beyond which reductions in HbA1C cease to be of benefit. Taking diabetes-related death as an example, this means that:
 HbA1C of 2% delivers a 42% reduction in risk
 HbA1C of 3% delivers a 63% reduction in risk, and so on.
Therefore, the greater the reduction in HbA1C, the greater the protection against complications.
Stratton MI Adler AI, Neil AW, Matthews DR, Manley SE, Cull CA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000;321:
-37%
Microvascular complications
-43%
Peripheral vascular disorders
*p<0.0001
UKPDS 35. BMJ 2000; 321:
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