Etiopathology of diabetes by Dr Shahjada Selim

1. Etiopathology of
Diabetes
Dr Shahjada Selim
Assistant Professor
Department of Endocrinology
Bangabandhu Sheikh Mujib Medical University, Dhaka
Email: selimshahjada@gmail.com, info@shahjadaselim.com

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% (6.8-10.8%‡
) 10.7% (8.5-13.7%‡
)
Age-adjusted comparative prevalence 9.1% (7.3-11.6%‡
) 9.9% (7.9-12.8%‡
)
Number of people with diabetes 78 million
(63-100
million‡
)
140 million
(112-180
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% (2.2-6.5%‡
) 5.6% (2.7-7.4%‡
)
Age-adjusted comparative prevalence 4.7% (2.4-6.7%‡
) 5.4% (2.5-7.2%‡
)
Number of people with impaired glucose tolerance 42.2 million
(20.7-60.2
million‡
)
73.9 million
(35.0-96.9
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. 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 20-79. 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
diabetes by age
(20-79 years) and sex
< 7
7 - 8
8 - 8.5
8.5 - 9
9 - 10
> 10
* comparative prevalence
93
Figure 4.6 Mortality due to diabetes, South-East Asia Region, 2015
Percentage of all-cause mortality due to diabetes by age (20-79 years) and sex Male
Female
35
30
25
20
15
10
5
0
20-29 30-39 40-49 50-59 60-69 70-79
Death due to diabetes by age
3% 8% 15% 27% 25% 22%
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
20-29
years
30-39
years
40-49
years
50-59 years 60-69 years 70-79 years
Pr
di (2
20
15
10
5
0
evalence (%) estimates of
Male
Female
20-29 30-39 40-49 50-59 60-69 70-79

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 Abdestroy Beta cells.
• Insulin production decreases.
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Etiopathogenesis of diabetes by Dr Shahjada
Selim
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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
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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
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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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Selim
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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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Selim
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14. Incidence of Type 1 diabetes.
• Incidence peaks at 11-13 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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19. Pathophysiology of type 2 diabetes
Cernea S & Raz I. Diabetes Care 2011;34(suppl 2):S264–S271
CNS, central nervous system; GI, gastrointestinal; T2DM, type 2 diabetes mellitus
Adipocyte
CNS
Incretin
deficiency
GI tract
Altered fat
metabolism
INSULIN RESISTANCE
INADEQUATE
INSULIN SECRETION
↑ HEPATIC
GLUCOSE
PRODUCTION
↑ BLOOD GLUCOSE
Hyperglucagonaemia
↑ hepatic sensitivity
to glucagon
β cells
α cells
Skeletal
Muscle
Pancreas
Muscle
Kidney
Enhanced glucose
reabsorption

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21. 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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Selim
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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:
1. Incorrect secretion pattern.
2. Ratio of proinsulin to insulin.
3. Amyloid deposits.
4. Slow destruction of beta cells
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Selim
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23. Mechanisms for insulin
resistance.
1. Receptor numbers are decreased. (Often seen in
obese and aged patients.)
2. Receptor structure is abnormal.
3. Insulin resistance at post receptor events.
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Selim
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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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Selim
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Selim
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Selim
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27. Insulin Secretion in Non-DiabeticsInsulin Secretion in Non-Diabetics
and Type 2 Diabeticsand Type 2 Diabetics
Clock Time (Hours)
06:00
Normal
Type 2 DM
10:00 14:00 18:00 22:00 02:00 06:00
800
700
600
500
400
300
200
100
InsulinSecretion(pmol/min)
O'MEARA et al. Am. J. Medicine, 1990;89
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28. Glucose Contributions to HbAGlucose Contributions to HbA1c1c
+
Postprandial Glucose,
Influenced by:
Preprandial glucose
Glucose load from meal
Insulin secretion
Insulin sensitivity in peripheral
tissues and liver
Fasting Glucose,
Influenced by:
Hepatic glucose production
Hepatic sensitivity to insulin
HbA1c =
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Selim
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29. 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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30. Hyperglycemic
"Peaks"
Fasting/Preprandial
glucose elevations
Acute toxicity Chronic toxicity
Tissue lesion
Complications
Overall Glycemic Control (HbA1c)
Possible Pathogenesis of DiabeticPossible Pathogenesis of Diabetic
ComplicationsComplications
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Selim
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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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Selim
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32. Link Between Obesity and Type 2 Diabetes:
Nurses’ Health Study
Colditz GA, et al. Ann Intern Med. 1995;122:481-486.
0
20
40
60
80
100
120
< 22 22-
22.9
23-
23.8
24-
24.9
25-
26.9
27-
28.9
29-
30.9
31-
32.9
33-
34.9
> 35
BMI (kg/m2
)
Age-AdjustedRelativeRisk
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33. EVERY 1%
reduction in HBA1C
REDUCED
RISK*
1%
Deaths from diabetes
Heart attacks
Microvascular
complications
Peripheral vascular
disorders
UKPDS 35. BMJ 2000; 321: 405-12
Lessons from UKPDS:
Better control means fewer complications
-37%
-43%
*p<0.000
1
-14%
-21%
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