Etiopathology of diabetes_Dr Selim

Etiopathology of Diabetes

Dr Shahjada Selim Assistant Professor

Department of EndocrinologyBangabandhu Sheikh Mujib Medical University, Dhaka

Email: [email protected], [email protected]

mailto:[email protected]

mailto:[email protected]

Diabetes: A global emergency

Diabetes around the world



South-East Asia

At a glance 2015 2040Adult population (20-79 years) 926 million 1.31 billionDiabetes (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 billionImpaired 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

Mauritius has one of the highest adult diabetesprevalence 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 expenditureA 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 in2015, 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 impairedglucose 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% ofthe adult population aged 20-79. This increase is largely a consequence of ongoing urbanisation and increasing life expectancy.

Data sourcesAll 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 theage of 15 living with type 1 diabetes in the South- East Asia Region. Approximately 13,100 children developed type 1 diabetes in the region during2015.

Estimates for type 1 diabetes in children werelargely based on data from India, the Maldives and Mauritius.

91

India is home to the second largest numberof 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.MortalityWith 1.2 million deaths in 2015, the region hadthe 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 under60 years of age. India was the largest contributor to regional mortality, with one million deaths attributable to diabetes.

Chapter 4 – Diabetes by region

Map 4.6 Prevalence* (%) estimates of diabetes (20-79 years), 2015

Prdiabetes by age(20-79 years) and sex

< 77 - 88 - 8.58.5 - 99 - 10> 10

* comparative prevalence

93Figure 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 MaleFemale35

30

25

20

15

10

5

020-29 30-39 40-49 50-59 60-69 70-79

Death due to diabetes by age3% 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

20-2

9 ye

ars

30-3

9 ye

ars

40-4

9 ye

ars 50-59 years 60-69 years 70-79 years

Pr di (2

20

15

10

5

0

evalence (%) estimates of

MaleFemale

20-29 30-39 40-49 50-59 60-69 70-79

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.

May 2, 2023 Etiopathogenesis of diabetes by Dr Shahjada Selim 9

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.


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.


Pathogenesis of Type 1 diabetes.Idiopathic Type 1 Diabetes• No known aetiology.• Permanent insulinopaenia.• This form is strongly inherited.• Not HLA associated.


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.


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.






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

cellsα cells

SkeletalMuscle Pancreas

Muscle

Kidney

Enhanced glucose reabsorption


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.


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


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.


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”).




Insulin Secretion in Insulin Secretion in Non-DiabeticsNon-Diabeticsand Type 2 Diabeticsand Type 2 Diabetics

Clock Time (Hours)06:00

NormalType 2 DM

10:00 14:00 18:00 22:00 02:00 06:00

800

700

600

500

400

300

200

100Insu

lin S

ecre

tion

(pm

ol/m

in)

O'MEARA et al. Am. J. Medicine, 1990;89May 2, 2023 Etiopathogenesis of diabetes by Dr Shahjada

Selim 27

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 =


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


Hyperglycemic "Peaks"

Fasting/Preprandial glucose elevations

Acute toxicity Chronic toxicity

Tissue lesion

Complications

Overall Glycemic Control (HbA1c)

Possible Pathogenesis of Diabetic Possible Pathogenesis of Diabetic ComplicationsComplications


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


Link Between Obesity and Type 2 Diabetes:Nurses’ Health Study

Colditz GA, et al. Ann Intern Med. 1995;122:481-486.

020406080

100120

<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-A

djuste

d Rela

tive R

isk


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<0.0001

-14%

-21%


Etiopathology of diabetes_Dr Selim

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