PROBLEM STATEMENT

Causes of the rise

NUMBER OF DEATHS ATTRIBUTABLE TO DIABETES BY AGE GROUP, SOUTH-EAST ASIAN REGION, 2007

Number of deaths

Huge losses in the form of foregone economic growth

(relatively a greater problem in poorer countries)

2005 – 2015, WHO predicts net losses in national

income from diabetes & cardiovascular disease of

some -

ID557 billion in China

ID303 billion in the Russian Federation

ID336 billion in India

Disease Burden on the World EconomyDisease Burden on the World Economy

PROBLEM STATEMENT- INDIA India leads the world, about 20% of the total diabetic

population, “diabetes capital of the world”. “diabetes capital of the world”.

“Asian Indian PhenotypeAsian Indian Phenotype” - unique clinical & biochemical abnormalities in Indians:

Madras Diabetes Research Foundation & MV Diabetes Specialities Centre, Chennai.

National prevalence (20-79 yrs) in 2007 was 6.2% Predicted- 7.6% in 2025

Diabetes type 1 incidence (0-14 yrs)

2007 is 4.2 per 100,000 children per year

IGT: national prevalence (20-79 yrs) 2007 is 5.4% 2025 might go upto 6.1%

Number of people with diabetes (20-79 yrs)

Mortality rates:

The age adjusted mortality rates :

1.5 – 2.5 times higher than in the general population

Deaths attributable to diabetes as percentage

of all deaths 2007:

Males 9.7%

Females 15.5%

Mean health expenditure 2007 - USD 47

o Diabetes related complications are coronary artery disease, peripheral vascular disease, neuropathy, retinopathy, nephropathy.

People with diabetes are likely to develop

Prevalence in CHENNAI1989 to 2004, the prevalence increased

significantly by 72.3% (P<0.001)IDDM incidence 10.5% per 100,000 children

(10-12yrs)

WHO Classification of Diabetes Mellitus

Type 1 : Insulin Dependent Diabetes Mellitus (IDDM)

Type 2 : Non- Insulin Dependent Diabetes Mellitus (NIDDM)

Malnutrition-related Diabetes Mellitus

Other Types:

Pancreatic

Hormonal Imbalance

Liver related

Drug induced

Impaired Glucose Tolerance

Gestational Diabetes mellitus

Type 1 IDDM Caused by complete deficiency of Insulin

resulting from Beta cell destruction

Onset : Abrupt and usually >30yrs of age

Idiopathic: 10 % of all IDDM

Auto Immunity: IDDM is 90% immune mediated Islet cell antibodies, Insulitis Associated with other autoimmune diseases such as

Hashimoto’s thyroiditis, Addison’s disease & pernicious anaemia

Genetic susceptibility:

18 regions of the genome linked with type 1 diabetes risk, IDDM1 to IDDM18

IDDM1, which contains the HLA (Human Leukocyte Antigens) genes that encode immune response proteins.

Environmental Factors:

Viral infections – congenital Rubella, Mumps, Measles and coxsackie B virus

Exposure to cow’s milk - Albumin from cow’s milk may react with islet cells of pancreas, leading to their destruction

OGTT : Increased fasting blood glucose (>120mg/dl)Post prandial blood glucose (>200mg/dl)

Type 2 NIDDMHigh blood glucose due to insulin resistance

and relative insulin deficiency

Little tendency towards ketoacidosis

Increasingly diagnosed in children in parallel

to rising obesity rates

INSU

LIN RESISTAN

CE

METABOLIC SYNDROME:

Defined as a clustering of

atherosclerotic

cardiovascular disease

risk factors and a

systemic proinflammatory

state.

Monogenic Forms of Diabetes Rare forms, accounting for about 1 – 5 % of all cases

Mostly the gene mutation is inherited; in others its spontaneous.

They are Neonatal DM and MODY

Neonatal DMNeonatal DM::

first 6 months of life, do not produce enough insulin,

one in 100,000 to 500,000 live births

Permanent neonatal diabetes mellitus Permanent neonatal diabetes mellitus (PNDM)

Transient neonatal diabetes mellitusTransient neonatal diabetes mellitus (TNDM).

Intrauterine growth retardation

Maturity Onset Diabetes of Young

Onset prior to age 25, a family history of diabetes in multiple successive generations Impaired β-cell function & insulin resistance and late β-cell failure

Mutations in 10-12 different genes

People with MODY

are generally not overweight

do not have other risk factors for type 2 diabetes,

may have only mild or no symptoms

(discovered on routine tests)

IMPAIRED GLUCOSE TOLERANCEIs an intermediate state of dysglycemia

Has an intermediately raised glucose level after 2 hours,

but less than would qualify for type 2 diabetes mellitus.

The fasting glucose may be either normal or mildly

elevated.

Venous blood Capillary blood

Fasting <120 <120

2hrs after glucose load

120-180 140-200

Due to a severe malnutrition.

On Starvation, there is nothing that the insulin can act upon. The body slowly reduces its production due to Negative Feedback

control.

A fasting glucose that is higher than the upper limit of normal, but not high enough to be classified as diabetes mellitus.

a pre-diabetic state, associated with insulin resistance & increased risk of cardiovascular pathology, although of lesser risk than IGT

There is a 50% risk over 10 years of progressing to overt diabetes

Malnutrition related Diabetes Mellitus

Impaired Fasting Glucose

Effect of Diabetes on the Pregnant Woman Effect of Diabetes on the Foetus

Gestational Diabetes MellitusA condition in which women without previously diagnosed

diabetes exhibit high blood glucose levels during pregnancy, affecting 3-10% of pregnancies

The hormones produced during pregnancy increase a woman's resistance to insulin, resulting in impaired glucose tolerance

TYPE 3 DIABETESA new diabetic condition referred to as type 3 diabetes,

which simply means that one has both type 1 and type 2 diabetes.

Type 1 to Type 3:

Type 2 to Type 3:

Need more insulin

Epidemiological DeterminantsAGENT

HOST FACTORS

ENVIRONMENTAL RISK FACTORS

AGENTPANCREATIC DISORDERS

Infections, Tumors , Obstructions, Removal

DEFECTS IN FORMATION OF INSULIN

BETA CELL DESTRUCTION

DECREASED INSULIN SENSITIVITY Decreased adipocyte & monocyte insulin receptors

AUTOIMMUNITY

GENETIC DEFECTS Mutation in insulin gene Mutations in insulin receptor gene :

Donohue syndrome, Rabson-Mendenhall syndrome, Type A insulin resistance

HOST FACTORS

AGESEXGENETIC FACTORSGENETIC MARKERSIMMUNE MECHANISMSOBESITYMATERNAL DIABETES

AGE & SEX NIDDM – usually middle years of life Malnutrition related DM - young people, worse prognosis In south east Asia, an excess of male diabetics.

GENETIC FACTORS GENETIC MARKERSInheritance factor for

IDDM is small

NIDDM has a concordance in twin studies of 80-90%, suggesting a strong genetic component.

Family History:

25 - 33% of type 2 diabetics have family members with diabetes.

A first-degree relative poses 40% risk of developing diabetes

IDDM is associated with HLA B8 and B15 & more strongly with HLA-DR3 and DR4

NIDDM is not HLA associated

Type-2 diabetics mutation in a zinc

transporter SLC30A8, which is involved in regulating insulin secretion.

IMMUNE MECHANISMS HORMONAL IMBALANCES

GlucagonomasPheochromocytomasCushing syndromeAcromegaly

ROLE OF OBESITY IN DM80 - 95% of the increases in type 2 diabetes are due

to obesity.Apple-shaped abdomen is associated with

insulin resistance and diabetes, heart disease, high blood pressure, stroke, unhealthy cholesterol levels.

Number of Insulin receptors are reduced in the adipose tissue

Waist circumferences > 35 inches in women >40 inches in men specifically associated with a greater risk

Metabolic syndromeNo role in IDDM

Effect of weight loss on fasting blood glucose

ENVIRONMENTAL RISK FACTORSSedentary lifestyle DietDietary fibreMalnutritionAlcoholViral infectionsChemical agentsStressOther factors

LIFESTYLE

Lack of exercise alters the interaction between insulin & its receptors

DIETARY FACTORS

DIETARY FIBREDIETARY FIBRE

• Rich in NSP, Reduces blood glucose

• Min Daily intake of 20g of fibre

MALNUTRITIONMALNUTRITION

• PEM (Partial beta cell failure)

ALCOHOLALCOHOL

• Damages Liver & Pancreas

• Promotes Obesity

. GnT-4a ENZYMEGnT-4a ENZYME

• Mutations affecting the enzyme

GnT-4a glycosyltransferase

disrupts insulin production

Other Factors

Smoking According to a 2006 study, smokers are

more than twice as likely to develop diabetes as people who have never smoked.

Passive smoking

SOCIAL FACTORS