DIABETES MELLITUS TYPE-2

CAROLINE KARUNYA PONNRASI KANAGARAJ

Group-04

WHAT IS DIABETES MELLITUS ?

• Diabetes mellitus is a chronic disease characterized by derangement in

carbohydrates, fat and protein metabolism

DIABETES TYPE-2

Type 2 diabetes mellitus comprises an array of dysfunctions resulting from:

1. the combination of resistance to insulin action

2. inadequate insulin secretion. It is disorders are characterized by hyperglycemia

and associated with microvascular (ie, retinal, renal, possibly neuropathic), macrovascular (ie, coronary, peripheral vascular), and neuropathic (ie, autonomic, peripheral) complications.

COMPONENTS OF DM-II

Type 2

diabetes

Insulinresistance

-celldysfunction

METABOLIC ABNORMALITIES IN DM-II

Obesity

Insulin resistance

Abnormal insulin secretion

Excess glucose production

Beta-cell failure

INSULIN RESISTANCE-IR

• Insulin resistance is a condition in which the body produces insulin but does not use it properly.

CAUSES OF IR

The circulating free fatty acids associated with obesity also responsible for insulin resistance of the muscle and liver.

WHAT DOES IR DOES TO OUR BODY METABOLISM ?

• Decreased glucose uptake by skeletal muscle and adipose tissue.

• Increased glucose output by Liver-Gluconeogenesis.

• In the early stages of obesity the pancreas compensates for the IR by overproducing insulin so that glucose homeostasis is maintained.

• This leads to HYPERGLYCEMIA & HYPER INSULINEMIA

BETA CELL -DYSFUNCTION

Chronic hyperglycemia

Glucotoxicity2

Lipotoxicity3

Oversecretion of insulin to compensate for insulin resistance1,2

-celldysfunction

Beta –cell failure

• The elevated levels of free fatty acids and or cytokines lead to gradual loss of the ability of the pancreas to overproduce insulin , a process called decompensation-Lipotoxity

• Glucose, the main regulator of insulin secretion and production, exerts negative effects on beta-cell function when present in excessive amounts over a prolonged period-glucotoxicity.

INSULIN RESISTANCE &

BETA CELL -DYSFUNCTION

IR

Insulinresistance

Liver

Muscle

Adiposetissue

Glucose output Glucose uptake Glucose uptake

Hyperglycemia

KETOACIDOSIS

• It rarely develops in DM-II• Insulin present in DM-II is enough to prevent

uncontrollable release of fatty acids from adipocytes and fattyacids reaching the liver or synthesized de novo are directed to triacyglycerol.

KETOACIDOSIS If it is develops:Insulin Deficiency

Increased GlycogenolysisIncreased Gluconeogenesis Increased Hepatic glucose

outputDecreased Peripheral glucose

uptakeElevates blood glucose

Increased LipolysisIncreased Release of FFA in

liverIncreased VLDL & ketones Ketonemia and hyperTG

Acidosis & Diuresis

HYPERTRIACYLGLYCEROLEMIA

It is a characteristics of DM-IIResults from an increase in VLDL without

hyperchylomicronemia.This happens by hepatic synthesis of fatty

acids and diversion of free fatty acids reaching the liver in to triacylglycerol and VLDL.

Hepatic Insulin Resistance Leads toHypertriglyceridaemia

Normal Normal TG

Type 2 diabetes

High TGLow HDL cholesterolSmall dense LDL(diabetic dyslipidaemia)

Normal insulin level

Impaired insulin actionto inhibitVLDL production

Increased liver fat

Insulin deficiency exacerbates hypertriglyceridaemia

COMPLICATIONS OF DM 2

• Chronic complications –

Microvascular- retinopathy, nephropathy,

neuropathy.

Macrovascular - cardiovascular,

cerebrovascular,

peripheral vascular

diseases.

Acute complications – diabetic ketoacidosis,

hyperosmalor coma.

POLYOL FORMATION AND RETINOPATHY

• Hyperglycaemia in insulin independent

tissues (nerve, lens, retina) gives rise to

polyol formation.

• The enzyme aldose reductase catalyses the

reduction of glucose to sorbitol, which is

converted to fructose.

• Sorbitol does not easily easily cross cell

membranes and its accumulation may cause

damage by osmotic effect (e.g. in the lens).

• Sorbitol trapped in retinal cells, the cells of

the lens, and the Schwann cells

that myelinate peripheral nerves can

damage these cells, leading to retinopathy,

cataracts and peripheral neuropathy.

TREATMENT OF DM-II

Carbohydrate

Glucose(G)-I

(I)-Insulin

Carbohydrate

AcarboseReduces absorption

SulphonylureaRepaglinide

Stimulates pancreas

MetforminReduces hepatic glucose output

(??muscle/fat effects)

ThiazolidinedionesReduce Insulin Resistance

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