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

Insulin

resistance

-cell

dysfunction

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 Glycogenolysis

Increased Gluconeogenesis

Increased Hepatic glucose output

Decreased Peripheral glucose uptake

Elevates blood glucose

Increased Lipolysis

Increased Release of FFA in liver

Increased VLDL & ketones

Ketonemia and hyperTG

Acidosis & Diuresis

HYPERTRIACYLGLYCEROLEMIA

It is a characteristics of DM-II

Results 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 TG

Low HDL cholesterol

Small dense LDL

(diabetic dyslipidaemia)

Normal insulin level

Impaired

insulin action

to inhibit

VLDL

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

(I)-Insulin

Carbohydrate

Acarbose

Reduces

absorption

Sulphonylurea

RepaglinideStimulates pancreas

Metformin

Reduces hepatic glucose output

(??muscle/fat effects)

ThiazolidinedionesReduce Insulin Resistance