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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.
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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