Type 2 diabetes mellitus is characterized by insulin resistance and inadequate insulin secretion. The combination of insulin resistance and impaired insulin secretion leads to high blood glucose levels. Over time, the pancreatic beta cells that produce insulin can become dysfunctional, worsening the condition. Without treatment, type 2 diabetes can result in serious complications affecting the eyes, kidneys, nerves, heart and blood vessels. Treatment aims to lower blood glucose levels through lifestyle changes, oral medications, and sometimes insulin therapy.

1. DIABETES
MELLITUS TYPE-2
CAROLINE KARUNYA PONNRASI KANAGARAJ
Group-04

2. WHAT IS DIABETES MELLITUS ?
• Diabetes mellitus is a chronic disease
characterized by derangement in
carbohydrates, fat and protein metabolism

3. 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.

4. COMPONENTS OF DM-II
Type 2
diabetes
Insulin
resistance
-cell
dysfunction

5. METABOLICABNORMALITIES IN DM-II
Obesity
Insulin resistance
Abnormal insulin secretion
Excess glucose production
Beta-cell failure

7. INSULIN RESISTANCE-IR
• Insulin resistance is a
condition in which the
body produces insulin
but does not use it
properly.

8. CAUSES OF IR
The circulating free fatty acids associated with
obesity also responsible for insulin resistance of
the muscle and liver.

9. WHATDOES 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

10. BETA CELL -DYSFUNCTION
Chronic
hyperglycemia
Glucotoxicity2
Lipotoxicity3
Oversecretion of insulin to
compensate for insulin
resistance1,2
-cell
dysfunction

11. 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.

12. INSULINRESISTANCE
&
BETACELL-DYSFUNCTION
IR
Insulin
resistance
Liver
Muscle
Adipose
tissue
 Glucose output  Glucose uptake
 Glucose uptake
Hyperglycemia

13. 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.

14. 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

15. 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.

16. Hepatic Insulin Resistance Leads to
Hypertriglyceridaemia
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

17. COMPLICATIONS OF DM 2
• Chronic complications –
 Microvascular- retinopathy,
nephropathy,
neuropathy.
 Macrovascular - cardiovascular,
cerebrovascular,
peripheral vascular
diseases.
 Acute complications – diabetic ketoacidosis,
hyperosmalor coma.

18. 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.

20. TREATMENT OF DM-II
Carbohydrate
(I)-Insulin
Carbohydrate
Acarbose
Reduces
absorption
Sulphonylurea
Repaglinide
Stimulates pancreas
Metformin
Reduces hepatic glucose output
(??muscle/fat effects)
Thiazolidinediones
Reduce Insulin Resistance