DIABETES MELLITUS Definition :It is a clinical syndrome characterized by hyperglycemia due to absolute or relative deficiency of insulin. Type 1 Diabetes : Charactarized by an absolute deficiency of insulin secretion caused by pancreatic beta cell destruction usually resulting from auto immune attack Type 2 Diabetes : Caused by relative insulin deficiency due to combination of peripheral resistance to insulin action and an inadequate compensatory response to insulin secretion by pancreatic beta cells. Introduction pancreas Pathology of insulin Pathogenesis of DM What is diabetes mellitus Types of diabetes mellitus Evaluation of plasma glucose levels Clinical features of DM Complications of DM Treatment

1. DrAmitha G
DIABETES MELLITUS

2. 1.Introduction
2.pancreas
3.Pathology of insulin
4.Pathogenesis of DM
5.What is diabetes mellitus
6.Types of diabetes mellitus
7.Evaluation of plasma glucose levels
8.Clinical features of DM
9.Complications of DM
10.Treatment

3. INTRODUCTION
 Diabetes mellitus (DM) is a chronic condition that is characterised by
raised blood glucose levels (Hyperglycemia).

4. Pancreas
Plasma glucose is tightly regulated by
hormones
Alpha cells: Glucagon : increase glucose
Beta cells: Insulin : decreases glucose
Delta cells : stomatostatin: regulate
endocrine system

5. Pancreas :
secretes 40-50 units of insulin daily in two steps:
• Secreted at low levels during fasting ( basal insulin secretion)
• Increased levels after eating (prandial)
• An early burst of insulin occurs within 10 minutes of eating
• Then proceeds with increasing release as long as hyperglycemia
is present

7. Hormone production in pancreatic islet cells.
insulin in β cells glucagon in  cells

8. Electron micrograph of a cell shows the
characteristic membrane-bound granules, each
containing a dense, often rectangular core and distinct
halo.
The  -cell granule exhibits a dense, round center.

9. Insulin and glucagon have opposing regulatory effects on glucose
homeostasis.
Fasting :
low insulin and high glucagon levels
hepatic gluconeogenesis and glycogenolysis
Decreasing glycogen synthesis
Prevent hypoglycemia.
Thus, fasting plasma glucose levels are determined primarily by hepatic
glucose output.
NORMAL INSULIN PHYSIOLOGY

10. Post meal:
insulin levels rise and glucagon levels fall ( due to large glucose load)
Insulin promotes glucose uptake and utilization in tissues.
The skeletal muscle is the major insulin-responsive site for
postprandial glucose utilization
prevent hyperglycemia
maintain glucose homeostasis.

11. Regulation of Insulin Release
Insulin is expressed in the β cells of the pancreatic islets.
Preproinsulin is synthesized in the rough endoplasmic reticulum from
insulin mRNA and delivered to the Golgi apparatus.
series of proteolytic cleavage steps generate the mature insulin and a
cleavage peptide, C-peptide.
Both insulin and C-peptide are stored in secretory granules and
secreted in equimolar quantities after physiologic stimulation;
increasingly, C-peptide oxidative metabolism in the β cell to yield ATP.

12. • ATP inhibits potassium channel receptor on the β-cell surface
• the receptor itself is a dimeric complex of the sulfonylurea
receptor and a K+ -channel protein.
• Inhibition of this receptor leads to membrane depolarization,
influx of Ca2+ ions, and release of stored insulin from β cells.

13. Pathogenesis of diabetes mellitus
1. Genetic factor :
• HLA gene ( common locus being affected is on chromosome 6p21(HLA D) like DR3/ DR4 with
DQ8 haplotype
2. Environmental factor :
• Viral infections
• Failure of self tolerance T cells is the main defect in type 1 DM.
The auto reactive T cells ( TH1 cells and cd8+ cytotoxic T cells) gets activated
beta cell injury
reduction of beta cell mass.
Autoantibodies against a verity of beta cell antigen, including insulin, islet cell autoantigen 512
and glutamic acid decarboxylase are also found in the patients.

14. 1. Insulin resistance : it is defined as resistance to the effects of insulin on glucose
uptake, metabolism, or storage.
2. Beta- cell dysfunction : inadequate insulin secretion in the presence of insulin
resistance and hyperglycemia.

15. Insulin
Insulin allows glucose to move into cells to make energy
Liver is first major organ to be reached
• Promotes production and storage of glycogen (glycogenisis)
• Inhibits glycogen breakdown into glucose (glycogenolysis)
• Increases protein and lipid synthesis
• Inhibits tissue breakdown by inhibiting liver glycogenolysis (ketogenesis-
converts fats to acids) & gluconeogenisis (conversion of proteins to glucose)
• In muscle, promotes protein and glycogen synthesis
• In fat cells, promotes triglyceride storage

16. GLUCOSE:
• Glucose is main fuel for CNS, Need 68-105 mg/dL to support brain
• Fatty acids can be used when glucose is not available ( triglycerides)
• Decreased levels of glucose, insulin and glucagon release is stopped
• Glucagon causes release of glucose from liver
• Liver glucose is made by glycogenolysis & Gluconeogenesis
• When liver glucose is not available, lypolysis ( breakdown of fat) OR
Proteinlysis (breakdown of amino acids) occurs.
• Insulin needed to move glucose into cells
• Without insulin, body enters a state of breaking down fats and proteins
• And if Glucose levels increase its called hyperglycemia

17. • Glucagon causes release of glucose from liver
• Liver glucose is made by glycogenolysis & Gluconeogenesis
• When liver glucose is not available, lypolysis ( breakdown of fat) OR
Proteinlysis (breakdown of amino acids) occurs.
• Insulin needed to move glucose into cells
• Without insulin, body enters a state of breaking down fats and proteins
• And if Glucose levels increase its called hyperglycemia

18. Physiology

19. DIABETES MELLITUS
Definition :
Itisaclinicalsyndromecharacterizedbyhyperglycemiaduetoabsoluteorrelativedeficiencyof
insulin.

20. Type 1 Diabetes :
Charactarized by an absolute deficiency of insulin secretion caused by
pancreatic beta cell destruction usually resulting from auto immune
attack
Type 2 Diabetes :
Caused by relative insulin deficiency due to combination of peripheral
resistance to insulin action and an inadequate compensatory response to
insulin secretion by pancreatic beta cells.

21. Types
Type I
• formerly known as Insulin – Dependent Diabetes Mellitus (IDDM)
• Autoimmune (Islet cell antibodies)
• destruction of beta cells of the pancreas  little or no insulin
production
• requires daily insulin admin.
• may occur at any age, usually appears below age 15

22. 2. Type II
• formerly known as Non Insulin–Dependent Diabetes Mellitus
(NIDDM)
• probably caused by:
• disturbance in insulin reception in the cells
•  number of insulin receptors
• loss of beta cell responsiveness to glucose leading to slow or 
insulin release by the pancreas
• occurs over age 40 but can occur in children
• common in overweight or obese

23. Evaluation of plasma glucose level:
Normal blood glucose : 80- 120 mg / dl
Fasting blood sugar (IFG)
Normal- 100-126mg/dL
Diabetes : < 126
Random blood sugar ( RBS)
Normal : RBS- < 140 mg/dl
Diabetes < 200mg/dl
Oral glucose tolerance / post prandial :
Normal < 140
Diabetes : OGTT 140-199mg/dL
HbA1c
Normal : 5.7-6.4%
Diabetes : < 7%
definition and diagnosis of diabetes mellitus and intermediate hyperglycemia : Report of a WHo/IDf ConsultatIon 2006

24. Clinical features
- Polyuria
- Polydipsia
- Polyphagia
- weight loss
- nausea / vomiting
- recurrent infection, prolonged wound healing
- altered immune and inflammatory response, prone to
infection (glucose inhibits the phagocytic action of WBC 
resistance)
- genital pruritus

25. Clinical feature of diabetes mellitus

26. CHRONIC COMPLICATIONS OF DIABETES MILLETUS
1. Macro vascular disease
^ cardio vascular complications like MI, stroke , gangrene
2. Microvascular disease
Diabetic nephropathy
Diabetic retinopathy
Diabetic neuropathy

27. Rx:
Insulin
Or
oral hypoglycemic drugs
Biguanates ( metformin) - ^ Peripheral glucose
uptake
Sulfonylurease( glipizole, glibincamide) - ^ Insulin secretion
Meglitinides ( Repaglinides)
glucosidase inhibitor (Acarbose) - v Intestinal glucose
absorbtion