Diabetes mellitus (DM)

FIGURE : Metabolic actions of insulin in striated muscle, adipose tissue, and liver.

Diabetes Mellitus• Diabetes mellitus is not a single disease entity but rather a

group of metabolic disorders sharing the common underlying feature of hyperglycemia

• Increased blood glucose level

• Hyperglycemia in diabetes results from defects in insulin secretion, insulin action, or both.

• Approximately 1.5 million new cases of diabetes are diagnosed each year in the United States, and diabetes is the leading cause of end-stage renal disease, adult-onset blindness, and nontraumatic lower extremity amputations

Diagnosis/Criteria• Normal blood glucose values : 70 to 120 mg/dL. • The diagnosis of diabetes is established by noting

elevation of blood glucose by any one of three criteria: 1. A random glucose concentration greater than 200

mg/dL, with classical signs and symptoms.2. A fasting glucose concentration greater than 126

mg/dL on more than one occasion 3. An abnormal oral glucose tolerance test (OGTT), in

which the glucose concentration is greater than 200 mg/dL 2 hours after a standard carbohydrate load

Classification1. Type 1 diabetes (β-cell destruction, usually leading to absolute

insulin deficiency) 2. Type 2 diabetes (combination of insulin resistance and β-cell

dysfunction) 3. Genetic defects of β-cell function

Maturity-onset diabetes of the young (MODY), caused by mutations in:

Hepatocyte nuclear factor Glucokinase

4. Gestational Diabetes5. Drugs: Glucocorticoides6. Genetic syndrome associated with diabetes

Down syndrome

• Type 1 diabetes is an autoimmune disease characterized bypancreatic β-cell destruction -an absolute deficiency of insulin.- It accounts for approximately 5% to 10% of all cases,

usually diagnosed in patients younger than 20 years of age.

• Type 2 diabetes is caused by a combination of peripheral resistance to insulin action - an inadequate secretory response by the pancreatic β

cells (“relative insulin deficiency”). Approximately 90% to 95% of diabetic patients have

type 2 diabetes, and the vast majority of such individuals are overweight.

Pathogenesis of type I DM

Synonyms: • juvenile diabetes• Insulin dependent diabetes mellitus (IDDM):Both are obsolete and are not used in classification

Result from severe lack of insulin caused by immunologically mediated destruction of beta (β) cells.

Type 1 diabetes is an autoimmune disease in which islet destruction is caused primarily by T cells reacting against endogenous β-cell antigens

A. Mechanisms of β-Cell Destruction1.T lymphocytes react against beta cell antigen and

cause cell damage.• CD4+T cell cause tissue injury by activating the

macrophages• CD8+ cytotoxic T lymphocytes which directly kill β cells

and secretes cytokines.2. Locally produced cytokines (TNF.IL-1) damage β cells.3. Autoantibody against islet cells and insulin are also

detected.

B. Genetic susceptibilityC. Enviornmental factor:Infection( esp viral): mumps/measles/CMV-Infection induce tissue damage and

inflammation---------->release of β cells antigen----->activation of lymphocytes/leucocytes-------> β cells damage.

-Virus produce protein that mimic self antigen and immune response to viral protein--->cross react with self tissue.

Type II DM

• Type 2 diabetes is a prototypic multifactorial complex disease

• Environmental factorsA sedentary life style dietary habits, obesity

Genetics

• The two metabolic defects that characterize type 2 diabetes are

• - a decreased response of peripheral tissues to insulin (insulin resistance): Insulin resistance is defined as the failure of target tissues to respond normally to insulin. It leads to decreased uptake of glucose in muscle, reduced glycolysis and fatty acid oxidation in the liver, and an inability to suppress hepatic gluconeogenesis

• - β-cell dysfunction: inadequate insulin secretion in the face of insulin resistance and hyperglycemia.

Clinical features

PolyuriaPolydipsia (Intense thirst)Polyphagia (increase

appetite)

Complication of Diabetes

Long term complication

Acute complication…

• Hyoglycemia: (blood glucose < 3.5 mmol/l (63 mg/dl) • Ketoacidosis: (hyperglycaemia ,hyperketonaemia and metabolic acidosis. )• Lactic acidosis