Diabetes Mellitus (DM)

 

Diabetes Mellitus (DM)

•    DM is a metabolic disease characterized by severe hyperglycemia

–  Persistently high blood glucose level leads to various long term complications

•    Diabetes is broadly divided into

–  Insulin dependent diabetes mellitus (IDDM)

–  Non-Insulin dependent diabetes mellitus (NIDDM)

i) Insulin dependent diabetes mellitus (IDDM)

•    Also called type-I diabetes or juvenile onset diabetes

–  Occurs in childhood (Between 12-15 years age)

–  10-20% of total known DM patients

•    Characterized by total deficiency of insulin

–  Destruction of β-cells of islets of Langerhans caused by

•    Autoimmunity

•    Drugs

•    Viruses

•    Obesity

•    Due to certain genetic variations β-cells are identified as foreign cells

– Destroyed by immune mediated injury

•    Symptoms appear when 80-90% of cells are lost

– Pancreas fail to produce insulin in response to sugar ingestion

•    Insulin therapy is needed for the treatment

ii) Non-insulin dependent diabetes mellitus (NIDDM)

•    Also called type-II diabetes or maturity onset diabetes or adult onset diabetes

•    Most common type of DM

–  80 to 90 % of known patients

•    Occurs in adults (above 30 to 35 Years of age)

–  Less severe than type-I DM

•    Causes are genetic, environmental and personal lifestyle based

–  Particularly linked with obesity (diabetogenic factor)

•    Decrease in insulin receptors on target cells

•    Amount of insulin may either be normal or even elevated

•    Many times weight loss alone is sufficient to treat it

– Mostly oral hypoglycemic agents are needed to control blood sugar levels

•    Recent studies shows insulin resistance is caused by

–  Increased level of Tumor necrosis factor-α (TNF-α)

–  Decreased secretions of adiponectin by adipocytes of obese people

•    Normal glucose levels

•    Fasting: >100mg/dL

•    Random: >150mg/dL

Signs & Symptoms of uncontrolled DM

•    Uncontrolled DM leads to the manifestation of the following signs & symptoms in patients:

–  Hyperglycemia

–  Glycosuria (Glucose in urine)

–  Polyuria (Increased urination)

–  Polydipsia (excessive drinking of water due to thirst)

–  Polyphagia (Hyperphagia: increased food intake)

–  Ketosis (Ketoacidosis)

–  Loss of body weight (increased catabolism of fats & proteins)

–  Water & electrolyte imbalance

–  Hyperlipidemia (elevated lipids in blood; LDL,VLDL etc.)

 

•    Severe and persistent hyperglycemia may cause

–  Glucose toxicity

•   Osmotic effects/hypertonic effects results in polyurea

•   β-cell damage due to enhanced oxidative phosphorylation

•   Increased glycation of proteins can be linked with Diabetes associated complications

–  Atherosclerosis

–  Gangrene

–  Neuropathy, Nephropathy and Retinopathy, etc.

–  Ketoacidosis

•     Increased mobilization of fatty acids

–   Overproduction of ketone bodies

–   Hypertriglyceridemia and hypercholesterolemia

•     Increased level of triglycerides, VLDL, chylomicrons and choleserol

Treatment of diabetes mellitus:

•     Management option of DM includes

–  Diet

•   Low caloric, low carbohydrates, high protein and fiber rich diet should be taken

•   Fat should be drastically reduced (unsaturated FA)

–  Exercise

–  Drugs and finally

•   Oral hypoglycemic agents are used (Sulfonylureas & biguinides)

–  Insulin (short acting & long acting (modified) insulin)

•    Most cases can be controlled only by diet & exercise or drugs

–  Only 20-30% patients need insulin

•    Elevated glucose level should not be used as index for DM

•    DM can be diagnosed on the basis of individual’s response to oral glucose load

–  Oral glucose tolerance test

•    10 Hours fasting blood and urine analysis

•    75g Glucose is administered orally in 1 glass (300mL) water

•    Continuous sampling every 30 minutes for 2 hours

 

•    Other indices for DM management are:

–  Random and Fasting BSL

•   Most significant and easy detection of short term control can be estimated by Fasting and random BSL

–  Glycosuria

•   Most commonest cause of glycosuria is DM

–  Glycated hemoglobin (HbA₁C) (2-3 months control)

•   Condensation of N-terminal valine of each β-chain with glucose 

•   Conc. of HbA1C can also be used for diagnosis (>7%)