11. DIABETES MELLITUS

Diabetes Mellitus is a metabolic disorder where the level of glucose (sugar) in the blood becomes higher than normal. This happens either because the pancreas does not make enough insulin, or because the body cells do not use insulin properly. Insulin is the hormone that allows glucose to enter body cells and be used for energy. When insulin is absent or not working well, glucose remains in the blood, leading to hyperglycemia.

Definition

Diabetes Mellitus is a group of metabolic disorders characterized by high blood glucose along with abnormal metabolism of carbohydrates, fats, and proteins.

Classification

Type 1 Diabetes

  • Also called Insulin-Dependent Diabetes or Juvenile Onset Diabetes.
  • Usually develops below 20 years of age.
  • Pancreas fails to produce insulin due to autoimmune destruction of β-cells.
  • Requires lifelong insulin therapy.

Type 2 Diabetes

  • Previously called Non-Insulin-Dependent or Adult-Onset Diabetes.
  • Common after 40 years of age.
  • Body cannot use insulin properly (insulin resistance) plus impaired insulin secretion.
  • Often associated with obesity; many require oral drugs and later insulin.

Type 3 Diabetes

  • Occurs due to drugs (steroids, thiazides, growth hormone) or diseases like pancreatitis.

Type 4 Diabetes (Gestational Diabetes)

  • Occurs during pregnancy, usually in the third trimester.
  • Caused by placental hormones that increase insulin resistance.

Pathophysiology (Simple Explanation)

Insulin helps glucose enter liver, muscle, and fat cells. After eating, glucose rises → pancreas releases insulin → glucose enters cells → blood sugar returns to normal. When insulin is low or cells become resistant, glucose cannot enter cells and remains in the bloodstream.

In Type 1: immune system destroys β-cells, so no insulin is produced. In Type 2: body cells do not respond to insulin properly; pancreas cannot keep up, leading to high blood sugar.

Clinical Presentation

Type 1 DM

  • Polyuria (frequent urination)
  • Polydipsia (increased thirst)
  • Polyphagia (increased hunger)
  • Weight loss, fatigue
  • May present with diabetic ketoacidosis

Type 2 DM

  • Often asymptomatic initially
  • May show polyuria, nocturia, or thirst
  • Usually overweight/obese; rarely lose weight

Diagnosis

  • Fasting Plasma Glucose (FPG): measured after 8 hours fasting.
  • Postprandial Plasma Glucose (PPG): measured 2 hours after a meal.
  • Random blood glucose: any time of day; ≥250 mg/dL suggests diabetes.
  • OGTT: 75 g glucose load; 2-hour value used for diagnosis.
  • Urine sugar: not reliable alone but may help.
  • Ketone testing: for severity assessment.

Treatment

Goals of Therapy

  • Relieve symptoms
  • Maintain blood glucose and A1C within target
  • Prevent long-term complications
  • Improve quality of life

Non-Pharmacological Therapy

  • Medical Nutrition Therapy: balanced diet, moderate carbohydrates, low saturated fat.
  • Weight reduction: important for Type 2 DM.
  • Exercise: improves insulin sensitivity and helps weight control.

Pharmacological Therapy

1. Oral Hypoglycemic Drugs

Sulfonylureas

Examples: Tolbutamide, Chlorpropamide, Glibenclamide, Glipizide, Gliclazide

Mechanism: Stimulate β-cells to release insulin by blocking ATP-sensitive K⁺ channels → Ca²⁺ influx → insulin secretion.

Adverse Effects

  • Hypoglycemia (dangerous)
  • Weight gain, edema
  • Skin rashes, photosensitivity
  • Disulfiram-like reaction with alcohol

2. Anti-Hyperglycemic Drugs

Biguanides (Metformin)

Reduces glucose production from liver, increases glucose uptake in muscles, and delays intestinal absorption. Does not cause hypoglycemia; preferred for overweight patients.

ADR:

  • Nausea, diarrhea, metallic taste
  • Vitamin B12 deficiency (long term)
  • Lactic acidosis risk (avoid in kidney/liver disease)

Thiazolidinediones (Pioglitazone)

Activate PPAR-γ receptors → improve insulin sensitivity in fat, muscle, and liver.

ADR:

  • Weight gain, fluid retention
  • Edema, anemia
  • Liver toxicity

α-Glucosidase Inhibitors (Acarbose, Miglitol)

Delay carbohydrate digestion and reduce post-meal glucose spikes.

  • Flatulence, diarrhea, abdominal pain

Parenteral Therapy

Insulin

Insulin binds to cell receptors, activates signaling pathways, increases glucose uptake (via GLUT-4), inhibits gluconeogenesis and glycogen breakdown, and promotes storage of glucose as fat and glycogen.

Clinical Use

  • Type 1 diabetes (mandatory)
  • Type 2 diabetes not controlled with oral drugs
  • Pregnancy, surgery, severe infections, diabetic coma

Complications of Poorly Controlled Diabetes

  • Ketoacidosis: excessive ketone formation → acidic blood → life-threatening.
  • Cardiovascular disease: atherosclerosis, heart attack, stroke.
  • Blindness: cataract, diabetic retinopathy.
  • Kidney failure: diabetic nephropathy.
  • Nerve damage: neuropathy.
  • Foot infections, gangrene
  • Sexual dysfunction

Detailed Notes:

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