Diabetes Mellitus: Clinical Diagnosis and Management

Posted on Feb 15, 2026 in Medicine

Chronic Complications of Diabetes Mellitus

Pathogenesis: Chronic hyperglycemia leads to the formation of Advanced Glycation End-products (AGEs), Protein Kinase C (PKC) activation, increased Reactive Oxygen Species (ROS), and the polyol pathway. These processes result in endothelial dysfunction, basement membrane thickening, and both microvascular and macrovascular damage.

Microvascular Complications

  • Retinopathy: Non-proliferative (microaneurysms, hemorrhages, cotton-wool spots, macular edema) and Proliferative (neovascularization leading to vitreous hemorrhage and retinal detachment). Treatment: Glycemic and BP control, anti-VEGF therapy, and laser photocoagulation.
  • Nephropathy: Characterized by GBM thickening, mesangial expansion, and Kimmelstiel-Wilson nodules. Progresses from microalbuminuria to proteinuria, decreased GFR, and eventually ESRD. Treatment: ACE inhibitors or ARBs, and glycemic/BP control.
  • Neuropathy: Distal symmetric (glove-and-stocking distribution, ulcers, Charcot joint); autonomic (orthostasis, gastroparesis, erectile dysfunction, hypoglycemia unawareness); and focal neuropathies.

Macrovascular Complications

Accelerated Atherosclerosis: Leads to Coronary Artery Disease (CAD), stroke, Peripheral Artery Disease (PAD), and Heart Failure (HF). Risk increases with HTN, dyslipidemia, smoking, and obesity. Treatment: Statins, BP control, Aspirin (ASA), and lifestyle modifications.

Other Complications

  • Diabetic Foot: A combination of neuropathy and ischemia leading to ulcers, gangrene, and amputations.
  • Infections: Increased susceptibility to skin infections, UTI, pneumonia, Candida, and mucormycosis.
  • Skin Manifestations: Acanthosis nigricans, necrobiosis lipoidica, xerosis, and granuloma annulare.

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Classification and Diagnosis of Diabetes Mellitus

Diabetes Mellitus is a chronic metabolic disorder characterized by persistent hyperglycemia due to insulin deficiency, insulin resistance, or both.

Major Types of Diabetes

  • Type 1 Diabetes Mellitus: Caused by absolute insulin deficiency due to autoimmune destruction of pancreatic β-cells. Associated autoantibodies include GAD65, ZnT8, and IA. The most common acute complication is Diabetic Ketoacidosis (DKA).
  • Type 2 Diabetes Mellitus: Characterized by insulin resistance in peripheral tissues followed by relative insulin deficiency. It has a strong genetic predisposition and is closely associated with obesity and a sedentary lifestyle. The major acute complication is Hyperglycemic Hyperosmolar State (HHS).

Other Forms of Diabetes

  • Gestational Diabetes Mellitus: Glucose intolerance first recognized during pregnancy.
  • Monogenic Diabetes (MODY): Genetic defects of β-cell function.
  • Secondary Diabetes: Due to pancreatic diseases, endocrinopathies, or drugs (e.g., glucocorticoids).

Clinical Presentation and Diagnostic Criteria

Clinical Symptoms: Polyuria, polydipsia, polyphagia, blurred vision, and recurrent infections.

Diagnostic Thresholds:

  • Fasting Plasma Glucose: ≥ 126 mg/dL (after ≥ 8 hours of fasting).
  • 2-hour Plasma Glucose: ≥ 200 mg/dL during an Oral Glucose Tolerance Test (OGTT).
  • Random Plasma Glucose: ≥ 200 mg/dL with classic symptoms.
  • HbA1c: ≥ 6.5%.

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Acute Hyperglycemic Emergencies

Diabetic Ketoacidosis (DKA)

Mechanism: Hyperglycemia > 250 mg/dL and reduced glucose utilization lead to increased lipolysis. This results in liver ketone bodies (acetoacetate, β-hydroxybutyrate, acetone) causing ketosis and metabolic acidosis (low bicarbonate, low pH). Osmotic diuresis leads to dehydration and Na+/K+ loss.

Clinical Features: Hyperglycemia symptoms, GI distress (nausea, vomiting), CNS depression (lethargy, confusion), Kussmaul breathing, and a fruity breath odor.

Diagnosis: Glucose > 250 mg/dL, positive serum/urine ketones, pH < 7.30, and bicarbonate < 18. Differential: Pancreatitis (check abdominal CT, amylase, and lipase).

Treatment Steps for DKA

  1. IV fluids: 0.9% saline initially.
  2. Switch to 0.45% saline if indicated by sodium levels.
  3. Ensure potassium is in range before starting insulin.
  4. Administer IV regular insulin.
  5. Add dextrose when glucose reaches approximately 200 mg/dL.
  6. Administer bicarbonate only if pH < 7.0.

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Hyperglycemic Hyperosmolar State (HHS)

Mechanism: Relative insulin deficiency (sufficient to prevent ketosis) leads to excessive hyperglycemia and severe dehydration without significant acidosis.

Clinical Features: Altered mental status and profound dehydration. Hyperglycemia symptoms are present, but GI symptoms are less common than in DKA.

Diagnosis: Plasma glucose > 600 mg/dL, absent ketonemia, and normal or high bicarbonate.

Treatment Steps for HHS

  1. IV fluids: Start with 0.9% saline, then switch to 0.45% saline based on sodium.
  2. Assess and correct potassium before insulin administration.
  3. IV insulin at lower doses (due to lack of severe acidosis).
  4. Add dextrose when glucose reaches 250–300 mg/dL.

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Management of Diabetes Mellitus

Type 1 Diabetes Management

Requires insulin therapy due to absolute deficiency.

  • Basal Insulin: Once daily (e.g., glargine).
  • Mealtime Insulin: Rapid analogs (physiologic) or regular insulin (slower), administered at meals.

Type 2 Diabetes Management

Utilizes oral medications with the addition of insulin if necessary.

  • Metformin (Biguanide): First-line therapy that enhances tissue sensitivity. Contraindicated in CKD due to lactic acidosis risk.
  • Sulfonylureas: Increase insulin release from β-cells. Risk of hypoglycemia and weight gain.
  • GLP-1 Receptor Agonists (Incretins) & DPP-4 Inhibitors: Both are cardioprotective. GLP-1 side effects include nausea and vomiting.
  • Thiazolidinediones: Increase insulin sensitivity via PPAR-γ activation. May cause fluid retention.
  • SGLT2 Inhibitors: Increase urinary glucose excretion. First-line for CKD but associated with increased UTI risk.

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