Diabetes Mellitus: Complete Symptoms, Causes, Diagnosis & Treatment Guide

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--- # **Diabetes Mellitus — Complete Clinical Reference** ## **1. Definition** A chronic metabolic disorder characterized by **persistent hyperglycemia** due to: 1. **Defective insulin secretion**, 2. **Defective insulin action**, or 3. **Both**. Major types: * **Type 1 DM** – autoimmune β-cell destruction → absolute insulin deficiency. * **Type 2 DM** – insulin resistance + relative insulin deficiency. * **GDM** – glucose intolerance during pregnancy. * **Other specific types** – MODY, pancreatic disease, endocrinopathies, drugs, genetic syndromes. --- # **2. Pathophysiology** ### **Type 1** * Autoimmune destruction (HLA-DR3, DR4). * T-cell mediated β-cell apoptosis → **no insulin** → lipolysis ↑ → ketogenesis ↑ → DKA risk. ### **Type 2** * **Insulin resistance** (muscle, liver, adipose). * β-cell dysfunction over time → inadequate insulin response. * Elevated FFA → lipotoxicity. * Incretin defect → reduced GLP-1 effect. ### **Hyperglycemia mechanisms** * ↑ hepatic gluconeogenesis. * ↓ glucose uptake in muscle. * Impaired insulin suppression of lipolysis. --- # **3. Causes / Risk Factors** ### **Type 1** * Autoimmune, genetic, viral triggers (Coxsackie B), other autoimmune diseases. ### **Type 2** * Obesity (central adiposity), sedentary lifestyle, family history, age >40, PCOS, ethnicity (South Asians ↑ risk). ### **Secondary causes** * Pancreatitis, pancreatic surgery, hemochromatosis, Cushing’s, acromegaly, glucocorticoids, antipsychotics. --- # **4. Clinical Features** ### **Classic symptoms** * Polyuria * Polydipsia * Polyphagia * Weight loss * Fatigue ### **Acute complications** * **DKA** (Type 1): abdominal pain, Kussmaul breathing, fruity odor. * **HHS** (Type 2): profound dehydration, high osmolality, altered sensorium. ### **Chronic complications** #### **Microvascular** * **Retinopathy:** non-proliferative → proliferative. * **Nephropathy:** microalbuminuria → CKD. * **Neuropathy:** distal symmetric polyneuropathy, autonomic neuropathy. #### **Macrovascular** * CAD, stroke, peripheral arterial disease. --- # **5. Diagnosis** ### **Diagnostic criteria (any one)** * FPG ≥ **126 mg/dL** * 2-hr OGTT ≥ **200 mg/dL** * HbA1c ≥ **6.5%** * Random glucose ≥ **200 mg/dL** with symptoms ### **Screening** * Adults ≥35 yrs, earlier if obese or high-risk. --- # **6. Investigations** * **HbA1c**, FPG, OGTT * Lipid profile * LFT, KFT * Urine microalbumin * Fundus exam * Foot exam * Thyroid panel (in Type 1) * Autoantibodies: GAD65, IA-2, ZnT8 (if Type 1 suspected). --- # **7. Differential Diagnosis** * Stress hyperglycemia * MODY * LADA (adult-onset type 1) * Cushing’s syndrome * Hyperthyroidism * Drug-induced hyperglycemia --- # **8. Management (Stepwise)** ## **Lifestyle** * Diet: calorie deficit, low refined carbs, high fiber. * Exercise: ≥150 min/week moderate intensity. * Weight loss ≥7% for Type 2. --- # **Pharmacologic Management** ## **First-line: Metformin** ### **Indication** Type 2 DM first-line (unless contraindicated). ### **Mechanism** ↓ hepatic gluconeogenesis, ↑ insulin sensitivity. ### **Dose** 500 mg once/twice daily → titrate to 1000 mg twice daily. ### **PK** Not metabolized, renal excretion. ### **Adverse effects** GI upset, B12 deficiency, lactic acidosis (rare). ### **Contraindications** eGFR <30, severe hepatic/cardiac disease. ### **Interactions** Cimetidine ↑ metformin levels. ### **Monitoring** Renal function, B12 annually. ### **Counselling** Take with meals; report fatigue/abdominal pain. --- ## **Add-on drugs** ### **SGLT2 inhibitors (Empagliflozin, Dapagliflozin)** * **MOA:** ↑ urinary glucose excretion. * **Benefits:** ↓ HF hospitalization, ↓ CKD progression. * **Adverse:** genital infections, euglycemic DKA. ### **GLP-1 agonists (Liraglutide, Semaglutide)** * **MOA:** ↑ insulin, ↓ glucagon, slowed gastric emptying. * **Benefits:** weight loss, CV protection. * **Adverse:** nausea, pancreatitis. ### **DPP-4 inhibitors (Sitagliptin, Vildagliptin)** * Well tolerated, modest HbA1c reduction. ### **Sulfonylureas (Glimepiride, Glipizide)** * **Risk:** hypoglycemia, weight gain. ### **Thiazolidinediones (Pioglitazone)** * **Risk:** edema, HF, fractures. --- # **Type 1 Diabetes** * **Insulin is mandatory** (basal-bolus or pump). * Carbohydrate counting, CGM recommended. --- # **Insulin Therapy (Brief)** * **Basal:** Glargine, Detemir, Degludec * **Bolus:** Lispro, Aspart, Glulisine * **Total daily dose:** 0.4–0.6 U/kg/day to start. --- # **9. Acute Complication Treatment** ### **DKA** * Fluids → Insulin infusion → Potassium management → Treat trigger. ### **HHS** * Aggressive fluids → Insulin → Correct electrolytes. --- # **10. Monitoring** * HbA1c every 3 months * Home glucose monitoring/CGM * Annual microalbumin * Annual eye exam * Foot exam each visit --- # **11. Patient Counselling** * Diet + exercise essential. * Foot care daily. * Recognize hypoglycemia symptoms. * Regular follow-ups mandatory. * Sick-day rules: never stop insulin. ---