Understanding Diabetes Mellitus: Types, Causes, Symptoms & Science-Based Management

Diabetes mellitus affects over 537 million adults worldwide and is the 9th leading cause of death globally. India alone has 101 million diabetics — the highest in the world. Yet much of what the public understands about diabetes is incomplete or incorrect. This guide explains the full science.

What is Diabetes Mellitus?

Diabetes mellitus is a group of metabolic diseases characterised by chronic hyperglycaemia (high blood glucose) resulting from defects in insulin secretion, insulin action, or both. The name comes from Greek (diabetes = to siphon) and Latin (mellitus = honey-sweet), reflecting the sweet urine observed in ancient times.

Insulin, produced by beta cells of the pancreatic islets of Langerhans, is the key hormone that allows glucose to enter cells for energy. When insulin signalling fails — through autoimmune destruction of beta cells, insulin resistance, or insufficient secretion — glucose accumulates in the blood, causing widespread damage to blood vessels, nerves, and organs over time.

How diabetes mellitus disrupts insulin-glucose signalling in the body. Image: Wikimedia Commons / Cancer Research UK

Types of Diabetes

Causes & Risk Factors

Type 1 Diabetes

• Autoimmune mechanism: T-lymphocytes attack and destroy insulin-producing beta cells in the pancreatic islets
• Genetic factors: HLA-DR3 and HLA-DR4 alleles confer significant risk — ~50% heritability
• Environmental triggers: Viral infections (Coxsackie B virus, rotavirus), early cow's milk exposure, and gut microbiome dysbiosis may trigger autoimmunity in genetically susceptible individuals
• Autoantibodies: Anti-GAD, anti-islet cell antibodies (ICA), and anti-insulin antibodies (IAA) are detectable months to years before clinical onset

Type 2 Diabetes

• Insulin resistance: Peripheral tissues (muscle, liver, adipose) fail to respond to insulin — driven by chronic inflammation, lipotoxicity, and ectopic fat deposition
• Beta cell failure: Years of compensatory overproduction lead to exhaustion and progressive beta cell loss
• Obesity: Visceral adiposity generates pro-inflammatory cytokines (TNF-α, IL-6) that directly impair insulin signalling
• Physical inactivity: Muscle — the body's largest glucose sink — becomes less responsive without regular contraction
• Genetics: Over 400 gene variants have been associated with T2DM risk. South Asians have uniquely high genetic susceptibility at lower BMI thresholds
• Age, family history, gestational diabetes history, PCOS are additional independent risk factors

Symptoms & Diagnosis

Classic Symptoms (the "3 Polys")

• Polyuria — excessive urination (osmotic diuresis as glucose spills into urine)
• Polydipsia — excessive thirst (compensating for fluid loss)
• Polyphagia — excessive hunger (cells starved of glucose despite high blood sugar)
• Unexplained weight loss (especially Type 1 — body breaks down fat and muscle for energy)
• Fatigue, blurred vision, slow-healing wounds, recurrent infections (fungal, urinary tract)
• Type 2 is often asymptomatic for years — diagnosed incidentally on routine blood tests

Diagnostic Criteria (WHO/ADA)

• Fasting plasma glucose ≥ 126 mg/dL (after 8 hours of fasting)
• 2-hour glucose ≥ 200 mg/dL during a 75g oral glucose tolerance test (OGTT)
• HbA1c ≥ 6.5% — reflects average blood glucose over the past 2–3 months
• Random glucose ≥ 200 mg/dL with classic symptoms
• Pre-diabetes: Fasting glucose 100–125 mg/dL or HbA1c 5.7–6.4% — highly reversible with lifestyle changes

Oral glucose tolerance test (OGTT) results comparing normal, impaired (pre-diabetic), and diabetic glucose responses. Image: Wikimedia Commons

Complications of Uncontrolled Diabetes

Chronic hyperglycaemia damages blood vessels and nerves throughout the body through multiple mechanisms — advanced glycation end products (AGEs), oxidative stress, and polyol pathway activation:

Microvascular (Small Vessel) Complications

• Diabetic retinopathy: Leading cause of new blindness in working-age adults. Hyperglycaemia damages retinal capillaries, causing microaneurysms, haemorrhages, and neovascularisation
• Diabetic nephropathy: Leading cause of chronic kidney disease worldwide. Glomerular basement membrane thickening, mesangial expansion → proteinuria → progressive kidney failure
• Diabetic neuropathy: Peripheral nerve damage causing numbness, tingling, and pain — especially in feet. Can lead to painless wounds, Charcot foot, and amputation

Macrovascular (Large Vessel) Complications

• Cardiovascular disease: 2–4× higher risk of heart attack and stroke. The leading cause of death in Type 2 diabetes
• Peripheral artery disease: Reduced blood flow to limbs → non-healing wounds → amputation. India has a very high rate of diabetes-related lower limb amputation

Science-Based Treatment

Type 1 Diabetes

• Insulin therapy: Lifelong and non-negotiable. Multiple daily injections or continuous subcutaneous insulin infusion (insulin pump)
• Basal-bolus regimen: Long-acting insulin (glargine, detemir) for background needs + rapid-acting insulin (lispro, aspart) at meals
• Continuous glucose monitoring (CGM): Real-time glucose tracking — transforms diabetes management and reduces hypoglycaemia risk
• Closed-loop systems ("artificial pancreas"): CGM linked to insulin pump for automated dosing — now commercially available

Type 2 Diabetes

• Lifestyle modification: The foundation. Weight loss of 5–10% body weight can normalise blood glucose in early T2DM. 150 min/week moderate exercise is as effective as metformin for prevention
• Metformin: First-line drug. Reduces hepatic glucose production, improves insulin sensitivity. Inexpensive, safe, weight-neutral
• SGLT2 inhibitors (dapagliflozin, empagliflozin): Promote urinary glucose excretion. Have additional cardiovascular and kidney-protective benefits — now recommended for patients with heart failure or CKD
• GLP-1 receptor agonists (semaglutide, liraglutide): Stimulate insulin secretion, reduce appetite, promote weight loss. Semaglutide also significantly reduces cardiovascular events (SUSTAIN trials)
• DPP-4 inhibitors, sulfonylureas, insulin: Additional options based on individual patient profile

Prevention

• Type 1 cannot currently be prevented (though research into immunotherapy is ongoing)
• Type 2 is largely preventable — the Diabetes Prevention Programme (DPP) trial showed lifestyle intervention reduced progression from pre-diabetes to diabetes by 58%
• Maintain healthy body weight (BMI 18.5–22.9 for South Asians)
• 150 minutes of moderate aerobic activity per week minimum
• Reduce refined carbohydrate and sugar intake — prioritise whole grains, legumes, vegetables
• Annual fasting glucose or HbA1c screening for adults over 35, or earlier if risk factors present
• Breastfeeding reduces childhood risk of Type 1 diabetes