Type 2 Diabetes — Causes, Symptoms, Diagnosis & Treatment Guide — Symptoms, Causes & Treatment | MyMedicPlus

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterised by relative insulin deficiency due to a combination of peripheral insulin resistance (reduced sensitivity of muscle, liver, and adipose tissue to insulin action) and progressive pancreatic beta-cell dysfunction and failure. Unlike type 1 diabetes, which involves absolute insulin deficiency due to autoimmune beta-cell destruction, type 2 diabetes is associated with excess body weight and is strongly influenced by lifestyle and environmental factors, though genetic predisposition plays a significant role. T2DM accounts for 90-95% of all diabetes cases. The International Diabetes Federation (IDF) estimates that 537 million adults (20-79 years) were living with diabetes in 2021, with the number projected to reach 783 million by 2045. Type 2 diabetes dramatically increases the risk of cardiovascular disease (the leading cause of mortality in T2DM), chronic kidney disease, diabetic retinopathy (leading cause of blindness in working-age adults), peripheral neuropathy, and foot complications. The landmark UKPDS (UK Prospective Diabetes Study) demonstrated that intensive glucose control significantly reduces microvascular complications. Modern therapy has shifted focus to cardiovascular and renal risk reduction beyond glucose control, driven by the cardiorenal protective effects of SGLT-2 inhibitors and GLP-1 receptor agonists.

Type 2 diabetes results from the interaction of genetic susceptibility with adverse metabolic stressors, primarily obesity and physical inactivity. The pathophysiology involves: insulin resistance (excess visceral adiposity releases free fatty acids and adipokines causing hepatic insulin resistance and ectopic fat deposition in pancreas and muscle); progressive pancreatic beta-cell loss (initial compensatory hyperinsulinaemia followed by exhaustion and apoptosis over years — beta-cell mass reduces by 50% by the time T2DM is diagnosed); impaired incretin effect (reduced GLP-1 and GIP secretion from gut); elevated glucagon (alpha-cell dysfunction); and renal glucose reabsorption (SGLT-2 upregulation in diabetes — the pharmacological target of gliflozins). Non-modifiable risk factors: family history (first-degree relative increases risk 3-fold); ethnicity (South Asian, Black African, Hispanic, and Pacific Islander populations have 2-4x higher T2DM risk at lower BMI levels and younger age); age (risk increases significantly over 40 years); prior gestational diabetes (50-70% lifetime T2DM risk); and polycystic ovary syndrome (PCOS — 5-10x increased T2DM risk). Modifiable risk factors: overweight and obesity (BMI above 25 — central adiposity — waist circumference above 80 cm women, 94 cm men — is the strongest modifiable risk); physical inactivity; unhealthy dietary pattern (high glycaemic index, high refined carbohydrate and processed food consumption, sugar-sweetened beverages); smoking; sleep deprivation; depression (bidirectional relationship); and medications (corticosteroids, antipsychotics — olanzapine, clozapine — cause significant glucose dysregulation).

T2DM often develops insidiously and may be asymptomatic for years — approximately 30-50% of people with T2DM are undiagnosed at presentation. Classic hyperglycaemia symptoms: polyuria (frequent urination — osmotic diuresis); polydipsia (excessive thirst — compensating for fluid losses); polyphagia (increased appetite); unexplained weight loss (in decompensated T2DM); fatigue; blurred vision (from osmotic changes in the lens); recurrent infections (urinary tract, skin, fungal — Candida — impaired phagocyte function in hyperglycaemia); and slow wound healing. Hyperosmolar hyperglycaemic state (HHS): a serious complication of uncontrolled T2DM (more common than DKA in T2DM) with extreme hyperglycaemia (above 30 mmol/L), severe dehydration, high plasma osmolality, altered consciousness without significant ketosis — carries 5-20% mortality. Long-term diabetic complications: retinopathy (leading cause of acquired blindness in working-age adults in high-income countries — 30% of T2DM patients have retinopathy at diagnosis); nephropathy (diabetic kidney disease — 40% of T2DM — leading cause of end-stage renal disease globally); peripheral neuropathy (sensory — 'glove and stocking' distribution numbness and tingling; autonomic — gastroparesis, postural hypotension, erectile dysfunction; 50% of T2DM at 10 years); macrovascular disease (cardiovascular — 2-4x increased MI, stroke, peripheral arterial disease risk); and diabetic foot disease (neuropathy + ischaemia — leading to ulceration and amputation).

T2DM is diagnosed using one of four criteria (WHO 2006, confirmed on repeat testing unless symptoms are present): (1) fasting plasma glucose (FPG) above 7.0 mmol/L (126 mg/dL) — minimum 8 hours fast; (2) 2-hour plasma glucose above 11.1 mmol/L (200 mg/dL) on a 75g oral glucose tolerance test (OGTT); (3) HbA1c at or above 48 mmol/mol (6.5%) — average blood glucose over the preceding 2-3 months; (4) random plasma glucose above 11.1 mmol/L with classic symptoms. In asymptomatic individuals, a single abnormal result must be confirmed by a second test on a separate day. Prediabetes (HbA1c 42-47 mmol/mol; FPG 6.1-6.9 mmol/L; IGT on OGTT) identifies high-risk individuals for prevention. Monitoring: HbA1c every 3 months until stable, then 6-monthly; annual diabetic review including: fasting lipids, eGFR (kidney function), urine albumin:creatinine ratio (ACR — albuminuria detection), blood pressure measurement, weight and BMI, dilated fundal examination (retinopathy screening), foot examination (neuropathy and vascular assessment), and vaccination review. CGM (continuous glucose monitoring) — particularly FreeStyle Libre — is now widely recommended for T2DM on insulin therapy and increasingly for non-insulin patients on sulphonylureas at hypoglycaemia risk. HbA1c target: individualised — typically 48-58 mmol/mol (6.5-7.5%) for most patients; higher target (58-64 mmol/mol) for frail elderly, high hypoglycaemia risk, or limited life expectancy.

T2DM management is multifactorial, targeting hyperglycaemia, cardiovascular risk factors, and organ protection simultaneously. Lifestyle intervention: the cornerstone — structured dietary modification (Mediterranean or low-carbohydrate diets are most evidence-based for glycaemic control and weight loss; aim 500-750 kcal daily deficit for weight reduction); regular aerobic exercise (150 minutes/week of moderate intensity) reduces HbA1c by 0.5-1.0% independently of weight loss; smoking cessation; alcohol moderation. Intensive weight loss (15 kg or more) achieves T2DM remission in 50-85% of patients within 5 years of diagnosis (DiRECT trial). Pharmacological therapy: metformin is the universal first-line agent (reduces hepatic gluconeogenesis, lowers HbA1c by 1-2%, weight-neutral to modest weight reduction, cheap, cardioprotective, contraindicated in severe eGFR under 30); SGLT-2 inhibitors (empagliflozin, dapagliflozin, canagliflozin — block renal glucose reabsorption, reducing HbA1c by 0.5-1%; proven to reduce major adverse cardiovascular events by 14% and heart failure hospitalisation by 35%; also slow progression of diabetic kidney disease — preferred in patients with established CVD, heart failure, or CKD); GLP-1 receptor agonists (semaglutide, liraglutide, dulaglutide — mimic incretin effect, stimulate insulin secretion, suppress glucagon, slow gastric emptying, reduce appetite — HbA1c reduction 1.0-1.5%; significant weight loss 5-15%; semaglutide reduces cardiovascular events by 26% and reduces CKD progression — preferred for weight management and high CVD risk); DPP-4 inhibitors (sitagliptin, alogliptin — weight-neutral, safe in renal impairment, modest HbA1c reduction 0.5-0.8%); sulphonylureas (gliclazide, glipizide — cheap, effective, but cause hypoglycaemia and weight gain — declining use); pioglitazone (useful in fatty liver, metabolic syndrome); insulin therapy (basal insulin — glargine, degludec — then intensification to basal-bolus as required). Cardiovascular risk management: statin therapy for LDL reduction to below 1.8 mmol/L in high CVD risk; ACE inhibitor or ARB for hypertension and/or albuminuria; aspirin for secondary prevention; blood pressure target below 140/90 mmHg (below 130/80 in high CVD risk).

Macrovascular complications (cardiovascular disease) represent the leading cause of morbidity and mortality in type 2 diabetes — accounting for 50% of all deaths. Compared with non-diabetic individuals, people with T2DM have 2 to 4-fold elevated risk of myocardial infarction (MI), stroke, and peripheral arterial disease (PAD). GLP-1 receptor agonists (semaglutide, liraglutide) and SGLT-2 inhibitors (empagliflozin, dapagliflozin) have demonstrated significant cardiovascular mortality reduction (EMPA-REG, LEADER, DECLARE, CREDENCE, DAPA-HF trials) and heart failure hospitalisation reduction, becoming standard of care in diabetic patients with established cardiovascular disease or high cardiovascular risk. Diabetic foot disease: peripheral neuropathy (painless sensory loss) plus PAD (reduced blood flow) creates the perfect environment for foot ulcers (affects 15% of T2DM over a lifetime) — which can progress to osteomyelitis, wet gangrene, and below-knee amputation; diabetes causes 50–70% of all non-traumatic lower limb amputations globally. Hyperosmolar hyperglycaemic state (HHS): a hyperglycaemic emergency in T2DM (plasma glucose above 30 mmol/L, osmolality above 320 mOsm/kg, no significant acidosis — distinguishing it from DKA) with mortality 5–20%; precipitated by dehydration, infection, and medications (steroids, diuretics); treatment is cautious rehydration with 0.9% saline and low-rate fixed IV insulin (to avoid rapid osmolarity change causing cerebral oedema). Microvascular complications: diabetic retinopathy (leading cause of blindness in working-age adults), diabetic nephropathy (40% of end-stage renal failure in most countries — CKD stage 3 affects 40% of T2DM patients at diagnosis when the condition has been undetected for years), and diabetic peripheral neuropathy (50–70% at 10 years). Hypoglycaemia from sulfonylurea or insulin therapy can cause cardiac arrhythmias (prolonged QT), falls in elderly, and dementia risk from repeated severe episodes.

Type 2 diabetes is largely preventable. The Diabetes Prevention Programme (DPP) and Finnish Diabetes Prevention Study (DPS) demonstrated that intensive lifestyle intervention (7% weight reduction + 150 minutes/week exercise) in high-risk individuals with prediabetes reduces T2DM risk by 58% — superior to metformin (31% reduction). Key prevention strategies: achieve and maintain healthy weight (BMI below 25 kg/m²; waist circumference below 80 cm women, 94 cm men); adopt a Mediterranean, plant-forward, or low-GI dietary pattern; undertake 150+ minutes of moderate physical activity weekly; eliminate sugar-sweetened beverages; screen high-risk groups (BMI above 25 + one additional risk factor; ethnicity risk groups; prediabetes; gestational diabetes history) annually with FPG or HbA1c; NHS Diabetes Prevention Programme and equivalent structured education programmes deliver evidence-based lifestyle support. T2DM remission: defined as HbA1c below 48 mmol/mol for at least 3 months without glucose-lowering medication — achievable through calorie-restricted diets producing 15+ kg weight loss (DiRECT trial: 50% remission at 1 year, 36% at 2 years), very low-calorie diets, or bariatric surgery (75-80% long-term remission with gastric bypass). Earlier diagnosis (shorter diabetes duration) and lower baseline HbA1c significantly improve remission likelihood.

Call emergency services immediately for: hyperosmolar hyperglycaemic state (HHS) — extreme thirst, confusion, drowsiness, or loss of consciousness with very high blood sugars (above 20 mmol/L); severe hypoglycaemia — inability to self-treat with oral glucose, loss of consciousness, or seizures (administer glucagon injection if available and call 999); symptoms of stroke or heart attack (chest pain, facial drooping, arm weakness, speech difficulty) — T2DM patients are at significantly elevated cardiovascular risk. See your doctor or diabetes team urgently for: blood glucose persistently above 15 mmol/L despite usual treatment; new or rapidly worsening foot ulcer, infection, or gangrene (foot emergencies can progress to amputation within days); sudden deterioration in vision; symptoms of urinary tract infection in a diabetic patient (higher risk of urosepsis); and chest pain or breathlessness. Annual diabetic reviews are not optional — diabetic complications (retinopathy, nephropathy, neuropathy) are asymptomatic in early stages and require systematic screening to detect and treat before irreversible damage occurs.