Type 2 diabetes

Definition
Type 2 diabetes mellitus is a chronic metabolic disorder characterised by insulin resistance and a relative insulin secretory defect, leading to persistent hyperglycaemia. It is the most common form of diabetes, accounting for over 90% of cases worldwide.

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Causes and Pathophysiology

• Insulin resistance: body’s tissues (muscle, liver, adipose) do not respond adequately to insulin

• Relative insulin deficiency: pancreatic β-cells fail to compensate for increased demand over time

• Genetic predisposition: strong family history link

• Environmental/lifestyle factors: obesity, physical inactivity, poor diet

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Risk Factors

• Overweight or obesity (especially central/abdominal obesity)

• Family history of T2DM

• Age >40 years (increasingly common in younger adults and adolescents)

• Sedentary lifestyle

• Ethnicity: higher prevalence in South Asian, African-Caribbean, Hispanic populations

• History of gestational diabetes

• Hypertension, dyslipidaemia

• Polycystic ovary syndrome (PCOS)

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Clinical Features

Often insidious onset; many diagnosed incidentally or during screening.

Symptoms:

• Polyuria, polydipsia, polyphagia (classic triad)

• Fatigue, blurred vision

• Recurrent infections (e.g., urinary tract, skin, genital yeast infections)

• Slow wound healing

• Paresthesia (peripheral neuropathy)

Complications:

• Acute: Hyperosmolar hyperglycaemic state (HHS)

• Chronic:

  • Microvascular: retinopathy, nephropathy, neuropathy

  • Macrovascular: coronary artery disease, stroke, peripheral arterial disease

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Diagnosis (any one of the following, confirmed on repeat unless unequivocal hyperglycaemia):

• Fasting plasma glucose ≥ 7.0 mmol/L (126 mg/dL)

• 2-hour plasma glucose ≥ 11.1 mmol/L (200 mg/dL) during OGTT

• HbA1c ≥ 6.5% (48 mmol/mol)

• Random plasma glucose ≥ 11.1 mmol/L with classic symptoms

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Treatment

1. Lifestyle modification (first-line for all)

• Healthy diet (reduced refined carbs, balanced macronutrients, increased fibre)

• Regular physical activity (≥150 minutes/week moderate-intensity)

• Weight loss (target 5–10% body weight)

• Smoking cessation

2. Pharmacological management (individualised according to comorbidities, HbA1c, and patient profile)

• First-line:

  • Metformin (unless contraindicated: e.g., severe renal impairment) – improves insulin sensitivity, weight-neutral/loss

• Second-line (if HbA1c target not met after 3–6 months):

  • Sulfonylureas (e.g., gliclazide) – increase insulin secretion, risk of hypoglycaemia and weight gain

  • DPP-4 inhibitors (e.g., sitagliptin) – weight-neutral, low hypoglycaemia risk

  • SGLT2 inhibitors (e.g., empagliflozin) – promote glycosuria, cardiovascular and renal benefits

  • GLP-1 receptor agonists (e.g., liraglutide) – promote satiety, weight loss, CV benefits

  • Thiazolidinediones (e.g., pioglitazone) – improve insulin sensitivity, risk of fluid retention

• Third-line / combination therapy: dual or triple therapy as per guidelines

• Insulin therapy: initiated if oral/GLP-1 agents insufficient or symptomatic hyperglycaemia present

3. Management of comorbidities and risk factors

• Blood pressure control (target usually <140/90 mmHg; <130/80 mmHg in some high-risk patients)

• Lipid management (statin therapy for most adults with T2DM)

• Antiplatelet therapy (aspirin) if established cardiovascular disease

4. Monitoring

• HbA1c every 3–6 months

• Annual screening for:

  • Diabetic retinopathy (eye exam)

  • Nephropathy (urinary albumin–creatinine ratio, serum creatinine, eGFR)

  • Peripheral neuropathy and foot examination

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Prognosis

• Progressive condition requiring ongoing treatment adjustments

• Good glycaemic control and cardiovascular risk management significantly reduce complications

• Patient education and engagement are key to long-term outcomes