Key Facts

Type 2 diabetes is a metabolic disorder characterised by insulin resistance and progressive beta-cell dysfunction, leading to chronic hyperglycaemia. It accounts for 90% of all diabetes and is a major contributor to cardiovascular disease, CKD, retinopathy, and neuropathy.

Epidemiology

• 4.7 million people in the UK with diabetes (90% type 2)
• Rising prevalence linked to obesity and ageing population
• Higher prevalence in South Asian (6× risk), Black African/Caribbean (3× risk), and deprived communities
• Pre-diabetes (HbA1c 42-47 mmol/mol): affects approximately 5 million in the UK
• Accounts for 10% of NHS spending (~£10 billion/year)

Aetiology

• Insulin resistance: skeletal muscle, liver, adipose tissue
• Progressive beta-cell failure: ongoing decline in insulin secretion
• Risk factors: obesity (especially central), family history, ethnicity, physical inactivity, gestational diabetes history, PCOS, age

Pathophysiology

• Insulin resistance leads to compensatory hyperinsulinaemia
• Over time, beta-cell exhaustion leads to relative insulin deficiency
• Chronic hyperglycaemia causes glucotoxicity and lipotoxicity, further impairing beta-cell function
• Microvascular complications: retinopathy, nephropathy, neuropathy
• Macrovascular complications: coronary artery disease, stroke, peripheral arterial disease
• Advanced glycation end-products (AGEs) and oxidative stress drive tissue damage

Typical Presentation

• Often asymptomatic — detected on routine blood testing or screening
• Polyuria, polydipsia, weight loss (if significantly hyperglycaemic)
• Fatigue
• Recurrent infections (UTIs, candidiasis)
• Blurred vision
• Slow wound healing

Complications at Presentation

• May present with established complications (up to 50% have complications at diagnosis)
• Diabetic foot ulcer
• Visual impairment (retinopathy)
• Proteinuria (nephropathy)
• Cardiovascular event

Red Flags

• DKA/HHS (rare in T2DM but can occur): vomiting, dehydration, altered consciousness
• Rapidly declining glycaemic control (consider latent autoimmune diabetes in adults — LADA)
• Young, lean patient diagnosed with T2DM (consider MODY or LADA)
• Foot ulcer with signs of infection/ischaemia
• Sudden visual loss (vitreous haemorrhage from proliferative retinopathy)

Diagnosis

• HbA1c ≥48 mmol/mol (6.5%) on two separate occasions if asymptomatic
• HbA1c ≥48 mmol/mol on one occasion if symptomatic
• Fasting plasma glucose ≥7.0 mmol/L or random glucose ≥11.1 mmol/L with symptoms
• Note: HbA1c unreliable in haemoglobinopathies, anaemia, pregnancy, CKD stage 5

Baseline Assessment

• HbA1c
• Lipid profile (total cholesterol, LDL, HDL, triglycerides)
• U&Es, eGFR
• Urine ACR (albumin:creatinine ratio)
• LFTs
• TFTs (associated autoimmune thyroid disease)
• BMI, BP
• ECG if cardiovascular risk factors

Annual Review (8 Care Processes)

1. HbA1c
2. Blood pressure
3. Cholesterol (total, HDL)
4. Serum creatinine/eGFR
5. Urine ACR
6. BMI
7. Foot examination
8. Retinal screening

Special Tests

• GAD antibodies, C-peptide: if LADA/T1DM suspected
• Genetic testing: if MODY suspected
• QRISK3: cardiovascular risk assessment

Non-pharmacological

• Structured education: DESMOND (newly diagnosed), X-PERT, DAFNE-equivalent programmes
• Weight loss: target 5-10% body weight reduction; consider low-calorie diet programmes
• Diet: low glycaemic index, reduce refined carbohydrates, Mediterranean diet
• Exercise: 150 minutes/week moderate intensity
• Smoking cessation: most important CVD risk reduction

Pharmacological — Glycaemic Management (NICE NG28)

• Step 1: Metformin 500mg OD, titrate to 1g BD (or MR if GI intolerance)
  • HbA1c target: 48 mmol/mol (6.5%)
• Step 2 (if HbA1c rises above target): add second agent to metformin:
  • SGLT2 inhibitor (empagliflozin 10mg OD, dapagliflozin 10mg OD): preferred if established CVD, HF, or CKD
  • DPP-4 inhibitor (sitagliptin 100mg OD): weight-neutral, well tolerated
  • Sulfonylurea (gliclazide 40-320mg/day): effective, cheap, risk of hypos and weight gain
  • Pioglitazone 15-45mg OD: if others unsuitable; avoid in HF, bladder cancer risk
• Step 3: triple therapy or consider GLP-1 receptor agonist (semaglutide, liraglutide) if BMI ≥35
• Step 4: add insulin (usually basal: insulin glargine or detemir) if above measures fail

Cardiovascular Risk Management

• Atorvastatin 20mg OD: all T2DM patients >40 years or QRISK3 ≥10%
• BP target: <140/80 mmHg (<130/80 if renal, eye, or cerebrovascular disease)
• ACEi/ARB: first-line antihypertensive if microalbuminuria or proteinuria
• Antiplatelet: aspirin 75mg only if established CVD (not for primary prevention)

Referral Criteria

• Diabetologist: uncertain diagnosis, LADA, MODY, complex insulin regimens, recurrent DKA
• Ophthalmology: retinopathy detected on screening
• Podiatry: diabetic foot disease
• Renal: progressive CKD (eGFR <30 or rapidly declining)
• Bariatric surgery: BMI ≥35 with diabetes (NICE recommendation)

• UKPDS: intensive glycaemic control reduces microvascular complications by 25%; legacy effect persists for decades
• Each 1% (11 mmol/mol) reduction in HbA1c reduces microvascular complications by 37% and MI by 14%
• Life expectancy reduced by 6-7 years on average vs general population
• Cardiovascular disease is the leading cause of death (50-60%)
• SGLT2 inhibitors: EMPA-REG showed 38% reduction in CV death with empagliflozin; DAPA-CKD showed 39% reduction in kidney disease progression
• With comprehensive management (glycaemia + BP + lipids + lifestyle), outcomes are significantly improved
• Remission possible with significant weight loss (>15kg) in early disease (DiRECT trial: 46% remission at 1 year)

NICE NG28 — Glycaemic Drug Selection Guide

Key Landmark Trials in Type 2 Diabetes

Diabetic Foot Risk Assessment