Diabetes - type 2
Exam Tips
- In asymptomatic adults, do not diagnose from one abnormal HbA1c or glucose result alone; repeat to confirm.
- Acanthosis nigricans strongly suggests insulin resistance and supports type 2 phenotype.
- Always assess cardio-renal risk at diagnosis (BP, lipids, UACR, eGFR) because CVD is the main cause of mortality in type 2 diabetes.
- Know emergency distinctions: HHS usually has profound dehydration/high osmolality with minimal ketosis, whereas DKA has ketonaemia and acidosis.
- For prescribing stations, pair each drug choice with a safety check (renal function for metformin/SGLT2 inhibitors, hypoglycaemia risk for sulfonylureas/insulin, heart failure contraindication for pioglitazone).
- Image-based OSCE/spotter prep: review fundoscopy and retinal screening photographs of diabetic retinopathy in your local course atlas (for example figures in ophthalmology/diabetes chapters).
Definition
Type 2 diabetes mellitus is a chronic metabolic disease defined by persistent hyperglycaemia caused by insulin resistance with progressive relative beta-cell insulin secretory failure. In UK practice, diagnosis is usually by HbA1c or plasma glucose thresholds, and the condition carries substantial long-term cardiovascular, renal, eye, and neurological risk if not treated early and comprehensively.
Pathophysiology
The core defect is reduced insulin sensitivity in liver, skeletal muscle, and adipose tissue, with failure of pancreatic beta cells to sustain compensatory hyperinsulinaemia over time. Increased hepatic gluconeogenesis, reduced peripheral glucose uptake, adipose-driven inflammation, and ectopic fat deposition worsen glycaemia; glucotoxicity and lipotoxicity then accelerate beta-cell dysfunction. Impaired incretin effect (reduced GLP-1/GIP response), altered renal glucose handling, and associated metabolic syndrome features (hypertension, dyslipidaemia, central obesity, prothrombotic tendency) contribute to both hyperglycaemia and high atherosclerotic cardiovascular risk.
Risk Factors
- Overweight/obesity (especially central adiposity) and physical inactivity
- Family history of type 2 diabetes (risk rises markedly if one or both parents are affected)
- Higher-risk ethnicity (South Asian, African, Afro-Caribbean backgrounds)
- Previous gestational diabetes or delivery of a high-risk offspring
- Polycystic ovary syndrome
- Metabolic syndrome (hypertension, dyslipidaemia, fatty liver disease, central obesity)
- Older age, but increasingly also seen in children and adolescents
- Diet pattern promoting weight gain (low-fibre, high glycaemic index intake)
- Drug exposure associated with hyperglycaemia (for example corticosteroids, some statin-associated dysglycaemia, thiazide plus beta-blocker combinations)
- Low birth weight for gestational age and preterm birth
Clinical Features
Symptoms
- Polyuria
- Polydipsia
- Tiredness/fatigue
- Blurred vision
- Recurrent infections (for example candidal or skin/urinary infections)
- Unintentional weight loss (less common than in type 1, but can occur)
- May be asymptomatic and detected on routine blood tests
Signs
- Acanthosis nigricans (suggesting insulin resistance)
- Central obesity/increased waist circumference
- Features of chronic complications at presentation (retinopathy, neuropathy, peripheral vascular disease, foot ulceration)
- Postural hypotension or autonomic features in established disease
- Signs of dehydration/confusion if hyperosmolar hyperglycaemic state develops
Investigations
Management
Lifestyle Modifications
- Structured education plus shared decision-making and individualised HbA1c targets
- Weight reduction strategy (dietary energy deficit, higher-fibre lower-refined-carbohydrate pattern, reduced ultra-processed high-GI intake)
- Regular physical activity (aerobic plus resistance exercise), reduce sedentary time
- Smoking cessation, alcohol moderation, sleep and mental health support
- Cardiovascular risk reduction: blood pressure control, lipid management, renal protection, annual review of eyes/feet/kidneys
Pharmacological Treatment
Biguanide (first-line for many adults)
- Metformin immediate-release 500 mg once daily with food, titrate every 1-2 weeks to 500 mg three times daily or 1 g twice daily (usual max 2 g/day; some patients up to 3 g/day depending on product)
Avoid starting if eGFR <30 mL/min/1.73 m2; review dose as renal function declines and consider temporary interruption during severe dehydration/sepsis/contrast studies. GI adverse effects are common initially; modified-release may improve tolerance.
SGLT2 inhibitors (especially with ASCVD, HF, or CKD benefit)
- Empagliflozin 10 mg once daily (increase to 25 mg once daily if needed and if renal function allows)
- Dapagliflozin 10 mg once daily
Counsel on genital mycotic infection risk and volume depletion. Give sick-day advice and warn about euglycaemic DKA risk (stop during acute illness, fasting, major surgery). Glycaemic efficacy falls at low eGFR; initiation thresholds are product-specific.
Sulfonylurea
- Gliclazide 40-80 mg daily initially, titrate according to glucose response (commonly up to 160 mg twice daily; max 320 mg/day)
Useful when rapid glucose lowering is needed, but causes hypoglycaemia and weight gain; caution in frailty, irregular meals, and renal/hepatic impairment.
DPP-4 inhibitor
- Sitagliptin 100 mg once daily (reduce dose in renal impairment)
Weight-neutral and low hypoglycaemia risk when not combined with sulfonylurea/insulin. Consider pancreatitis warning symptoms.
GLP-1 receptor agonist
- Semaglutide subcutaneous 0.25 mg weekly for 4 weeks, then 0.5 mg weekly; can increase to 1 mg weekly
Promotes weight loss and improves glycaemia; common nausea/vomiting initially. Caution with history of pancreatitis; can worsen dehydration if severe GI side effects occur.
Thiazolidinedione
- Pioglitazone 15-30 mg once daily, increase to 45 mg once daily if required
Contraindicated in heart failure and active/history of bladder cancer; may cause fluid retention, weight gain, and fracture risk.
Insulin (when oral/injectable non-insulin therapy insufficient or symptomatic hyperglycaemia)
- Insulin glargine 10 units once daily as a common starting basal regimen, titrated to fasting glucose
Provide hypoglycaemia education, driving advice, and injection technique review. Continue/metformin if tolerated; individualise regimen intensification.
Cardiovascular and renal risk modification
- Atorvastatin 20 mg once daily for primary prevention in many adults with type 2 diabetes
- Ramipril 2.5 mg once daily, titrate (for hypertension or albuminuric kidney disease when indicated)
Check interactions, renal function, and potassium with RAAS blockers. Statins are contraindicated in pregnancy; discuss contraception and preconception planning where relevant.
Surgical / Interventional
- Metabolic (bariatric) surgery in selected people with obesity and inadequately controlled diabetes despite optimal medical/lifestyle therapy
Complications
- Atherosclerotic cardiovascular disease (myocardial infarction, stroke/TIA, peripheral arterial disease) and heart failure
- Diabetic kidney disease progressing to chronic kidney disease/end-stage kidney disease
- Diabetic retinopathy and vision loss
- Peripheral neuropathy (including painful neuropathy) and autonomic neuropathy
- Diabetic foot ulceration, infection, osteomyelitis, gangrene, and amputation
- Hyperosmolar hyperglycaemic state (more typical in older adults with type 2 diabetes)
- Diabetic ketoacidosis (less common than in type 1 but can occur, including with SGLT2 inhibitors)
- Psychological comorbidity (depression, anxiety, diabetes distress)
- Sexual dysfunction including erectile dysfunction
Prognosis
With early diagnosis, multifactorial risk-factor control, and sustained engagement, many people achieve good quality and length of life. However, beta-cell function typically declines over years, so treatment often needs stepwise intensification. Younger-onset type 2 diabetes generally progresses faster and carries higher lifetime microvascular and cardiovascular burden.
Sources & References
💊BNF Drug References(3)
- Irbesartan[management.pharmacological]
- Losartan potassium[management.pharmacological]
- Repaglinide[management.pharmacological]
✅NICE Guidelines(1)
- Diabetes - type 2[overview]
📖Textbook References(20)
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 559)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1250, 1251)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 803)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1298)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1276, 1277)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1247)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1253)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1775, 1776)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1276)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 295)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1243, 1244)[context]
- Guyton and Hall Textbook of Medical Physiology (John E. Hall, Michael E. Hall) (Z-Library).pdf(pp. 881)[context]
- Guyton and Hall Textbook of Medical Physiology (John E. Hall, Michael E. Hall) (Z-Library).pdf(pp. 967)[context]
- Guyton and Hall Textbook of Medical Physiology (John E. Hall, Michael E. Hall) (Z-Library).pdf(pp. 978, 979)[context]
- Guyton and Hall Textbook of Medical Physiology (John E. Hall, Michael E. Hall) (Z-Library).pdf(pp. 785)[context]
- Guyton and Hall Textbook of Medical Physiology (John E. Hall, Michael E. Hall) (Z-Library).pdf(pp. 881)[context]
- Guyton and Hall Textbook of Medical Physiology (John E. Hall, Michael E. Hall) (Z-Library).pdf(pp. 921)[context]
- Guyton and Hall Textbook of Medical Physiology (John E. Hall, Michael E. Hall) (Z-Library).pdf(pp. 967, 968)[context]
- [Oxford Medical Handbooks] Ian Wilkinson, Tim Raine, Kate Wiles, Anna Goodhart, Catriona Ha - Oxford Handbook of Clinical Medicine (2017, Oxford University Press) - libgen.li.pdf(pp. 705)[context]
- [Oxford Medical Handbooks] Ian Wilkinson, Tim Raine, Kate Wiles, Anna Goodhart, Catriona Ha - Oxford Handbook of Clinical Medicine (2017, Oxford University Press) - libgen.li.pdf(pp. 873)[context]