Type 2 Diabetes — Symptoms, Causes & Treatment | MyMedicPlus

Type 2 diabetes mellitus (T2DM) is a chronic progressive metabolic disorder characterised by insulin resistance — impaired ability of target tissues (muscle, liver, adipose tissue) to respond to insulin — combined with declining pancreatic beta-cell function and relative insulin deficiency, resulting in persistent hyperglycaemia. It accounts for 90-95% of all diabetes cases globally, affecting 537 million adults (IDF 2021) — projected to increase to 783 million by 2045. T2DM is strongly associated with obesity, physical inactivity, and metabolic syndrome — but is not exclusively a lifestyle condition; genetic factors, ethnicity, and age are important risk factors. The condition is typically insidious in onset, with an average of 7 years between true disease onset and clinical diagnosis. During this asymptomatic period, hyperglycaemia silently damages blood vessels, nerves, and kidneys — many people already have microvascular complications at the time of first diagnosis. HbA1c above 6.5% (48 mmol/mol) is diagnostic. T2DM is largely preventable through lifestyle modification: intensive lifestyle intervention (7% weight loss plus 150 minutes of moderate activity weekly) reduces T2DM onset by 58% in high-risk individuals — a greater effect than metformin alone (31%). Bariatric surgery and low-calorie diet programmes can achieve full diabetes remission in a substantial proportion of people with recent-onset T2DM.

The fundamental defect in T2DM is a combination of peripheral insulin resistance (failure of muscle and adipose tissue to adequately respond to insulin signalling, leading to impaired glucose uptake) and hepatic insulin resistance (failure to suppress glucose output from the liver — causing fasting hyperglycaemia). Initially, the pancreas compensates by producing more insulin (hyperinsulinaemia), but over years, beta-cell secretory capacity progressively declines from glucotoxicity, lipotoxicity, and amyloid deposition in pancreatic islets — resulting in relative and eventually absolute insulin deficiency. Risk factors: obesity (particularly visceral adiposity — BMI above 30, or above 23 in South Asian populations — abdominal fat releases pro-inflammatory adipokines that worsen insulin resistance); physical inactivity (skeletal muscle is the primary tissue for insulin-stimulated glucose disposal); family history (first-degree relative with T2DM — 40% lifetime risk; identical twin concordance approximately 70%); age above 45; impaired fasting glucose (IFG) or impaired glucose tolerance (IGT/prediabetes — 10% annual progression to T2DM); gestational diabetes history (50% develop T2DM within 10 years); polycystic ovary syndrome (PCOS) — insulin resistance is central to PCOS pathophysiology; South Asian, African-Caribbean, and Hispanic/Latino ethnicity (higher visceral fat at any given BMI); and hypertension. Non-modifiable risk factors: genetic predisposition (over 400 genetic loci identified) and advancing age.

T2DM is often asymptomatic for years, diagnosed incidentally on routine blood testing. When symptomatic, classic features of hyperglycaemia include: polyuria (frequent urination — from glycosuria: glucose spills into urine above the renal threshold of 10 mmol/L, dragging water osmotically); polydipsia (excessive thirst — from osmotic dehydration); fatigue and lethargy (from cellular glucose starvation despite hyperglycaemia); blurred vision (osmotic changes in the lens refractive index); unexplained weight loss (in later-stage T2DM when beta-cell failure leads to relative insulin deficiency — more common in thin or older individuals); recurrent infections — urinary tract infections, fungal skin infections, genital thrush (Candida vulvovaginitis in women, balanitis in men) — glucose-rich urine and mucous membranes promote microbial growth; slow or impaired wound healing — early indicator of vascular and neuropathic complications; peripheral neuropathy symptoms — tingling, numbness, burning, or stabbing pains in the feet and lower legs in a stocking distribution; and acanthosis nigricans — dark, velvety skin discolouration in neck flexures, axillae, and groin — a clinical marker of significant insulin resistance. Nocturia from polyuria may be an early but non-specific presentation.

Diagnostic criteria (WHO/NICE — any one of the following, or two separate tests in asymptomatic individuals): HbA1c above 6.5% (48 mmol/mol); fasting plasma glucose above 7.0 mmol/L; 2-hour plasma glucose above 11.1 mmol/L on a 75 g oral glucose tolerance test (OGTT); or random plasma glucose above 11.1 mmol/L with symptoms of diabetes. HbA1c reflects average blood glucose over the preceding 2-3 months — it is the most practical test, unaffected by recent meals; may be unreliable in haemolytic anaemia, haemoglobin variants, or pregnancy (use glucose-based tests instead). Prediabetes (high risk of progression): HbA1c 39-47 mmol/mol (5.7-6.4%), IFG 6.1-6.9 mmol/L, or IGT (2-hour OGTT 7.8-11.0 mmol/L). Screening: screen all adults above 45 every 3 years; earlier (from age 35-40) in people with obesity, first-degree relatives with T2DM, gestational diabetes history, PCOS, South Asian or Black or Hispanic ethnicity, or hypertension. Distinguishing T2DM from T1DM/LADA in adults: C-peptide (normal or elevated in T2DM); anti-GAD65 and IA-2 autoantibodies (positive in T1DM/LADA). Baseline investigations: fasting lipid profile, renal function with eGFR, urine albumin-to-creatinine ratio (ACR — microalbuminuria detection), liver function tests, blood pressure, BMI, and fundus photography to assess for existing complications at diagnosis.

Lifestyle modification is foundational: Mediterranean-style or low-glycaemic index diet; 150 minutes per week of moderate aerobic exercise (improves insulin sensitivity, reduces HbA1c by 0.5-1.5%, lowers cardiovascular risk); structured weight loss (7% body weight reduction reduces HbA1c by 1-2% and delays insulin requirement). For remission: low-calorie dietary programme (total diet replacement 800 kcal/day — DiRECT trial: 46% remission at 1 year with mean 10 kg weight loss); bariatric surgery achieves remission in 60-80% of obese T2DM patients. Pharmacotherapy — first-line: metformin 500-1000 mg twice daily (eGFR above 30 required; reduces HbA1c 1-1.5%; cardiovascular benefit in UKPDS; GI side effects minimised by slow titration). Second-line — selection based on comorbidities: GLP-1 receptor agonists (semaglutide 0.5-2 mg SC weekly or oral 14 mg daily; liraglutide 1.2-1.8 mg SC daily — reduce HbA1c 1-1.5%, body weight 5-10%; SUSTAIN-6 and LEADER trials demonstrated CV death, MI, and stroke reduction in established CVD); SGLT-2 inhibitors (empagliflozin 10-25 mg, dapagliflozin 10 mg — reduce HbA1c 0.5-1%, 2-3 kg weight loss; EMPA-REG OUTCOME trial: empagliflozin reduced CV death by 38% and heart failure hospitalisation by 35%; recommended in all T2DM with CKD or heart failure); DPP-4 inhibitors (sitagliptin 100 mg — HbA1c reduction 0.5-0.8%; weight-neutral; safe in CKD with dose adjustment). Insulin therapy: when HbA1c remains above 7.5% (58 mmol/mol) on dual or triple oral therapy — start with basal insulin (glargine U-100/U-300 or degludec once daily); progress to basal-plus or full basal-bolus. Target HbA1c: below 7% (53 mmol/mol) for most adults; individualise for elderly or those at high hypoglycaemia risk.

Microvascular: diabetic retinopathy (leading cause of preventable adult blindness globally — affects 30-40% of T2DM patients; annual retinal photography screening is mandatory); diabetic nephropathy (the leading cause of end-stage renal disease worldwide — detected early by urine albumin-to-creatinine ratio (ACR) screening for microalbuminuria; ACE inhibitors and SGLT-2 inhibitors slow progression); peripheral neuropathy (affecting up to 50% after 10 years — stocking-distribution numbness, burning, and pain) and autonomic neuropathy (gastroparesis, erectile dysfunction, postural hypotension, and cardiac autonomic neuropathy increasing sudden cardiac death risk). Macrovascular: coronary artery disease (2-4x increased risk — responsible for 50-70% of T2DM deaths), ischaemic stroke (2x risk), and peripheral artery disease (claudication and critical limb ischaemia). Diabetic foot (combined neuropathy plus ischaemia): neuropathic and ischaemic ulcers, Charcot neuroarthropathy, osteomyelitis, spreading cellulitis, and non-traumatic lower limb amputations — T2DM accounts for approximately 70% of all non-traumatic amputations globally. Non-alcoholic fatty liver disease (NAFLD/MASLD) affects 60-70% of T2DM patients and can progress to cirrhosis and hepatocellular carcinoma. Hypoglycaemia from insulin or sulfonylureas causes loss of consciousness, cardiac arrhythmias, and increased cardiovascular mortality — a major barrier to tight glycaemic control.

Prediabetes intervention: intensive lifestyle modification (7% weight loss plus 150 minutes of moderate-intensity aerobic exercise per week) reduces T2DM onset by 58% — a greater benefit than metformin alone (31%); NICE recommends referral to the NHS Diabetes Prevention Programme for all adults with confirmed prediabetes. Annual monitoring: HbA1c, fasting lipid profile, renal function (eGFR and urine ACR — microalbuminuria), retinal photography, foot examination (neuropathy by 10 g monofilament and vibration, and peripheral pulses), and blood pressure (target below 130/80 mmHg). Structured patient education (DESMOND programme — Diabetes Education and Self-Management for Ongoing and Newly Diagnosed). Smoking cessation: smokers with T2DM have 40-50% higher cardiovascular mortality — smoking cessation is as important as glucose control. Semaglutide 2.4 mg weekly (Wegovy) achieves 15-20% weight loss and significantly improves glycaemia. Metformin for high-risk prediabetes (BMI above 35 or history of gestational diabetes) reduces T2DM onset by 31%.

Seek emergency care for: hyperglycaemic hyperosmolar state (HHS) — severe dehydration, very high blood glucose (above 30 mmol/L), confusion, and reduced consciousness in Type 2 diabetes (rare but life-threatening emergency); hypoglycaemia with loss of consciousness or seizure — call emergency services and administer glucagon. See your GP for: persistent increased thirst, frequent urination, unexplained fatigue, blurred vision, slow-healing wounds, or recurrent infections — these are classic diabetes symptoms. Anyone with risk factors (BMI above 25, family history, gestational diabetes, sedentary lifestyle, South Asian/Black ethnicity) should have HbA1c tested every 1-3 years. See your diabetes team promptly for: HbA1c above 75 mmol/mol despite treatment, recurrent severe hypoglycaemia, any new foot ulcer or cellulitis (diabetic foot emergency), sudden visual deterioration, or any concern about complications.