Impaired Glucose Tolerance

Impaired glucose tolerance is intermediate hyperglycaemia defined by a 2-hour plasma glucose of 7.8 to 11.0 mmol/L (140 to 199 mg/dL) following a 75 g oral glucose load, with fasting glucose below 7.0 mmol/L. It reflects mainly peripheral (muscle) insulin resistance with reduced early insulin release and carries a higher risk of cardiovascular disease than impaired fasting glucose.

• Progression to type 2 diabetes is about 5 to 10 percent per year, around 30 percent over 5 years, and risk is greater when combined with impaired fasting glucose.
• Associated with obesity, metabolic syndrome, dyslipidaemia, hypertension, fatty liver, polycystic ovary syndrome, previous gestational diabetes, steroids, antipsychotics, and a sedentary lifestyle.
• The 2-hour result often rises before fasting glucose does, so it can be missed if only fasting glucose or HbA1c is measured.
• Lifestyle intervention reduces progression to diabetes by about 40 to 60 percent.

• Usually asymptomatic.
• Postprandial symptoms occasionally (fatigue, drowsiness, sweating or hunger 2 to 4 hours after carbohydrate meals).
• Signs of insulin resistance: central obesity, acanthosis nigricans, skin tags, hirsutism, hypertension.
• No osmotic symptoms; if present, test for diabetes.

• 75 g oral glucose tolerance test: fast for 8 to 14 hours overnight, with unrestricted carbohydrate intake (at least 150 g daily) for 3 days before; drink 75 g anhydrous glucose in 250 to 300 mL water over 5 minutes; rest seated, no smoking; sample at 0 and 2 hours.
• Interpretation: fasting below 7.0 mmol/L and 2-hour glucose 7.8 to 11.0 mmol/L means impaired glucose tolerance; 2-hour glucose 11.1 mmol/L or more means diabetes.
• HbA1c may be normal or borderline, so a normal HbA1c does not exclude it.
• Baseline: lipid profile, liver function, creatinine and eGFR, urine albumin creatinine ratio, blood pressure, weight and waist circumference.
• Exclude secondary causes: Cushing syndrome, acromegaly, thyrotoxicosis, pancreatic disease, haemochromatosis, drugs (steroids, thiazides, antipsychotics).
• Differentials: early diabetes, stress hyperglycaemia, dumping or rapid glucose absorption after gastric surgery, test error.

Lifestyle (first line)

• Weight loss of 5 to 10 percent; hypocaloric diet with low glycaemic index foods, reduced refined carbohydrate and sugary drinks, increased fibre (at least 30 g daily).
• Physical activity at least 150 minutes per week of brisk walking or equivalent, plus resistance work twice weekly; short walks of 10 to 15 minutes after meals blunt postprandial peaks.
• Smoking cessation, alcohol moderation, sleep optimisation.
• Structured group education programmes have the best results.

Pharmacological (if high risk or lifestyle insufficient)

• Metformin immediate release 500 mg orally once daily with food, increasing by 500 mg weekly to 850 mg to 1 g twice daily (maximum 2 g daily; modified release preparations also acceptable). Check eGFR (avoid below 30 mL/min/1.73 m2, reduce dose at 30 to 45) and annual B12; stop during acute illness with dehydration or before iodinated contrast in renal impairment.
• Acarbose 50 mg orally once daily with the first bite of a meal, increased to 100 mg three times daily over 4 to 8 weeks, reduces postprandial glucose and progression; flatulence and diarrhoea limit use; avoid in inflammatory bowel disease and significant renal impairment.
• Pioglitazone 15 to 30 mg once daily reduces progression but causes weight gain, fluid retention and fracture risk; avoid in heart failure, bladder cancer risk, and osteoporosis (specialist use only).
• Weight loss agents where obesity coexists: semaglutide 2.4 mg subcutaneously weekly (titrated from 0.25 mg) or liraglutide 3 mg daily, under specialist care where licensed.

Cardiovascular risk

• Assess 10-year risk; atorvastatin 20 mg orally at night if risk is 10 percent or more; treat blood pressure to target.

Special groups

• Previous gestational diabetes: annual testing; encourage breastfeeding.
• Pregnancy: oral glucose tolerance test at 24 to 28 weeks; diagnosis and treatment follow the gestational diabetes thresholds for pregnancy.
• Older adults: moderate goals, avoid hypoglycaemia prone agents.
• Post-bariatric patients with late dumping: test with caution; dietary measures.

Follow up and referral

• Annual HbA1c and fasting glucose (6 monthly in high risk), repeat oral glucose tolerance test every 1 to 3 years if HbA1c remains normal but risk is high.
• Annual lipids, blood pressure, weight.
• Refer to a diabetes prevention programme; refer to specialist if diabetes confirmed or secondary endocrine disease suspected.