Impaired Fasting Glucose

Impaired fasting glucose is a category of intermediate hyperglycaemia defined by a fasting plasma glucose of 6.1 to 6.9 mmol/L (110 to 125 mg/dL), with a 2-hour value below 7.8 mmol/L if an oral glucose tolerance test is performed. It reflects chiefly hepatic insulin resistance with excessive overnight glucose output and impaired early insulin secretion.

• Some bodies define the lower threshold as 5.6 mmol/L (100 mg/dL); use the local cut off.
• Progression to type 2 diabetes is about 5 to 10 percent per year, higher when combined with impaired glucose tolerance.
• Associated with central adiposity, metabolic syndrome, fatty liver, hypertension, dyslipidaemia, polycystic ovary syndrome, obstructive sleep apnoea, and increased cardiovascular risk.
• Risk factors: age, family history, ethnicity (South Asian, African-Caribbean), obesity, previous gestational diabetes, steroids, antipsychotics, sedentary lifestyle.

• Typically asymptomatic and found on routine testing.
• Signs of insulin resistance: abdominal obesity, acanthosis nigricans, skin tags, hirsutism.
• Possible hypertension, fatty liver features, snoring.
• Absence of osmotic symptoms (if present, test for diabetes).

• Fasting plasma glucose after at least 8 hours without calories, taken in the morning, in a laboratory sample or properly handled venous sample; repeat on a separate day to confirm.
• HbA1c (42 to 47 mmol/mol) alongside; discordance is common.
• 75 g oral glucose tolerance test for those with fasting glucose 6.1 to 6.9 mmol/L when diagnosis is uncertain, to identify diabetes or impaired glucose tolerance (2-hour glucose 7.8 mmol/L or more).
• Baseline: lipid profile, liver enzymes, creatinine and eGFR, urine albumin creatinine ratio, blood pressure, BMI and waist circumference.
• Exclude secondary causes: steroid use, Cushing syndrome, acromegaly, pancreatitis, haemochromatosis, hyperthyroidism, stress hyperglycaemia.
• Differentials: pre-analytical error (delayed sample processing causing falsely low glucose; non-fasting sample), dawn phenomenon, early type 2 diabetes, latent autoimmune diabetes in adults (if young or lean with rapid rise).

Lifestyle (mainstay)

• Weight loss of 5 to 10 percent of body weight in overweight patients.
• Reduce refined carbohydrate, sugary drinks, alcohol and saturated fat; avoid late heavy evening meals; increase fibre and vegetables; Mediterranean style dietary pattern.
• 150 minutes per week of moderate intensity exercise plus resistance training twice weekly.
• Smoking cessation, sleep optimisation, treatment of sleep apnoea.

Pharmacological

• Metformin immediate release 500 mg orally with the evening meal, increased weekly by 500 mg to 1 g twice daily (or modified release up to 2 g once daily with the evening meal) for patients with high progression risk (BMI over 30, age under 60, previous gestational diabetes, HbA1c rising, fasting glucose at the upper end). Check eGFR and B12.
• Modified release metformin taken in the evening can lower the fasting glucose most effectively.
• Avoid unnecessary sulfonylureas or insulin in this range.

Cardiovascular risk

• Calculate 10-year risk; atorvastatin 20 mg orally at night if risk at or above 10 percent; treat hypertension (target below 140/90 mmHg in clinic).

Special groups

• Women of childbearing age with previous gestational diabetes: annual testing; contraception counselling is important if metformin or other agents are started, with preconception glucose check.
• Pregnancy: oral glucose tolerance test at 24 to 28 weeks (earlier if prior gestational diabetes); diagnosed and treated as gestational diabetes where thresholds are met, rather than as impaired fasting glucose.
• Older adults: moderate targets and activity.

Follow up and referral

• Repeat fasting glucose or HbA1c every 12 months (6 months if high risk).
• Refer to a diabetes prevention programme; refer to specialist if diabetes diagnosed, atypical features, or if secondary endocrine disease is suspected.