Fasting Plasma Glucose

Fasting plasma glucose is the venous plasma glucose after at least 8 hours without energy intake, usually overnight. It reflects hepatic glucose output and basal insulin secretion, and it is the most widely used test for detecting and classifying disordered glucose regulation. It is measured by glucose oxidase or hexokinase methods in a laboratory.

Diabetes affects over 10% of adults worldwide, and roughly 40 to 50% of people with diabetes in many low income regions are undiagnosed. Prediabetes is more common than diabetes. The test is cheap and easily available, but it identifies fewer people with abnormal glucose handling than the 2-hour glucose tolerance test, and its use alone misses some of those with diabetes, particularly older adults.

Indications. Screening of asymptomatic adults at raised risk (overweight, family history, hypertension, dyslipidaemia, polycystic ovary syndrome, previous gestational diabetes, cardiovascular disease, ancestries at high risk), diagnosis of diabetes in symptomatic patients, investigation of fasting hypoglycaemia, monitoring in drug treatment, and follow up of prediabetes.

Specimen. An overnight fast of 8 to 14 hours with water allowed, taken in the morning. Afternoon fasting values read lower. Blood goes into a fluoride oxalate tube, or is centrifuged and the plasma separated within 30 minutes. Glycolysis lowers an unseparated sample by about 5 to 7% an hour.

Adults.

• Normal: under 5.6 mmol/L (100 mg/dL).
• Impaired fasting glucose: 5.6 to 6.9 mmol/L (100 to 125 mg/dL). Some services use a lower limit of 6.1 mmol/L (110 mg/dL).
• Diabetes: 7.0 mmol/L (126 mg/dL) or more.

Confirmation. A value in the diabetic range is repeated on another day unless unequivocal hyperglycaemia with symptoms is present, or 2 different tests (for example fasting glucose and HbA1c) are abnormal on the same sample. When 2 tests disagree, the abnormal one is repeated.

Pregnancy. A fasting plasma glucose of 7.0 mmol/L or more in early pregnancy indicates overt diabetes. A value of 5.1 to 6.9 mmol/L (92 to 125 mg/dL) meets criteria for gestational diabetes in many services, usually on a glucose tolerance test at 24 to 28 weeks, and thresholds differ between services.

Hypoglycaemia. A fasting value under 3.0 mmol/L (54 mg/dL) with symptoms relieved by glucose, in a person without diabetes, requires investigation. A prolonged supervised fast is used when spontaneous episodes cannot be captured.

Screening interval. Usual practice is to retest every 3 years when normal, and yearly in prediabetes. Testing starts earlier in people of South Asian, African, Hispanic and East Asian ancestry, who develop diabetes at lower body weight.

Raised fasting glucose.

• Type 2 diabetes and prediabetes, with insulin resistance, obesity, metabolic syndrome, fatty liver disease and polycystic ovary syndrome.
• Type 1 diabetes, including latent autoimmune diabetes in adults.
• Monogenic diabetes (neonatal diabetes under 6 months of age, MODY in young non-obese people with a strong family history).
• Pancreatic diabetes (pancreatitis, pancreatic cancer, cystic fibrosis, haemochromatosis, pancreatectomy).
• Endocrine causes: Cushing syndrome, acromegaly, phaeochromocytoma, hyperthyroidism, glucagonoma, primary aldosteronism.
• Drugs: glucocorticoids, thiazides, beta blockers, antipsychotics (olanzapine, clozapine), tacrolimus, ciclosporin, protease inhibitors, some antidepressants.
• Dawn phenomenon, recent illness or stress.

Lowered fasting glucose.

• Insulinoma, post-bariatric hypoglycaemia, non-islet cell tumour, autoimmune insulin syndrome.
• Adrenal insufficiency, hypopituitarism, hypothyroidism, growth hormone deficiency.
• Liver failure, alcohol, sepsis, critical illness, malnutrition, renal failure.
• Drugs: insulin, sulphonylureas, quinine, pentamidine, salicylates, alcohol.
• Inherited: glycogen storage disease, fatty acid oxidation disorders, hereditary fructose intolerance, hyperinsulinism.

Investigation of hypoglycaemia. A critical sample taken at a glucose under 3.0 mmol/L includes insulin, C-peptide, proinsulin, beta hydroxybutyrate, cortisol, growth hormone and a sulphonylurea screen. Inappropriately detectable insulin with a low glucose, and a suppressed beta hydroxybutyrate, indicate hyperinsulinism. A raised C-peptide with a positive sulphonylurea screen indicates drug induced hypoglycaemia, and a low C-peptide with a high insulin indicates exogenous insulin.

Critical values and findings needing immediate action.

• Fasting glucose over 25 mmol/L (450 mg/dL), or any value with symptoms, ketones or acidosis (ketoacidosis or hyperosmolar state).
• Glucose under 2.5 mmol/L (45 mg/dL), or under 3.0 mmol/L with neuroglycopenic symptoms.
• A new diagnosis of diabetes with weight loss, vomiting, dehydration or abdominal pain in a young patient needs immediate ketone testing.

Interferences and pitfalls.

• A non-fasting sample (including tea with sugar, juice or recent snacks) falsely raises the value, and an unfasted result should be recorded as a random sample.
• An unspun or slowly processed sample reads low and causes under diagnosis, particularly with leucocytosis, and in neonates.
• Capillary meters are not used for diagnosis.
• Acute illness, stress, recent steroid courses, poor sleep, vigorous exercise and a prolonged fast over 16 hours alter the result.
• Day-to-day variation within the same person is about 5 to 7%, so a single value near a threshold can misclassify a person.
• Fasting glucose is less sensitive than the 2-hour glucose tolerance test and misses some people with isolated post-load hyperglycaemia.
• HbA1c can be unreliable in haemoglobinopathies, anaemia, pregnancy, chronic kidney disease and after transfusion, so fasting glucose or the glucose tolerance test is preferred in those groups.

Special groups.

• Children: the same thresholds apply. Islet autoantibodies and ketones are checked when type 1 diabetes is suspected, and type 2 diabetes is increasingly found in obese adolescents.
• Pregnancy: pre-pregnancy and early pregnancy screening applies to high risk women, and fasting values fall in the first trimester.
• Older adults: fasting glucose rises only slightly with age while post-load glucose rises more, so fasting values under diagnose. Hypoglycaemia is atypical and falls are common.
• Neonates: timed fasting is not used, and hypoglycaemia thresholds are age and context specific.
• People of African and South Asian ancestry: diabetes appears at lower body weight and younger age.

Follow up tests. Repeat fasting glucose, oral glucose tolerance test, HbA1c, urine albumin-to-creatinine ratio, urea and electrolytes, lipid profile, liver function tests, islet autoantibodies (GAD65, IA-2, ZnT8), C-peptide, genetic testing for monogenic diabetes, cortisol, IGF-1, thyroid function tests, imaging of the pancreas, retinal assessment.