Oral Glucose Tolerance Test

The oral glucose tolerance test measures plasma glucose fasting and 2 hours after a fixed oral glucose load. It tests how well the body disposes of glucose, which depends on early insulin secretion, peripheral insulin sensitivity and suppression of hepatic glucose output. It detects post-load hyperglycaemia that fasting glucose and HbA1c miss. It is the reference test for gestational diabetes and for impaired glucose tolerance.

It is less convenient, less reproducible and more costly than fasting glucose or HbA1c, so it is kept for situations where those tests are inconclusive or insufficient. Impaired glucose tolerance carries a risk of progression to diabetes of about 5 to 10% each year, and is an independent marker of cardiovascular risk.

Indications.

• Fasting glucose of 5.6 to 6.9 mmol/L (100 to 125 mg/dL), or discordant fasting glucose and HbA1c.
• Gestational diabetes screening at 24 to 28 weeks, and earlier in high risk women.
• Women with previous gestational diabetes, 4 to 12 weeks after delivery and then at intervals.
• Annual screening in cystic fibrosis from 10 years of age.
• Suspected diabetes in polycystic ovary syndrome, post-transplant status, HIV, or with high cardiovascular risk when the other tests are normal.
• Conditions where HbA1c is unreliable (haemoglobinopathy, haemolysis, recent transfusion).

Contraindications and cautions.

• A fasting glucose already in the diabetic range (7.0 mmol/L or more), or a random value of 11.1 mmol/L or more with symptoms. The test adds nothing and risks marked hyperglycaemia.
• Acute illness, vomiting, or within about 2 weeks of recovery.
• Previous gastric or bariatric surgery (dumping gives misleading results), and malabsorption.

Preparation.

• Three days of an unrestricted diet with at least 150 g of carbohydrate daily, and usual physical activity.
• An overnight fast of 8 to 14 hours, with water allowed.
• No smoking, caffeine or vigorous exercise on the morning of the test. The patient stays seated and rested during it.
• Drugs that raise glucose (corticosteroids, thiazides) are withheld where this is safe.

Method.

• Adults: 75 g of anhydrous glucose (or 82.5 g of glucose monohydrate) in 250 to 300 mL of water, drunk over 5 minutes. Time zero is the start of drinking.
• Children: 1.75 g/kg to a maximum of 75 g.
• Samples: fasting and at 120 minutes. In pregnancy, fasting, 60 and 120 minutes.
• Venous blood goes into a fluoride oxalate tube, or is centrifuged within 30 minutes. Glycolysis lowers an unseparated sample by about 5 to 7% an hour.
• Extended tests of 3 to 5 hours for reactive hypoglycaemia are not advised, since low values occur in healthy people.

Adults and children (75 g load).

Some services place the lower limit of impaired fasting glucose at 6.1 mmol/L (110 mg/dL). Impaired fasting glucose and impaired glucose tolerance together carry a higher risk of progression than either alone. Isolated 2-hour hyperglycaemia is more frequent in older adults, women, and people of South Asian and East Asian ancestry.

Gestational diabetes (one step, 75 g). One abnormal value is diagnostic.

• Fasting 5.1 to 6.9 mmol/L (92 to 125 mg/dL).
• 1 hour 10.0 mmol/L (180 mg/dL) or more.
• 2 hours 8.5 to 11.0 mmol/L (153 to 199 mg/dL).
• Fasting 7.0 mmol/L or more, or 2 hours 11.1 mmol/L or more, indicates overt diabetes.

Some services use a lower 2-hour limit of 7.8 mmol/L and a fasting limit of 5.6 mmol/L. A two step approach starts with a non-fasting 50 g challenge and a 1-hour value of 7.8 to 10.0 mmol/L (140 to 180 mg/dL) or more. A positive result is followed by a 100 g, 3-hour test, with thresholds of 5.3, 10.0, 8.6 and 7.8 mmol/L (95, 180, 155 and 140 mg/dL) at fasting, 1, 2 and 3 hours, and two or more values at or over threshold diagnose gestational diabetes.

Cystic fibrosis related diabetes. A 2-hour value of 11.1 mmol/L or more diagnoses it. A normal HbA1c does not exclude it, and a midpoint value of 11.1 mmol/L or more is also abnormal.

Critical values and findings needing immediate action.

• A baseline capillary or plasma glucose of 7.0 mmol/L or more in a symptomatic patient: stop the test and begin assessment and treatment for diabetes.
• A glucose over 25 mmol/L with vomiting, abdominal pain or drowsiness: check ketones and venous gas.
• Vomiting within the first hour in pregnancy invalidates the test.

Pitfalls.

• Reproducibility is poor. The day-to-day variation of the 2-hour value is about 16 to 17%, against about 5 to 8% for fasting glucose, and a substantial minority are reclassified on repeat testing.
• A low carbohydrate diet in the days before, an inadequate fast, smoking, caffeine, anxiety, bed rest, exercise and acute illness distort the result.
• Hypokalaemia, hypomagnesaemia, corticosteroids, thiazides, beta blockers, antipsychotics and tacrolimus raise glucose.
• Delayed processing lowers the result. Vomiting of the load makes the test uninterpretable.
• Dumping after gastric surgery gives an early high peak with late hypoglycaemia, and the test is not used.

Special groups.

• Pregnancy: for women who cannot tolerate the load (hyperemesis, previous bariatric surgery), use fasting glucose with home glucose monitoring over 1 to 2 weeks.
• Older adults: the 2-hour glucose rises with age much more than fasting glucose.
• Women with previous gestational diabetes: repeat testing every 1 to 3 years, since lifetime risk of type 2 diabetes is high.
• Children: use weight based dosing and the same diagnostic thresholds.

Follow up tests. HbA1c, repeat fasting glucose, urine albumin-to-creatinine ratio, lipid profile, liver function tests, islet autoantibodies and C-peptide when type 1 diabetes or a young onset form is suspected, annual repeat OGTT in prediabetes.