Glucose Tolerance Testing

Glucose tolerance testing (GTT) is used to evaluate the ability to regulate glucose metabolism and is indicated when random/fasting blood glucose testing alone is insufficient in establishing or ruling out the diagnosis of diabetes mellitus. ^[1]

Table 1. Fasting Blood Glucose ^[2] (Open Table in a new window)

Table 2. Random Blood Glucose ^[2] (Open Table in a new window)

 

Table 3. Reference Range for Oral Glucose Tolerance Test ^[2] (Open Table in a new window)

 

Hemoglobin A1c (HbA1c) testing

In conjunction with glucose tolerance testing (GTT), another useful indicator for the diagnosis and monitoring of diabetes mellitus includes hemoglobin A1c (HbA1c) testing. HbA1c is glycated hemoglobin. Its value, measured in percentage of all hemoglobin, is used as an indicator of the serum glucose value over the last 3-4 months. The American Diabetes Association considers an HbA1c value of 6.5% or greater to be diagnostic of diabetes mellitus, and a value of 5.7-6.4% to be associated with a high risk for developing diabetes or prediabetes. ^[2]

A retrospective study by Poon et al indicated that in pediatric patients with overweight or obesity, a combination of HbA1c and alanine transaminase levels, as well as family history of type 2 diabetes mellitus, can be used to predict which children should undergo oral GTT. The investigators reported that there was a 61.6% positive predictive value for an abnormal GTT when the HbA1c was 5.5% or above, the family history was positive for type 2 diabetes, and the serum ALT level was abnormal. ^[3]  However, these study results have not yet been incorporated into national guidelines.

Glucose tolerance testing in preventative medicine

A glucose tolerance test can be used to identify patients at high risk of developing type 2 diabetes based on clinical risk factors, with a view to beginning preventive therapy. ^[4] Approximately 25% of patients with either impaired glucose tolerance or impaired fasting glucose will develop type 2 diabetes over the following 3-5 years. ^[5] However, the results of a glucose tolerance test cannot distinguish between type 1 and type 2 diabetes mellitus, and cannot be used to predict response to therapy, or likelihood of future complications. ^[6] Although glucose tolerance testing is more specific than other options, fasting blood glucose and haemoglobin A1c testing are usually more convenient and thus are used more frequently for screening. ^[4]

Higher plasma glucose levels are linked to increased cardiovascular risk, with this risk increase extending into the non-diabetic range. ^[7] Impaired glucose tolerance (as demonstrated on a GTT) has also been demonstrated to be a better predictor of increased cardiovascular risk and mortality than fasting glucose. ^{[8, 9]}  

Specifics for collection and panels are as follows:

• Specimen type: Blood serum or plasma

• Container: Vacutainer, red top (serum) gray top (plasma)

• Collection method: Venipuncture

• Specimen volume: 1 mL

Related tests include serum or plasma glucose, hemoglobin A1c, urinalysis, C-peptide, and insulin.

Description

Glucose tolerance testing (GTT) evaluates the ability to regulate glucose metabolism. Plasma glucose reflects a combination of carbohydrate uptake from the gastrointestinal tract, hepatic glucose output, and peripheral glucose uptake. GTT is used when the serum glucose level alone is equivocal in diagnosing diabetes (ie, when the glucose level falls in the equivocal range). ^{[6, 2]}

For three days preceeding the GTT, the patient should have a diet containing approximately 150 g of carbohydrate daily. The patient should fast overnight for a minimum of 8 hours and a maximum of 16 hours. ^[10]  GTT is usually performed in the morning, and the patient should remain seated throughout the test. After baseline fasting plasma glucose testing, the glucose load is administered—either intravenously or, more commonly, orally—and plasma glucose is measured at specified intervals thereafter. In standard oral GTT, plasma glucose concentration is measured 2 hours after a 75 g oral glucose load; for gestational diabetes mellitus, an additional measurement may be made at 1 hour. The recommended glucose dose for a child is 1.75 g/kg body weight, with a maximum of 75 g. ^[10]

Indications/Applications

Oral GTT is unnecessary if fasting or random blood glucose levels are clearly in the nondiabetic or diabetic range (refer to Reference Range section).

Indications for oral GTT include the following:

• Equivocal fasting plasma/random plasma glucose results

• To screen for gestational diabetes mellitus at 24–28 weeks of gestation in all pregnant women not known to have diabetes

• To screen for diabetes mellitus at 6–12 weeks postpartum in women with a history of gestational diabetes mellitus, using nonpregnant oral GTT criteria

• To screen for impaired glucose tolerance, which is associated with an increased risk of developing diabetes mellitus. ^{[6, 2]}

Reliability of the GTT

Results of the GTT can be unreliable due to patient non-compliance to the preparation protocol; the timing of the test; and the activity of the patient on the test day. If the results are marginally abnormal and it is suspected that results may be incorrect, repeating the GTT may be considered. ^[6]

Oral GTT in pregnancy

Oral GTTs are commonly used to screen women for gestational diabetes. There is a strong correlation between increasing maternal glucose levels at 24–32 weeks’ gestation and a range of adverse maternal and fetal outcomes. ^[11] Several different strategies are used worldwide in the screening and diagnosis of gestational diabetes. 

The American Diabetes Association offers two approaches to gestational diabetes screening; a "one-step" approach with a single 2 hour 75 g OGTT, or a "two-step" approach with a 1 hour 50 g screening OGTT followed by a confirmatory 3 hour 100 g OGTT in patients who screen positive. ^[4]

The Australian Diabetes in Pregnancy Society (ADIPS) Consensus Guidelines for the Testing and Diagnosis of Gestational Diabetes Mellitus in Australia ^[12] recommend early testing for gestational diabetes mellitus in women with risk factors, in a tiered approach to early glucose testing.

Moderate risk factors include the following:

• Ethnicity: Asian, Indian subcontinent, Aboriginal, Torres Strait Islander, Pacific Islander, Maori, Middle Eastern, non‐white African

• Body mass index (BMI) of 25–35 kg/m²

High risk factors include the following:

• Previous gestational diabetes mellitus

• Previous elevated blood glucose value

• Maternal age of 40 years or older

• Family history diabetes mellitus (first-degree relative with diabetes mellitus or a sister with gestational diabetes mellitus)

• BMI higher than 35 kg/m²

• Previous macrosomia (baby with birth weight >4500 g or >90th percentile)

• Polycystic ovarian syndrome

• Medications (corticosteroids, antipsychotics)

Women with one moderate risk factor should initially be screened with a random or a fasting glucose test in early pregnancy, followed by pregnancy oral GTT if clinically indicated. High-risk (one or more high risk factor or 2 moderate risk factors) women should undergo 75 g pregnancy oral GTT, with venous plasma samples taken fasting, 1 hour and 2 hours, and at the first opportunity after conception.

Moderate- or high-risk women with normal early pregnancy glucose testing should have repeat pregnancy oral GTT at 24–28 weeks’ gestation ^[13] or earlier if indicated. As risk stratification by risk factors is unreliable, all women should be tested, and all women not known to have gestational diabetes mellitus should have 75 g pregnancy oral GTT at 24–28 weeks.

In a 75 g oral GTT, a diagnosis of gestational diabetes mellitus is made if one or more of the following glucose levels is elevated:

• Fasting: ≥92 mg/dL (5.1 mmol/L),

• One hour: ≥180 mg/dL (10 mmol/L),

• Two hour: ≥153 mg/dL (8.5 mmol/L)

The diagnostic criteria for 0-, 1-, and 2-hour values were chosen to identify the same risk of an adverse fetal outcome at each time point. ^[14]

A retrospective, single-center study by Rodrigo et al indicated that with a 75 g oral GTT, fasting hyperglycemia, either by itself or in addition to elevated 1- or 2-hour glucose levels, at the time of gestational diabetes diagnosis can be linked to a requirement for pharmacotherapy with metformin and/or insulin. More specifically, fasting hyperglycemia levels of 4.6-5.1 mmol/L correlated with an almost three-fold chance of needing pharmacotherapy, while such treatment was required in 73.6% of women in the study with a fasting level of more than 5.1 mmol/L. Moreover, a higher body mass index (BMI) was associated with a greater likelihood of fasting hyperglycemia on the oral GTT. ^[15]

Unless contraindicated, women in the postpartum period with gestational diabetes mellitus should have another GTT, usually at 6–12 weeks. ^[13]  They should also have regular ongoing surveillance as there is an increased risk of recurrence in future pregnancies and an increased risk of developing type 2 diabetes mellitus.