What sources of glucose should be used for an oral glucose tolerance test?

If a patient presents with clinical signs of diabetes mellitus (DM), such as polyuria, polydipsia, or unintended weight loss, the diagnosis of DM is confirmed once hyperglycemia or a diabetic crisis (e.g., diabetic ketoacidosis or hyperglycemic hyperosmolar state) is confirmed. In symptomatic patients, hyperglycemia is defined as a random plasma glucose (PG) of ≥200 mg/dL, a fasting PG of ≥126 mg/dL, a 2-hour PG during a 75-g oral glucose tolerance test (OGTT) of ≥200 mg/dL, or a hemoglobin A1c level of ≥6.5%.

In asymptomatic patients, DM is diagnosed when hyperglycemia is confirmed using two different tests on the same day or on two different days. The criteria for defining hyperglycemia are the same as for symptomatic patients, except that random PG levels are not used for asymptomatic individuals.

In individuals who are not pregnant, the OGTT is performed after an overnight fast. A fasting plasma glucose (FPG) sample is obtained, followed by ingestion of 75 grams of glucose in ≥300 mL of water over no more than 5 minutes. Two hours after beginning the glucose challenge, the 2-hour PG sample is collected. Children receive 1.75 grams of glucose per kilogram, up to a maximum of 75 grams.

During the test, participants should not smoke, eat, or engage in physical activity. Morning medications should be withheld until the test is completed. The patient should be in stable health, as recent illness, stress, hospitalization, or surgery may cause falsely abnormal results. The OGTT is rarely used to screen for type 2 DM unless the patient has a hemoglobinopathy or shortened red blood cell survival. Most commonly, screening for type 2 DM is performed using hemoglobin A1c.

If DM is diagnosed in the first trimester of pregnancy, it is considered preexisting DM (typically type 2 DM). The diagnosis of DM in the second or third trimesters [gestational diabetes mellitus (GDM)] is approached in several ways. Screening for GDM is recommended between 24 and 28 weeks of gestation. Traditionally, a 1-hour PG is measured following a 50-gram oral glucose challenge. If the 1-hour PG is ≥130 mg/dL or ≥140 mg/dL, depending on the physician's choice, a 100-gram, 3-hour, four-point OGTT is performed. For the 50-gram screening test, the patient need not be fasting.

For the 3-hour OGTT, GDM is diagnosed if any two of the following Carpenter-Coustan cut points are met or exceeded: fasting, 95 mg/dL; 1-hour, 180 mg/dL; 2-hour, 155 mg/dL; or 3-hour, 140 mg/dL. Alternatively (with no 50-gram screening test), a 75-gram, 2-hour, three-point OGTT can be performed, with GDM diagnosed if any one of the following thresholds are met or exceeded: fasting 92 mg/dL, 1-hour 180 mg/dL, or 2-hour 153 mg/dL. Hemoglobin A1c is not used to screen for GDM.

Challenges with Reproducibility and Standardization
Classifying patients as normoglycemic, prediabetic, or hyperglycemic using the OGTT has significant variability (1-5). Given this, it is critical for laboratorians conducting OGTTs to standardize the procedure.

One ongoing debate surrounds the type of sugar that should be used in the test. The only acceptable form of glucose for an OGTT is glucose diluted in water, with a maximum concentration of ~0.33 g/mL. Various commercial glucose beverages, often called “glucolas,” are available in 50 g, 75 g, and 100 g serving sizes.

Unfortunately, many patients, particularly pregnant patients, find glucola beverages nauseating. Consequently, some researchers have explored alternative glucose sources, such as jellybeans or licorice. However, the sugar composition (e.g., glucose, fructose, sucrose, or lactose) and sizes of candies vary widely, making reproducibility unacceptable. One small study showed that jellybeans had lower sensitivity than traditional glucose challenges (6). Similarly, in older studies, jellybeans also proved less sensitive (7). In two separate studies with 20 pregnant women each, Racusin et al. found that licorice was an acceptable alternative to glucola in GDM testing (8,9). However, more data is needed before nonglucola sugar sources can be justified.
 
Medico-Legal Implications and Solutions

Using unvalidated sources of glucose for screening presents significant medico-legal risks. If candy is used and a false-negative result occurs, delaying the diagnosis of GDM, it would be difficult to defend the use of candy as an appropriate diagnostic tool. The risk of missing a diagnosis necessitates validated and reliable glucose sources for testing.

Some patients express concerns about dyes and artificial flavors in glucola beverages. To address these concerns, dye- and flavor-free options such as Fresh Test are available (thefreshtest.com). However, before using more expensive alternatives, patients’ experience with standard glucolas beverages can be improved by chilling the beverage, diluting it, or sipping it slowly over 5 minutes—the maximum time allowed for consuming the glucose beverage.

In conclusion, glucose-containing beverages (such as glucola or Fresh Test) are the only suitable glucose challenges for an OGTT. Although the OGTT is far from perfect, it remains a standard diagnostic tool requiring careful preanalytical performance.

William E. Winter, MD, is a professor emeritus in the department of pathology at the University of Florida in Gainesville, Florida. +Email: [email protected]

Read the full November/December 2024 CLN issue here. 

References

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3. Libman IM, Barinas-Mitchell E, Bartucci A, et al. Reproducibility of the oral glucose tolerance test in overweight children. J Clin Endocrinol Metab. 2008; doi: 10.1210/jc.2008-0801.
4. Munang YN, Noubiap JJ, Danwang C, et al. Reproducibility of the 75 g oral glucose tolerance test for the diagnosis of gestational diabetes mellitus in a sub-Saharan African population. BMC Res Notes 2017; doi: 10.1186/s13104-017-2944-7.
5. Catalano PM, Avallone DA, Drago NM, et al. Reproducibility of the oral glucose tolerance test in pregnant women. Am J Obstet Gynecol 1993; doi: 10.1016/0002-9378(93)90019-f.
6. Lamar ME, Kuehl TJ, Cooney AT, et al. Jelly beans as an alternative to a fifty-gram glucose beverage for gestational diabetes screening. Am J Obstet Gynecol 1999; doi: 10.1016/s0002-9378(99)70099-2.
7. Boyd KL, Ross EK, Sherman SJ. Jelly beans as an alternative to a cola beverage containing fifty grams of glucose. Am J Obstet Gynecol 1995; doi: 10.1016/0002-9378(95)90447-6.
8. Racusin DA, Antony K, Showalter L, et al. Candy twists as an alternative to the glucola beverage in gestational diabetes mellitus screening. Am J Obstet Gynecol 2015; doi: 10.1016/j.ajog.2014.11.010.
9. Racusin DA, Crawford NS, Andrabi S, et al. Twizzlers as a cost-effective and equivalent alternative to the glucola beverage in diabetes screening. Diabetes Care 2013; doi: 10.2337/dc13-1130.