The Oral Glucose Tolerance Test (OGTT), a cornerstone in diagnosing and monitoring disorders related to glucose metabolism, has been widely used in clinical practice and medical research for several decades. This critical tool has an indelible impact on how clinicians approach diabetes mellitus, gestational diabetes, and insulin resistance, fundamentally shaping our understanding of these common and potentially debilitating conditions.
The OGTT is a relatively simple but highly informative test that evaluates the body’s ability to metabolize a known quantity of glucose, providing essential insights into pancreatic function and insulin sensitivity. It is predicated on the principle that glucose ingestion in a healthy individual will prompt a proportional secretion of insulin, facilitating glucose uptake into the cells and restoring blood glucose levels to a normal range. However, in conditions where this dynamic homeostasis is perturbed, the OGTT can serve as a potent indicator, unraveling these metabolic anomalies.
Despite the advent of novel biomarkers and advanced technologies, the OGTT remains an indispensable, robust, and accessible diagnostic modality. Its importance extends beyond endocrinology, influencing various fields such as obstetrics, pediatrics, and even psychiatry due to the pervasive effects of glucose dysregulation on numerous physiological processes.
Pathophysiology of the oral glucose tolerance test
Under normal physiological conditions, carbohydrate ingestion leads to the breakdown of complex sugars into glucose, which subsequently enters the bloodstream. The resulting elevation in blood glucose levels stimulates pancreatic insulin secretion, a hormone that facilitates cellular glucose uptake and maintains glucose homeostasis[1,2].
Individuals with insulin resistance, as observed in prediabetes (impaired glucose tolerance) or type 2 diabetes mellitus, experience persistent hyperglycemia after oral glucose challenge due to the diminished capacity of insulin to promote glucose uptake by cells[3].
Oral Glucose Tolerance Test (Practice Guide)
The oral glucose tolerance test (OGTT) is a diagnostic procedure used to assess an individual’s ability to metabolize glucose and is particularly helpful in diagnosing diabetes.
The patient must fast for at least 8 hours prior to the test to ensure accurate results. Patients should be instructed not to consume any food or caloric beverages during this period. A blood sample is taken from the patient before the glucose load is administered. This fasting blood glucose measurement serves as a baseline for comparison with subsequent samples. The patient receives a glucose-containing solution to drink, which typically contains 75 grams of glucose for adults or a weight-adjusted dose for children[4]. Blood samples are collected at specific intervals after the patient has consumed the glucose solution. These intervals usually include 1 and 2 hours after ingestion, although additional time points can be included depending on the specific protocol followed[5].
Blood samples are analyzed to determine glucose levels at each time point. These measurements are then compared to the baseline fasting blood glucose level and established diagnostic criteria. Based on blood glucose levels obtained during the OGTT, a diagnosis of normal glucose tolerance, impaired glucose tolerance (prediabetes), or diabetes can be made. In general, higher blood glucose levels and slower return to baseline levels indicate a reduced ability to metabolize glucose, suggesting the presence of diabetes or prediabetes.
For adults, the standard diagnostic criteria for an OGTT are as follows.
Blood glucose 2 hours after consuming the glucose solution.
Normal: less than 140 mg/dL (7.8 mmol/L)
Impaired glucose tolerance (prediabetes): 140-199 mg/dL (7.8-11.0 mmol/L)
Diabetes: 200 mg/dL (11.1 mmol/L) or higher[6]
Clinical Trial Evidence
This study aimed to determine to what extent insulin sensitivity and release could be predicted from an oral glucose tolerance test (OGTT). The researchers evaluated insulin sensitivity using the euglycemic-hyperinsulinemic clamp and insulin release using the hyperglycemic clamp in 104 non-diabetic volunteers who also underwent an OGTT. Demographic parameters, plasma glucose, and insulin values were used in multiple linear regression models to predict glucose metabolic clearance rate (MCR), insulin sensitivity index (ISI), and insulin release in the first phase (1st PH) and second phase (2nd PH) insulin release.
The resulting equations for MCR and ISI, which included BMI, insulin (120 min) and glucose (90 min), demonstrated strong correlations with measured MCR (r = 0.80, P < 0.00005) and ISI (r = 0.79, P < 0.00005). Similarly, the equations for the 1st and 2nd PH, which included insulin (0 and 30 min) and glucose (30 min), showed strong correlations with the 1st PH (r = 0.78, P < 0.00005) and the 2nd PH (r = 0.79, P < 0.00005). The study concluded that insulin sensitivity and release could be predicted with reasonable precision using demographic parameters and values obtained during an OGTT. The derived equations could be useful in clinical settings where clamping is used, or the minimal model would be impractical[7].
References
1. Norton, L., Shannon, C., Gastaldelli, A., and DeFronzo, R.A. (2022) Insulin: The master regulator of glucose metabolism. Metabolism, 129, 155142.
2. Giugliano, D., Ceriello, A., and Esposito, K. (2008) Glucose metabolism and hyperglycemia. Am J Clin Nutr, 87 (1), 217S-222S.
3. Kuo, F.Y., Cheng, K.-C., Li, Y., and Cheng, J.-T. (2021) Oral glucose tolerance test in diabetes, the old method revisited. World J Diabetes, 12 (6), 786–793.
4. Jagannathan, R., Neves, J.S., Dorcely, B., Chung, S.T., Tamura, K., Rhee, M., and Bergman, M. (2020) The Oral Glucose Tolerance Test: 100 Years Later. Diabetes Metab Syndr Obes, 13, 3787–3805.
5. Eyth, E., Basit, H., and Swift, C.J. (2023) Glucose Tolerance Test, in StatPearls, StatPearls Publishing, Treasure Island (FL).
6. American Diabetes Association (2020) 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2020. Diabetes Care, 43 (Suppl 1), S14–S31.
7. Stumvoll, M., Mitrakou, A., Pimenta, W., Jenssen, T., Yki-Järvinen, H., Van Haeften, T., Renn, W., and Gerich, J. (2000) Use of the oral glucose tolerance test to assess insulin release and insulin sensitivity. Diabetes Care, 23 (3), 295–301.
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