Methods for Measuring Risk for Type 2 Diabetes in Youth: the Oral Glucose Tolerance Test (OGTT)
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Purpose of Review
The oral glucose tolerance test (OGTT) is used both in clinical practice and research to assess glucose tolerance. In addition, the OGTT is utilized for surrogate measures of insulin sensitivity and the insulin response to enteral glucose and has been widely applied in the evaluation of β-cell dysfunction in obesity, prediabetes, and type 2 diabetes. Here we review the use of the OGTT and the OGTT-derived indices for measurement of risk markers for type 2 diabetes in youth.
Advantages of using the OGTT for measures of diabetes risk include its accessibility and the incorporation of physiological contributions of the gut-pancreas axis in the measures of insulin response to glucose. Mathematical modeling expands the potential gains from the OGTT in physiology and clinical research. Disadvantages include individual differences in the rate of glucose absorption that modify insulin responses, imperfect control of the glycemic stimulus, and poor intraindividual reproducibility.
Available research suggests the OGTT provides valuable information about the development of impaired glycemic control and β-cell function in obese youth along the spectrum of glucose tolerance.
KeywordsInsulin sensitivity β-cell function Prediabetes Adolescent Pediatric
Compliance with Ethical Standards
Conflict of Interest
Melinda E. Chen, Rebecca S. Aguirre, and Tamara S. Hannon declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major Importance
- 4.•• Chen ME, Chandramouli AG, Considine RV, Hannon TS, Mather KJ. Comparison of beta-cell function between overweight/obese adults and adolescents across the spectrum of glycemia. Diabetes Care. 2018;41(2):318–25. This manuscript describes the comparison of adult and adolescent OGTT test results with model-derived and direct measures of insulin secretion and insulin sensitivity across a spectrum of glucose tolerance levels. Adolescents have much lower insulin sensitivity as compared with adults, whereas, adults have poorer beta-cell responses to glucose at earlier stages of glucose intolerance. These results may suggest different approaches to diabetes prevention in youths versus adults. CrossRefPubMedGoogle Scholar
- 5.• Hannon TS, Kahn SE, Utzschneider KM, Buchanan TA, Nadeau KJ, Zeitler PS, et al. Review of methods for measuring beta-cell function: design considerations from the Restoring Insulin Secretion (RISE) Consortium. Diabetes Obes Metab. 2018;20(1):14–24. A current review of intravenous and oral techniques for measuring beta-cell function. CrossRefPubMedGoogle Scholar
- 6.American Diabetes Association. Classification and Diagnosis of Diabetes: Standards of medical care in diabetes. Diabetes Care. 2018;41(Suppl 1):S13–S27.Google Scholar
- 7.Burns SF, Bacha F, Lee SJ, Tfayli H, Gungor N, Arslanian SA. Declining beta-cell function relative to insulin sensitivity with escalating OGTT 2-h glucose concentrations in the nondiabetic through the diabetic range in overweight youth. Diabetes Care. 2011;34(9):2033–40.CrossRefPubMedPubMedCentralGoogle Scholar
- 9.TODAY Study Group. Effects of metformin, metformin plus rosiglitazone, and metformin plus lifestyle on insulin sensitivity and beta-cell function in TODAY. Diabetes Care. 2013;36(6):1749–57.Google Scholar
- 15.O'Connor MD, Landahl H, Grodsky GM. Comparison of storage- and signal-limited models of pancreatic insulin secretion. Am J Phys. 1980;238(5):R378–89.Google Scholar
- 18.Byrne MM, Sturis J, Polonsky KS. Insulin secretion and clearance during low-dose graded glucose infusion. Am J Phys. 1995;268(1 Pt 1):E21–7.Google Scholar
- 23.• Chan CL, Pyle L, Newnes L, Nadeau KJ, Zeitler PS, Kelsey MM. Continuous glucose monitoring and its relationship to hemoglobin A1c and oral glucose tolerance testing in obese and prediabetic youth. J Clin Endocrinol Metab. 2015;100(3):902–10. This manuscript describes the utility of HbA1c and OGTT in the evaluation of obese youth at risk for type 2 diabetes. CrossRefPubMedGoogle Scholar
- 26.Moran A, Brunzell C, Cohen RC, Katz M, Marshall BC, Onady G, et al. Clinical care guidelines for cystic fibrosis-related diabetes: a position statement of the American Diabetes Association and a clinical practice guideline of the Cystic Fibrosis Foundation, endorsed by the Pediatric Endocrine Society. Diabetes Care. 2010;33(12):2697–708.CrossRefPubMedPubMedCentralGoogle Scholar
- 30.Dalla Man C, Campioni M, Polonsky KS, Basu R, Rizza RA, Toffolo G, et al. Two-hour seven-sample oral glucose tolerance test and meal protocol: minimal model assessment of beta-cell responsivity and insulin sensitivity in nondiabetic individuals. Diabetes. 2005;54(11):3265–73.CrossRefPubMedGoogle Scholar
- 45.Cali AM, Man CD, Cobelli C, Dziura J, Seyal A, Shaw M, et al. Primary defects in beta-cell function further exacerbated by worsening of insulin resistance mark the development of impaired glucose tolerance in obese adolescents. Diabetes Care. 2009;32(3):456–61.CrossRefPubMedPubMedCentralGoogle Scholar
- 48.Hannon TS, Kirkman MS, Patel YR, Considine RV, Mather KJ. Profound defects in beta-cell function in screen-detected type 2 diabetes are not improved with glucose-lowering treatment in the Early Diabetes Intervention Program (EDIP). Diabetes Metab Res Rev. 2014;30(8):767–76.CrossRefPubMedPubMedCentralGoogle Scholar
- 56.• Kim JY, Michaliszyn SF, Nasr A, Lee S, Tfayli H, Hannon T, et al. The shape of the glucose response curve during an oral glucose tolerance test heralds biomarkers of type 2 diabetes risk in obese youth. Diabetes Care. 2016;39(8):1431–9. This manuscript describes the usefullness of data collected at different time-points during a research OGTT as compared with clamp studies for evaluating risk for type 2 diabetes in obese youth. CrossRefPubMedPubMedCentralGoogle Scholar
- 69.•• Michaliszyn SF, Mari A, Lee S, Bacha F, Tfayli H, Farchoukh L, et al. Beta-cell function, incretin effect, and incretin hormones in obese youth along the span of glucose tolerance from normal to prediabetes to type 2 diabetes. Diabetes. 2014;63(11):3846–55. This manuscript describes OGTT-modeled beta-cell function and incretin effect in obese adolescents spanning the range of glucose tolerance. There is an impairment in incretin effect with decreasing glucose tolerance. CrossRefPubMedPubMedCentralGoogle Scholar
- 72.• Cobelli C, Dalla Man C, Toffolo G, Basu R, Vella A, Rizza R. The oral minimal model method. Diabetes. 2014;63(4):1203–13. This review describes the methodology used to develop and utilize the oral minimal method, the measures it provides, and how it can provide novel insights regarding the regulation of postprandial metabolism. CrossRefPubMedPubMedCentralGoogle Scholar