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Title: The shape of glucose response curve during an oral glucose tolerance test: Forerunner of heightened glycemic failure rates and accelerated decline in B-Cell function in TODAY

item ARSLANIAN, SILVA - University Of Pittsburgh
item EL GHORMLI, LAURE - George Washington University
item KIM, JOON - University Of Pittsburgh
item BACHA, FIDA - Children'S Nutrition Research Center (CNRC)
item CHAN, CHRISTINE - University Of Colorado
item ISMAIL, HEBA - University Of Pittsburgh
item LEVITT KATZ, LORRAINE - Children'S Hospital - Philadelphia, Pennsylvania
item LEVITSKY, LYNNE - Massachusetts General Hospital
item TRYGGESTAD, JEANIE - University Of Oklahoma Health Sciences Center
item WHITE, NEIL - Washington University

Submitted to: Diabetes Care
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/18/2018
Publication Date: 1/1/2019
Citation: Arslanian, S., El Ghormli, L., Kim, J.Y., Bacha, F., Chan, C., Ismail, H.M., Levitt Katz, L., Levitsky, L., Tryggestad, J., White, N.H. 2019. The shape of glucose response curve during an oral glucose tolerance test: Forerunner of heightened glycemic failure rates and accelerated decline in B-Cell function in TODAY. Diabetes Care. 42(1):164-172.

Interpretive Summary: We previously showed that the way the glucose levels in the blood increase after a glucose drink challenge, may indicate the risk for diabetes as the glucose levels and how they rise. The shape of the glucose response can be incessant (continuous increase), monophasic (increase then decrease) vs. biphasic (more stepped response). The shape of the glucose curve was found to be related to the insulin response so that the monophasic shape indicates worse pancreatic beta cell function. We wanted to see if the same applies in the setting of diabetes. We studied the glucose response curves in 662 youth enrolled in the multicenter TODAY study. The majority (about 70%) had a monophasic glucose response at randomization in the study, 10% had a biphasic response and about 20% had an incessant increase. Those with an incessant glucose response curve were more likely to fail to maintain glucose control on oral medications during follow-up in the study. This was related to worse beta cell function and lower insulin secretion. Therefore, in youth with type 2 diabetes, the shape of the glucose response curve after a glucose challenge can be helpful to determine the response to treatment.

Technical Abstract: Obese youth without diabetes with monophasic oral glucose tolerance test (OGTT) glucose response curves have lower insulin sensitivity and impaired B-cell function compared with those with biphasic curves. The OGTT glucose response curve has not been studied in youth-onset type 2 diabetes. Here we test the hypothesis that the OGTT glucose response curve at randomization in youth in the TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) study forecasts heightened glycemic failure rates and accelerated decline in B-cell function. OGTTs (n = 662) performed at randomization were categorized as monophasic, biphasic, or incessant increase. Demographics, insulin sensitivity (1/fasting insulin), C-peptide index (DeltaC30/DeltaG30), and B-cell function relative to insulin sensitivity (oral disposition index [oDI]) were compared among the three groups. At randomization, 21.7% had incessant increase, 68.6% monophasic, and 9.7% biphasic glucose response curves. The incessant increase group had similar insulin sensitivity but significantly lower C-peptide index and lower oDI, despite similar diabetes duration, compared with the other two groups. Glycemic failure rates were higher in the incessant increase group (58.3%) versus the monophasic group (42.3%) versus the biphasic group (39.1%) (P < 0.0001). The 6-month decline in C-peptide index (32.8% vs. 18.1% vs. 13.2%) and oDI (32.2% vs. 11.6% vs. 9.1%) was greatest in incessant increase versus monophasic and biphasic with no difference in insulin sensitivity. In the TODAY study cohort, an incessant increase in the OGTT glucose response curve at randomization reflects reduced B-cell function and foretells increased glycemic failure rates with accelerated deterioration in B-cell function independent of diabetes duration and treatment assignment compared with monophasic and biphasic curves. The shape of the OGTT glucose response curve could be a metabolic biomarker prognosticating the response to therapy in youth with type 2 diabetes.