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Title: The shape of the glucose response curve during an oral glucose tolerance test heralds biomarkers of type 2 diabetes risk in obese youth

Author
item KIM, JOON - University Of Pittsburgh Medical Center
item MICHALISZYN, SARA - Youngstown State University
item NASR, ALEXIS - University Of Pittsburgh Medical Center
item LEE, SOJUNG - University Of Pittsburgh Medical Center
item TFAYLI, HALA - American University Of Beirut
item HANNON, TAMARA - Indiana University School Of Medicine
item HUGHAN, KARA - University Of Pittsburgh Medical Center
item BACHA, FIDA - Children'S Nutrition Research Center (CNRC)
item ARSLANIAN, SILVA - University Of Pittsburgh Medical Center

Submitted to: Diabetes Care
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/10/2016
Publication Date: 8/1/2016
Citation: Kim, J.Y., Michaliszyn, S.F., Nasr, A., Lee, S., Tfayli, H., Hannon, T., Hughan, K.S., Bacha, F., Arslanian, S. 2016. 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. 39(8):1431-1439.

Interpretive Summary: It is important to be able to identify individuals at high risk for developing diabetes using a simple test. In this study, we investigated whether the pattern of the glucose response after an oral glucose tolerance test (OGTT) can help determine whether individuals are at higher risk for diabetes. We studied 277 obese adolescents without diabetes. They underwent body composition evaluation, OGTT and hormone testing. Despite similar fasting and 2 hour glucose concentrations, those individuals who had a monophasic glucose response to the OGTT (continuous increase in the glucose response) vs. biphasic (increase then decrease in the glucose levels) manifested: overall higher glucose and insulin levels during the OGTT, had evidence of greater insulin resistance, and impairment in beta cell function. We conclude that the shape of the glucose response curve after the OGTT can identify youth at higher risk for type 2 diabetes.

Technical Abstract: The shape of the glucose response curve during an oral glucose tolerance test (OGTT), monophasic versus biphasic, identifies physiologically distinct groups of individuals with differences in insulin secretion and sensitivity. We aimed to verify the value of the OGTT-glucose response curve against more sensitive clamp-measured biomarkers of type 2 diabetes risk, and to examine incretin/pancreatic hormones and free fatty acid associations in these curve phenotypes in obese adolescents without diabetes. A total of 277 obese adolescents without diabetes completed a 2-h OGTT and were categorized to either a monophasic or a biphasic group. Body composition, abdominal adipose tissue, OGTT-based metabolic parameters, and incretin/pancreatic hormone levels were examined. A subset of 106 participants had both hyperinsulinemic-euglycemic and hyperglycemic clamps to measure in vivo insulin sensitivity, insulin secretion, and beta-cell function relative to insulin sensitivity. Despite similar fasting and 2-h glucose and insulin concentrations, the monophasic group had significantly higher glucose, insulin, C-peptide, and free fatty acid OGTT areas under the curve compared with the biphasic group, with no differences in levels of glucagon, total glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide, and pancreatic polypeptide. Furthermore, the monophasic group had significantly lower in vivo hepatic and peripheral insulin sensitivity, lack of compensatory first and second phase insulin secretion, and impaired beta-cell function relative to insulin sensitivity. In obese youth without diabetes, the risk imparted by the monophasic glucose curve compared with biphasic glucose curve, independent of fasting and 2-h glucose and insulin concentrations, is reflected in lower insulin sensitivity and poorer beta-cell function, which are two major pathophysiological biomarkers of type 2 diabetes in youth.