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Title: B-cell function, incretin response, and insulin sensitivity of glucose and fat metabolism in obese youth: Relationship of OGTT-time-to-glucose-peak

item KIM, JOON - Syracuse University
item TFAYLI, HALA - American University Of Beirut
item BACHA, FIDA - Children'S Nutrition Research Center (CNRC)
item LEE, SOJUNG - Kyung Hee University
item MICHALISZYN, SARA - Youngstown State University
item YOUSUF, SHAHWAR - University Of Pittsburgh Medical Center
item GEBARA, NOUR - University Of Pittsburgh Medical Center
item ARSLANIAN, SILVA - University Of Pittsburgh Medical Center

Submitted to: Pediatric Diabetes
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/26/2019
Publication Date: 11/2/2019
Citation: Kim, J.Y., Tfayli, H., Bacha, F., Lee, S., Michaliszyn, S.F., Yousuf, S., Gebara, N., Arslanian, S. 2019. B-cell function, incretin response, and insulin sensitivity of glucose and fat metabolism in obese youth: Relationship of OGTT-time-to-glucose-peak. Pediatric Diabetes. 21:18-27.

Interpretive Summary: It is important to identify individuals who are at risk for diabetes. In adults, some studies suggest that the time it takes for the blood glucose to rise after intake of a sugary drink, can inform about how sensitive the body is to insulin and can help to indicate the risk for diabetes. By examining the blood glucose rise, one can identify 2 groups of individuals: those with a rapid rise (Early-peak) in blood sugar after a sugary drink (oral glucose tolerance test) and those with a later rise (Late-peak). We investigated if the time for the glucose to reach a peak after a sugary drink informs about the hormones that regulate glucose metabolism and the ability of the pancreas to secrete insulin in children and adolescents. We measured their glucose response, their body fat and abdominal (belly) fat. In a subset of 100 adolescents, we performed more detailed evaluations of how sensitive their body is to insulin and how much insulin their pancreas can make after giving glucose in the vein to rapidly raise their blood sugar. This test informs about beta-cell function (ability to make insulin) of the pancreas. We found that youth in the "Late-peak" compared with the "Early-peak" in blood sugar level after the glucose drink, had worse beta-cell function with lower insulin than is required to meet the body's demand, and higher fat in the blood. They were more likely to have insulin resistance in various tissues (muscle, liver and fat) and more likely to have impaired glucose regulation. Our study indicates that examining the body's response to glucose and how quickly the blood sugar levels rise after a glucose load (oral glucose tolerance test) can inform about the risk for diabetes. We need to pursue this observation in follow-up studies to see if youth who have this "late-peak" pattern end up progressing into having diabetes.

Technical Abstract: In adults, the time-to-glucose-peak at or after 30 minutes during an oral glucose tolerance test (OGTT) identifies physiologically distinct groups with differences in insulin sensitivity, B-cell function and risk for type 2 diabetes. In obese nondiabetic adolescents, we investigated if the OGTT-time-to-glucose-peak also reflects incretin and free fatty acid (FFA) responses besides insulin sensitivity and B-cell function, measured by the clamp. Obese adolescents (n = 278) were categorized according to their OGTTtime-to-glucose-peak by early-peak (at 30 minutes) vs Late-peak (>30 minutes) groups. Body composition, visceral adipose tissue, oral disposition index and OGTT-area under the curve (AUC) were examined. A subset of 102 participants had both hyperinsulinemic-euglycemic and hyperglycemic clamps to measure in vivo insulin sensitivity, insulin secretion, and B-cell function relative to insulin sensitivity. Compared with the Early-peak group, the Late-peak group had impaired B-cell function relative to insulin sensitivity, lower glucose-dependent insulinotropic polypeptide-AUC, and higher FFA-AUC despite higher insulin- and C-peptide-AUC. They also had lower hepatic and peripheral insulin sensitivity despite similar percent body fat and visceral adipose tissue, and had higher prevalence of impaired glucose tolerance (all P < .05). In obese non-diabetic youth, those with a Late-peak vs an early-peak glucose during an OGTT showed diminished B-cell function, blunted incretin secretion, and lower insulin sensitivity of glucose and FFA metabolism. It remains to be determined if Late-peak glucose predicts the future development of type 2 diabetes in these high-risk youth.