OGTT Glucose Response Curves, Insulin Sensitivity, and β-Cell Function in RISE: Comparison Between Youth and Adults at Randomization and in Response to Interventions to Preserve β-Cell Function
Authors: Arslanian Silva A. , El ghormli Laure , Kim Joon Young , Tjaden Ashley H. , Barengolts Elena , Caprio Sonia , Hannon Tamara S. , Mather Kieren J. , Nadeau Kristen J. , Utzschneider Kristina M. , Kahn Steven E. ,   RISE Consortium, Ehrmann David A. , Temple Karla A. , Rue Abby , Barengolts Elena , Mokhlesi Babak , Van Cauter Eve , Sam Susan , Miller M. Annette , Kahn Steven E. , Atkinson Karen M. , Palmer Jerry P. , Utzschneider Kristina M. , Gebremedhin Tsige , Kernan-Schloss Abigail , Kozedub Alexandra , Montgomery Brenda K. , Morse Emily J. , Mather Kieren J. , Garrett Tammy , Hannon Tamara S. , Lteif Amale , Patel Aniket , Chisholm Robin , Moore Karen , Pirics Vivian , Pratt Linda , Nadeau Kristen J. , Gross Susan , Zeitler Philip S. , Williams Jayne , Green Melanie-Cree , Garcia Reyes Yesenia , Vissat Krista , Arslanian Silva A. , Brown Kathleen , Guerra Nancy , Porter Kristin , Caprio Sonia , Savoye Mary , Pierpont Bridget , Buchanan Thomas A. , Xiang Anny H. , Trigo Enrique , Beale Elizabeth , Hendee Fadi N. , Katkhouda Namir , Nayak Krishan , Martinez Mayra , Montgomery Cortney , Wang Xinhui , Edelstein Sharon L. , Lachin John M. , Hogan Ashley N. , Marcovina Santica , Harting Jessica , Albers John , Hill Dave , Savage Peter J. , Leschek Ellen W. 
Published: January 2021

OBJECTIVE
We examined the glucose response curves (biphasic [BPh], monophasic [MPh], incessant increase [IIn]) during an oral glucose tolerance test (OGTT) and their relationship to insulin sensitivity (IS) and β-cell function (βCF) in youth versus adults with impaired glucose tolerance or recently diagnosed type 2 diabetes.

RESEARCH DESIGN AND METHODS
This was both a cross-sectional and a longitudinal evaluation of participants in the RISE study randomized to metformin alone for 12 months or glargine for 3 months followed by metformin for 9 months. At baseline/randomization, OGTTs (85 youth, 353 adults) were categorized as BPh, MPh, or IIn. The relationship of the glucose response curves to hyperglycemic clamp–measured IS and βCF at baseline and the change in glucose response curves 12 months after randomization were assessed.

RESULTS
At randomization, the prevalence of the BPh curve was significantly higher in youth than adults (18.8% vs. 8.2%), with no differences in MPh or IIn. IS did not differ across glucose response curves in youth or adults. However, irrespective of curve type, youth had lower IS than adults (P &lt; 0.05). βCF was lowest in IIn versus MPh and BPh in youth and adults (P &lt; 0.05), yet compared with adults, youth had higher βCF in BPh and MPh (P &lt; 0.005) but not IIn. At month 12, the change in glucose response curves did not differ between youth and adults, and there was no treatment effect.

CONCLUSIONS
Despite a twofold higher prevalence of the more favorable BPh curve in youth at randomization, RISE interventions did not result in beneficial changes in glucose response curves in youth compared with adults. Moreover, the typical β-cell hypersecretion in youth was not present in the IIn curve, emphasizing the severity of β-cell dysfunction in youth with this least favorable glucose response curve.