60-OR: OGTT Glucose Response Curves (GRC), Insulin Sensitivity (IS), and ß-Cell Function (ßCF) in RISE: Youth–Adult Contrast at Randomization and in Response to Interventions to Preserve ßCF

Abstract

In adults and youth without diabetes, the shape of the OGTT-GRC [Biphasic (BPh), Monophasic (MPh), Incessant Increase (IIn)], identifies individuals with impairment in IS and βCF, worst in IIn, and least in BPh. Youth in the TODAY Study with IIn OGTT-GRC had higher glycemic failure rates and accelerated decline in βCF. In RISE we examined: 1) the shape of the OGTT-GRC in youth (n=85) vs. adults (n=353) at randomization; 2) the association between OGTT-GRCs and hyperglycemic clamp-measured IS and C-peptide-derived βCF; and 3) the change in OGTT-GRC [improvement: change from IIn to MPh or BPh, or MPh to BPh; deterioration: the opposite; and no change] at month 12 (M12) in each intervention arm [Metformin (M), and Glargine followed by M (G-M)]. At randomization, more youth had a BPh curve than adults (18.8% vs. 8.2%, p=0.022), with no difference in prevalence of MPh (70.6% vs. 77.3%) or IIn (10.6% vs. 14.5%) curves. IS did not differ across OGTT-GRCs in youth or adults. However, irrespective of curve type, youth had lower IS than adults (p<0.05). Across OGTT-GRCs, βCF was lowest in IIn vs. MPh and BPh in youth and adults (p <0.05 for each). However, youth compared with adults had higher βCF in BPh and MPh curves (p<0.005), but not IIn. Following intervention, the change in OGTT-GRC did not differ significantly between youth and adults (improvement: 14.5% vs. 18.0%, worsening 21.0% vs. 17.3%, no change 64.5% vs. 64.6% respectively). Moreover, there was no impact of M or G-M treatment on the change in OGTT-GRC from randomization to M12 in youth and adults. In summary, despite a 2-fold higher prevalence of the most favorable BPh OGTT-GRC in youth at randomization, it did not translate to better response to interventions in youth. Moreover, OGTT-GRCs reveal that the typical β-cell hypersecretion in youth is not present with the IIn GRC, emphasizing the severity of β-cell dysfunction in youth with this least favorable OGTT curve shape. Disclosure S.A. Arslanian: Research Support; Self; National Institutes of Health. Other Relationship; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk Inc. L. El Ghormli: None. J. Kim: None. T.S. Hannon: None. K.J. Mather: Research Support; Self; Abbott, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. S. Caprio: None. E. Barengolts: None. K.J. Nadeau: None. K. Utzschneider: Other Relationship; Self; Medtronic. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Intarcia Therapeutics, Janssen Scientific Affairs, LLC., Merck & Co., Inc., Novo Nordisk A/S, Pfizer Inc. T. Consortium: None. Funding American Diabetes Association (1-14-RISE-01 to S.E.K.); National Institute of Diabetes and Digestive and Kidney Diseases