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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

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posted on 12.01.2021, 23:37 by Silva Arslanian, Laure El ghormli, Joon Young Kim, Ashley H. Tjaden, Elena Barengolts, Sonia Caprio, Tamara S. Hannon, Kieren Mather, Kristen Nadeau, Kristina M. Utzschneider, Steven E. Kahn, The RISE Consortium
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 b-cell function (bCF) in youth vs. adults with IGT or recently diagnosed type 2 diabetes.

Research Design and Methods: This was both a cross-sectional and 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 bCF 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<0.05). bCF was lowest in IIn vs. MPh and BPh in youth and adults (p <0.05). Yet, compared with adults, youth had higher bCF in BPh and MPh (p<0.005), but not IIn curves. 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 2-fold 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 b-cell hypersecretion in youth was not present in the IIn curve, emphasizing the severity of b-cell dysfunction in youth with this least- favorable glucose-response-curve.

Funding

RISE is supported by grants from the National Institutes of Health (U01DK-094406, U01DK-094430, U01DK-094431, U01DK-094438, U01DK-094467, P30DK-017047, P30DK-020595, P30DK-045735, P30DK-097512, UL1TR-000430, UL1TR-001082, UL1TR-001108, UL1TR-001855, UL1TR-001857, UL1TR-001858, UL1TR-001863), the Department of Veterans Affairs and Kaiser Permanente Southern California. Additional financial and material support from the American Diabetes Association, Allergan Corporation, Apollo Endosurgery, Abbott Laboratories and Novo Nordisk A/S is gratefully acknowledged.

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