1320-P: Baseline Predictors of Change in Glycemia in the Restoring Insulin Secretion (RISE) Pediatric Medication Study
Authors: NADEAU KRISTEN J. , EDELSTEIN SHARON , ARSLANIAN SILVA A. , CAPRIO SONIA , ZEITLER PHILIP , BUCHANAN THOMAS A. , EHRMANN DAVID A. , MATHER KIEREN J. , LESCHEK ELLEN , TRIPPUTI MARK , KAHN STEVEN E. , HANNON TAMARA S. ,   RISE CONSORTIUM
Published: June 2019

Identifying features of obese dysglycemic youth that predict deterioration of glucose homeostasis is key to planning interventions and future management. In RISE, we evaluated β-cell responses by hyperglycemic clamp and 3-h oral glucose tolerance testing (OGTT), and glycemic progression in 91 obese 10-19 year old youth with impaired glucose tolerance (IGT, 60%) or recent-onset type 2 diabetes (T2D, 40%). Outcomes were measured at baseline (BAS) and following 12 months (M12) of treatment with metformin alone or glargine for 3 months followed by metformin for 9 months. Both treatment groups were then followed for an additional 9 months after treatment withdrawal (M21) to determine if the interventions preserved or improved β-cell function. Logistic regression models evaluated the predictive value of BAS characteristics on glycemic worsening in these youth. Evaluated features included: sex, race, BMI; HbA1c, fasting and 2-h OGTT glucose, OGTT glucose area under the curve (GAUC); T2D vs. IGT status; β-cell response measures from a hyperglycemic clamp (acute C-peptide response to glucose [ACPRg], steady-state C-peptide, maximal β-cell response [ACPRmax]); and OGTT C-peptide index (CPI, [ΔC-Peptide0-30/ΔGlucose0-30]). Glycemic worsening was defined as &gt;10% increase in GAUC from BAS to M12 (on treatment, n=86) and M21 (9 months off treatment, n=82). Glycemic worsening was not different by randomized treatment or T2D vs. IGT status. No BAS factors predicted M12 on-treatment GAUC status. The odds ratio (OR) for worsening M21 off-treatment GAUC was 3.7 in black youth vs. other races (p=0.02). Per 1 SD, the odds of worsened M21 GAUC was higher with higher BAS fasting glucose (OR 1.7, p=0.03), 2-h glucose (OR 2.0, p=0.01), and GAUC (OR 2.0, p=0.01), and with lower CPGI (OR 0.5, p=0.03) and ACPRg (OR 0.6, p=0.06). In sum, black race, OGTT glycemic variables and early C-peptide responses to oral and intravenous glucose challenges predict responses to treatment withdrawal in youth with IGT and recent-onset T2D.

Disclosure
K.J. Nadeau: None. S. Edelstein: None. S.A. Arslanian: None. S. Caprio: None. P. Zeitler: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Research & Development, Merck & Co., Inc., Novo Nordisk Inc. T.A. Buchanan: Research Support; Self; Allergan, Apollo EndoSurgery. D.A. Ehrmann: None. K.J. Mather: Advisory Panel; Self; Roche Diabetes Care. Research Support; Self; Abbott, Merck & Co., Inc., Novo Nordisk A/S, Sanofi. E. Leschek: None. M. Tripputi: None. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S. Consultant; Self; Neurimmune. Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S. T.S. Hannon: Advisory Panel; Self; Eli Lilly and Company. R. Consortium: None.

Funding
American Diabetes Association (1-14-RISE-01 to S.E.K.); National Institute of Diabetes and Digestive and Kidney Diseases