1320-P: Baseline Predictors of Change in Glycemia in the Restoring Insulin Secretion (RISE) Pediatric Medication Study

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-Peptide_0-30/ΔGlucose_0-30]). Glycemic worsening was defined as >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.