Table 1.

Summary of RISE papers in this issue

Article	Primary objective	Participants and intervention	Findings
Baseline Predictors of Glycemic Worsening in Youth and Adults With Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes in the Restoring Insulin Secretion (RISE) Study (13)	Identify baseline predictors of glycemic worsening in youth and adults with IGT or recently diagnosed T2D	Youth: 10–19 years of age with IGT or T2D <6 months’ duration and treated with metformin alone or insulin for <2 weeks; randomized to MET or G/M for 12 months. Adults: 20–65 years of age with IGT or drug-naive T2D <12 months’ duration; randomized to placebo, MET, G/M, or L+M.	Youth: β-cell dysfunction at baseline appeared to be the primary predictor of glycemic worsening in youth. Treatment had no impact on glycemic worsening. Adults: both β-cell dysfunction at baseline and insulin sensitivity were predictive of glycemic worsening. Dysglycemia was not. Significant benefits with L+M vs. placebo largely disappear after drug withdrawal. Takeaway: differences in baseline predictors of glycemic worsening highlight potential pathophysiologic differences between youth- and adult-onset T2D.
Hyperglucagonemia Does Not Explain the β-Cell Hyperresponsiveness and Insulin Resistance in Dysglycemic Youth Compared With Adults: Lessons From the RISE Study (14)	Determine whether β-cell hyperresponsiveness and insulin resistance in youth are related to hyperglucagonemia	Youth: 10–19 years of age with IGT or T2D <6 months’ duration. No intervention; baseline only. Adults: 20–65 years of age with IGT or drug-naive T2D <12 months’ duration. No intervention; baseline only.	Fasting and steady-state glucagon levels were not different between youth and adults. While data in adults demonstrated a positive correlation between glucagon levels and fasting glucose, data in youth suggested a negative correlation. Takeaway: α-cell dysfunction cannot account for β-cell hyperresponsiveness observed in youth compared with adults.
Effect of Medical and Surgical Interventions on α-Cell Function in Dysglycemic Youth and Adults in the RISE Study (15)	Compare the effects of medical and surgical interventions on alpha-cell function in youth and adults.	Youth: 10–19 years of age with IGT or T2D <6 months’ duration and treated with metformin alone or insulin for <2 weeks; randomized to MET or G/M. Adult Medication Study: 20–65 years of age with IGT or drug-naive T2D <12 months’ duration; randomized to placebo, MET, G/M, or L+M. Adult Surgery Study: 20–65 years of age with BMI 30–40 kg/m2 despite at least 2 months on a lifestyle modification program; randomized to MET or LB.	No change in glucagon levels was observed in youth. In adults, L+M and LB reduced glucagon. Statistical adjustments suggest that glucagon-lowering effects were largely mediated by weight loss. Takeaway: weight loss appears to preserve α-cell function in adults. Medical or surgical weight management trials may be essential to halt the progression of T2D in vulnerable youth.

MET, metformin G/M, glargine for 3 months, followed by metformin for 9 months; LB, laparoscopic gastric band surgery; L+M, liraglutide + metformin.