Differential loss of beta-cell function in youth vs. adults following treatment withdrawal in the Restoring Insulin Secretion (RISE) study

AIMS: To compare OGTT-derived estimates of beta-cell function between youth and adults with impaired glucoslerance (IGT) or recently diagnosed type 2 diabetes after treatment discontinuation in RISE. METHODS: Youth (n = 89) and adults (n = 132) were randomized to 3 months glargine followed by 9 months metformin (G/M) or 12 months metformin (MET). Insulin sensitivity and beta-cell responses were estimated from 3-hour OGTTs over 21 months. Linear mixed models tested for differences by time and age group within each treatment arm. RESULTS: After treatment withdrawal, HbA1c increased in both youth and adults with a larger net increase in G/M youth vs. adults at 21 months. Among youth, beta-cell function decreased starting at 12 months in G/M and 15 months in MET. Among adults, beta-cell function remained relatively stable although insulin secretion rates decreased in G/M at 21 months. At 21 months vs. baseline beta-cell function declined to a greater extent in youth vs. adults in both the G/M and MET treatment arms. CONCLUSIONS: After treatment withdrawal youth demonstrated progressive decline in beta-cell function after stopping treatment with either G/M or MET. In contrast, beta-cell function in adults remained stable despite an increase in HbA1c over time. ClinicalTrials.gov Identifier: NCT01779375 and NCT01779362 at clinical trials.gov.