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

Abstract

AIMS:

To compare OGTT-derived estimates of β-cell function between youth and adults with impaired glucose tolerance (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 β-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, β-cell function decreased starting at 12 months in G/M and 15 months in MET. Among adults, β-cell function remained relatively stable although insulin secretion rates decreased in G/M at 21 months. At 21 months vs. baseline β-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 β-cell function after stopping treatment with either G/M or MET. In contrast, β-cell function in adults remained stable despite an increase in HbA1c over time. ClinicalTrials.gov Identifier: NCT01779375 and NCT01779362 at clinical trials.gov.

• Authors: Kristina M Utzschneider, Mark T Tripputi, Alexandra Kozedub, Elena Barengolts, Sonia Caprio, Melanie Cree-Green, Sharon L Edelstein, Laure El Ghormli, Tamara S Hannon, Kieren J Mather, Jerry Palmer, Kristen J Nadeau, RISE Consortium
• Journal: Diabetes research and clinical practice (Diabetes Res Clin Pract) Vol. 178 Pg. 108948 (Aug 2021) ISSN: 1872-8227 [Electronic] Ireland
• PMID: 34274407 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Blood Glucose
• Insulin

Topics

• Adolescent
• Adult
• Blood Glucose
• Diabetes Mellitus, Type 2 (drug therapy)
• Glucose Intolerance
• Glucose Tolerance Test
• Humans
• Insulin (metabolism)
• Insulin Resistance
• Insulin Secretion