Variation in Maturity-Onset Diabetes of the Young Genes Influence Response to Interventions for Diabetes Prevention.

J Clin Endocrinol Metab
Authors
Keywords
Abstract

Context: Variation in genes that cause maturity-onset diabetes of the young (MODY) has been associated with diabetes incidence and glycemic traits.

Objectives: This study aimed to determine whether genetic variation in MODY genes leads to differential responses to insulin-sensitizing interventions.

Design and Setting: This was a secondary analysis of a multicenter, randomized clinical trial, the Diabetes Prevention Program (DPP), involving 27 US academic institutions. We genotyped 22 missense and 221 common variants in the MODY-causing genes in the participants in the DPP.

Participants and Interventions: The study included 2806 genotyped DPP participants randomized to receive intensive lifestyle intervention (n = 935), metformin (n = 927), or placebo (n = 944).

Main Outcome Measures: Association of MODY genetic variants with diabetes incidence at a median of 3 years and measures of 1-year β-cell function, insulinogenic index, and oral disposition index. Analyses were stratified by treatment group for significant single-nucleotide polymorphism × treatment interaction (Pint

Results: After 1 year, the minor allele of rs3212185 (HNF4A) was associated with improved β-cell function in the metformin and lifestyle groups but not the placebo group; the minor allele of rs6719578 (NEUROD1) was associated with an increase in insulin secretion in the metformin group but not in the placebo and lifestyle groups.

Conclusions: These results provide evidence that genetic variation among MODY genes may influence response to insulin-sensitizing interventions.

Year of Publication
2017
Journal
J Clin Endocrinol Metab
Volume
102
Issue
8
Pages
2678-2689
Date Published
2017 Aug 01
ISSN
1945-7197
DOI
10.1210/jc.2016-3429
PubMed ID
28453780
PubMed Central ID
PMC5546852
Links
Grant list
U01 DK048437 / DK / NIDDK NIH HHS / United States
U01 DK048407 / DK / NIDDK NIH HHS / United States
K24 DK110550 / DK / NIDDK NIH HHS / United States
U01 DK048412 / DK / NIDDK NIH HHS / United States
U01 DK048375 / DK / NIDDK NIH HHS / United States
T32 DK007028 / DK / NIDDK NIH HHS / United States
U01 DK048413 / DK / NIDDK NIH HHS / United States
U01 DK048397 / DK / NIDDK NIH HHS / United States
U01 DK048381 / DK / NIDDK NIH HHS / United States
U01 DK048339 / DK / NIDDK NIH HHS / United States
L30 DK089944 / DK / NIDDK NIH HHS / United States
U01 DK048514 / DK / NIDDK NIH HHS / United States
U01 DK048485 / DK / NIDDK NIH HHS / United States
U01 DK048443 / DK / NIDDK NIH HHS / United States
U01 DK048380 / DK / NIDDK NIH HHS / United States
U01 DK048400 / DK / NIDDK NIH HHS / United States
U01 DK048404 / DK / NIDDK NIH HHS / United States
U01 DK048489 / DK / NIDDK NIH HHS / United States
P30 DK017047 / DK / NIDDK NIH HHS / United States