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Journal article
Association of Type 2 Diabetes Susceptibility Loci With One-Year Weight Loss in the Look AHEAD Clinical Trial
Obesity (Silver Spring, Md.), v 20(8), pp 1675-1682
01 Aug 2012
PMID: 22307069
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The importance of lifestyle intervention for the prevention and treatment of type 2 diabetes (T2D) has been underscored by the limited benefit of pharmacologic therapies. We sought to determine whether genetic variants that contribute to T2D risk modify the response of weight and waist circumference to an intensive lifestyle intervention (ILI) in patients with obesity and T2D. Look AHEAD (Action for Health in Diabetes) is a randomized clinical trial comparing an ILI with a control condition on the risk of cardiovascular disease in overweight adults with T2D. We analyzed 28 single-nucleotide polymorphisms (SNPs) at/near 17 T2D-susceptibility genes in 3,903 consented participants. We genetically characterized the cohort by assessing whether T2D-susceptibility loci were overrepresented compared with a nondiabetic community-based cohort (N = 1,016). We evaluated the association of individual variants and a composite genetic risk score (GRS) with anthropometric traits at baseline and after 1-year of intervention. Look AHEAD subjects carried more T2D-susceptibility alleles than the control population. At baseline, TCF7L2 risk alleles and the highest GRS were associated with lower BMI and waist circumference. Nominally significant genotype-by-intervention interactions were detected for 1-year change in waist circumference with JAZF1, MTNR1B, and IRS1, and BMI with JAZF1. Highest GRS was associated with a greater reduction in waist circumference at year 1, although the variance in change attributable to the GRS was small. This study shows that the genetic burden associated with T2D risk does not undermine the effect of lifestyle intervention and suggests the existence of additional genomic regions, distinct from the T2D-susceptibility loci, which may enhance or mitigate weight loss.
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Details
- Title
- Association of Type 2 Diabetes Susceptibility Loci With One-Year Weight Loss in the Look AHEAD Clinical Trial
- Creators
- Inga Peter - Icahn School of Medicine at Mount SinaiJeanne M. McCaffery - Brown UniversityAlyson Kelley-Hedgepeth - Tufts Medical CenterHakon Hakonarson - Children's Hospital of PhiladelphiaSteven Reis - University of PittsburghLynne E. Wagenknecht - Wake Forest UniversityAlan S. Kopin - Tufts Medical CenterGondon S. Huggins - Tufts Medical CenterGenetics Subgrp Look AHEAD StudyEllen Stephanie Krauthamer Ewing - Drexel University
- Publication Details
- Obesity (Silver Spring, Md.), v 20(8), pp 1675-1682
- Publisher
- Wiley
- Number of pages
- 8
- Grant note
- DK 046204; DK072497 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA M01RR000051 / NATIONAL CENTER FOR RESEARCH RESOURCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) M01RR01066 / Massachusetts General Hospital Mallinckrodt General Clinical Research Center; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) M01RR02719 / Johns Hopkins Medical Institutions Bayview General Clinical Research Center; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) DK57136; DK57149; DK56990; DK57177; DK57171; DK57151; DK57182; DK57131; DK57002; DK57078; DK57154; DK57178; DK57219; DK57008; DK57135; DK56992 / Department of Health and Human Services from the National Institutes of Health T32HL069770 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) P30DK017047 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) M01RR00051 / University of Colorado Health Sciences Center General Clinical Research Center; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) 5T32HL069770 / Training Program in Cardiovascular Research (NIH) M01RR0021140 / University of Tennessee at Memphis General Clinical Research Center; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) P30 DK48520 / Clinical Nutrition Research Unit National Institute of Diabetes and Digestive and Kidney Diseases; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) M01RR000056 44 / University of Pittsburgh General Clinical Research Center; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) M01RR01346 / University of Washington/VA Puget Sound Health Care System Medical Research Service, Department of Veterans Affairs, Frederic C. Bartter General Clinical Research Center P20MD006899 / National Institute on Minority Health and Health Disparities; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Minority Health & Health Disparities (NIMHD)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Counseling and Family Therapy; Drexel University
- Web of Science ID
- WOS:000306920900018
- Scopus ID
- 2-s2.0-84864351302
- Other Identifier
- 991020099191304721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Endocrinology & Metabolism
- Nutrition & Dietetics