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United States Department of Agriculture

Agricultural Research Service

Research Project: Dietary Guidelines Adherence and Healthy Body Weight Maintenance Title: Association of Type 2 diabetes susceptibility loci with one- year weight loss in the Look AHEAD Clinical Trial

Author
item Raatz, Susan

Submitted to: Obesity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 19, 2012
Publication Date: August 17, 2012
Citation: Raatz, S.K. 2012. Association of Type 2 diabetes susceptibility loci with one- year weight loss in the Look AHEAD Clinical Trial. Obesity. 20(8):1675-1682.

Interpretive Summary: The importance of lifestyle intervention for the prevention and treatment of type 2 diabetes (T2D) has been underscored. We sought to determine whether genetics contribute to T2D. Look AHEAD (Action for Health in Diabetes) is a randomized clinical trial comparing an intensive lifestyle intervention (ILI) with a control condition on the risk of cardiovascular disease in overweight adults with T2D. We analyzed genes in 3,903 consented participants. Look AHEAD subjects carried more T2D-susceptibility genes than the control population. This study shows that the genetic burden associated with T2D risk does not undermine the effect of lifestyle intervention.

Technical 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.

Last Modified: 9/21/2014
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