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Am J Clin Nutr. 2016 Jul;104(1):198-204. doi: 10.3945/ajcn.115.121186. Epub 2016 Jun 8.

Genetic susceptibility to diabetes and long-term improvement of insulin resistance and β cell function during weight loss: the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial.

Author information

1
Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA; Epidemiology Domain, Saw Swee Hock School of Public Health and Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore;
2
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA;
3
Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA;
4
Pennington Biomedical Research Center of the Louisiana State University System, Baton Rouge, LA; and.
5
Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA nhlqi@channing.harvard.edu.

Abstract

BACKGROUND:

Diet interventions have shown effectiveness in improving diabetes risk factors; however, little is known about whether the effects of diet intervention are different according to genetic susceptibility.

OBJECTIVE:

We examined interactions between weight-loss diets and the genetic risk score (GRS) for diabetes on 2-y changes in markers of insulin resistance and β cell function in a randomized controlled trial.

DESIGN:

Data from the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial were analyzed. A GRS was calculated on the basis of 31 diabetes-associated variants in 744 overweight or obese nondiabetic adults (80% white Americans). We assessed the changes in insulin resistance and β cell function over the 2-y intervention.

RESULTS:

Dietary protein significantly interacted with the diabetes GRS on fasting insulin, glycated hemoglobin (HbA1c), the homeostasis model assessment of β cell function (HOMA-B), and the homeostasis model assessment of insulin resistance (HOMA-IR) at 2 y in white Americans (P-interaction = 0.02, 0.04, 0.01, and 0.05, respectively). The lower GRS was associated with a greater decrease in fasting insulin (P = 0.04), HbA1c (P = 0.0001), and HOMA-IR (P = 0.02), and a lesser increase in HOMA-B (P = 0.004) in participants consuming a low-protein diet. Participants with a higher GRS might have a greater reduction in fasting insulin when consuming a high-protein diet (P = 0.03).

CONCLUSIONS:

Our data suggest that individuals with a lower genetic risk of diabetes may benefit more from consuming a low-protein weight-loss diet in improving insulin resistance and β cell function, whereas a high-protein diet may be more beneficial for white patients with a higher genetic risk. This trial was registered at clinicaltrials.gov as NCT00072995.

KEYWORDS:

genetic risk score; gene–diet interaction; insulin resistance; weight-loss diets; β cell function

PMID:
27281308
PMCID:
PMC4919524
DOI:
10.3945/ajcn.115.121186
[Indexed for MEDLINE]
Free PMC Article

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