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.
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.


METHODS
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.
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;
Tao
T
Huang
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA;
Sylvia H
SH
Ley
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA;
Yan
Y
Zheng
Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA;
Tiange
T
Wang
Pennington Biomedical Research Center of the Louisiana State University System, Baton Rouge, LA; and.
George A
GA
Bray
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA;
Frank M
FM
Sacks
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.
Lu
L
Qi
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003920:Diabetes Mellitus / Q000178:diet therapy / Q000235:genetics; D004038:Diet, Reducing; D004044:Dietary Proteins / Q000008:administration & dosage*; D005215:Fasting; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics*; D050417:Insulin-Secreting Cells / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000178:diet therapy*; D050177:Overweight; D015431:Weight Loss / Q000502:physiology*; D044465:White People / Q000235:genetics
D001786:Blood Glucose; D004044:Dietary Proteins; D006442:Glycated Hemoglobin; D007328:Insulin
genetic risk score; gene–diet interaction; insulin resistance; weight-loss diets; β cell function