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

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 ? 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 ? 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 ? 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 ? 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.

SUBMITTER: Huang T

PROVIDER: S-EPMC4919524 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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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.

Huang Tao T Ley Sylvia H SH Zheng Yan Y Wang Tiange T Bray George A GA Sacks Frank M FM Qi Lu L

The American journal of clinical nutrition 20160608 1

<h4>Background</h4>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.<h4>Objective</h4>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.<h4>Design</h4>Data from the Preventing Overweight Using Novel ...[more]

PMID: 27281308

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Project description:BackgroundThe effects of dietary composition on weight loss are incompletely understood. In addition to energy intake, fiber intake, energy density, macronutrient composition, and demographic characteristics have all been suggested to contribute to weight loss.ObjectiveThe primary aim of this analysis was to assess the role of dietary fiber as a predictor of weight loss in participants who consumed calorie-restricted diets (-750 kcal/d from estimated energy needs) for 6 mo, using data from the POUNDS Lost (Preventing Overweight Using Novel Dietary Strategies) Study-a randomized trial that examined the effects of calorie-restricted diets varying in macronutrient composition on weight loss in adults.MethodsData were randomly partitioned to a training data set (70%) in which the effects of fiber and other weight-loss predictors were identified using adjusted Least Absolute Shrinkage and Selection Operator and model averaging. The retained predictors were then fit on the testing data set to assess predictive performance.ResultsThree hundred and forty-five participants (53.9% female) provided dietary records at baseline and 6 mo. Mean ± SD age and BMI for the full sample was 52.5 ± 8.7 y and 32.6 ± 3.9 kg/m2, respectively. Mean ± SD (99% CI) weight change at 6 mo for the full sample was -7.27 ± 5.6 kg (-8.05, -6.48 kg). The final, best fit model (R2 = 0.41) included fiber, energy density, fat, age, adherence, baseline weight, race, and changes from baseline in carbohydrate, fiber, PUFA, and MUFA intake, but the most influential predictor was fiber intake ($\hat{\beta }$ = -0.37; P < 0.0001). In addition, fiber was strongly associated with adherence to the macronutrient prescriptions (P < 0.0001). Interactions between race and adherence, age, baseline weight, carbohydrate, energy density, and MUFAs were also retained in the final model.ConclusionDietary fiber intake, independently of macronutrient and caloric intake, promotes weight loss and dietary adherence in adults with overweight or obesity consuming a calorie-restricted diet. This trial was registered at clinicaltrials.gov as NCT00072995.

Project description:BackgroundObesity is closely associated with bone health. Although diet and weight loss produce many metabolic benefits, studies of weight loss diets on bone health are conflicting. Genetic variations, such as vitamin D levels, may partly account for these conflicting observations by regulating bone metabolism.ObjectiveWe investigated whether the genetic variation associated with vitamin D concentration affected changes in bone mineral density (BMD) in response to a weight-loss diet intervention.DesignIn the 2-y Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) trial, BMD was measured for 424 participants who were randomly assigned to 1 of 4 diets varying in macronutrient intakes. A genetic risk score (GRS) was calculated based on 3 genetic variants [i.e., 7-dehydrocholesterol reductase (DHCR7) rs12785878, cytochrome P450 2R1 (CYP2R1) rs10741657 and group-specific component globulin (GC) rs2282679] related to circulating vitamin D levels. A dual-energy X-ray absorptiometry scan was performed to assess changes in whole-body BMD over 2 y. The final analysis included 370 participants at baseline.ResultsWe found a significant interaction between dietary fat intake and vitamin D GRS on 2-y changes in whole-body BMD (P-interaction = 0.02). In the high-fat diet group, participants with higher GRS showed significantly less reduction in whole-body BMD than those with lower GRS, whereas the genetic associations were not significant in the low-fat diet group. We also found a significant interaction between dietary fat intake and the GRS on 6-mo change in femur neck BMD (P-interaction = 0.02); however, the interaction became nonsignificant at 2 y.ConclusionOur data indicate that dietary fat intake may modify the effect of vitamin D-related genetic variation on changes in BMD. Overweight or obese patients predisposed to sufficient vitamin D may benefit more in maintaining BMD along with weight loss by eating a low-fat diet. This trial was registered at clinicaltrials.gov as NCT03258203.

Dataset Information

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

Publications

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.

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