Dataset Information

Genetic Susceptibility, Dietary Protein Intake, and Changes of Blood Pressure: The POUNDS Lost Trial.

ABSTRACT: High blood pressure (BP) is closely related to obesity, and weight loss lowers BP. Evidence has shown considerable interpersonal variation of changes in BP among people experiencing weight loss, and such variation might be partly determined by genetic factors. We assessed the changes in systolic and diastolic BP (SBP/DBP) among 692 participants randomly assigned to 1 of 4 diets varying in macronutrient content for 2 years. Two separate polygenic scores (SBP/DBP-PGS derived from 52/50 single nucleotide polymorphisms) were built for each participant based on 66 BP-associated single nucleotide polymorphisms. During a 2-year intervention, participants in the bottom versus upper tertile of SBP/DBP-PGS had a greater decrease in SBP (?SBP at 6, 12, and 24 months: -3.84 versus -1.61, -4.76 versus -2.75, -2.49 versus -1.63; P=0.001) or in DBP (?DBP at 6, 12, and 24 months: -3.09 versus -1.34, -2.69 versus -1.44, -1.82 versus -0.53; P<0.001). We also found gene-diet interaction on changes in SBP from baseline to 24 months (P_interaction=0.009). Among participants assigned to a high-protein diet, those with a lower SBP-polygenic scores had greater decreases in SBP at months 6 (P=0.018), months 12 (P=0.007), and months 24 (P=0.089); while no significant difference was observed across the SBP-polygenic scores tertile groups among those assigned to an average-protein diet (all P values >0.05). Our data indicate that genetic susceptibility may affect BP changes in response to weight-loss diet interventions, and protein intake may modify the genetic associations with changes in BP. This trial was registered at URL: http://www.clinicaltrials.gov. Unique identifier: NCT00072995.

SUBMITTER: Sun D

PROVIDER: S-EPMC6854315 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Genetic Susceptibility, Dietary Protein Intake, and Changes of Blood Pressure: The POUNDS Lost Trial.

Sun Dianjianyi D Zhou Tao T Li Xiang X Heianza Yoriko Y Liang Zhaoxia Z Bray George A GA Sacks Frank M FM Qi Lu L

Hypertension (Dallas, Tex. : 1979) 20191028 6

High blood pressure (BP) is closely related to obesity, and weight loss lowers BP. Evidence has shown considerable interpersonal variation of changes in BP among people experiencing weight loss, and such variation might be partly determined by genetic factors. We assessed the changes in systolic and diastolic BP (SBP/DBP) among 692 participants randomly assigned to 1 of 4 diets varying in macronutrient content for 2 years. Two separate polygenic scores (SBP/DBP-PGS derived from 52/50 single nucl ...[more]

PMID: 31656094

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Project description:To examine associations between sleep disturbance and changes in weight and body composition and the mediating role of changes of appetite and food cravings in the Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) 2-year weight-loss diet intervention trial, this study included 810 overweight or obese individuals with baseline sleep disturbance assessment who were randomly assigned one of four diets varying in macronutrient composition. Changes in body weight and fat distribution were assessed by DEXA and computed tomography during the 2-year intervention. Participants were asked to provide sleep disturbance levels (no, slight, moderate, or great) at baseline and to recall their sleep disturbances since last visit at 6, 12, 18, and 24 months. Weight loss during the first 6 months was followed by 1.5 years of steady weight regain. Participants with greater sleep disturbance from baseline to 6 months showed significant losses of body weight (Ptrend <0.001) and waist circumference (Ptrend = 0.002) at 6 months, after multivariate adjustment. Compared with individuals without sleep disturbance at all from baseline to 6 months, those with slight, moderate, or great sleep disturbance showed an elevated risk of failure to lose weight (-5% or more loss) at 6 months, when the maximum weight loss was achieved, with an odds ratio of 1.24 (95% CI 0.87, 1.78), 1.27 (95% CI 0.75, 2.13), or 3.12 (95% CI 1.61, 6.03), respectively. In addition, we observed that the repeatedly measured levels of sleep disturbance over 2 years were inversely associated with the overall weight loss rate (weight changes per 6 months) (Ptrend <0.001). Further, sleep disturbances during weight loss from baseline to 6 months and weight regain from 6 months to 24 months were significantly predictive of total fat, total fat mass percent, and trunk fat percent changes during the 2 years. Our results also indicated that food cravings for carbohydrates/starches, fast food fats, and sweets; cravings, prospective consumption, hunger of appetite measurements; and dietary restraint, disinhibition, and hunger subscales measured at 6 months significantly mediated the effects of sleep disturbance on weight loss. In conclusion, our results suggested that more severe sleep disturbance during weight loss was associated with an elevated risk of failure to lose weight during the dietary intervention. Food cravings and eating behaviors may partly mediate these associations.

Project description:BackgroundThioredoxin Interacting Protein (TXNIP) functions as a master regulator for glucose homeostasis. Hypomethylation at the 5'-cytosine-phosphate-guanine-3' (CpG) site cg19693031 of TXNIP has been consistently related to islet dysfunction, hyperglycemia, and type 2 diabetes. DNA methylation (DNAm) may reveal the missing mechanistic link between obesity and type 2 diabetes. We hypothesize that baseline DNAm level at TXNIP in blood may be associated with glycemic traits and their changes in response to weight-loss diet interventions.MethodsWe included 639 adult participants with overweight or obesity, who participated in a 2-year randomized weight-loss diet intervention. Baseline blood DNAm levels were profiled by high-resolution methylC-capture sequencing. We defined the regional DNAm level of TXNIP as the average methylation level over CpGs within 500 bp of cg19693031. Generalized linear regression models were used for main analyses.ResultsWe found that higher regional DNAm at TXNIP was significantly correlated with lower fasting glucose, HbA1c, and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at baseline (P < 0.05 for all). Significant interactions were observed between dietary protein intake and DNAm on changes in insulin (P-interaction = 0.007) and HOMA-IR (P-interaction = 0.009) at 6 months. In participants with the highest tertile of regional DNAm at TXNIP, average protein (15%) intake was associated with a greater reduction in insulin (β: -0.14; 95% CI: -0.24, -0.03; P = 0.011) and HOMA-IR (β: -0.15; 95% CI: -0.26, -0.03; P = 0.014) than high protein (25%) intake, whereas no significant associations were found in those with the lower tertiles (P > 0.05). The interaction was attenuated to be non-significant at 2 years, presumably related to decreasing adherence to the diet intervention.ConclusionsOur data indicate that higher regional DNAm level at TXNIP was significantly associated with better fasting glucose, HbA1c, and HOMA-IR; and people with higher regional DNAm levels benefited more in insulin and HOMA-IR improvement by taking the average-protein weight-loss diet.

Dataset Information

Genetic Susceptibility, Dietary Protein Intake, and Changes of Blood Pressure: The POUNDS Lost Trial.

Publications

Genetic Susceptibility, Dietary Protein Intake, and Changes of Blood Pressure: The POUNDS Lost Trial.

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