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The risk of consequent nephropathy following initial weight loss in diabetic patients treated with sodium glucose cotransporter 2 inhibitors.
Chan, YH, Chen, SW, Chao, TF, Kao, YW, Huang, CY, Chu, PH
Cardiovascular diabetology. 2021;(1):167
Abstract
BACKGROUND There is a controversy over the association between obesity and the risk of renal events in patients with type 2 diabetes mellitus (T2DM). Furthermore, whether body weight (BW) loss following sodium glucose cotransporter 2 inhibitor (SGLT2i) treatment associated with risk of adverse renal events is unknown. METHODS We used medical data from a multi-center healthcare provider in Taiwan, enrolling 8992 T2DM patients with a baseline/following-up BW data available after around 12 weeks of SGLT2i treatment, from June 1, 2016 to December 31, 2018. Patients were followed up until the occurrence of composite renal outcome (estimated glomerular filtration rate decline > 40% or end-stage kidney disease) or the end of study period, whichever occurred first. RESULTS Participants were divided into six baseline BMI categories: < 18.5 (n = 55); 18.5-22.9 (n = 985); 23.0-24.9 (n = 1389); 25.0-29.9 (n = 3941); 30.0-34.9 (n = 1973); and ≥ 35.0 kg/m2 (n = 649). There were 38.9%, 23.5%, 24.7%, 8.4%, 2.7%, and 1.8% of patients experienced no-BW loss, initial BW loss of 0.0-2.4%, 2.5-4.9%, 5.0-7.4%, 7.5-9.9%, and ≥ 10.0%, associated with SGLT2i treatment, respectively. Compared with patients with normal BMI (BMI: 18.5-22.9 kg/m2), underweight (BMI: < 18.5 kg/m2) was associated with a higher risk of composite renal outcome (adjusted hazard ratio (aHR) [95% confidence intervals (CI)]: 2.17; [1.16-4.04]), whereas pre-obese (BMI: 25.0-29.9 kg/m2) associated with the lowest risk of composite renal outcome (0.52; [0.40-0.68]) after multivariate adjustment. Compared with those without BW loss after SGLT2i treatment, BW loss of 0.0-2.4% (0.55; [0.43-0.70]) and 2.5-4.9% (0.78; [0.63-0.98]) were associated with a lower risk, whereas BW loss ≥ 10.0% associated with a higher risk of composite renal outcome (1.61; [1.06-2.46]) after multivariate adjustment. CONCLUSION A modest BW loss of 0-5% associated with SGLT2i treatment was associated with a favorable renal outcome. Caution should be taken for whom are underweight at baseline or have a pronounced BW loss ≥ 10.0% associated with SGLT2i treatment, which was associated with a worse renal outcome.
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Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial.
Rubino, D, Abrahamsson, N, Davies, M, Hesse, D, Greenway, FL, Jensen, C, Lingvay, I, Mosenzon, O, Rosenstock, J, Rubio, MA, et al
JAMA. 2021;(14):1414-1425
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Abstract
IMPORTANCE The effect of continuing vs withdrawing treatment with semaglutide, a glucagon-like peptide 1 receptor agonist, on weight loss maintenance in people with overweight or obesity is unknown. OBJECTIVE To compare continued once-weekly treatment with subcutaneous semaglutide, 2.4 mg, with switch to placebo for weight maintenance (both with lifestyle intervention) in adults with overweight or obesity after a 20-week run-in with subcutaneous semaglutide titrated to 2.4 mg weekly. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind, 68-week phase 3a withdrawal study conducted at 73 sites in 10 countries from June 2018 to March 2020 in adults with body mass index of at least 30 (or ≥27 with ≥1 weight-related comorbidity) and without diabetes. INTERVENTIONS A total of 902 participants received once-weekly subcutaneous semaglutide during run-in. After 20 weeks (16 weeks of dose escalation; 4 weeks of maintenance dose), 803 participants (89.0%) who reached the 2.4-mg/wk semaglutide maintenance dose were randomized (2:1) to 48 weeks of continued subcutaneous semaglutide (n = 535) or switched to placebo (n = 268), plus lifestyle intervention in both groups. MAIN OUTCOMES AND MEASURES The primary end point was percent change in body weight from week 20 to week 68; confirmatory secondary end points were changes in waist circumference, systolic blood pressure, and physical functioning (assessed using the Short Form 36 Version 2 Health Survey, Acute Version [SF-36]). RESULTS Among 803 study participants who completed the 20-week run-in period (with a mean weight loss of 10.6%) and were randomized (mean age, 46 [SD, 12] years; 634 [79%] women; mean body weight, 107.2 kg [SD, 22.7 kg]), 787 participants (98.0%) completed the trial and 741 (92.3%) completed treatment. With continued semaglutide, mean body weight change from week 20 to week 68 was -7.9% vs +6.9% with the switch to placebo (difference, -14.8 [95% CI, -16.0 to -13.5] percentage points; P < .001). Waist circumference (-9.7 cm [95% CI, -10.9 to -8.5 cm]), systolic blood pressure (-3.9 mm Hg [95% CI, -5.8 to -2.0 mm Hg]), and SF-36 physical functioning score (2.5 [95% CI, 1.6-3.3]) also improved with continued subcutaneous semaglutide vs placebo (all P < .001). Gastrointestinal events were reported in 49.1% of participants who continued subcutaneous semaglutide vs 26.1% with placebo; similar proportions discontinued treatment because of adverse events with continued semaglutide (2.4%) and placebo (2.2%). CONCLUSIONS AND RELEVANCE Among adults with overweight or obesity who completed a 20-week run-in period with subcutaneous semaglutide, 2.4 mg once weekly, maintaining treatment with semaglutide compared with switching to placebo resulted in continued weight loss over the following 48 weeks. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03548987.
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Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial.
Wadden, TA, Bailey, TS, Billings, LK, Davies, M, Frias, JP, Koroleva, A, Lingvay, I, O'Neil, PM, Rubino, DM, Skovgaard, D, et al
JAMA. 2021;(14):1403-1413
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IMPORTANCE Weight loss improves cardiometabolic risk factors in people with overweight or obesity. Intensive lifestyle intervention and pharmacotherapy are the most effective noninvasive weight loss approaches. OBJECTIVE To compare the effects of once-weekly subcutaneous semaglutide, 2.4 mg vs placebo for weight management as an adjunct to intensive behavioral therapy with initial low-calorie diet in adults with overweight or obesity. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind, parallel-group, 68-week, phase 3a study (STEP 3) conducted at 41 sites in the US from August 2018 to April 2020 in adults without diabetes (N = 611) and with either overweight (body mass index ≥27) plus at least 1 comorbidity or obesity (body mass index ≥30). INTERVENTIONS Participants were randomized (2:1) to semaglutide, 2.4 mg (n = 407) or placebo (n = 204), both combined with a low-calorie diet for the first 8 weeks and intensive behavioral therapy (ie, 30 counseling visits) during 68 weeks. MAIN OUTCOMES AND MEASURES The co-primary end points were percentage change in body weight and the loss of 5% or more of baseline weight by week 68. Confirmatory secondary end points included losses of at least 10% or 15% of baseline weight. RESULTS Of 611 randomized participants (495 women [81.0%], mean age 46 years [SD, 13], body weight 105.8 kg [SD, 22.9], and body mass index 38.0 [SD, 6.7]), 567 (92.8%) completed the trial, and 505 (82.7%) were receiving treatment at trial end. At week 68, the estimated mean body weight change from baseline was -16.0% for semaglutide vs -5.7% for placebo (difference, -10.3 percentage points [95% CI, -12.0 to -8.6]; P < .001). More participants treated with semaglutide vs placebo lost at least 5% of baseline body weight (86.6% vs 47.6%, respectively; P < .001). A higher proportion of participants in the semaglutide vs placebo group achieved weight losses of at least 10% or 15% (75.3% vs 27.0% and 55.8% vs 13.2%, respectively; P < .001). Gastrointestinal adverse events were more frequent with semaglutide (82.8%) vs placebo (63.2%). Treatment was discontinued owing to these events in 3.4% of semaglutide participants vs 0% of placebo participants. CONCLUSIONS AND RELEVANCE Among adults with overweight or obesity, once-weekly subcutaneous semaglutide compared with placebo, used as an adjunct to intensive behavioral therapy and initial low-calorie diet, resulted in significantly greater weight loss during 68 weeks. Further research is needed to assess the durability of these findings. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03611582.
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Health wearable devices for weight and BMI reduction in individuals with overweight/obesity and chronic comorbidities: systematic review and network meta-analysis.
McDonough, DJ, Su, X, Gao, Z
British journal of sports medicine. 2021;(16):917-925
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OBJECTIVE To analyse the comparative effectiveness of different health wearable-based physical activity (PA) promotion intervention strategies against each other and control for reducing body weight and body mass index (BMI) in individuals with overweight/obesity and chronic comorbidities. DESIGN Systematic review and network meta-analysis (PROSPERO identifier: CRD42020158191). DATA SOURCES We performed two independent searches from December 2019 to September 2020 in PubMed, MEDLINE, Scopus, Web of Science, Central Register of Controlled Trials, EMBASE and PsycINFO databases for articles published in English between 2007 and 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES Inclusion criteria were based on the PICOS framework. We included randomised controlled trials of health wearable-based interventions using two or more PA intervention arms/strategies and compared their effects on participants' body weight (kg) and BMI (kg/m2) with a control group. Data were analysed using a Bayesian network meta-analysis to directly and indirectly compare the effects of the six different intervention strategies (comparators). The six comparators were: (1) control group (ie, usual care, waitlist); (2) comparison group (ie, traditional, non-health wearable PA interventions); (3) commercial health wearable-only intervention (eg, Fitbit, Polar M400); (4) research grade health wearable-only intervention (ie, accelerometers or pedometers); (5) multicomponent commercial health wearable intervention (eg, Fitbit + nutrition counselling); and (6) multicomponent research grade health wearable intervention. The results were reported as standardised mean differences (SMDs) with associated 95% credible intervals (CrIs). RESULTS From 641 screened records, 31 studies were included. For body weight reduction in individuals with overweight/obesity and chronic comorbidities, accelerometer/pedometer-only (SMD -4.44, 95% CrI -8.94 to 0.07) and commercial health wearable-only (SMD -2.76, 95% CrI -4.80 to -0.81) intervention strategies were the most effective compared with the three other treatments and control. For BMI reduction, multicomponent accelerometer/pedometer (SMD -3.43, 95% CrI -4.94 to -2.09) and commercial health wearable-only (SMD -1.99, 95% CrI -4.95 to 0.96) intervention strategies were the most effective compared with the other four conditions. CONCLUSION Health wearable devices are effective intervention tools/strategies for reducing body weight and BMI in individuals with overweight/obesity and chronic comorbidities.
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Flexible vs. rigid dieting in resistance-trained individuals seeking to optimize their physiques: A randomized controlled trial.
Conlin, LA, Aguilar, DT, Rogers, GE, Campbell, BI
Journal of the International Society of Sports Nutrition. 2021;(1):52
Abstract
BACKGROUND The purpose of this study was to compare a flexible vs. rigid diet on weight loss and subsequent weight regain in resistance-trained (RT) participants in a randomized, parallel group design. METHODS Twenty-three males and females (25.6 ± 6.1 yrs; 170 ± 8.1 cm; 75.4 ± 10.3 kg) completed the 20-week intervention (consisting of a 10-week diet phase and a 10-week post-diet phase). Participants were randomized to a flexible diet (FLEX) comprised of non-specific foods or a rigid diet (RIGID) comprised of specific foods. Participants adhered to an ~20%kcal reduction during the first 10-weeks of the intervention and were instructed to eat ad libitum for the final 10-weeks. Body composition and resting metabolic rate were assessed 5 times: (baseline, 5, 10 [end of diet phase], 16, and 20 weeks). RESULTS During the 10-week diet phase, both groups significantly reduced bodyweight (FLEX: baseline = 76.1 ± 8.4kg, post-diet = 73.5 ± 8.8 kg, ▲2.6 kg; RIGID baseline = 74.9 ± 12.2 kg, post-diet = 71.9 ± 11.7 kg, ▲3.0 kg, p < 0.001); fat mass (FLEX: baseline = 14.8 ± 5.7 kg, post-diet = 12.5 ± 5.0 kg, ▲2.3 kg; RIGID baseline = 18.1 ± 6.2 kg, post-diet = 14.9 ± 6.5 kg, ▲3.2 kg p < 0.001) and body fat% (FLEX: baseline = 19.4 ± 8.5%, post-diet = 17.0 ± 7.1%, ▲2.4%; RIGID baseline = 24.0 ± 6.2%, post-diet = 20.7 ± 7.1%, ▲3.3%; p < 0.001). There were no significant differences between the two groups for any variable during the diet phase. During the post-diet phase, a significant diet x time interaction (p < 0.001) was observed for FFM with the FLEX group gaining a greater amount of FFM (+1.7 kg) in comparison with the RIGID group (-0.7 kg). CONCLUSIONS A flexible or rigid diet strategy is equally effective for weight loss during a caloric restriction diet in free-living, RT individuals. While post-diet FFM gains were greater in the FLEX group, there were no significant differences in the amount of time spent in resistance and aerobic exercise modes nor were there any significant differences in protein and total caloric intakes between the two diet groups. In the absence of a clear physiological rationale for increases in FFM, in addition to the lack of a standardized diet during the post-diet phase, we refrain from attributing the increases in FFM in the FLEX group to their diet assignment during the diet phase of the investigation. We recommend future research investigate additional physiological and psychological effects of flexible diets and weight regain in lean individuals.
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Liraglutide vs. lixisenatide in obese type 2 diabetes mellitus patients: What effect should we expect in routine clinical practice?
Moreno-Fernandez, J, Garcia-Seco, JA, Seco Segura, AM, Garcia-Seco, F, Rozas Moreno, PJ, Aguirre Sanchez-Covisa, M
Primary care diabetes. 2020;(1):68-74
Abstract
AIM: Liraglutide and lixisenatide improved glycemic control, weight and cardiovascular risk factors (CVRF) in type 2 diabetes mellitus (T2DM) patients. Our objective was to analyze clinical efficacy and safety differences in routine clinical practice. METHODS A 24-week prospective observational study to compare the effect of liraglutide versus lixisenatide in obese T2DM patients in routine clinical practice. The main objective was to analyze between-group glycosylated hemoglobin (HbA1c) differences at the end of the study. Secondary objectives included differences in body weight, other CVRF, changes in medication, side effects, satisfaction and safety. RESULTS A total of 100 patients (50 liraglutide, 50 lixisenatide) were included. Both groups experienced a decrease in HbA1c values (liraglutide, -1.4%, CI 95% -2, -0.8, P < 0.001 vs. lixisenatide, -0.8%, 95% CI -1.2, -0.5, P < 0.001). No differences were found in final HbA1c values between both groups (liraglutide 7.3 ± 0.9% vs. lixisenatide 7.2 ± 1.5%, P = 0.7). We did not detect between groups differences in anthropometric variables or CVRF at the study end. A lower proportion of patients received treatment with a maximum dose of liraglutide compared with lixisenatide (27% vs. 95%, P < 0.001). In contrast, a greater percentage of patients in the lixisenatide group than in liraglutide group (29% vs. 9%, P = 0.026) intensified treatment by the addition of sodium-glucose transporter type 2 inhibitors. Adverse events were less frequently reported in liraglutide treated patients compared with lixisentatide (80% vs. 96%, P = 0.014). No serious adverse events were detected. CONCLUSIONS These results confirm the efficacy and safety of liraglutide and lixisenatide in routine clinical practice. Moreover, a different therapeutic effect between liraglutide and lixisenatide was detected.
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Efficacy of the treatment with dapagliflozin and metformin compared to metformin monotherapy for weight loss in patients with class III obesity: a randomized controlled trial.
Ferreira-Hermosillo, A, Molina-Ayala, MA, Molina-Guerrero, D, Garrido-Mendoza, AP, Ramírez-Rentería, C, Mendoza-Zubieta, V, Espinosa, E, Mercado, M
Trials. 2020;(1):186
Abstract
BACKGROUND Mexico has one of the highest prevalence rates of obesity worldwide. New pharmacological strategies that focus on people with class III obesity are required. Metformin and dapagliflozin are two drugs approved for the treatment of diabetes. Beyond its effects on glucose, metformin has been suggested by some studies to result in weight loss. Therapy with dapagliflozin is associated with a mild but sustained weight loss in patients with diabetes. The primary outcome of the study is to determine if the combined treatment with dapagliflozin and metformin is more effective than monotherapy with metformin for weight loss in patients with class III obesity and prediabetes or diabetes who are awaiting bariatric surgery (including those patients who do have surgery). We also aimed to assess the effect of this combined treatment on waist circumference, triglycerides, blood pressure, and inflammatory cytokines. METHODS This randomized phase IV clinical trial will include patients with diabetes or prediabetes who are between the ages of 18 and 60 years and exhibit grade III obesity (defined as body mass index ≥ 40 kg/m2). Patients using insulin will be excluded. Subjects will be randomized to one of two groups as follows: 1) metformin tablets 850 mg PO bid or 2) metformin tablets 850 mg PO bid plus dapagliflozin tablets 10 mg PO qd. The sample size required is 108 patients, which allows for a 20% dropout rate: 54 patients in the metformin group and 54 in the metformin/dapagliflozin group. All participants will receive personalized nutritional advice during the study. A run-in period of one month will be used to assess tolerance and adherence to treatment regimens. Anthropometric and biochemical variables will be recorded at baseline and at 1, 3, 6, and 12 months. A serum sample to determine glucagon, ghrelin, adiponectin, resistin, interleukin 6, and interleukin 10 will be collected at baseline and before surgery, or at 12 months (whatever happens first). Adherence to treatment and adverse and secondary events will be recorded throughout the study. An intention-to-treat analysis will be used. DISCUSSION Forty-six percent of the patients in our Obesity Clinic have been diagnosed with prediabetes (32%) or diabetes (14%). The use of dapagliflozin in this population could improve weight loss and other cardiovascular factors. This effect could be translated into less time before undergoing bariatric surgery and better control of associated comorbidities. TRIAL REGISTRATION Clinicaltrials.gov, ID: NCT03968224. Retrospectively registered on May 29, 2019.
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Effect of two different dietary fatty acid profiles and variant rs266729 in ADIPOQ on weight loss and adiponectin concentrations.
de Luis, DA, Primo, D, Izaola, O, Aller, R
Endocrinologia, diabetes y nutricion. 2020;(6):374-382
Abstract
BACKGROUND The role of ADIPOQ gene rs266729 variants on weight loss after a dietary intervention are still unclear. OBJECTIVE To analyze the effects of the ADIPOQ gene rs266729 variant n weight loss, cardiovascular risk factors, and adiponectin levels after two hypocaloric diets with different dietary fatty profiles. DESIGN A population of 362 obese patients was enrolled in a randomized clinical trial with two diets (Diet M, monounsaturated fat-enriched diet, and Diet P, polyunsaturated-fat enriched diet). Anthropometric measurements, an assessment of nutritional intake, and biochemical tests were performed at baseline and after 12 weeks. RESULTS Weight loss was similar with both diets. After Diet M, only subjects with CC genotype showed significant improvements in total cholesterol (CC vs. CG±GG) (-9.0±1.1mU/L vs. -4.5±2.4mg/dL, p=0.01), LDL cholesterol (-6.0±1.1mg/dL vs. -3.0±0.9mg/dL, p=0.03), glucose (-4.7±1.1mg/dL vs. -0.6±0.5mg/dL, p=0.01), and insulin levels (-2.6±1.0mU/L vs. -0.7±0.3mU/L, p=0.02) and in HOMA-IR (-0.5±0.2 units vs. -0.2±0.4 units, p=0.03). The same improvement was reported after Diet P in all parameters, including total cholesterol (CC vs. CG±GG) (-8.0±1.2mU/L vs. -2.1±1.4mg/dL, p=0.02), LDL cholesterol (-7.3±1.2mg/dL vs. -2.1±0.8mg/dL, p=0.02), glucose (-3.2±0.1mg/dL vs. -0.2±0.5mg/dL, p=0.01), and insulin levels (-2.5±1.0mU/L vs. -1±0.6mU/L, p=0.02) and HOMA-IR (-0.5±0.1 units vs. -0.3±0.4 units, p=0.02). Only subjects with CC genotype showed significant increases in adiponectin levels after both diets: (Diet M: 10.3±2.0ng/dL vs. Diet P: 9.3±2.9ng/dL, p=0.43). CONCLUSION The CC genotype of ADIPOQ gene rs266729 variant is associated to increased adiponectin levels and decreases in LDL cholesterol, glucose, insulin, and HOMA-IR levels after weight loss.
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Comparative Effects of Medical Versus Surgical Weight Loss on Body Composition: a Pilot Randomized Trial.
Varma, S, Lee, CJ, Brown, TT, Maruthur, NM, Schweitzer, M, Magnuson, T, Kamel, I, Clark, JM
Obesity surgery. 2019;(8):2503-2510
Abstract
OBJECTIVE Bariatric surgery leads to more rapid and greater weight loss (WL) compared to medical weight loss (MWL), but the differences in body composition (BC) changes for these modalities remain unclear. Due to the known health risks associated with central adiposity, we compared the changes in regional distribution of fat mass (FM) and lean mass (LM) after surgical versus MWL. METHODS In this 1:1:1 randomized trial among 15 persons with type 2 diabetes and body mass index (BMI) 30-39.9 kg/m2, we compared changes in BC, by dual-energy X-ray absorptiometry and abdominal computerized tomography, at time of 10%WL or 9 months after intervention (whichever came first). Participants underwent MWL, adjustable gastric banding (AGB), or Roux-en-Y gastric bypass (RYGB). Non-parametric tests evaluated BC differences (FM, LM, and visceral adipose tissue [VAT]) within and across all three arms and between pair-wise comparisons. RESULTS Twelve female participants (75% African American) completed the study. Patient age, BMI, and baseline anthropometric characteristics were similar across study arms. AGB lost more LM (MWL - 5.2%, AGB - 10.3%, p = 0.021) and VAT (MWL + 10.9%, AGB - 28.0%, p = 0.049) than MWL. RYGB tended to lose more VAT (MWL +10.9%, RYGB - 20.2%, p = 0.077) than MWL. AGB tended to lose more LM than RYGB (AGB - 12.38%, RYGB - 7.29%, p = 0.15). CONCLUSIONS At similar WL, AGB lost more LM and VAT than MWL; RYGB similarly lost more VAT. Given the metabolic benefits of reducing VAT and retaining LM, larger studies should confirm the changes in BC after surgical versus medical WL. CLINICAL TRIAL REGISTRATION NCTDK089557 - ClinicalTrials.gov.
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Genetic Susceptibility, Dietary Protein Intake, and Changes of Blood Pressure: The POUNDS Lost Trial.
Sun, D, Zhou, T, Li, X, Heianza, Y, Liang, Z, Bray, GA, Sacks, FM, Qi, L
Hypertension (Dallas, Tex. : 1979). 2019;(6):1460-1467
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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 (Pinteraction=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.