Associations of obesity phenotypes with weight change, cardiometabolic benefits, and type 2 diabetes incidence during a lifestyle intervention: results from the PREVIEW study.

BACKGROUND/OBJECTIVES: Some individuals with overweight/obesity may be relatively metabolically healthy (MHO) and have a lower risk of cardiovascular disease than those with metabolically unhealthy overweight/obesity (MUO). We aimed to compare changes in body weight and cardiometabolic risk factors and type 2 diabetes incidence during a lifestyle intervention between individuals with MHO vs MUO. METHODS: This post-hoc analysis included 1012 participants with MHO and 1153 participants with MUO at baseline in the randomized trial PREVIEW. Participants underwent an eight-week low-energy diet phase followed by a 148-week lifestyle-based weight-maintenance intervention. Adjusted linear mixed models and Cox proportional hazards regression models were used. RESULTS: There were no statistically significant differences in weight loss (%) between participants with MHO vs MUO over 156 weeks. At the end of the study, weight loss was 2.7% (95% CI, 1.7%-3.6%) in participants with MHO and 3.0% (2.1%-4.0%) in those with MUO. After the low-energy diet phase, participants with MHO had smaller decreases in triglyceride (mean difference between MHO vs MUO 0.08 mmol·L-1 [95% CI, 0.04-0.12]; P < 0.001) but similar reductions in fasting glucose and HOMA-IR than those with MUO. However, at the end of weight maintenance, those with MHO had greater reductions in triglyceride (mean difference -0.08 mmol·L-1 [-0.12--0.04]; P < 0.001), fasting glucose, 2-hour glucose (difference -0.28 mmol·L-1 [-0.41--0.16]; P < 0.001), and HOMA-IR than those with MUO. Participants with MHO had smaller decreases in diastolic blood pressure and HbA1c and greater decreases in HDL cholesterol after weight loss than those with MUO, whereas the statistically significant differences disappeared at the end of weight maintenance. Participants with MHO had lower 3-year type 2 diabetes incidence than those with MUO (adjusted hazard ratio 0.37 [0.20-0.66]; P < 0.001). CONCLUSIONS: Individuals with MUO had greater improvements in some cardiometabolic risk factors during the low-energy diet phase, but had smaller improvements during long-term lifestyle intervention than those with MHO.

Age- and sex-specific effects of a long-term lifestyle intervention on body weight and cardiometabolic health markers in adults with prediabetes: results from the diabetes prevention study PREVIEW.

AIMS/HYPOTHESIS: Lifestyle interventions are the first-line treatment option for body weight and cardiometabolic health management. However, whether age groups or women and men respond differently to lifestyle interventions is under debate. We aimed to examine age- and sex-specific effects of a low-energy diet (LED) followed by a long-term lifestyle intervention on body weight, body composition and cardiometabolic health markers in adults with prediabetes (i.e. impaired fasting glucose and/or impaired glucose tolerance). METHODS: This observational study used longitudinal data from 2223 overweight participants with prediabetes in the multicentre diabetes prevention study PREVIEW. The participants underwent a LED-induced rapid weight loss (WL) period followed by a 3 year lifestyle-based weight maintenance (WM) intervention. Changes in outcomes of interest in prespecified age (younger: 25-45 years; middle-aged: 46-54 years; older: 55-70 years) or sex (women and men) groups were compared. RESULTS: In total, 783 younger, 319 middle-aged and 1121 older adults and 1503 women and 720 men were included in the analysis. In the available case and complete case analyses, multivariable-adjusted linear mixed models showed that younger and older adults had similar weight loss after the LED, whereas older adults had greater sustained weight loss after the WM intervention (adjusted difference for older vs younger adults -1.25% [95% CI -1.92, -0.58], p<0.001). After the WM intervention, older adults lost more fat-free mass and bone mass and had smaller improvements in 2 h plasma glucose (adjusted difference for older vs younger adults 0.65 mmol/l [95% CI 0.50, 0.80], p<0.001) and systolic blood pressure (adjusted difference for older vs younger adults 2.57 mmHg [95% CI 1.37, 3.77], p<0.001) than younger adults. Older adults had smaller decreases in fasting and 2 h glucose, HbA1c and systolic blood pressure after the WM intervention than middle-aged adults. In the complete case analysis, the above-mentioned differences between middle-aged and older adults disappeared, but the direction of the effect size did not change. After the WL period, compared with men, women had less weight loss (adjusted difference for women vs men 1.78% [95% CI 1.12, 2.43], p<0.001) with greater fat-free mass and bone mass loss and smaller improvements in HbA1c, LDL-cholesterol and diastolic blood pressure. After the WM intervention, women had greater fat-free mass and bone mass loss and smaller improvements in HbA1c and LDL-cholesterol, while they had greater improvements in fasting glucose, triacylglycerol (adjusted difference for women vs men -0.08 mmol/l [-0.11, -0.04], p<0.001) and HDL-cholesterol. CONCLUSIONS/INTERPRETATION: Older adults benefited less from a lifestyle intervention in relation to body composition and cardiometabolic health markers than younger adults, despite greater sustained weight loss. Women benefited less from a LED followed by a lifestyle intervention in relation to body weight and body composition than men. Future interventions targeting older adults or women should take prevention of fat-free mass and bone mass loss into consideration. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT01777893.

The PREVIEW intervention study: Results from a 3-year randomized 2 x 2 factorial multinational trial investigating the role of protein, glycaemic index and physical activity for prevention of type 2 diabetes.

AIM: To compare the impact of two long-term weight-maintenance diets, a high protein (HP) and low glycaemic index (GI) diet versus a moderate protein (MP) and moderate GI diet, combined with either high intensity (HI) or moderate intensity physical activity (PA), on the incidence of type 2 diabetes (T2D) after rapid weight loss. MATERIALS AND METHODS: A 3-year multicentre randomized trial in eight countries using a 2 x 2 diet-by-PA factorial design was conducted. Eight-week weight reduction was followed by a 3-year randomized weight-maintenance phase. In total, 2326 adults (age 25-70 years, body mass index ≥ 25 kg/m2 ) with prediabetes were enrolled. The primary endpoint was 3-year incidence of T2D analysed by diet treatment. Secondary outcomes included glucose, insulin, HbA1c and body weight. RESULTS: The total number of T2D cases was 62 and the cumulative incidence rate was 3.1%, with no significant differences between the two diets, PA or their combination. T2D incidence was similar across intervention centres, irrespective of attrition. Significantly fewer participants achieved normoglycaemia in the HP compared with the MP group (P < .0001). At 3 years, normoglycaemia was lowest in HP-HI (11.9%) compared with the other three groups (20.0%-21.0%, P < .05). There were no group differences in body weight change (-11% after 8-week weight reduction; -5% after 3-year weight maintenance) or in other secondary outcomes. CONCLUSIONS: Three-year incidence of T2D was much lower than predicted and did not differ between diets, PA or their combination. Maintaining the target intakes of protein and GI over 3 years was difficult, but the overall protocol combining weight loss, healthy eating and PA was successful in markedly reducing the risk of T2D. This is an important clinically relevant outcome.

High Compared with Moderate Protein Intake Reduces Adaptive Thermogenesis and Induces a Negative Energy Balance during Long-term Weight-Loss Maintenance in Participants with Prediabetes in the Postobese State: A PREVIEW Study.

BACKGROUND: Weight loss has been associated with adaptations in energy expenditure. Identifying factors that counteract these adaptations are important for long-term weight loss and weight maintenance. OBJECTIVE: The aim of this study was to investigate whether increased protein/carbohydrate ratio would reduce adaptive thermogenesis (AT) and the expected positive energy balance (EB) during weight maintenance after weight loss in participants with prediabetes in the postobese state. METHODS: In 38 participants, the effects of 2 diets differing in protein/carbohydrate ratio on energy expenditure and respiratory quotient (RQ) were assessed during 48-h respiration chamber measurements ∼34 mo after weight loss. Participants consumed a high-protein (HP) diet (n = 20; 13 women/7 men; age: 64.0 ± 6.2 y; BMI: 28.9 ± 4.0 kg/m 2) with 25:45:30% or a moderate-protein (MP) diet (n = 18; 9 women/9 men; age: 65.1 ± 5.8 y; BMI: 29.0 ± 3.8 kg/m 2) with 15:55:30% of energy from protein:carbohydrate:fat. Predicted resting energy expenditure (REEp) was calculated based on fat-free mass and fat mass. AT was assessed by subtracting measured resting energy expenditure (REE) from REEp. The main outcomes included differences in components of energy expenditure, substrate oxidation, and AT between groups. RESULTS: EB (MP = 0.2 ± 0.9 MJ/d; HP = -0.5 ± 0.9 MJ/d) and RQ (MP = 0.84 ± 0.02; HP = 0.82 ± 0.02) were reduced and REE (MP: 7.3 ± 0.2 MJ/d compared with HP: 7.8 ± 0.2 MJ/d) was increased in the HP group compared with the MP group (P < 0.05). REE was not different from REEp in the HP group, whereas REE was lower than REEp in the MP group (P < 0.05). Furthermore, EB was positively related to AT (rs = 0.74; P < 0.001) and RQ (rs = 0.47; P < 0.01) in the whole group of participants. CONCLUSIONS: In conclusion, an HP diet compared with an MP diet led to a negative EB and counteracted AT ∼34 mo after weight loss, in participants with prediabetes in the postobese state. These results indicate the relevance of compliance to an increased protein/carbohydrate ratio for long-term weight maintenance after weight loss. The trial was registered at clinicaltrials.gov as NCT01777893.

Role of Eating Behavior and Stress in Maintenance of Dietary Changes During the PREVIEW Intervention.

OBJECTIVE: To examine whether eating behavior and perceived stress predict the maintenance of self-reported dietary change and adherence to dietary instructions during an intervention. DESIGN: A secondary analysis of the behavior maintenance stage (6-36 months) of the 3-year PREVIEW intervention (PREVention of diabetes through lifestyle Intervention and population studies in Europe and around the World). PARTICIPANTS: Adults (n = 1,311) with overweight and prediabetes at preintervention baseline. VARIABLES MEASURED: Eating behavior (Three-Factor Eating Questionnaire), stress (Perceived Stress Scale), and dietary intake (4-day food records on 4 occasions) were reported. ANALYSIS: Associations between predictors and dietary outcomes were examined with linear mixed-effects models for repeated measurements. RESULTS: Eating behaviors and stress at 6 months did not predict the subsequent change in dietary outcomes, but higher cognitive restraint predicted lower energy intake, and both higher disinhibition and hunger predicted higher energy intake during the following behavior maintenance stage. In addition, higher disinhibition predicted higher saturated fat intake and lower fiber intake, and higher hunger predicted lower fiber intake. Stress was not associated with energy intake or dietary quality. Eating behaviors and stress were not consistently associated with adherence to dietary instructions. CONCLUSIONS AND IMPLICATIONS: Higher cognitive restraint predicted lower energy intake (food quantity), but disinhibition and hunger were also associated with dietary quality.

Influence of the gut microbiota on satiety signaling.

Recent studies show a link between the gut microbiota and the regulation of satiety and energy intake, processes that contribute to the development and pathophysiology of metabolic diseases. However, this link is predominantly established in animal and in vitro studies, whereas human intervention studies are scarce. In this review we focus on recent evidence linking satiety and the gut microbiome, with specific emphasis on gut microbial short-chain fatty acids (SCFAs). Based on a systematic search we provide an overview of human studies linking the intake of prebiotics with gut microbial alterations and satiety signaling. Our outcomes highlight the importance of in-depth examination of the gut microbiota in relation to satiety and provide insights into recent and future studies in this field.

The effect of weight loss on whole-body and tissue-specific insulin sensitivity and hepatic lipid content and composition: SWEET substudy.

OBJECTIVE: This study (1) investigated the effect of weight loss on whole-body and tissue-specific insulin sensitivity and on intrahepatic lipid (IHL) content and composition and (2) investigated the association between weight-loss-induced changes in insulin sensitivity and IHL content in individuals with overweight or obesity. METHODS: In this secondary analysis of the European SWEET project, 50 adults (age 18-65 years) with overweight or obesity (BMI ≥ 25 kg/m2 ) followed a low-energy diet (LED) for 2 months. At baseline and after the LED, body composition (dual-energy x-ray absorptiometry), IHL content and composition (proton magnetic resonance spectroscopy), whole-body insulin sensitivity (Matsuda index), muscle insulin sensitivity index (MISI), and hepatic insulin resistance index (HIRI) were determined (7-point oral glucose tolerance test). RESULTS: The LED reduced body weight (p < 0.001). This was accompanied by increased Matsuda index and reduced HIRI (both p < 0.001) but no change in MISI (p = 0.260). Weight loss decreased IHL content (mean [SEM], 3.9% [0.7%] vs. 1.6% [0.5%], p < 0.001) and the hepatic saturated fatty acid fraction (41.0% [1.5%] vs. 36.6% [1.9%], p = 0.039). The reduced IHL content was associated with an improvement in HIRI (r = 0.402, p = 0.025). CONCLUSIONS: Weight loss decreased IHL content and the hepatic saturated fatty acid fraction. The decrease in IHL content was associated with weight-loss-induced improvement in hepatic insulin sensitivity in individuals with overweight or obesity.

Longer-term soy nut consumption improves vascular function and cardiometabolic risk markers in older adults: Results of a randomized, controlled cross-over trial.

BACKGROUND: Soy foods may contribute to the beneficial health effects of healthy plant-based diets on the risk to develop cardiovascular disease (CVD). However, their effects on vascular function have hardly been studied. OBJECTIVE: To investigate longer-term effects of soy nut consumption on vascular function and cardiometabolic risk markers in healthy older men and women. DESIGN: Twenty-three healthy participants (age: 60-70 years; BMI: 20-30 kg/m2) participated in a randomized, controlled, single-blinded cross-over trial with an intervention (67 g/day of soy nuts providing 25.5 g protein and 174 mg isoflavones) and control period (no nuts) of 16 weeks, separated by eight weeks wash-out. Adults followed the Dutch food-based dietary guidelines. RESULTS: No serious adverse events were reported and the soy nut regime was well tolerated. Body weights remained stable during the whole study. A higher protein (3.1 energy percent [En%]) and a lower carbohydrate intake (2.0 En%) was observed during the intervention period. Total fat intake was comparable, but that of saturated (-1.3 En%), cis-monounsaturated (-1.5 En%) and cis-polyunsaturated fatty acids (+1.9 En%) differed. Serum isoflavone concentrations were higher after the intervention as compared with the control period (daidzein: 127.8 ng/mL; 95% CI: 74.3-181.3 ng/mL; p < 0.001 and genistein: 454.2 ng/mL; 95% CI: 266.6-641.8 ng/mL; p < 0.001). Brachial artery flow-mediated vasodilation was 1.48 percent points (pp; 95% CI: 0.08-2.89 pp; p = 0.040) higher following soy nut intake. The carotid artery reactivity response and arterial stiffness did not differ. Serum LDL-cholesterol was lower (0.17 mmol/L; 95% CI: 0.02-0.32 mmol/L; p = 0.027), while HDL-cholesterol and triacylglycerol concentrations were comparable. Mean arterial pressure (MAP) was lower (3 mmHg; 95% CI: 0-6 mmHg; p = 0.035). CONCLUSIONS: Longer-term soy nut intake as part of a healthy diet improved endothelial function, LDL-cholesterol concentrations and MAP levels, suggesting mechanisms by which an increased soy food intake beneficially affects CVD risk in older adults. Registered under ClinicalTrials.gov Identifier no. NCT03627637.

Protocol for a multicentre, parallel, randomised, controlled trial on the effect of sweeteners and sweetness enhancers on health, obesity and safety in overweight adults and children: the SWEET project.

INTRODUCTION: The aim of this randomised controlled trial (RCT) is to investigate whether prolonged consumption of sweeteners and sweetness enhancers (S&SEs) within a healthy diet will improve weight loss maintenance and obesity-related risk factors and affect safety markers compared with sugar. METHODS AND ANALYSIS: SWEET (S&SEs: prolonged effects on health, obesity and safety) is a 1-year multicentre RCT including at least 330 adults with overweight (18-65 years, body mass index (BMI) >25 kg/m2) and 40 children (6-12 years, BMI-for-age >85th percentile). In an initial 2-month period, adults will consume a low-energy diet with the aim to achieve ≥5% weight loss. Children are advised to consume a generally healthy diet to maintain body weight, thus reducing their BMI-for-age z-score. In the following 10 months, participants will be randomised to follow a healthy ad libitum diet with or without S&SE products. Clinical investigations are scheduled at baseline, after 2, 6 and 12 months. The primary outcomes are body weight for efficacy and gut microbiota composition (in relation to metabolic health) for safety, both in adults. Secondary outcomes include anthropometry, risk markers for type-2 diabetes and cardiovascular diseases, questionnaires including, for example, food preferences, craving and appetite and tests for allergenicity. ETHICS AND DISSEMINATION: The trial protocol has been approved by the following national ethical committees; The research ethics committees of the capital region (Denmark), approval code: H-19040679, The medical ethics committee of the University Hospital Maastricht and Maastricht University (the Netherlands), approval code: NL70977.068.19/METC19-056s, Research Ethics Committee of the University of Navarra (Spain), approval code: 2019.146 mod1, Research Ethics Committee of Harokopio University (Greece), approval code: 1810/18-06-2019. The trial will be conducted in accordance with the Declaration of Helsinki. Results will be published in international peer-reviewed scientific journals regardless of whether the findings are positive, negative or inconclusive. TRIAL REGISTRATION NUMBER: NCT04226911 (Clinicaltrials.gov).

Does the Effect of a 3-Year Lifestyle Intervention on Body Weight and Cardiometabolic Health Differ by Prediabetes Metabolic Phenotype? A Post Hoc Analysis of the PREVIEW Study.

OBJECTIVE: To examine whether the effect of a 3-year lifestyle intervention on body weight and cardiometabolic risk factors differs by prediabetes metabolic phenotype. RESEARCH DESIGN AND METHODS: This post hoc analysis of the multicenter, randomized trial, PREVention of diabetes through lifestyle interventions and population studies In Europe and around the World (PREVIEW), included 1,510 participants with prediabetes (BMI ≥25 kg ⋅ m-2; defined using oral glucose tolerance tests). Of these, 58% had isolated impaired fasting glucose (iIFG), 6% had isolated impaired glucose tolerance (iIGT), and 36% had IFG+IGT; 73% had normal hemoglobin A1c (HbA1c; <39 mmol ⋅ mol-1) and 25% had intermediate HbA1c (39-47 mmol ⋅ mol-1). Participants underwent an 8-week diet-induced rapid weight loss, followed by a 148-week lifestyle-based weight maintenance intervention. Linear mixed models adjusted for intervention arm and other confounders were used. RESULTS: In the available-case and complete-case analyses, participants with IFG+IGT had greater sustained weight loss after lifestyle intervention (adjusted mean at 156 weeks -3.5% [95% CI, -4.7%, -2.3%]) than those with iIFG (mean -2.5% [-3.6%, -1.3%]) relative to baseline (P = 0.011). Participants with IFG+IGT and iIFG had similar cardiometabolic benefits from the lifestyle intervention. The differences in cardiometabolic benefits between those with iIGT and IFG+IGT were minor or inconsistent in different analyses. Participants with normal versus intermediate HbA1c had similar weight loss over 3 years and minor differences in cardiometabolic benefits during weight loss, whereas those with normal HbA1c had greater improvements in fasting glucose, 2-h glucose (adjusted between-group difference at 156 weeks -0.54 mmol ⋅ L-1 [95% CI -0.70, -0.39], P < 0.001), and triglycerides (difference -0.07 mmol ⋅ L-1 [-0.11, -0.03], P < 0.001) during the lifestyle intervention. CONCLUSIONS: Individuals with iIFG and IFG+IGT had similar improvements in cardiometabolic health from a lifestyle intervention. Those with normal HbA1c had greater improvements than those with intermediate HbA1c.

Longer-term soy nut consumption improves cerebral blood flow and psychomotor speed: results of a randomized, controlled crossover trial in older men and women.

BACKGROUND: Effects of soy foods on cerebral blood flow (CBF)-a marker of cerebrovascular function-may contribute to the beneficial effects of plant-based diets on cognitive performance. OBJECTIVES: We aimed to investigate longer-term effects of soy nut consumption on CBF in older adults. Changes in 3 different domains of cognitive performance were also studied. METHODS: Twenty-three healthy participants (age: 60-70 y; BMI: 20-30 kg/m2) participated in a randomized, controlled, single-blinded crossover trial with an intervention (67 g/d of soy nuts providing ∼25.5 g protein and 174 mg isoflavones) and control period (no nuts) of 16 wk, separated by an 8-wk washout period. Adults followed the Dutch food-based dietary guidelines. At the end of each period, CBF was assessed with arterial spin labeling MRI. Psychomotor speed, executive function, and memory were assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB). RESULTS: No serious adverse events were reported, and soy nut intake was well tolerated. Body weights remained stable during the study. Serum isoflavone concentrations increased (daidzein mean difference ± SD: 128 ± 113 ng/mL, P < 0.001; genistein: 454 ± 256 ng/mL, P < 0.001), indicating excellent compliance. Regional CBF increased in 4 brain clusters located in the left occipital and temporal lobes (mean ± SD increase: 11.1 ± 12.4 mL · 100 g-1 · min-1, volume: 11,296 mm3, P < 0.001), bilateral occipital lobe (12.1 ± 15.0 mL · 100 g-1 · min-1, volume: 2632 mm3, P = 0.002), right occipital and parietal lobes (12.7 ± 14.3 mL · 100 g-1 · min-1, volume: 2280 mm3, P = 0.005), and left frontal lobe (12.4 ± 14.5 mL · 100 g-1 · min-1, volume: 2120 mm3, P = 0.009) which is part of the ventral network. These 4 regions are involved in psychomotor speed performance, which improved as the movement time reduced by (mean ± SD) 20 ± 37 ms (P = 0.005). Executive function and memory did not change. CONCLUSIONS: Longer-term soy nut consumption may improve cerebrovascular function of older adults, because regional CBF increased. Effects may underlie observed improvements in psychomotor speed.This trial was registered at clinicaltrials.gov as NCT03627637.

What Is the Profile of Overweight Individuals Who Are Unsuccessful Responders to a Low-Energy Diet? A PREVIEW Sub-study.

This study was performed to evaluate the profile of overweight individuals with pre-diabetes enrolled in PREVIEW who were unable to achieve a body weight loss of ≥8% of the baseline value in response to a 2-month low-energy diet (LED). Their baseline profile reflected potential stress-related vulnerability that predicted a reduced response of body weight to a LED programme. The mean daily energy deficit maintained by unsuccessful weight responders of both sexes was less than the estimated level in successful female (656 vs. 1,299 kcal, p < 0.01) and male (815 vs. 1,659 kcal, p < 0.01) responders. Despite this smaller energy deficit, unsuccessful responders displayed less favorable changes in susceptibility to hunger and appetite sensations. They also did not benefit from the intervention regarding the ability to improve sleep quality. In summary, these results show that some individuals display a behavioral vulnerability which may reduce the ability to lose weight in response to a diet-based weight loss program. They also suggest that this vulnerability may be accentuated by a prolonged diet restriction.

Association of Psychobehavioral Variables With HOMA-IR and BMI Differs for Men and Women With Prediabetes in the PREVIEW Lifestyle Intervention.

OBJECTIVE: Stress, sleep, eating behavior, and physical activity are associated with weight change and insulin resistance (IR). The aim of this analysis was the assessment of the overall and sex-specific associations of psychobehavioral variables throughout the 3-year PREVIEW intervention using the homeostatic model assessment of IR (HOMA-IR), BMI, and length of time in the study. RESEARCH DESIGN AND METHODS: Associations of psychobehavioral variables, including stress, mood, eating behavior, physical activity (PA), and sleep, with BMI, HOMA-IR, and time spent in the study were assessed in 2,184 participants with prediabetes and overweight/obesity (n = 706 men; n = 1,478 women) during a 3-year lifestyle intervention using linear mixed modeling and general linear modeling. The study was a randomized multicenter trial using a 2 × 2 diet-by-PA design. RESULTS: Overall, cognitive restraint and PA increased during the intervention compared with baseline, whereas BMI, HOMA-IR, disinhibition, hunger, and sleepiness decreased (all P < 0.05). Cognitive restraint and PA were negatively, whereas disinhibition, hunger, stress, and total mood disturbance were positively, associated with both BMI and HOMA-IR. Sleep duration, low sleep quality, total mood disturbance, disinhibition, and hunger scores were positively associated with HOMA-IR for men only. Participants who dropped out at 6 months had higher stress and total mood disturbance scores at baseline and throughout their time spent in the study compared with study completers. CONCLUSIONS: Eating behavior and PA, control of stress, mood disturbance, and sleep characteristics were associated with BMI, HOMA-IR, and time spent in the study, with different effects in men and women during the PREVIEW lifestyle intervention study.

Associations of changes in reported and estimated protein and energy intake with changes in insulin resistance, glycated hemoglobin, and BMI during the PREVIEW lifestyle intervention study.

BACKGROUND: Observed associations of high-protein diets with changes in insulin resistance are inconclusive. OBJECTIVES: We aimed to assess associations of changes in both reported and estimated protein (PRep; PEst) and energy intake (EIRep; EIEst) with changes in HOMA-IR, glycated hemoglobin (HbA1c), and BMI (in kg/m2), in 1822 decreasing to 833 adults (week 156) with overweight and prediabetes, during the 3-y PREVIEW (PREVention of diabetes through lifestyle intervention and population studies In Europe and around the World) study on weight-loss maintenance. Eating behavior and measurement errors (MEs) of dietary intake were assessed. Thus, observational post hoc analyses were applied. METHODS: Associations of changes in EIEst, EIRep, PEst, and PRep with changes in HOMA-IR, HbA1c, and BMI were determined by linear mixed-model analysis in 2 arms [high-protein-low-glycemic-index (GI) diet and moderate-protein-moderate-GI diet] of the PREVIEW study. EIEst was derived from energy requirement: total energy expenditure = basal metabolic rate × physical activity level; PEst from urinary nitrogen, and urea. MEs were calculated as [(EIEst - EIRep)/EIEst] × 100% and [(PRep - PEst)/PEst] × 100%. Eating behavior was determined using the Three Factor Eating Questionnaire, examining cognitive dietary restraint, disinhibition, and hunger. RESULTS: Increases in PEst and PRep and decreases in EIEst and EIRep were associated with decreases in BMI, but not independently with decreases in HOMA-IR. Increases in PEst and PRep were associated with decreases in HbA1c. PRep and EIRep showed larger changes and stronger associations than PEst and EIEst. Mean ± SD MEs of EIRep and PRep were 38% ± 9% and 14% ± 4%, respectively; ME changes in EIRep and En% PRep were positively associated with changes in BMI and cognitive dietary restraint and inversely with disinhibition and hunger. CONCLUSIONS: During weight-loss maintenance in adults with prediabetes, increase in protein intake and decrease in energy intake were not associated with decrease in HOMA-IR beyond associations with decrease in BMI. Increases in PEst and PRep were associated with decrease in HbA1c.This trial was registered at clinicaltrials.gov as NCT01777893.

Dose-Dependent Associations of Dietary Glycemic Index, Glycemic Load, and Fiber With 3-Year Weight Loss Maintenance and Glycemic Status in a High-Risk Population: A Secondary Analysis of the Diabetes Prevention Study PREVIEW.

OBJECTIVE: To examine longitudinal and dose-dependent associations of dietary glycemic index (GI), glycemic load (GL), and fiber with body weight and glycemic status during 3-year weight loss maintenance (WLM) in adults at high risk of type 2 diabetes. RESEARCH DESIGN AND METHODS: In this secondary analysis we used pooled data from the PREVention of diabetes through lifestyle Intervention and population studies in Europe and around the World (PREVIEW) randomized controlled trial, which was designed to test the effects of four diet and physical activity interventions. A total of 1,279 participants with overweight or obesity (age 25-70 years and BMI ≥25 kg ⋅ m-2) and prediabetes at baseline were included. We used multiadjusted linear mixed models with repeated measurements to assess longitudinal and dose-dependent associations by merging the participants into one group and dividing them into GI, GL, and fiber tertiles, respectively. RESULTS: In the available-case analysis, each 10-unit increment in GI was associated with a greater regain of weight (0.46 kg ⋅ year-1; 95% CI 0.23, 0.68; P < 0.001) and increase in HbA1c. Each 20-unit increment in GL was associated with a greater regain of weight (0.49 kg ⋅ year-1; 0.24, 0.75; P < 0.001) and increase in HbA1c. The associations of GI and GL with HbA1c were independent of weight change. Compared with those in the lowest tertiles, participants in the highest GI and GL tertiles had significantly greater weight regain and increases in HbA1c. Fiber was inversely associated with increases in waist circumference, but the associations with weight regain and glycemic status did not remain robust in different analyses. CONCLUSIONS: Dietary GI and GL were positively associated with weight regain and deteriorating glycemic status. Stronger evidence on the role of fiber is needed.

Effects of a High-Protein Diet on Cardiometabolic Health, Vascular Function, and Endocannabinoids-A PREVIEW Study.

An unfavorable lipid profile and being overweight are known mediators in the development of cardiovascular disease (CVD) risk. The effect of diet, particularly high in protein, remains under discussion. Therefore, this study examines the effects of a high-protein (HP) diet on cardiometabolic health and vascular function (i.e., endothelial function, arterial stiffness, and retinal microvascular structure), and the possible association with plasma endocannabinoids and endocannabinoid-related compounds in overweight participants. Thirty-eight participants (64.5 ± 5.9 (mean ± SD) years; body mass index (BMI) 28.9 ± 4.0 kg/m2) were measured for 48 h in a respiration chamber after body-weight maintenance for approximately 34 months following weight reduction. Diets with either a HP (n = 20) or moderate protein (MP; n = 18) content (25%/45%/30% vs. 15%/55%/30% protein/carbohydrate/fat) were provided in energy balance. Validated markers for cardiometabolic health (i.e., office blood pressure (BP) and serum lipoprotein concentrations) and vascular function (i.e., brachial artery flow-mediated vasodilation, pulse wave analysis and velocity, and retinal microvascular calibers) were measured before and after those 48 h. Additionally, 24 h ambulatory BP, plasma anandamide (AEA), 2-arachidonoylglycerol (2-AG), oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and pregnenolone (PREG) were analyzed throughout the day. Office and ambulatory BP, serum lipoprotein concentrations, and vascular function markers were not different between the groups. Only heart rate (HR) was higher in the HP group. HR was positively associated with OEA, while OEA and PEA were also positively associated with total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol concentrations. Vascular function markers were not associated with endocannabinoids (or endocannabinoid-related substances). In conclusion, the HP diet did not affect cardiometabolic health and vascular function in overweight participants after completing a weight-loss intervention. Furthermore, our data indicate a possible association between OEA and PEA with TC and LDL cholesterol.

Insulin resistance, weight, and behavioral variables as determinants of brain reactivity to food cues: a Prevention of Diabetes through Lifestyle Intervention and Population Studies in Europe and around the World - a PREVIEW study.

Background: Obesity and type 2 diabetes have been linked to alterations in food reward processing, which may be linked to insulin resistance. Objectives: In this clinical study, we investigated the respective contribution of insulin resistance, anthropometric measurements, and behavioral factors to brain reward activation in response to visual stimuli. Design: Food reward-related brain reward activation was assessed with functional magnetic resonance imaging in 39 overweight or obese individuals with impaired fasting glucose, impaired glucose tolerance, or both [22 women, 17 men; mean ± SD insulin sensitivity index (ISI): 2.7 ± 1.3; body mass index (BMI; kg/m2): 32.3 ± 3.7; body fat percentage: 40.5% ± 7.9%; fasting glucose: 6.3 ± 0.6 mmol/L]. Food and nonfood images were shown in a randomized block design. Brain activation (food compared with nonfood images) was correlated with anthropometric and behavioral variables. Behavioral variables included eating behavior [Three-Factor Eating Questionnaire (TFEQ)] and habitual physical activity (Baecke). Glucose and insulin concentrations, determined during an oral-glucose challenge, were used to assess the homeostatic model assessment for insulin resistance (HOMA-IR) and Matsuda ISI. Results: Food compared with nonfood brain activation was positively associated with HOMA-IR in the nucleus accumbens, right and left insula, and right cingulate gyrus (P < 0.005, corrected for multiple comparisons). TFEQ factor 2 was positively related to food compared with nonfood brain activation in the supramarginal gyrus (P < 0.005, corrected for multiple comparisons). Habitual physical activity during leisure time was negatively associated with food compared with nonfood brain activation in multiple regions associated with the attention and reward network (P < 0.005, corrected for multiple comparisons). Conclusions: Individuals with increased insulin resistance and emotional eating or disinhibition showed higher brain reactivity to food cues, which may imply changes in food preference and hyperphagia. Individuals with higher habitual physical activity showed less food reward-related brain activation.

Effects of a High-Protein/Moderate-Carbohydrate Diet on Appetite, Gut Peptides, and Endocannabinoids-A Preview Study.

Favorable effects of a high-protein/moderate-carbohydrate (HP/MCHO) diet after weight loss on body weight management have been shown. To extend these findings, associations between perception of hunger and satiety with endocannabinoids, and with glucagon-like peptide-1 (GLP-1) and polypeptide YY (PYY) were assessed. At approximately 34 months after weight loss, 22 female and 16 male participants (mean age 64.5 ± 5.9 years; body mass index (BMI) 28.9 ± 3.9 kg/m2) completed a 48 h respiration chamber study. Participants were fed in energy balance with a HP/MCHO diet with 25%:45%:30% or a moderate-protein/high-carbohydrate (MP/HCHO) diet with 15%:55%:30% of energy from protein:carbohydrate:fat. Endocannabinoids and related compounds, relevant postprandial hormones (GLP-1, PYY), hunger, satiety, and ad libitum food intake were assessed. HP/MCHO versus MP/HCHO reduced hunger perception. The lower decremental area under the curve (dAUC) for hunger in the HP/MCHO diet (-56.6% compared to MP, p < 0.05) was associated with the higher AUC for 2-arachidonoylglycerol (2-AG) concentrations (p < 0.05). Hunger was inversely associated with PYY in the HP/MCHO group (r = -0.7, p < 0.01). Ad libitum food intake, homeostatic model assessment for insulin resistance (HOMA-IR) and incremental AUCs for gut peptides were not different between conditions. HP/MCHO versus MP/HCHO diet-induced reduction in hunger was present after 34 months weight maintenance in the post-obese state. HP/MCHO diet-induced decrease of hunger is suggested to interact with increased 2-AG and PYY concentrations.

Cerebral Blood Flow Measurements in Adults: A Review on the Effects of Dietary Factors and Exercise.

Improving cerebrovascular function may be a key mechanism whereby a healthy lifestyle, of which a healthy diet combined with increased physical activity levels is a cornerstone, protects against cognitive impairments. In this respect, effects on cerebral blood flow (CBF)—a sensitive physiological marker of cerebrovascular function—are of major interest. This review summarizes the impact of specific dietary determinants and physical exercise on CBF in adults and discusses the relation between these effects with potential changes in cognitive function. A limited number of randomized controlled trials have already demonstrated the beneficial effects of an acute intake of nitrate and polyphenols on CBF, but evidence for a relationship between these effects as well as improvements in cognitive functioning is limited. Moreover, long-term trans-resveratrol supplementation has been shown to increase CBF in populations at increased risk of accelerated cognitive decline. Long-term supplementation of n-3 long-chain polyunsaturated fatty acids may also increase CBF, but related effects on cognitive performance have not yet been found. Significant decreases in cerebral perfusion were observed by commonly consumed amounts of caffeine, while alcohol intake was shown to increase CBF in a dose-dependent way. However, the long-term effects are not clear. Finally, long-term exercise training may be a promising approach to improve CBF, as increases in perfusion may contribute to the beneficial effects on cognitive functioning observed following increased physical activity levels.

Associations of Brain Reactivity to Food Cues with Weight Loss, Protein Intake and Dietary Restraint during the PREVIEW Intervention.

The objective was to assess the effects of a weight loss and subsequent weight maintenance period comprising two diets differing in protein intake, on brain reward reactivity to visual food cues. Brain reward reactivity was assessed with functional magnetic resonance imaging in 27 overweight/obese individuals with impaired fasting glucose and/or impaired glucose tolerance (HOMA-IR: 3.7 ± 1.7; BMI: 31.8 ± 3.2 kg/m²; fasting glucose: 6.4 ± 0.6 mmol/L) before and after an 8-week low energy diet followed by a 2-year weight maintenance period, with either high protein (HP) or medium protein (MP) dietary guidelines. Brain reactivity and possible relationships with protein intake, anthropometrics, insulin resistance and eating behaviour were assessed. Brain reactivity, BMI, HOMA-IR and protein intake did not change differently between the groups during the intervention. In the whole group, protein intake during weight maintenance was negatively related to changes in high calorie images>low calorie images (H > L) brain activation in the superior/middle frontal gyrus and the inferior temporal gyrus (p < 0.005, corrected for multiple comparisons). H > L brain activation was positively associated with changes in body weight and body-fat percentage and inversely associated with changes in dietary restraint in multiple reward, gustatory and processing regions (p < 0.005, corrected for multiple comparisons). In conclusion, changes in food reward-related brain activation were inversely associated with protein intake and dietary restraint during weight maintenance after weight loss and positively associated with changes in body weight and body-fat percentage.