Weight loss improves ß-cell function independently of dietary carbohydrate restriction in people with type 2 diabetes: A 6-week randomized controlled trial.

Background: Carbohydrate restriction may benefit ß-cell function and glucose metabolism in type 2 diabetes (T2D) but also leads to weight loss which in itself is beneficial. Methods: In order to determine the additional effect of carbohydrate restriction in addition to a fixed body weight loss, we randomly assigned 72 adults with T2D and obesity (mean ± SD HbA1c 7.4 ± 0.7%, BMI 33 ± 5 kg/m2) to a carbohydrate-reduced high-protein diet (CRHP; energy percent from carbohydrate/protein/fat: 30/30/40) or an isocaloric conventional diabetes diet (CD; 50/17/33) for 6 weeks. All foods were provided free of charge and total energy intake was tailored individually, so both groups lost 6% of baseline body weight. Results: Despite significantly greater reductions in HbA1c (mean [95% CI] -1.9 [-3.5, -0.3] mmol/mol) after 6 weeks, the CRHP diet neither improved glucose tolerance, ß-cell response to glucose, insulin sensitivity, during a 4-h oral glucose tolerance test, nor basal proinsulin secretion when compared to the CD diet, but increased C-peptide concentration and insulin secretion rate (area under the curve [AUC] and peak) significantly more (~10%, P ≤ 0.03 for all). Furthermore, compared with the CD diet, the CRHP diet borderline increased basal glucagon concentration (16 [-0.1, 34]%, P = 0.05), but decreased glucagon net AUC (-2.0 [-3.4, -0.6] mmol/L ×240 min, P < 0.01), decreased basal triglyceride and total AUC (~20%, P < 0.01 for both), and increased gastric inhibitory polypeptide total AUC (14%, P = 0.01). Conclusion: A moderately carbohydrate-restricted diet for 6 weeks decreased HbA1c but did not improve ß-cell function or glucose tolerance beyond the effects of weight loss when compared with a conventional diabetes diet in people with T2D. Clinical trials registration: www.Clinicaltrials.gov, Identifier: NCT02472951.

Forming new health behavior habits during weight loss maintenance-The PREVIEW study.

INTRODUCTION: Changing lifestyle habits to achieve and maintain weight loss can be effective in prevention of Type II diabetes. Ability to resist temptations is considered one of the key factors in behavior change. This study examined how habit strength, motivation, and temptations for an energy-dense diet developed during the maintenance stage of a behavior modification intervention tool. METHOD: Participants with prediabetes and overweight/obesity were recruited in the two-phase trial PREVIEW with the aim to achieve ≥ 8% body weight loss over 2 months and maintain weight loss over a subsequent 34-month period. The four-stage intervention (PREVIEW Behavior Modification Intervention Toolbox, or PREMIT) supported participants in weight maintenance. Uni- and multivariate analyses were completed from the beginning of the PREMIT maintenance stage (Week 26 of the PREVIEW trial) with 962 individuals who completed the trial. RESULTS: Habit strength and ability to resist temptations increased during the early PREMIT adherence stage (Weeks 26 to 52) before plateauing during middle (Weeks 52 to 104) and late (Weeks 104 to 156) PREMIT adherence stages. Higher habit strength for energy-dense diet was significantly associated with larger weight regain (p ≤ .007). No changes in motivation or interactions with PREMIT attendance were observed. DISCUSSION: Changing diet habits is a complex, multifactorial process, with participants struggling at least with some aspects of weight maintenance. Habits against consuming energy-dense, sweet, and fatty food appeared effective in protecting against weight regain. The observed effect sizes were small, reflecting the complexity of breaking old habits and forming new ones to support long-term maintenance of weight loss. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Dietary carbohydrate restriction augments weight loss-induced improvements in glycaemic control and liver fat in individuals with type 2 diabetes: a randomised controlled trial.

AIMS/HYPOTHESIS: Lifestyle modification and weight loss are cornerstones of type 2 diabetes management. However, carbohydrate restriction may have weight-independent beneficial effects on glycaemic control. This has been difficult to demonstrate because low-carbohydrate diets readily decrease body weight. We hypothesised that carbohydrate restriction enhances the beneficial metabolic effects of weight loss in type 2 diabetes. METHODS: This open-label, parallel RCT included adults with type 2 diabetes, HbA1c 48-97 mmol/mol (6.5-11%), BMI >25 kg/m2, eGFR >30 ml min-1 [1.73 m]-2 and glucose-lowering therapy restricted to metformin or dipeptidyl peptidase-4 inhibitors. Participants were randomised by a third party and assigned to 6 weeks of energy restriction (all foods were provided) aiming at ~6% weight loss with either a carbohydrate-reduced high-protein diet (CRHP, percentage of total energy intake [E%]: CH30/P30/F40) or a conventional diabetes diet (CD, E%: CH50/P17/F33). Fasting blood samples, continuous glucose monitoring and magnetic resonance spectroscopy were used to assess glycaemic control, lipid metabolism and intrahepatic fat. Change in HbA1c was the primary outcome; changes in circulating and intrahepatic triacylglycerol were secondary outcomes. Data were collected at Copenhagen University Hospital (Bispebjerg and Herlev). RESULTS: Seventy-two adults (CD 36, CRHP 36, all white, 38 male sex) with type 2 diabetes (mean duration 8 years, mean HbA1c 57 mmol/mol [7.4%]) and mean BMI of 33 kg/m2 were enrolled, of which 67 (CD 33, CRHP 34) completed the study. Body weight decreased by 5.8 kg (5.9%) in both groups after 6 weeks. Compared with the CD diet, the CRHP diet further reduced HbA1c (mean [95% CI] -1.9 [-3.5, -0.3] mmol/mol [-0.18 (-0.32, -0.03)%], p = 0.018) and diurnal mean glucose (mean [95% CI] -0.8 [-1.2, -0.4] mmol/l, p < 0.001), stabilised glucose excursions by reducing glucose CV (mean [95% CI] -4.1 [-5.9, -2.2]%, p < 0.001), and augmented the reductions in fasting triacylglycerol concentration (by mean [95% CI] -18 [-29, -6]%, p < 0.01) and liver fat content (by mean [95% CI] -26 [-45, 0]%, p = 0.051). However, pancreatic fat content was decreased to a lesser extent by the CRHP than the CD diet (mean [95% CI] 33 [7, 65]%, p = 0.010). Fasting glucose, insulin, HOMA2-IR and cholesterol concentrations (total, LDL and HDL) were reduced significantly and similarly by both diets. CONCLUSIONS/INTERPRETATION: Moderate carbohydrate restriction for 6 weeks modestly improved glycaemic control, and decreased circulating and intrahepatic triacylglycerol levels beyond the effects of weight loss itself compared with a CD diet in individuals with type 2 diabetes. Concurrent differences in protein and fat intakes, and the quality of dietary macronutrients, may have contributed to these results and should be explored in future studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT03814694. FUNDING: The study was funded by Arla Foods amba, The Danish Dairy Research Foundation, and Copenhagen University Hospital Bispebjerg Frederiksberg.

Associations of quantity and quality of carbohydrate sources with subjective appetite sensations during 3-year weight-loss maintenance: Results from the PREVIEW intervention study.

BACKGROUND & AIMS: The association of quantity and quality of carbohydrate sources with appetite during long-term weight-loss maintenance (WLM) after intentional weight loss (WL) is unclear. We aimed to investigate longitudinal associations of quantity and quality of carbohydrate sources with changes in subjective appetite sensations during WLM. METHODS: This secondary analysis evaluated longitudinal data from the 3-year WLM phase of the PREVIEW study, a 2 × 2 factorial (diet-physical activity arms), multi-center, randomized trial. 1279 individuals with overweight or obesity and prediabetes (25-70 years; BMI≥25 kg m-2) were included. Individuals were merged into 1 group to assess longitudinal associations of yearly changes in appetite sensations. Quantity and quality of carbohydrate sources including total carbohydrate, glycemic index (GI), glycemic load (GL), and total dietary fiber were assessed via 4-day food diaries at 4 timepoints (26, 52, 104, and 156 weeks) during WLM. Visual analog scales were used to assess appetite sensations in the previous week. RESULTS: During WLM, participants consumed on average 160.6 (25th, 75th percentiles 131.1, 195.8) g·day-1 of total carbohydrate, with GI 53.8 (48.7, 58.8) and GL 85.3 (67.2, 108.9) g day-1, and 22.3 (17.6, 27.3) g·day-1 of dietary fiber. In the available-case analysis, multivariable-adjusted linear mixed models with repeated measures showed that each 30-g increment in total carbohydrate was associated with increases in hunger (1.36 mm year-1, 95% CI 0.77, 1.95, P < 0.001), desire to eat (1.10 mm year-1, 0.59, 1.60, P < 0.001), desire to eat something sweet (0.99 mm year-1, 0.30, 1.68, P = 0.005), and weight regain (0.20%·year-1, 0.03, 0.36, P = 0.022). Increasing GI was associated with weight regain, but not associated with increases in appetite sensations. Each 20-unit increment in GL was associated with increases in hunger (0.92 mm year-1, 0.33, 1.51, P = 0.002), desire to eat (1.12 mm year-1, 0.62, 1.62, P < 0.001), desire to eat something sweet (1.13 mm year-1, 0.44, 1.81, P < 0.001), and weight regain (0.35%·year-1, 0.18, 0.52, P < 0.001). Surprisingly, dietary fiber was also associated with increases in desire to eat, after adjustment for carbohydrate or GL. CONCLUSIONS: In participants with moderate carbohydrate and dietary fiber intake, and low to moderate GI, we found that higher total carbohydrate, GL, and total fiber, but not GI, were associated with increases in subjective desire to eat or hunger over 3 years. This study was registered as ClinicalTrials.gov, NCT01777893.

Appraisal of Triglyceride-Related Markers as Early Predictors of Metabolic Outcomes in the PREVIEW Lifestyle Intervention: A Controlled Post-hoc Trial.

Background: Individuals with pre-diabetes are commonly overweight and benefit from dietary and physical activity strategies aimed at decreasing body weight and hyperglycemia. Early insulin resistance can be estimated via the triglyceride glucose index {TyG = Ln [TG (mg/dl) × fasting plasma glucose (FPG) (mg/dl)/2]} and the hypertriglyceridemic-high waist phenotype (TyG-waist), based on TyG x waist circumference (WC) measurements. Both indices may be useful for implementing personalized metabolic management. In this secondary analysis of a randomized controlled trial (RCT), we aimed to determine whether the differences in baseline TyG values and TyG-waist phenotype predicted individual responses to type-2 diabetes (T2D) prevention programs. Methods: The present post-hoc analyses were conducted within the Prevention of Diabetes through Lifestyle intervention and population studies in Europe and around the world (PREVIEW) study completers (n = 899), a multi-center RCT conducted in eight countries (NCT01777893). The study aimed to reduce the incidence of T2D in a population with pre-diabetes during a 3-year randomized intervention with two sequential phases. The first phase was a 2-month weight loss intervention to achieve ≥8% weight loss. The second phase was a 34-month weight loss maintenance intervention with two diets providing different amounts of protein and different glycemic indices, and two physical activity programs with different exercise intensities in a 2 x 2 factorial design. On investigation days, we assessed anthropometrics, glucose/lipid metabolism markers, and diet and exercise questionnaires under standardized procedures. Results: Diabetes-related markers improved during all four lifestyle interventions. Higher baseline TyG index (p < 0.001) was associated with greater reductions in body weight, fasting glucose, and triglyceride (TG), while a high TyG-waist phenotype predicted better TG responses, particularly in those randomized to physical activity (PA) of moderate intensity. Conclusions: Two novel indices of insulin resistance (TyG and TyG-waist) may allow for a more personalized approach to avoiding progression to T2D. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT01777893 reference, identifier: NCT01777893.

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.

Corrigendum: A High-Protein, Low Glycemic Index Diet Suppresses Hunger but Not Weight Regain After Weight Loss: Results From a Large, 3-Years Randomized Trial (PREVIEW).

[This corrects the article DOI: 10.3389/fnut.2021.685648.].

Effects of a Self-Prepared Carbohydrate-Reduced High-Protein Diet on Cardiovascular Disease Risk Markers in Patients with Type 2 Diabetes.

We previously observed beneficial effects of a carbohydrate-reduced, high-protein (CRHP) diet on cardiovascular risk markers in patients with type 2 diabetes mellitus (T2DM) in a crossover 2 × 6-week trial, when all food was provided to subjects as ready-to-eat meals. Here, we report the results from a 6-month open label extension: 28 patients with T2DM were instructed to self-prepare the CRHP diet with dietetic guidance. At weeks 0, 6, 12, and 36, fasting and postprandial (4-h meal test) blood samples were collected for measurements of total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, triacylglycerol (TG), apolipoproteins A1 and B, non-esterified fatty acids (NEFA), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6. Diurnal blood pressure and heart rate were also assessed. At the end of the study (week 36), concentrations of fasting total and LDL-cholesterol, fasting and postprandial NEFA and TG, and fasting apolipoprotein-B, CRP and TNF-α concentrations were significantly lower compared with week 0 (p < 0.05). A significant decrease in diurnal heart rate was also observed. From week 12 to 36, an increase in HDL-cholesterol and apolipoprotein-A1 concentrations and a further reduction in fasting and postprandial NEFA (p < 0.05) were found. These changes were independent of minor fluctuations in body weight. We conclude that the substitution of dietary carbohydrate for protein and fat has beneficial effects on several cardiovascular risk markers in patients with T2DM, which are maintained or augmented over the next 6 months when patients select and prepare the CRHP diet on their own in a dietitian-supported setting.

A High-Protein, Low Glycemic Index Diet Suppresses Hunger but Not Weight Regain After Weight Loss: Results From a Large, 3-Years Randomized Trial (PREVIEW).

Background: Previous studies have shown an increase in hunger during weight-loss maintenance (WLM) after diet-induced weight loss. Whether a combination of a higher protein, lower glycemic index (GI) diet and physical activity (PA) can counteract this change remains unclear. Aim: To compare the long-term effects of two diets [high protein (HP)-low GI vs. moderate protein (MP)-moderate GI] and two PA programs [high intensity (HI) vs. moderate intensity (MI)] on subjective appetite sensations during WLM after ≥8% weight loss (WL). Methods: Data derived from the 3-years PREVIEW randomized intervention study. An 8-weeks WL phase using a low-energy diet was followed by a 148-weeks randomized WLM phase. For the WLM phase, participants were assigned to one of the four groups: HP-MI, HP-HI, MP-MI, and MP-HI. Available data from 2,223 participants with overweight or obesity (68% women; BMI ≥ 25 kg/m2). Appetite sensations including satiety, hunger, desire to eat, and desire to eat something sweet during the two phases (at 0, 8 weeks and 26, 52, 104, and 156 weeks) were assessed based on the recall of feelings during the previous week using visual analogue scales. Differences in changes in appetite sensations from baseline between the groups were determined using linear mixed models with repeated measures. Results: There was no significant diet × PA interaction. From 52 weeks onwards, decreases in hunger were significantly greater in HP-low GI than MP-moderate GI (P time × diet = 0.018, P dietgroup = 0.021). Although there was no difference in weight regain between the diet groups (P time × diet = 0.630), hunger and satiety ratings correlated with changes in body weight at most timepoints. There were no significant differences in appetite sensations between the two PA groups. Decreases in hunger ratings were greater at 52 and 104 weeks in HP-HI vs. MP-HI, and greater at 104 and 156 weeks in HP-HI vs. MP-MI. Conclusions: This is the first long-term, large-scale randomized intervention to report that a HP-low GI diet was superior in preventing an increase in hunger, but not weight regain, during 3-years WLM compared with a MP-moderate GI diet. Similarly, HP-HI outperformed MP-HI in suppressing hunger. The role of exercise intensity requires further investigation. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: 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.

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.

Effects of carbohydrate restriction on postprandial glucose metabolism, ß-cell function, gut hormone secretion, and satiety in patients with Type 2 diabetes.

Dietary carbohydrate restriction may improve the phenotype of Type 2 diabetes (T2D) patients. We aimed to investigate 6 wk of carbohydrate restriction on postprandial glucose metabolism, pancreatic α- and ß-cell function, gut hormone secretion, and satiety in T2D patients. Methods In a crossover design, 28 T2D patients (mean HbA1c: 60 mmol/mol) were randomized to 6 wk of carbohydrate-reduced high-protein (CRHP) diet and 6 wk of conventional diabetes (CD) diet (energy-percentage carbohydrate/protein/fat: 30/30/40 vs. 50/17/33). Twenty-four-hour continuous glucose monitoring (CGM) and mixed-meal tests were undertaken and fasting intact proinsulin (IP), 32,33 split proinsulin concentrations (SP), and postprandial insulin secretion rates (ISR), insulinogenic index (IGI), ß-cell sensitivity to glucose (Bup), glucagon, and gut hormones were measured. Gastric emptying was evaluated by postprandial paracetamol concentrations and satiety by visual analog scale ratings. A CRHP diet reduced postprandial glucose area under curve (net AUC) by 60% (P < 0.001), 24 h glucose by 13% (P < 0.001), fasting IP and SP concentrations (both absolute and relative to C-peptide, P < 0.05), and postprandial ISR (24%, P = 0.015), while IGI and Bup improved by 31% and 45% (both P < 0.001). The CRHP diet increased postprandial glucagon net AUC by 235% (P < 0.001), subjective satiety by 18% (P = 0.03), delayed gastric emptying by 15 min (P < 0.001), decreased gastric inhibitory polypeptide net AUC by 29% (P < 0.001), but had no significant effect on glucagon-like-peptide-1, total peptide YY, and cholecystokinin responses. A CRHP diet reduced glucose excursions and improved ß-cell function, including proinsulin processing, and increased subjective satiety in patients with T2D.

Compositional analysis of the associations between 24-h movement behaviours and cardio-metabolic risk factors in overweight and obese adults with pre-diabetes from the PREVIEW study: cross-sectional baseline analysis.

BACKGROUND: Physical activity, sedentary time and sleep have been shown to be associated with cardio-metabolic health. However, these associations are typically studied in isolation or without accounting for the effect of all movement behaviours and the constrained nature of data that comprise a finite whole such as a 24 h day. The aim of this study was to examine the associations between the composition of daily movement behaviours (including sleep, sedentary time (ST), light intensity physical activity (LIPA) and moderate-to-vigorous activity (MVPA)) and cardio-metabolic health, in a cross-sectional analysis of adults with pre-diabetes. Further, we quantified the predicted differences following reallocation of time between behaviours. METHODS: Accelerometers were used to quantify daily movement behaviours in 1462 adults from eight countries with a body mass index (BMI) ≥25 kg·m- 2, impaired fasting glucose (IFG; 5.6-6.9 mmol·l- 1) and/or impaired glucose tolerance (IGT; 7.8-11.0 mmol•l- 1 2 h following oral glucose tolerance test, OGTT). Compositional isotemporal substitution was used to estimate the association of reallocating time between behaviours. RESULTS: Replacing MVPA with any other behaviour around the mean composition was associated with a poorer cardio-metabolic risk profile. Conversely, when MVPA was increased, the relationships with cardiometabolic risk markers was favourable but with smaller predicted changes than when MVPA was replaced. Further, substituting ST with LIPA predicted improvements in cardio-metabolic risk markers, most notably insulin and HOMA-IR. CONCLUSIONS: This is the first study to use compositional analysis of the 24 h movement composition in adults with overweight/obesity and pre-diabetes. These findings build on previous literature that suggest replacing ST with LIPA may produce metabolic benefits that contribute to the prevention and management of type 2 diabetes. Furthermore, the asymmetry in the predicted change in risk markers following the reallocation of time to/from MVPA highlights the importance of maintaining existing levels of MVPA. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01777893).

Pretreatment Prevotella-to-Bacteroides ratio and salivary amylase gene copy number as prognostic markers for dietary weight loss.

BACKGROUND: The inconsistent link observed between salivary amylase gene copy number (AMY1 CN) and weight management is likely modified by diet and microbiome. OBJECTIVE: Based on analysis of a previously published study, we investigated the hypothesis that interaction between diet, Prevotella-to-Bacteriodes ratio (P/B ratio), and AMY1 CN influence weight change. METHODS: Sixty-two people with increased waist circumference were randomly assigned to receive an ad libitum New Nordic Diet (NND) high in dietary fiber, whole grain, intrinsic sugars, and starch or an Average Danish (Western) Diet (ADD) for 26 weeks. All foods were provided free of charge. Before subjects were randomly assigned to receive the NND or ADD diet, blood and fecal samples were collected, from which AMY1 CN and P/B ratio, respectively, were determined. Body weight change was described by using linear mixed models, including biomarker [log10(P/B ratio) and/or AMY1 CN] diet-group interactions. RESULTS: Baseline means ± SDs of log10(P/B ratio) and AMY1 CN were -2.1 ± 1.8 and 6.6 ± 2.4, respectively. Baseline P/B ratio predicted a 0.99-kg/unit (95% CI: 0.40, 1.57; n = 54; P < 0.001) higher weight loss for those subjects on the NND compared with those on the ADD diet, whereas AMY1 CN was not found to predict weight loss differences between the NND and ADD groups [0.05 kg/CN (95% CI: -0.40, 0.51; n = 54; P = 0.83)]. However, among subjects with low AMY1 CN (<6.5 copies), baseline P/B ratio predicted a 2.12-kg/unit (95% CI: 1.37, 2.88; n = 30; P < 0.001) higher weight loss for the NND group than the ADD group. No such differences in weight loss were found among subjects in both groups with high AMY1 CN [-0.17 kg/unit (95% CI: -1.01, 0.66; n = 24; P = 0.68)]. CONCLUSIONS: The combined use of low AMY1 CN and pretreatment P/B ratio for weight loss prediction led to highly individualized weight loss results with the introduction of more fiber, whole grain, intrinsic sugars, and starch in the diet. These preliminary observations suggest that more undigested starch reaches the colon in individuals with low AMY1 CN, and that the fate of this starch depends on the gut microbiota composition. This trial was registered at clinicaltrials.gov as NCT01195610.

Associations between the proportion of fat-free mass loss during weight loss, changes in appetite, and subsequent weight change: results from a randomized 2-stage dietary intervention trial.

BACKGROUND: Dynamic changes in body composition which occur during weight loss may have an influential role on subsequent energy balance behaviors and weight. OBJECTIVES: The aim of this article is to consider the effect of proportionate changes in body composition during weight loss on subsequent changes in appetite and weight outcomes at 26 wk in individuals engaged in a weight loss maintenance intervention. METHODS: A subgroup of the Diet, Obesity, and Genes (DiOGenes) study (n = 209) was recruited from 3 European countries. Participants underwent an 8-wk low-calorie diet (LCD) resulting in ≥8% body weight loss, during which changes in body composition (by DXA) and appetite (by visual analog scale appetite perceptions in response to a fixed test meal) were measured. Participants were randomly assigned into 5 weight loss maintenance diets based on protein and glycemic index content and followed up for 26 wk. We investigated associations between proportionate fat-free mass (FFM) loss (%FFML) during weight loss and 1) weight outcomes at 26 wk and 2) changes in appetite perceptions. RESULTS: During the LCD, participants lost a mean ± SD of 11.2 ± 3.5 kg, of which 30.4% was FFM. After adjustment, there was a tendency for %FFML to predict weight regain in the whole group (ß: 0.041; 95% CI: -0.001, 0.08; P = 0.055), which was significant in men (ß: 0.09; 95% CI: 0.02, 0.15; P = 0.009) but not women (ß: 0.01; 95% CI: -0.04, 0.07; P = 0.69). Associations between %FFML and change in appetite perceptions during weight loss were inconsistent. The strongest observations were in men for hunger (r = 0.69, P = 0.002) and desire to eat (r = 0.61, P = 0.009), with some tendencies in the whole group and no associations in women. CONCLUSIONS: Our results suggest that composition of weight loss may have functional importance for energy balance regulation, with greater losses of FFM potentially being associated with increased weight regain and appetite. This trial was registered at clinicaltrials.gov as NCT00390637.

A carbohydrate-reduced high-protein diet improves HbA1c and liver fat content in weight stable participants with type 2 diabetes: a randomised controlled trial.

AIMS/HYPOTHESIS: Dietary recommendations for treating type 2 diabetes are unclear but a trend towards recommending a diet reduced in carbohydrate content is acknowledged. We compared a carbohydrate-reduced high-protein (CRHP) diet with an iso-energetic conventional diabetes (CD) diet to elucidate the effects on glycaemic control and selected cardiovascular risk markers during 6 weeks of full food provision of each diet. METHODS: The primary outcome of the study was change in HbA1c. Secondary outcomes reported in the present paper include glycaemic variables, ectopic fat content and 24 h blood pressure. Eligibility criteria were: men and women with type 2 diabetes, HbA1c 48-97 mmol/mol (6.5-11%), age >18 years, haemoglobin >6/>7 mmol/l (women/men) and eGFR >30 ml min-1 (1.73 m)-2. Participants were randomised by drawing blinded ballots to 6 + 6 weeks of an iso-energetic CRHP vs CD diet in an open label, crossover design aiming at body weight stability. The CRHP/CD diets contained carbohydrate 30/50 energy per cent (E%), protein 30/17E% and fat 40/33E%, respectively. Participants underwent a meal test at the end of each diet period and glycaemic variables, lipid profiles, 24 h blood pressure and ectopic fat including liver and pancreatic fat content were assessed at baseline and at the end of each diet period. Data were collected at Copenhagen University Hospital, Bispebjerg and Copenhagen University Hospital, Herlev. RESULTS: Twenty-eight participants completed the study. Fourteen participants carried out 6 weeks of the CRHP intervention followed by 6 weeks of the CD intervention, and 14 participants received the dietary interventions in the reverse order. Compared with a CD diet, a CRHP diet reduced the primary outcome of HbA1c (mean ± SEM: -6.2 ± 0.8 mmol/mol (-0.6 ± 0.1%) vs -0.75 ± 1.0 mmol/mol (-0.1 ± 0.1%); p < 0.001). Nine (out of 37) pre-specified secondary outcomes are reported in the present paper, of which five were significantly different between the diets, (p < 0.05); compared with a CD diet, a CRHP diet reduced the secondary outcomes (mean ± SEM or medians [interquartile range]) of fasting plasma glucose (-0.71 ± 0.20 mmol/l vs 0.03 ± 0.23 mmol/l; p < 0.05), postprandial plasma glucose AUC (9.58 ± 0.29 mmol/l × 240 min vs 11.89 ± 0.43 mmol/l × 240 min; p < 0.001) and net AUC (1.25 ± 0.20 mmol/l × 240 min vs 3.10 ± 0.25 mmol/l × 240 min; p < 0.001), hepatic fat content (-2.4% [-7.8% to -1.0%] vs 0.2% [-2.3% to 0.9%]; p < 0.01) and pancreatic fat content (-1.7% [-3.5% to 0.6%] vs 0.5% [-1.0% to 2.0%]; p < 0.05). Changes in other secondary outcomes, i.e. 24 h blood pressure and muscle-, visceral- or subcutaneous adipose tissue, did not differ between diets. CONCLUSIONS/INTERPRETATION: A moderate macronutrient shift by substituting carbohydrates with protein and fat for 6 weeks reduced HbA1c and hepatic fat content in weight stable individuals with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02764021. FUNDING: The study was funded by grants from Arla Food for Health; the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen; the Department of Clinical Medicine, Aarhus University; the Department of Nutrition, Exercise and Sports, University of Copenhagen; and Copenhagen University Hospital, Bispebjerg.

Weight loss at your fingertips: personalized nutrition with fasting glucose and insulin using a novel statistical approach.

BACKGROUND/OBJECTIVES: Precision medicine is changing the way people are diagnosed and treated into a more personalized approach. Using a novel statistical approach, we demonstrate how two diets cause differential weight loss depending on pre-treatment fasting plasma glucose (FPG) and fasting insulin (FI) levels. SUBJECTS/METHODS: One hundred and eighty-one overweight people with increased waist circumference were randomly assigned to receive an ad libitum New Nordic Diet (NND) high in dietary fiber and whole grain or an Average Danish (Western) Diet (ADD) for 26 weeks. All foods were provided free of charge. Body weight was measured throughout the study and blood was drawn before randomization from where FPG and FI were analyzed. Weight was described by linear mixed models including biomarker (FPG or FI) diet group interactions. Individualized predictions were estimated as contrasts of intercepts and slopes of pre-treatment biomarkers. RESULTS: Every mmol/L increase in baseline FPG predicted a between-diet difference of 3.00 (1.18;4.83, n = 181, P = 0.001) kg larger weight loss from choosing NND over ADD. For instance, a baseline FPG level of 4.7 mmol/L would lead to an average of 1.42 kg larger weight loss on NND vs. ADD (above 0.41 kg with 95% certainty), whereas the average effect size would be 8.33 kg (above 5.50 kg with 95% certainty) among subjects with FPG level of 7.0 mmol/L. Among individuals with FPG <5.6 mmol/L, each pmol/L lower baseline FI predicted a 0.039 (95% CI 0.017;0.061, n = 143, P < 0.001) kg larger weight loss from choosing NND over ADD. CONCLUSIONS: Use of pre-treatment FPG and FI led to truly individualized predictions of treatment effect of introducing more fiber and whole grain in the diet on weight loss, ranging from almost no effect to losing >8 kg. These findings suggest that this novel statistical approach has great potential when re-evaluating data from existing randomized controlled trials.

Higher Protein Intake Is Not Associated with Decreased Kidney Function in Pre-Diabetic Older Adults Following a One-Year Intervention-A Preview Sub-Study.

Concerns about detrimental renal effects of a high-protein intake have been raised due to an induced glomerular hyperfiltration, since this may accelerate the progression of kidney disease. The aim of this sub-study was to assess the effect of a higher intake of protein on kidney function in pre-diabetic men and women, aged 55 years and older. Analyses were based on baseline and one-year data in a sub-group of 310 participants included in the PREVIEW project (PREVention of diabetes through lifestyle Intervention and population studies in Europe and around the World). Protein intake was estimated from four-day dietary records and 24-hour urinary urea excretion. We used linear regression to assess the association between protein intake after one year of intervention and kidney function markers: creatinine clearance, estimated glomerular filtration rate (eGFR), urinary albumin/creatinine ratio (ACR), urinary urea/creatinine ratio (UCR), serum creatinine, and serum urea before and after adjustments for potential confounders. A higher protein intake was associated with a significant increase in UCR (p = 0.03) and serum urea (p = 0.05) after one year. There were no associations between increased protein intake and creatinine clearance, eGFR, ACR, or serum creatinine. We found no indication of impaired kidney function after one year with a higher protein intake in pre-diabetic older adults.

Objectively Measured Physical Activity and Sedentary Time Are Associated With Cardiometabolic Risk Factors in Adults With Prediabetes: The PREVIEW Study.

OBJECTIVE: The aim of the present cross-sectional study was to examine the association among physical activity (PA), sedentary time (ST), and cardiometabolic risk in adults with prediabetes. RESEARCH DESIGN AND METHODS: Participants (n = 2,326; 25-70 years old, 67% female) from eight countries, with a BMI >25 kg ⋅ m-2 and impaired fasting glucose (5.6-6.9 mmol ⋅ L-1) or impaired glucose tolerance (7.8-11.0 mmol ⋅ L-1 at 2 h), participated. Seven-day accelerometry objectively assessed PA levels and ST. RESULTS: Multiple linear regression revealed that moderate-to-vigorous PA (MVPA) was negatively associated with HOMA of insulin resistance (HOMA-IR) (standardized ß = -0.078 [95% CI -0.128, -0.027]), waist circumference (WC) (ß = -0.177 [-0.122, -0.134]), fasting insulin (ß = -0.115 [-0.158, -0.072]), 2-h glucose (ß = -0.069 [-0.112, -0.025]), triglycerides (ß = -0.091 [-0.138, -0.044]), and CRP (ß = -0.086 [-0.127, -0.045]). ST was positively associated with HOMA-IR (ß = 0.175 [0.114, 0.236]), WC (ß = 0.215 [0.026, 0.131]), fasting insulin (ß = 0.155 [0.092, 0.219]), triglycerides (ß = 0.106 [0.052, 0.16]), CRP (ß = 0.106 [0.39, 0.172]), systolic blood pressure (BP) (ß = 0.078 [0.026, 0.131]), and diastolic BP (ß = 0.106 [0.39, -0.172]). Associations reported between total PA (counts ⋅ min-1), and all risk factors were comparable or stronger than for MVPA: HOMA-IR (ß = -0.151 [-0.194, -0.107]), WC (ß = -0.179 [-0.224, -0.134]), fasting insulin (ß = -0.139 [-0.183, -0.096]), 2-h glucose (ß = -0.088 [-0.131, -0.045]), triglycerides (ß = -0.117 [-0.162, -0.071]), and CRP (ß = -0.104 [-0.146, -0.062]). CONCLUSIONS: In adults with prediabetes, objectively measured PA and ST were associated with cardiometabolic risk markers. Total PA was at least as strongly associated with cardiometabolic risk markers as MVPA, which may imply that the accumulation of total PA over the day is as important as achieving the intensity of MVPA.