Combining diaries and accelerometers to explain change in physical activity during a lifestyle intervention for adults with pre-diabetes: A PREVIEW sub-study.

Self-report and device-based measures of physical activity (PA) both have unique strengths and limitations; combining these measures should provide complementary and comprehensive insights to PA behaviours. Therefore, we aim to 1) identify PA clusters and clusters of change in PA based on self-reported daily activities and 2) assess differences in device-based PA between clusters in a lifestyle intervention, the PREVIEW diabetes prevention study. In total, 232 participants with overweight and prediabetes (147 women; 55.9 ± 9.5yrs; BMI ≥25 kg·m-2; impaired fasting glucose and/or impaired glucose tolerance) were clustered using a partitioning around medoids algorithm based on self-reported daily activities before a lifestyle intervention and their changes after 6 and 12 months. Device-assessed PA levels (PAL), sedentary time (SED), light PA (LPA), and moderate-to-vigorous PA (MVPA) were assessed using ActiSleep+ accelerometers and compared between clusters using (multivariate) analyses of covariance. At baseline, the self-reported "walking and housework" cluster had significantly higher PAL, MVPA and LPA, and less SED than the "inactive" cluster. LPA was higher only among the "cycling" cluster. There was no difference in the device-based measures between the "social-sports" and "inactive" clusters. Looking at the changes after 6 months, the "increased walking" cluster showed the greatest increase in PAL while the "increased cycling" cluster accumulated the highest amount of LPA. The "increased housework" and "increased supervised sports" reported least favourable changes in device-based PA. After 12 months, there was only minor change in activities between the "increased walking and cycling", "no change" and "increased supervised sports" clusters, with no significant differences in device-based measures. Combining self-report and device-based measures provides better insights into the behaviours that change during an intervention. Walking and cycling may be suitable activities to increase PA in adults with prediabetes.

Metabolite-based dietary supplementation in human type 1 diabetes is associated with microbiota and immune modulation.

BACKGROUND: Short-chain fatty acids (SCFAs) produced by the gut microbiota have beneficial anti-inflammatory and gut homeostasis effects and prevent type 1 diabetes (T1D) in mice. Reduced SCFA production indicates a loss of beneficial bacteria, commonly associated with chronic autoimmune and inflammatory diseases, including T1D and type 2 diabetes. Here, we addressed whether a metabolite-based dietary supplement has an impact on humans with T1D. We conducted a single-arm pilot-and-feasibility trial with high-amylose maize-resistant starch modified with acetate and butyrate (HAMSAB) to assess safety, while monitoring changes in the gut microbiota in alignment with modulation of the immune system status. RESULTS: HAMSAB supplement was administered for 6 weeks with follow-up at 12 weeks in adults with long-standing T1D. Increased concentrations of SCFA acetate, propionate, and butyrate in stools and plasma were in concert with a shift in the composition and function of the gut microbiota. While glucose control and insulin requirements did not change, subjects with the highest SCFA concentrations exhibited the best glycemic control. Bifidobacterium longum, Bifidobacterium adolescentis, and vitamin B7 production correlated with lower HbA1c and basal insulin requirements. Circulating B and T cells developed a more regulatory phenotype post-intervention. CONCLUSION: Changes in gut microbiota composition, function, and immune profile following 6 weeks of HAMSAB supplementation were associated with increased SCFAs in stools and plasma. The persistence of these effects suggests that targeting dietary SCFAs may be a mechanism to alter immune profiles, promote immune tolerance, and improve glycemic control for the treatment of T1D. TRIAL REGISTRATION: ACTRN12618001391268. Registered 20 August 2018, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375792 Video Abstract.

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.

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.

Can a Higher Protein/Low Glycemic Index vs. a Conventional Diet Attenuate Changes in Appetite and Gut Hormones Following Weight Loss? A 3-Year PREVIEW Sub-study.

Background: Previous research showed that weight-reducing diets increase appetite sensations and/or circulating ghrelin concentrations for up to 36 months, with transient or enduring perturbations in circulating concentrations of the satiety hormone peptide YY. Objective: This study assessed whether a diet that is higher in protein and low in glycemic index (GI) may attenuate these changes. Methods: 136 adults with pre-diabetes and a body mass index of ≥25 kg/m2 underwent a 2-month weight-reducing total meal replacement diet. Participants who lost ≥8% body weight were randomized to one of two 34-month weight-maintenance diets: a higher-protein and moderate-carbohydrate (CHO) diet with low GI, or a moderate-protein and higher-CHO diet with moderate GI. Both arms involved recommendations to increase physical activity. Fasting plasma concentrations of total ghrelin and total peptide YY, and appetite sensations, were measured at 0 months (pre-weight loss), at 2 months (immediately post-weight loss), and at 6, 12, 24, and 36 months. Results: There was a decrease in plasma peptide YY concentrations and an increase in ghrelin after the 2-month weight-reducing diet, and these values approached pre-weight-loss values by 6 and 24 months, respectively (P = 0.32 and P = 0.08, respectively, vs. 0 months). However, there were no differences between the two weight-maintenance diets. Subjective appetite sensations were not affected by the weight-reducing diet nor the weight-maintenance diets. While participants regained an average of ~50% of the weight they had lost by 36 months, the changes in ghrelin and peptide YY during the weight-reducing phase did not correlate with weight regain. Conclusion: A higher-protein, low-GI diet for weight maintenance does not attenuate changes in ghrelin or peptide YY compared with a moderate-protein, moderate-GI diet. Clinical Trial Registry: ClinicalTrials.gov registry ID NCT01777893 (PREVIEW) and ID NCT02030249 (Sub-study).

Goal achievement and adaptive goal adjustment in a behavioral intervention for participants with prediabetes.

Participants with prediabetes were supported to achieve and maintain weight loss with a stage-based behavior change group program named PREview behavior Modification Intervention Toolbox (PREMIT). The tendency to engage in a process of goal adjustment was examined in relation to PREMIT attendance. Analyses were based on 1857 participants who had achieved ⩾8percent weight loss. Tendency to engage in a process of goal adjustment appeared not to be influenced by PREMIT attendance. Instead, results suggested that when unsure about reaching an intervention goal, participants were more likely to engage in a process of goal adjustment, possibly lessening distress due to potentially unachievable goals, either weight loss or maintenance.

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.

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).

Men and women respond differently to rapid weight loss: Metabolic outcomes of a multi-centre intervention study after a low-energy diet in 2500 overweight, individuals with pre-diabetes (PREVIEW).

AIMS: The PREVIEW lifestyle intervention study (ClinicalTrials.gov Identifier: NCT01777893) is, to date, the largest, multinational study concerning prevention of type-2 diabetes. We hypothesized that the initial, fixed low-energy diet (LED) would induce different metabolic outcomes in men vs women. MATERIALS AND METHODS: All participants followed a LED (3.4 MJ/810 kcal/daily) for 8 weeks (Cambridge Weight Plan). Participants were recruited from 8 sites in Europe, Australia and New Zealand. Those eligible for inclusion were overweight (BMI ≥ 25 kg/m2 ) individuals with pre-diabetes according to ADA-criteria. Outcomes of interest included changes in insulin resistance, fat mass (FM), fat-free mass (FFM) and metabolic syndrome Z-score. RESULTS: In total, 2224 individuals (1504 women, 720 men) attended the baseline visit and 2020 (90.8%) completed the follow-up visit. Following the LED, weight loss was 16% greater in men than in women (11.8% vs 10.3%, respectively) but improvements in insulin resistance were similar. HOMA-IR decreased by 1.50 ± 0.15 in men and by 1.35 ± 0.15 in women (ns). After adjusting for differences in weight loss, men had larger reductions in metabolic syndrome Z-score, C-peptide, FM and heart rate, while women had larger reductions in HDL cholesterol, FFM, hip circumference and pulse pressure. Following the LED, 35% of participants of both genders had reverted to normo-glycaemia. CONCLUSIONS: An 8-week LED induced different effects in women than in men. These findings are clinically important and suggest gender-specific changes after weight loss. It is important to investigate whether the greater decreases in FFM, hip circumference and HDL cholesterol in women after rapid weight loss compromise weight loss maintenance and future cardiovascular health.

Lower glycemic load meals reduce diurnal glycemic oscillations in women with risk factors for gestational diabetes.

OBJECTIVE: Maternal glycemia plays a key role in fetal growth. We hypothesized that lower glycemic load (GL) meals (lower glycemic index, modestly lower carbohydrate) would substantially reduce day-long glucose variability in women at risk of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: A crossover study of 17 women (mean±SD age 34.8±4 years; gestational weeks 29.3±1.3; body mass index 23.8±4.7 kg/m2) who consumed a low GL or a high GL diet in random order, 1-day each, over 2 consecutive days. Diets were energy-matched and fiber-matched with 5 meals per 24 hours. All food was provided. Continuous glucose monitoring was used to assess diurnal glycemia. RESULTS: Maternal glucose levels were 51% lower on the low GL day with lower incremental area under the curve (iAUC±SEM 549±109 vs 1120±198 mmol/L min, p=0.015). Glycemic variability was significantly lower on the low GL day, as demonstrated by a lower average SD (0.7±0.1 vs 0.9±0.1, p<0.001) and lower mean amplitude of glycemic excursions (2.1±0.2 vs 2.7±0.2 mmol/L, p<0.001). CONCLUSIONS: A lower GL meal plan in pregnancy acutely halves day-long maternal glucose levels and reduces glucose variability, providing further evidence to support the utility of a low GL diet in pregnancy.

Macronutrient Balance and Dietary Glycemic Index in Pregnancy Predict Neonatal Body Composition.

The influence of maternal macronutrient balance and dietary glycemic index (GI) on neonatal body composition has received little study. We hypothesized that the overall quantity and quality of macronutrients, particularly carbohydrate, in the maternal diet could have trimester-specific effects on neonatal growth and body composition in women at risk of gestational diabetes. Maternal diet was assessed using 3-day food records in mid (n = 96) and late (n = 88) pregnancy as part of the GI Baby 3 study. Neonatal body composition was assessed by air-displacement plethysmography within 48 h of birth, adjusted for length, and expressed as fat mass index (FMI) and fat-free mass index (FFMI). In mid pregnancy, higher maternal intake of carbohydrate energy was negatively correlated with infant FFMI (p = 0.037). In late pregnancy, higher dietary GI was associated with lower FFMI (p = 0.010) and higher carbohydrate energy predicted lower FMI (p = 0.034). Higher fat intake (%E) and saturated fat, but not protein, also predicted neonatal body composition (higher FFMI in mid pregnancy and higher FMI in late pregnancy). Depending on pregnancy stage, a high carbohydrate-low fat diet, particularly from high glycemic sources, may reduce neonatal indices of both lean mass and adiposity.

Effects of a low-glycemic index diet during pregnancy on offspring growth, body composition, and vascular health: a pilot randomized controlled trial.

BACKGROUND: Elevated maternal blood glucose concentrations may contribute to macrosomia, adiposity, and poorer vascular health in the offspring. OBJECTIVE: The aim was to explore the effect of a low-glycemic index (low-GI) diet during pregnancy on offspring growth, adiposity, and arterial wall thickness during infancy. DESIGN: This was a longitudinal follow-up study in a self-selected subgroup of mother-infant pairs (n= 59) participating in a larger randomized trial comparing the effects on perinatal outcomes of a low-GI diet and a conventional high-fiber (HF) diet during pregnancy. Infant anthropometric measurements were taken every month for 6 mo and then at 9 and 12 mo of age. Adiposity was assessed at birth and at 3 mo by air-displacement plethysmography by using the Pea Pod system (Cosmed) and at 6 and 12 mo by bioimpedance analysis (Bodystat). Aortic intima-media thickness was assessed at 12 mo by high-resolution ultrasound (Philips). RESULTS: Maternal dietary GI was lower in the low-GI group than in the HF group (51 ± 1 compared with 57 ± 1;P< 0.001). No differences in neonatal outcomes were observed in the main trial. In the self-selected subsample, birth weight and length z scores were lower in the low-GI group than in the HF group (birth weight z score: 0.2 ± 0.2 compared with 0.7 ± 0.2, respectively;P= 0.04; birth length z score: 0.3 ± 0.2 compared with 0.9 ± 0.2, respectively;P= 0.04), but adiposity from birth to 12 mo of age and growth trajectories from 1 to 12 mo of age were similar. Aortic intima-media thickness was lower in the low-GI group than in the HF group (657 ±12 compared with 696 ± 12 µm, respectively;P= 0.02), which was partly mediated by differences in birth weight. CONCLUSION: In women at risk of gestational diabetes mellitus, a low-GI diet influences offspring birth weight, birth length, and arterial wall thickness in early childhood, but not adiposity or growth trajectory during the first year of life. This trial was registered at anzctr.org.au as ACTRN12610000681055.