AimsThe PREVIEW lifestyle intervention study (http://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 methodsAll 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.ResultsIn 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.ConclusionsAn 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.

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.

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

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.

ObjectiveMaternal 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 methodsA 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.ResultsMaternal 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).ConclusionsA 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.

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. (Continued on next page)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).

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.

This finding of an unbalanced translocation provides further evidence to support previous linkage studies of a potential causative gene on 8q for bipolar disorder.