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/m ² ) 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.

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/m ² ) 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.

Type-2 diabetes (T2D) is one of the fastest growing chronic diseases worldwide. The PREVIEW project has been initiated to find the most effective lifestyle (diet and physical activity) for the prevention of T2D, in overweight and obese participants with increased risk for T2D. The study is a three-year multi-centre, 2 × 2 factorial, randomised controlled trial. The impact of a high-protein, low-glycaemic index (GI) vs. moderate protein, moderate-GI diet in combination with moderate or high-intensity physical activity on the incidence of T2D and the related clinical end-points are investigated. The intervention started with a two-month weight reduction using a low-calorie diet, followed by a randomised 34-month weight maintenance phase comprising four treatment arms. Eight intervention centres are participating (Denmark, Finland, United Kingdom, The Netherlands, Spain, Bulgaria, Australia, and New Zealand). Data from blood specimens, urine, faeces, questionnaires, diaries, body composition assessments, and accelerometers are collected at months 0, 2, 6, 12, 18, 24, and 36. In total, 2326 adults were recruited. The mean age was 51.6 (SD 11.6) years, 67% were women. PREVIEW is, to date, the largest multinational trial to address the prevention of T2D in pre-diabetic adults through diet and exercise intervention. Participants will complete the final intervention in March, 2018.

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, HbA_1c 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 HbA_1c, LDL-cholesterol and diastolic blood pressure. After the WM intervention, women had greater fat-free mass and bone mass loss and smaller improvements in HbA_1c 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. Graphical

Obesity and type 2 diabetes have been linked to alterations in food reward processing, which may be linked to insulin resistance. 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. 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. 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). 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.

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. 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. 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. 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 (r_s = 0.74; P < 0.001) and RQ (r_s = 0.47; P < 0.01) in the whole group of participants. 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.