Tanja C. Adam

We investigated the effects of sweeteners and sweetness enhancers (S&SEs) in replacement of sugar on gene expression markers of adipose tissue (AT) function, adipocyte morphology, and metabolic health in adults during weight maintenance (WM) following weight loss (WL). As part of a randomized controlled trial (European SWEET-project), 83 adults were enrolled in the study, which consists of a dietary intervention, comprising a 2-month WL-phase and a 10-month WM-phase during which participants followed a healthy diet (<10E%-added sugar) with (S&SEs group) or without S&SEs (sugar group). At baseline, after WL, and at the end of WM, we determined body composition, whole-body/tissue-specific insulin sensitivity (oral glucose tolerance test), abdominal subcutaneous adipocyte size and AT gene expression. WL decreased adipocyte size and improved insulin sensitivity (both P < 0.001), which was accompanied by a significant downregulation of genes involved in adipogenesis (CEBPɑ, P = 0.004), fatty acid uptake (LPL and SREBF1, both P < 0.001), fatty acid synthesis (FASN and SCD, both P < 0.001), intracellular lipolysis (ATGL, P < 0.001; HSL, P = 0.001), leptin (LEP, P < 0.001), and mitochondrial function (CS, P = 0.048) in AT. The S&SEs-group tended to regain less weight than the sugar group during the WM-phase (3.0 ± 1.2 vs. 5.9 ± 1.0 kg, respectively; P = 0.050). During the WM-phase, the S&SEs group showed a less pronounced increase in AT LPL gene expression (P = 0.041), while ABHD5 expression decreased compared to the sugar group (P = 0.036). No group differences in adipocyte size, expression of genes involved adipogenesis/oxidative metabolism/inflammation, the sweet taste receptor TAS1R3 and insulin sensitivity were found. S&SE-intake during a 10-month WM-phase following WL altered AT gene expression of lipolytic markers, without affecting adipocyte morphology and insulin sensitivity in adults with overweight/obesity. ClinicalTrials.gov NCT04226911, Sweeteners and Sweetness Enhancers: Prolonged Effects on Health, Obesity and Safety (SWEET).

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 HbA_1c 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.

Background: To better support participants to achieve long-lasting results within interventions aiming for weight loss and maintenance, more information is needed about the maintenance of behavioral changes. Therefore, we examined whether perceived stress predicts the maintenance of changes in eating behavior (flexible and rigid restraint of eating, disinhibition, and hunger). Methods: The present study was a secondary analysis of the PREVIEW intervention including participants with overweight (BMI ≥ 25 kg/m²) at baseline and high risk of type 2 diabetes (n = 1311). Intervention included a 2-month low-energy diet phase and a 34-month subsequent weight maintenance phase. The first 6 months were considered an active behavior change stage and the remaining 2.5 years were considered a behavior maintenance stage. Eating behavior was measured using the Three Factor Eating Questionnaire and stress using the Perceived Stress Scale. The associations between stress and eating behavior were analyzed using linear mixed effects models for repeated measurements. Results: Perceived stress measured after the active behavior change stage (at 6 months) did not predict changes in eating behavior during the behavior maintenance stage. However, frequent high stress during this period was associated with greater lapse of improved flexible restraint (p = 0.026). The mean (SD) change in flexible restraint from 6 to 36 months was −1.1 (2.1) in participants with frequent stress and −0.7 (1.8) in participants without frequent stress (Cohen’s d_s (95% CI) = 0.24 (0.04–0.43)). Higher perceived stress at 6 months was associated with less flexible restraint and more disinhibition and hunger throughout the behavior maintenance stage (all p < 0.001). Conclusions: Perceived stress was associated with features of eating behavior that may impair successful weight loss maintenance. Future interventions should investigate, whether incorporating stress reduction techniques results in more effective treatment, particularly for participants experiencing a high stress level.

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.

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], ppp1c 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], p1c, 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

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. 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. 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). 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. 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.

Background Circadian rhythm is altered in individuals with obesity and insulin resistance, showing a smaller amplitude, less stability, and increased intradaily variation. Objective We compared reproducibility of circadian-rhythm parameters over time and under free-living vs. controlled conditions in participants with obesity and pre-diabetes after 2- and 3-year weight-loss maintenance during the 3-year PREVIEW (PREVention of diabetes through lifestyle intervention and population studies In Europe and around the World) study. Associations of obesity and insulin resistance with circadian-rhythm parameters were assessed. Subjects and methods Circadian-rhythm parameters were determined using continuous wrist-temperature measurements in free-living environments at year 2 (n = 24; age 56.8 ± 10.3 y; body mass index (BMI) = 30 ± 3.9 kg/m²; homeostatic model assessment of insulin resistance (HOMA-IR) 2.4 ± 1.1), at year 3 (n = 97; age 61.7 ± 7.8; BMI = 29.7 ± 3.9; HOMA-IR 2.9 ± 2.1), and at year 3 in a controlled condition (n = 38; age 63.4 ± 6.7; BMI = 28.7 ± 3.9; HOMA-IR 3.8 ± 1.4). Reproducibility was assessed by analyzing repeatability coefficients (CR), differences, and associations, over time as well as between conditions. Associations of BMI and HOMA-IR with circadian-rhythm parameters were assessed at y-3 in both conditions using factor analysis, followed by Pearson’s correlations. Results Reproducibility of circadian-rhythm parameters over time in the free-living environments was high (CR 0.002–5.26; no significant differences; associated amplitudes r = 0.57; p < 0.01). In contrast, reproducibility between different conditions was low (CR 0.02–11.36; significant differences between most parameters (p < 0.05); yet associated amplitudes r = 0.59; p < 0.01). In the controlled vs. free-living condition circadian-rhythm was more stable; BMI and HOMA-IR were associated with the physiological amplitude-related parameters (r = −0.45; p < 0.01; r = −0.33; p < 0.05). In the free-living environment, BMI and behavioral circadian-rhythm parameters indicating circadian alignment, contributed most to the explained variation (47.1%), and were inversely associated (r = −0.22; p < 0.05), while HOMA-IR was inversely associated with stability-related circadian-rhythm parameters (r = −0.21; p < 0.05). Conclusions Circadian rhythm was highly reproducible over time in the free-living environments, yet different under different conditions, being more stable in the controlled condition. BMI may play a significant role in circadian alignment and vice versa in the free-living environment.