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.

Associations Between Physical Activity and Gastrointestinal Transit Times in People with Normal Weight, Overweight, and Obesity.

BACKGROUND: Rapid gastric emptying is associated with obesity and overeating, whereas delayed gastric emptying is associated with anorexia. Acute effects of exercise on gastric emptying have been investigated extensively, but the influence of habitual physical activity on gastric emptying and transit time in other regions of the gastrointestinal tract is poorly understood. OBJECTIVE: The objective was to investigate associations between objectively measured habitual physical activity and gastrointestinal transit times in adults with varying degrees of adiposity. METHODS: 50 adults (58% women) were included in this cross-sectional study. Physical activity was measured by an accelerometer placed on the lower back for 7 d. Gastric emptying time, small bowel transit time, colonic transit time, and whole gut transit time were simultaneously evaluated by a wireless motility capsule, which was ingested together with a standardized mixed meal. Linear regression models were applied to assess the associations of total activity counts and time spent at different intensities-sedentary activity (0-100 counts/min), low light activity (101-759 counts/min), high light activity (760-1951 counts/min); moderate and vigorous activity (≥1952 counts/min)) with gastrointestinal transit times. RESULTS: Median [Q1; Q3] age was 56.5 [46.6-65.5] y, and body mass index (BMI) was 32.1 [28.5-35.1] kg/m2. For every additional hour spent performing high light intensity physical activity, colonic transit time was 25.5 % [95% CI: 3.10, 42.7] more rapid (P = 0.028), and whole gut transit time was 16.2 % [95% CI: 1.84, 28.4] more rapid (P = 0.028) when adjusted for sex, age, and body fat. No other associations were observed. CONCLUSIONS: More time spent on physical activity at high light intensity was associated with more rapid colonic and whole gut transit time, independent of age, sex, and body fat, whereas other intensities of physical activity and gastrointestinal transit times were not associated. TRIAL REGISTRATION: Clinicaltrials.gov IDs (NCT03894670, NCT03854656).

The association between sleep duration and detailed measures of obesity: A cross sectional analysis in the ADDITION-PRO study.

Background: Sleep duration is associated with BMI and waist circumference. However, less is known about whether sleep duration affects different measurements of obesity differently. Objective: To investigate the association between sleep duration and different measures of obesity. Methods: In this cross-sectional analysis 1309, Danish, older adults (55% men) completed at least 3 days of wearing a combined accelerometer and heart rate-monitor for assessing sleep duration (hours/night) within self-reported usual bedtime. Participants underwent anthropometry and ultrasonography to assess BMI, waist circumference, visceral fat, subcutaneous fat, and fat percentage. Linear regression analyses examined the associations between sleep duration and obesity-related outcomes. Results: Sleep duration was inversely associated with all obesity-related outcomes, except visceral-/subcutaneous-fat-ratio. After multivariate adjustment the magnitude of associations became stronger and statistically significant for all outcomes except visceral-/subcutaneous-fat-ratio, and subcutaneous fat in women. The associations with BMI and waist circumference demonstrated the strongest associations, when comparing standardized regression coefficients. Conclusions: Shorter sleep duration were associated with higher obesity across all outcomes except visceral-/subcutaneous-fat-ratio. No specifically salient associations with local or central obesity were observed. Results suggest that poor sleep duration and obesity correlate, however, further research is needed to conclude on beneficial effects of sleep duration regarding health and weight loss.

The GDF15-GFRAL pathway is dispensable for the effects of metformin on energy balance.

Metformin is a blood-glucose-lowering medication with physiological effects that extend beyond its anti-diabetic indication. Recently, it was reported that metformin lowers body weight via induction of growth differentiation factor 15 (GDF15), which suppresses food intake by binding to the GDNF family receptor α-like (GFRAL) in the hindbrain. Here, we corroborate that metformin increases circulating GDF15 in mice and humans, but we fail to confirm previous reports that the GDF15-GFRAL pathway is necessary for the weight-lowering effects of metformin. Instead, our studies in wild-type, GDF15 knockout, and GFRAL knockout mice suggest that the GDF15-GFRAL pathway is dispensable for the effects of metformin on energy balance. The data presented here question whether metformin is a sufficiently strong stimulator of GDF15 to drive anorexia and weight loss and emphasize that additional work is needed to untangle the relationship among metformin, GDF15, and energy balance.

Effects of sleep manipulation on markers of insulin sensitivity: A systematic review and meta-analysis of randomized controlled trials.

Poor sleep habits are associated with increased risk of developing type 2 diabetes. In this review and meta-analysis, we aimed to investigate the effects of sleep manipulation on markers of insulin sensitivity from randomized, controlled trials. Sleep manipulation was defined as reduction in sleep duration, sleep quality, and circadian misalignment. A systematic literature search was conducted in three databases and resulted in 35 eligible articles. The studies included interventions on sleep restriction (26 studies), slow wave sleep suppression and rapid eye movement sleep disturbance (2 studies), sleep fragmentation (2 studies), and circadian misalignment (5 studies). The meta-analysis included 21 sleep restriction studies. Sleep restriction reduced insulin sensitivity assessed by oral or intravenous glucose tolerance test and homeostatic model assessment of insulin resistance. Whole-body insulin sensitivity was also reduced after short sleep when measured by the hyperinsulinemic euglycemic clamp, but peripheral insulin sensitivity was not affected. In addition, circadian misalignment and slow wave sleep suppression negatively affected insulin sensitivity, while rapid eye movement sleep disturbance and sleep fragmentation had no effect. In summary, the studies indicated that duration, quality, and timing of sleep are essential for metabolic function and risk of type 2 diabetes.

The day-night pattern of colonic contractility is not impaired in type 1 diabetes and distal symmetric polyneuropathy.

Colonic contractility normally shows circadian variability regulated by sleep and especially food intake. However, individuals with type 1 diabetes have a reduced or even absent gastrocolic response to a meal, indicating that colonic contractility may be affected by the disease. We hypothesized that individuals with type 1 diabetes and distal symmetric polyneuropathy (DSPN) have decreased motility (expressed as the motility index) and contractility of the colon and a reduced increase in motility index from night to morning compared to healthy controls and individuals with type 1 diabetes without DSPN. Cohorts of 35 individuals with type 1 diabetes and DSPN, 40 individuals with type 1 diabetes without DSPN, and 28 healthy controls were included in this post-hoc, cross-sectional analysis. We investigated, using a wireless motility capsule that measures pH, temperature, and pressure throughout the gastrointestinal tract, whether individuals with type 1 diabetes with and without DSPN, compared to healthy controls, exhibit altered colonic contractility in the evening, night, and morning. Max amplitude, mean peak amplitude, mean contraction, and motility index of the colon were calculated at the afore-designated times. Motility index of the colon tended to be higher in individuals with type 1 diabetes and DSPN compared to controls in the evening (P = .064), but the effect size was small (1.74%). There was no difference in motility index between the groups in the morning or evening. Furthermore, there was no difference in max amplitude, mean peak amplitude, or mean contraction between groups in the morning, evening, and night. As expected, overall contractility increased from night to morning in all groups, but there was no difference between groups in the increase in contractility from night to morning. Colonic contractility generally peaked in the morning, decreased in the evening, and was almost absent at night. Type 1 diabetes and/or DSPN did not impair contractility of the colon at any time point. Contractility and motility increased from morning to night unaffected by type 1 diabetes and/or DSPN.

No effects of dapagliflozin, metformin or exercise on plasma glucagon concentrations in individuals with prediabetes: A post hoc analysis from the randomized controlled PRE-D trial.

AIM: To assess the effects of dapagliflozin, metformin and exercise treatment on changes in plasma glucagon concentrations in individuals with overweight and HbA1c-defined prediabetes. MATERIALS AND METHODS: One-hundred and twenty individuals with overweight (body mass index ≥ 25 kg/m2 ) and prediabetes (HbA1c of 39-47 mmol/mol) were randomized to a 13-week intervention with dapagliflozin (10 mg once daily), metformin (850 mg twice daily), exercise (30 minutes of interval training 5 days per week) or control (habitual living). A 75-g oral glucose tolerance test (OGTT) (0, 30, 60 and 120 minutes) was administered at baseline, at 13 weeks (end of intervention) and at 26 weeks (end of follow-up). Linear mixed effects models with participant-specific random intercepts were used to investigate associations of the interventions with fasting plasma glucagon concentration, insulin/glucagon ratio and glucagon suppression during the OGTT. RESULTS: At baseline, the median (Q1; Q3) age was 62 (54; 68) years, median fasting plasma glucagon concentration was 11 (7; 15) pmol/L, mean (SD) HbA1c was 40.9 (2.3) mmol/mol and 56% were women. Compared with the control group, fasting glucagon did not change in any of the groups from baseline to the end of the intervention (dapagliflozin group: -5% [95% CI: -29; 26]; exercise group: -8% [95% CI: -31; 24]; metformin group: -2% [95% CI: -27; 30]). Likewise, there were no differences in insulin/glucagon ratio and glucagon suppression during the OGTT between the groups. CONCLUSIONS: In individuals with prediabetes, 13 weeks of treatment with dapagliflozin, metformin or exercise was not associated with changes in fasting or post-OGTT glucagon concentrations.

Protocol for a single-centre, parallel-group, randomised, controlled, superiority trial on the effects of time-restricted eating on body weight, behaviour and metabolism in individuals at high risk of type 2 diabetes: the REStricted Eating Time (RESET) study.

INTRODUCTION: The aim of this study is to investigate the effects of time-restricted eating (TRE) on change in body weight and describe changes in behaviour and metabolism in individuals at high risk of type 2 diabetes. METHODS AND ANALYSIS: The REStricted Eating Time (RESET) study is a randomised controlled parallel-group open-label trial. 100 women and men with (1) overweight (body mass index (BMI)≥25 kg/m2) and prediabetes (glycated haemoglobin 39-47 mmol/mol); or (2) obesity (BMI≥30 kg/m2) will be randomised to a control group (habitual living) or TRE (self-selected 10-hours eating window within the period from 06:00 to 20:00 in a 1:1 ratio. Testing is scheduled at baseline and after 6 weeks (mid-intervention), 3 months (post-intervention) and 6 months (follow-up). The primary outcome is change in body weight after 3 months of intervention. Secondary outcomes include changes in body composition; measures of glucose metabolism including glycaemic variability, hormones and metabolites; subjective and metabolic markers of appetite, food preferences and reward; dietary intake; physical activity, sleep, chronotype; gastric emptying, gastrointestinal transit time and motility; respiratory and glycolytic capacities; the plasma proteome and metabolome; blood pressure, resting heart rate and heart rate variability; and resting energy expenditure and substrate oxidation. Motivation and feasibility will be examined based on interviews at baseline and after 3 months. After the 3-month intervention, a 3-month follow-up period and subsequent testing are scheduled to assess maintenance and longer-term effects. ETHICS AND DISSEMINATION: The study has been approved by the Ethics Committee of the Capital Region of Denmark (H-18059188) and the Danish Data Protection Agency. The study will be conducted in accordance with the Declaration of Helsinki. Results from the study will address whether TRE is effective and feasible in improving health outcomes in individuals at risk of lifestyle-related diseases and can potentially inform the design of feasible health recommendations. TRIAL REGISTRATION NUMBER: NCT03854656.

Role of fasting duration and weekday in incretin and glucose regulation.

Fasting duration has been associated with lower fasting blood glucose levels, but higher 2-h post-load levels, and research has indicated an adverse effect of 'weekend behavior' on human metabolism. We investigated associations of fasting duration and weekday of examination with glucose, insulin, glucagon and incretin responses to an oral glucose tolerance test (OGTT). This cross-sectional study is based on data from the ADDITION-PRO study, where 2082 individuals attended a health examination including an OGTT. Linear regression analysis was applied to study the associations of overnight fasting duration and day of the week with glucose, insulin, glucagon, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) responses to an OGTT. We found that a 1 h longer fasting duration was associated with 1.7% (95% CI: 0.8,2.5) higher 2-h glucose levels, as well as a 3.0% (95% CI: 1.3,4.7) higher GIP and 2.3% (95% CI: 0.3,4.4) higher GLP-1 response. Fasting insulin levels were 20.6% (95% CI: 11.2,30.7) higher on Mondays compared to the other weekdays, with similar fasting glucose levels (1.7%, 95% CI: 0.0,3.4). In this study, longer overnight fasting duration was associated with a worsening of glucose tolerance and increased incretin response to oral glucose. We found higher fasting insulin levels on Mondays compared to the other days of the week, potentially indicating a worsened glucose regulation after the weekend.

Physical Activity, Sedentary Time, and Sleep and the Association With Inflammatory Markers and Adiponectin in 8- to 11-Year-Old Danish Children.

BACKGROUND: Inflammatory markers, adiponectin, and movement/nonmovement behaviors have all been linked to risk factors for cardiovascular disease; however, the association between childhood movement/nonmovement behaviors and inflammatory markers and adiponectin is unknown. METHODS: We explored the association between accelerometer determined moderate-to-vigorous physical activity (MVPA), sedentary time, and sleep (7 days/8 nights) and fasting C-reactive protein (CRP), interleukin-6 (IL-6), and adiponectin in 806 school children. A sleep variability score was calculated. RESULTS: MVPA was negatively associated with adiponectin in boys and girls (P < .001) and with CRP and IL-6 in girls (P < .05) independent of sleep duration, sedentary time, age, fat mass index (FMI), and pubertal status. Sedentary time was positively associated with adiponectin in boys and girls (both P < .001), and sleep duration with adiponectin in boys independent of age, FMI, and pubertal status (P < .001); however, these associations disappeared after mutual adjustments for movement behavior. Sleep duration variability was positively associated with CRP in girls independent of all covariates (P < .01). CONCLUSION: MVPA remained negatively associated with inflammatory markers and adiponectin, and sleep duration variability positively associated with CRP after adjustment for FMI, pubertal status, and other movement behavior. The inverse association between MVPA and adiponectin conflicts with the anti-inflammatory properties of adiponectin.

Sleep and cardiometabolic risk in children and adolescents.

The evidence for a link between sleep and cardiometabolic risk factors in children and adolescents is accumulating; however, the literature has not yet been reviewed. Seventy-five studies investigating associations between sleep variables and measures of abdominal adiposity, glucose homeostasis, blood lipids, blood pressure (BP), and inflammatory markers were included in the present review. The current evidence indicates that inadequate sleep may play a role in cardiometabolic risk at a later age for children and adolescents. Most compelling is the evidence for an association between inadequate sleep and abdominal adiposity, decreased insulin sensitivity as well as high BP, whereas the evidence for potential links between sleep and blood lipids as well as inflammatory markers is less convincing. It should, however, be noted that the majority of studies linking sleep with cardiometabolic outcomes are cross-sectional in nature, and sleep is often assessed using parent or self-report. We suggest that future studies should investigate longitudinal associations between sleep and cardiometabolic risk factors with the use of objective sleep measurements conducted for several days, including weekdays and weekend days, at multiple time points over time. Meanwhile, based on the available evidence, we recommend that children and adolescents get adequate amounts of good sleep in a regular pattern.