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).

Occurrence of Gastrointestinal Adverse Events Upon GLP-1 Receptor Agonist Initiation With Concomitant Metformin Use: A Post Hoc Analysis of LEADER, STEP 2, SUSTAIN-6, and PIONEER 6.

OBJECTIVE: To assess the impact of concomitant metformin use on gastrointestinal adverse events during the initiation and titration of a glucagon-like peptide 1 receptor agonist (GLP-1RA). RESEARCH DESIGN AND METHODS: Using data from four clinical trials of liraglutide and semaglutide (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results [LEADER], Semaglutide Treatment Effect in People with Obesity [STEP 2], Trial to Evaluate Cardiovascular and Other Long-Term Outcomes With Semaglutide in Subjects With Type 2 Diabetes [SUSTAIN-6], and Peptide Innovation for Early Diabetes Treatment [PIONEER] 6), we compared the incidence of gastrointestinal adverse events during GLP-1RA initiation and titration in participants with and without concomitant metformin use. RESULTS: Of 16,996 participants, 12,928 (76%) were treated with metformin. Concomitant metformin use did not increase the percentage of participants who developed gastrointestinal adverse events or their severity during the observation window. Among participants experiencing gastrointestinal adverse events, metformin use did not increase study product discontinuation. Within treatment arms (GLP-1RA and placebo), a numerically higher percentage of metformin nonusers experienced gastrointestinal adverse events and discontinued the study product compared with metformin users. CONCLUSIONS: Concomitant metformin use does not increase occurrence of gastrointestinal symptoms during GLP-1RA initiation or impact GLP-1RA discontinuation.

Predicting the HbA1c level following glucose-lowering interventions in individuals with HbA1c-defined prediabetes: a post-hoc analysis from the randomized controlled PRE-D trial.

PURPOSE: To investigate whether the prediction of post-treatment HbA1c levels can be improved by adding an additional biomarker of the glucose metabolism in addition to baseline HbA1c. METHODS: We performed an exploratory analysis based on data from 112 individuals with prediabetes (HbA1c 39-47 mmol) and overweight/obesity (BMI ≥ 25 kg/m2), who completed 13 weeks of glucose-lowering interventions (exercise, dapagliflozin, or metformin) or control (habitual living) in the PRE-D trial. Seven prediction models were tested; one basic model with baseline HbA1c as the sole glucometabolic marker and six models each containing one additional glucometabolic biomarker in addition to baseline HbA1c. The additional glucometabolic biomarkers included: 1) plasma fructosamine, 2) fasting plasma glucose, 3) fasting plasma glucose × fasting serum insulin, 4) mean glucose during a 6-day free-living period measured by a continuous glucose monitor 5) mean glucose during an oral glucose tolerance test, and 6) mean plasma glucose × mean serum insulin during the oral glucose tolerance test. The primary outcome was overall goodness of fit (R2) from the internal validation step in bootstrap-based analysis using general linear models. RESULTS: The prediction models explained 46-50% of the variation (R2) in post-treatment HbA1c with standard deviations of the estimates of ~2 mmol/mol. R2 was not statistically significantly different in the models containing an additional glucometabolic biomarker when compared to the basic model. CONCLUSION: Adding an additional biomarker of the glucose metabolism did not improve the prediction of post-treatment HbA1c in individuals with HbA1c-defined prediabetes.

Role of Weekday Variation on Glucose, Insulin, and Triglyceride: A Cross-Sectional Analysis From the Maastricht Study.

CONTEXT: The timing of sleep, physical activity, and dietary intake show variation over the week, with different timings in the weekend compared to the weekdays, which may potentially lead to impaired glucose and lipid regulation on Mondays compared to other weekdays. OBJECTIVE: The aim of the study was to investigate differences in glucose metabolism and fasting triglyceride concentrations on Mondays compared to the rest of the week. DESIGN, SETTING AND PARTICIPANTS: This cross-sectional study is based on data from the Maastricht Study, including 6067 participants without known diabetes and 1568 previously diagnosed with type 2 diabetes. MAIN OUTCOME MEASURES: Confounder-adjusted linear regression analysis was applied to study the associations of day of the week of examination with glucose and insulin responses to an oral glucose tolerance test and fasting triglyceride concentrations. RESULTS: In fully confounder-adjusted models, mean (95% CI) concentrations of fasting glucose, insulin, and triglycerides were slightly higher on Mondays compared with the other weekdays [glucose: 1% (0-2); insulin: 9% (1-18); triglycerides: 5% (2-8)]. Interaction analyses revealed that the association of weekday with insulin was only pronounced in men [18% (3-35)], but not in women [1% (-8-10)], whereas the associations with glucose and triglycerides were only apparent for individuals with known type 2 diabetes [glucose: 4% (0-7); triglycerides: 14% (6-23)] compared to the background population [glucose: 0% (0-1); triglycerides: 3% (0-6)]. DISCUSSION: Being examined on a Monday was associated with higher fasting insulin concentrations among men but not women.

The effects of dapagliflozin, metformin or exercise on glycaemic variability in overweight or obese individuals with prediabetes (the PRE-D Trial): a multi-arm, randomised, controlled trial.

AIMS/HYPOTHESIS: We aimed to investigate the short-term efficacy and safety of three glucose-lowering interventions in overweight or obese individuals with prediabetes defined by HbA1c. METHODS: The PRE-D Trial was a randomised, controlled, parallel, multi-arm, open-label, non-blinded trial performed at Steno Diabetes Center Copenhagen, Gentofte, Denmark. One hundred and twenty participants with BMI ≥25 kg/m2, 30-70 years of age, and prediabetes (HbA1c 39-47 mmol/mol [5.7-6.4%]) were randomised 1:1:1:1 to dapagliflozin (10 mg once daily), metformin (1700 mg daily), interval-based exercise (5 days/week, 30 min/session) or control (habitual lifestyle). Participants were examined at baseline and at 6, 13 and 26 weeks after randomisation. The primary outcome was the 13 week change in glycaemic variability (calculated as mean amplitude of glycaemic excursions [MAGE]) determined using a continuous glucose monitoring system (pre-specified minimal clinically important difference in MAGE ∼30%). RESULTS: One hundred and twelve participants attended the examination at 13 weeks and 111 attended the follow-up visit at 26 weeks. Compared with the control group, there was a small decrease in MAGE in the dapagliflozin group (17.1% [95% CI 0.7, 30.8], p = 0.042) and a small, non-significant, reduction in the exercise group (15.3% [95% CI -1.2, 29.1], p = 0.067), whereas MAGE was unchanged in the metformin group (0.1% [95% CI -16.1, 19.4], p = 0.991)). Compared with the metformin group, MAGE was 17.2% (95% CI 0.8, 30.9; p = 0.041) lower in the dapagliflozin group and 15.4% (95% CI -1.1, 29.1; p = 0.065) lower in the exercise group after 13 weeks, with no difference between exercise and dapagliflozin (2.2% [95% CI -14.8, 22.5], p = 0.815). One serious adverse event occurred in the control group (lung cancer). CONCLUSIONS/INTERPRETATION: Treatment with dapagliflozin and interval-based exercise lead to similar but small improvements in glycaemic variability compared with control and metformin therapy. The clinical importance of these findings in prediabetes is uncertain. TRIAL REGISTRATION: ClinicalTrials.gov NCT02695810 FUNDING: The study was funded by the Novo Nordisk Foundation, AstraZeneca AB, the Danish Innovation Foundation, the University of Copenhagen and Ascensia Diabetes Care Denmark ApS Graphical abstract.

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.

Hand eczema patients' knowledge of skin protection following a guided talk-A retrospective study with a follow-up questionnaire.

BACKGROUND: Several studies have assessed the effect of patient education regarding hand eczema (HE) severity and quality of life. Few studies, however, have evaluated patients' knowledge. OBJECTIVES: To examine knowledge of skin protection in HE patients following a guided talk, and to identify variables associated with knowledge. METHODS: HE patients referred to the outpatient dermatological clinic, Bispebjerg Hospital, between January 2013 and July 2014 were offered a guided talk on HE prevention. HE severity and the Dermatology Life Quality Index (DLQI) score were assessed. A questionnaire comprising 10 questions about skin protection was sent 1 to 2.5 years later. RESULTS: One hundred and twenty patients responded to the questionnaire (response 53.5%). The mean percentage of correct answers was 74.7%. Sixty per cent responded correctly to at least eight questions. Male sex, older age and education for >5 years were associated with a low level of knowledge. Education for 3 to 4 years (P = 0.045) was associated with a higher level of knowledge. No significant impact of previous/current atopic dermatitis, HE severity or previous information on skin protection was found with respect to level of knowledge. CONCLUSIONS: Females and patients with education for 3 to 4 years showed the highest level of knowledge, whereas males, older patients and patients with education for >5 years should be brought more into focus in skin protection programmes.

Hyperkeratotic hand eczema compared to other subgroups of hand eczema - a retrospective study with a follow-up questionnaire.

BACKGROUND: Only a few clinical trials on hand eczema have included further classification into subtypes, and there is a need for studies evaluating the present classifications. OBJECTIVES: To examine differences in demographic factors, lifestyle factors and severity between subgroups of hand eczema patients, with a focus on hyperkeratotic hand eczema. METHODS: This was a retrospective study including hand eczema patients referred to the outpatient dermatological clinic, Bispebjerg Hospital, between January 2013 and July 2014. The study comprises information on subdiagnoses, treatment and foot eczema from patient files, as well as a follow-up questionnaire. RESULTS: A total of 120 patients were included, 10 of whom were diagnosed with hyperkeratotic hand eczema. A significantly higher proportion of the patients with hyperkeratotic hand eczema were male (p = 0.002) and received systemic or ultraviolet (UV) treatment (p = 0.026). The frequency of tobacco smoking was significantly higher in patients with hyperkeratotic hand eczema (p = 0.016), as well as in the other subgroups combined (p = 0.049), than in the background population. CONCLUSIONS: Studies evaluating the subdiagnoses of hand eczema are needed, to further validate the classification system, and to provide more detailed information about demographic factors, severity and possible risk factors for different subgroups of hand eczema.

Associations between lifestyle factors and hand eczema severity: are tobacco smoking, obesity and stress significantly linked to eczema severity?

BACKGROUND: It has been suggested that lifestyle factors such as smoking, overweight and stress may influence the prevalence and severity of hand eczema. OBJECTIVES: To investigate the association between lifestyle factors and hand eczema severity in a cohort of patients with work-related hand eczema. METHODS: Individuals with work-related hand eczema notified in the period between June 2012 and November 2013 were included in this questionnaire-based cross-sectional study. Participants responded to a questionnaire including questions on lifestyle factors, as well as a photographic guide for assessment of severity of hand eczema and questions on quality of life. RESULTS: A total of 773 individuals (546 women and 227 men) responded to the questionnaire and were included in the study. A strong association was found between tobacco smoking and hand eczema severity (p = 0.003), whereas no significant association was found for body weight and stress. Other factors linked to severe eczema were male sex and older age (p = 0.04 and p = 0.01, respectively), and wet work (p = 0.08). CONCLUSION: The data from the present study strongly support an association between smoking and hand eczema severity. However, owing to the cross-sectional design of the study, no conclusion on causation can be drawn.

Occupational allergic contact dermatitis in a 2-year follow-up study: how well does the patient remember the result of patch testing?

BACKGROUND: Patch testing is mandatory for diagnosing contact dermatitis. It is, however, crucial that patients understand and remember the result of the test. OBJECTIVES: The aim of our study was to evaluate the impact of patch testing with respect to patients' ability to remember patch test results and the results of natural rubber latex protein allergy after 2 years. METHODS: One hundred and ninety-nine patients diagnosed with relevant occupational epoxy or rubber chemical contact allergy, or allergy to natural rubber latex protein, were invited to participate in a questionnaire study about their knowledge of contact allergies after 2 years. RESULTS: The response rate was 75%. Of the respondents, 13% did not remember their occupational contact allergy to rubber chemicals or epoxy. Ability to remember was not significantly influenced by sex or Dermatology Life Quality Index, but was decreased by age >60 years (p < 0.01). Of patients with an additional contact allergy, <36% remembered this correctly. Of patients allergic to natural rubber latex proteins, 50% remembered this correctly. CONCLUSIONS: The impact of patch testing depends on the patients' ability to understand and remember the results of the test. Attention should be drawn to the importance of this, and patients with increased need for information should be identified.

Evidence-based training as primary prevention of hand eczema in a population of hospital cleaning workers.

BACKGROUND: Skin disorders accounted for one third of all recognised occupational diseases in Denmark in 2010. Wet work is a risk factor for the development of occupational hand eczema. The consequences of occupational hand eczema include sick leave, loss of job and impaired quality of life. OBJECTIVES: The aim of the present study was to investigate exposures related to cleaning and the effect of an evidence-based educational intervention on the prevention of hand eczema among hospital cleaners. PATIENTS/MATERIALS/METHODS: The intervention consisted of a 1 hr course in hand protective behaviour. All full-time cleaners working at Bispebjerg Hospital in January 2013 were invited to participate. The outcome measures were self-reported skin behaviour, exposures, knowledge of skin protection and hand eczema severity index (HECSI). RESULTS: One hundred and five cleaners were invited to participate, of these 86 (82%) were included. At follow-up after 3 months there was a shift towards fewer daily hand washings and hand disinfections (p < 0.001 and p = 0.001 respectively). The number of correct answers to the knowledge questions rose from 6.3 to 7.3 (p = 0.006). The mean HECSI score decreased from 2.8 to 1.8 at follow-up (p = 0.002). CONCLUSIONS: Data indicates a positive effect of a low-cost on-site educational intervention for hospital cleaners.

The circadian schedule for childhood acute lymphoblastic leukemia maintenance therapy does not influence event-free survival in the NOPHO ALL92 protocol.

BACKGROUND: The event-free survival of childhood acute lymphoblastic leukemia (ALL) has been reported to be superior when oral methotrexate (MTX) and 6-mercaptopurine (6MP) maintenance therapy (MT) is administered in the evening compared to the morning. PROCEDURE: In the ALL92 MT study we prospectively registered the intake of MTX/6MP. The registration was done when blood samples for erythrocyte MTX/6MP metabolite measurements were collected, and referred to the time of intake in the period since last registration. Nine thousand one hundred ninety-five registrations in total. The administration of MTX/6MP was scored as morning, midday, or evening. RESULTS: Of 532 patients, 296 took their medication consistently in the evening, 129 in the evening 50.0-99.9% of the time, and 101 in the evening <50% of the time, six did not have any registrations. The circadian schedule did not differ significantly by age, sex, MTX/6MP doses, and average absolute neutrophil counts. The circadian schedule groups did differ on risk groups (P = 0.003) with fewer HR patients in the 50-99.9% group, and there was a negative correlation between percentage of time on evening schedule and average WBC (Spearman's rho -0.15; P = 0.0004). Average WBC was not associated with relapse on ALL92. In a Cox multivariate model the circadian schedule of MTX/6MP was not of prognostic significance for the risk of relapse, and the 10-year cumulative relapse risk was below 20% in all groups. CONCLUSION: An evening schedule may still be recommended based on the previous publications, but in this study morning administration of MTX and 6MP does not seem to impact EFS.

Nationwide tobacco surveys and sales data in Denmark from 1920 to 2010.

INTRODUCTION: Tobacco smoking is an important cause of premature death and morbidity in Denmark. It is therefore important to monitor tobacco consumption. In this paper, tobacco consumption in Denmark is illustrated by two methods: sale of tobacco products and smoking habit surveys. MATERIAL AND METHODS: Data on sale of tobacco products in Denmark were available for the 1920-2010-period. National smoking habit surveys were found through grey-zone literature, a PubMed search and a report on the Danish population's smoking habits. Ten smoking habit surveys were identified from the 1953-2010-period, three of which have data from multiple years and annual surveys from 1969 onwards. RESULTS: The changes in tobacco consumption found by the two methods were not parallel. Furthermore, there were significant differences between the proportions of smokers found in smoking habit questionnaires from the same year. This difference may be due to changes in cross-border trade, smuggling, smokers' willingness to participate in smoking habit studies, recognition of own smoking and actual tobacco consumption, and differences in the composition of participants in the smoking habit studies both over time and between different studies. CONCLUSION: Both sales statistics and surveys have advantages and disadvantages. It may therefore be important to use both when estimating tobacco consumption.