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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.

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 [Figure not available: see fulltext.]

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.

Gut-derived hormones have been suggested to play a role in bone homeostasis following food intake, although the associations are highly complex and not fully understood. In a randomized, two-day cross-over study on 14 healthy individuals, we performed postprandial time-course studies to examine the associations of the bone remodeling markers carboxyl-terminal collagen type I crosslinks (CTX) and procollagen type 1 N-terminal propeptide (P1NP) with the gut hormones glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1), and peptide YY (PYY) using two different meal types—a standardized mixed meal (498 kcal) or a granola bar (260 kcal). Plasma concentrations of total GIP, total GLP-1, total PYY, CTX, and P1NP were measured up to 240 min after meal intake, and the incremental area under the curve (iAUC) for each marker was calculated. The iAUC of CTX and P1NP were used to assess associations with the iAUC of GIP, GLP-1, and PYY in linear mixed effect models adjusted for meal type. CTX was positively associated with GIP and GLP-1, and it was inversely associated with PYY (all p < 0.001). No associations of P1NP with GIP or GLP-1 and PYY were found. In conclusion, the postprandial responses of the gut hormones GIP, GLP-1, and PYY are associated with the bone resorption marker CTX, supporting a link between gut hormones and bone homeostasis following food intake.

Pervasive exposure to a vast and varied food repertoire has contributed to the obesity epidemic. Within this issue, there is a need for a better understanding of the psychophysiological responses to food cues that precede food choice and food intake to establish how these responses contribute to the link between food availability and increasing obesity levels. Biometric measures such as eye tracking, electrodermal activity and facial expressions may separately or collectively provide deeper insight into psychophysiological processes underlying food reward and food intake. We examined how biometric responses differed in foods varying in fat and taste and explored how these biometric signatures to food cues were related to food preference behaviours, food choice, and food intake. We developed and tested a biometric food preference task designed to concurrently assess biometric responses (eye tracking, electrodermal activity and facial expressions) and food reward to visual food stimuli from different food categories in 100 normal weight adults. Food intake and selection was examined using a simultaneous choice ad libitum buffet. The results from this cross-sectional study showed significant differences in visual attention towards foods varying in fat content and taste prior to making rapid food choice decisions. Furthermore, the study found positive associations between maintained attention during a forced choice paradigm and subsequent food reward and food intake measures. Attention, arousal and facial expression during passive viewing were not associated with food reward or intake measures, except for an association between negative valence and explicit liking such that less liked foods elicited stronger negative facial expressions. The findings indicate that implicit, biometric responses to food cues predict both food reward and actual food intake.

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.

Knowledge on how energy intake and macronutrients are distributed during the day and the role of daily eating patterns in body composition among adults with overweight/obesity and prediabetes is lacking. Therefore, we evaluated the diurnal dietary intake and studied the associations of daily eating patterns with body fat percentage. A total of 119 adults with prediabetes were included (mean (SD) HbA1c 41 (2.3) mmol/mol, BMI 31.5 (5.0) kg/m2, age 57.8 (9.3) years, 44% men). Information on dietary intake was obtained from self-reported food records for three consecutive days. All foods and beverages (except water) were registered with information on time of ingestion. Body fat was measured by dual-energy X-ray absorptiometry. A total of 60.5% of the participants reported a daily eating window of 12 or more hours/day, and almost half of the daily total energy intake was reported in the evening. In analyses adjusted for age, gender, and total daily energy intake, having the first daily energy intake one hour later was associated with slightly higher body fat percentage (0.64% per hour, 95% CI: 0.28, 1.01, p &lt, 0.001), whereas higher meal frequency was associated with slightly lower body fat percentage (0.49% per extra daily meal, 95% CI: &minus, 0.81, &minus, 0.18, p = 0.002). Prospective studies are warranted to address the clinical implications of daily eating patterns on body fat and cardiometabolic health.

IntroductionBlood oxygen saturation is low compared with healthy controls (CONs) in the supine body position in individuals with type 1 diabetes (T1D) and has been associated with complications. Since most of daily life occurs in the upright position, it is of interest if this also applies in the standing body position. In addition, tissue oxygenation in other anatomical sites could show different patterns in T1D. Therefore, we investigated blood, arm and forehead oxygen levels in the supine and standing body positions in individuals with T1D (n=129) and CONs (n=55).Research design and methodsBlood oxygen saturation was measured with pulse oximetry. Arm and forehead mixed tissue oxygen levels were measured with near-infrared spectroscopy sensors applied on the skin.ResultsData are presented as least squares means±SEM and differences (95% CIs). Overall blood oxygen saturation was lower in T1D (CON: 97.6%±0.2%; T1D: 97.0%±0.1%; difference: −0.5% (95% CI −0.9% to −0.0%); p=0.034). In all participants, blood oxygen saturation increased after standing up (supine: 97.1%±0.1%; standing: 97.6%±0.2%; difference: +0.6% (95% CI 0.4% to 0.8%); pConclusionCompared with CON, individuals with T1D exhibit possible detrimental patterns of tissue oxygen adaptation to standing, with preserved adaptation of forehead oxygenation. Further studies are needed to explore the consequences of these differences.

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/m(2)) 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.

Introduction: Glucagon plays a role in the pathogenesis of type 2 diabetes. Yet, little is known about the effect of interventions aimed at preventing progression from prediabetes to diabetes on glucagon concentrations. We examined the effects of dapagliflozin, metformin or exercise on plasma glucagon concentration in individuals with HbA1c-defined prediabetes. Methods: 120 individuals were randomized to a 13-week intervention with dapagliflozin (10 mg once daily), metformin (850 mg twice daily), exercise (interval training 30 min 5 days/week) or control (habitual living). A 75 g oral glucose tolerance test (OGTT; 0, 30, 60 and 120 min) was administered at baseline, at 13 weeks (end of intervention) and at 26 weeks (end of follow-up). Linear mixed-effects models were used to assess effects on fasting concentration, early (0-30 min) area under the curve relative to the fasting level (rAUC0-30 min) and full rAUC0-120 min for glucagon. Results: At baseline, the median (Q1;Q3) age was 62 (54;68) years, HbA1c 5.9% (5.7;6.1%), fasting glucagon 11 (7;15) pmol/L, and 56% were men. No differences in the glucagon measures between groups from baseline to 13 or 26 weeks were observed (Table 1). Conclusions: 13 weeks of treatment with dapagliflozin, metformin or exercise was not associated with changes in fasting or post-OGTT glucagon concentrations in individuals with prediabetes. Disclosure K.K.B. Clemmensen: Research Support; Self; AstraZeneca, Novo Nordisk Foundation. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. M.B. Blond: None. H. Amadid: None. L.B. Nielsen: None. D. Vistisen: Stock/Shareholder; Self; Novo Nordisk A/S. K. Karstoft: Employee; Spouse/Partner; Novo Nordisk A/S. F. Persson: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Research Support; Self; Amgen, AstraZeneca, Novo Nordisk A/S. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Mundipharma International, Novo Nordisk A/S. M. Ried-Larsen: None. J.J. Holst: Advisory Panel; Self; AstraZeneca, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Zealand Pharma A/S. Other Relationship; Spouse/Partner; Antag Therapeutics. N.J. Wewer Albrechtsen: Research Support; Self; Mercodia, Novo Nordisk A/S, Novo Nordisk Foundation. Speaker’s Bureau; Self; Merck Sharp & Dohme Corp. S.S. Torekov: Research Support; Self; Novo Nordisk Inc. J.S. Quist: None. M.E. Jørgensen: Research Support; Self; Amgen, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi-Aventis. Stock/Shareholder; Self; Novo Nordisk A/S. K. Færch: None. Funding Novo Nordisk Foundation; AstraZeneca; University of Copenhagen; Innovation Foundation

Background: Plasma levels of liver enzymes are elevated in prediabetes but may improve in response to weight loss and glucose-lowering interventions. We examined the effects of dapagliflozin, metformin, or exercise on plasma levels of alanine transferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) in people with prediabetes. Methods: 120 adults with prediabetes (30-70 years, BMI≥25 kg/m2, HbA1c 5.7-6.4%) were randomized to 13 weeks of dapagliflozin (10 mg once daily), metformin (850 mg twice daily), exercise (30 min, 5 days/week) or control (habitual living). Fasting plasma levels of ALT, AST, and GGT were measured at baseline and after 6 and 13 weeks of intervention and after 26 weeks of follow-up. Linear mixed-effects models were performed. Results: At baseline, median (Q1;Q3) HbA1c was 5.9% (5.7; 6.1). 17% had elevated ALT levels, 3% elevated AST levels, and 6% elevated GGT levels. ALT and AST levels did not change in response to the interventions (Table 1). Small within-group changes in GGT were observed in the active groups after 6, 13 or 26 weeks, but they did not differ from the control group (P≥0.09 for all comparisons). Conclusions: 13 weeks of treatment with dapagliflozin, metformin or exercise was not associated with changes in liver function markers compared with habitual living in people with prediabetes. Disclosure M.B. Blond: None. K.K. Clemmensen: Research Support; Self; AstraZeneca, Novo Nordisk Foundation. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. H. Amadid: None. L.B. Nielsen: None. M. Ried-Larsen: None. K. Karstoft: Employee; Spouse/Partner; Novo Nordisk A/S. F. Persson: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Research Support; Self; Amgen, AstraZeneca, Novo Nordisk A/S. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Mundipharma International, Novo Nordisk A/S. M.E. Jørgensen: Research Support; Self; Amgen, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi-Aventis. Stock/Shareholder; Self; Novo Nordisk A/S. K. Faerch: None. Funding Novo Nordisk Foundation; AstraZeneca; University of Copenhagen; Innovation Foundation

We aimed to investigate the short-term efficacy and safety of three glucose-lowering interventions in overweight or obese individuals with prediabetes defined by HbAThe 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/mOne 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).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.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.

Background: In recent years, human papillomavirus (HPV) vaccination of boys has been added to childhood vaccination programmes in several countries but, so far, no systematic population-based assessment with long-term follow-up has been undertaken of the relative incidence of adverse outcomes following HPV vaccination in this group. We investigated if quadrivalent HPV (qHPV) vaccination of 10-17-year-old boys is associated with any unusual risk of autoimmune diseases, neurological diseases or venous thromboembolism.Methods: We conducted a national cohort study of 568 410 boys born in Denmark 1988-2006 and followed for 4 million person-years during 2006-16, using nationwide registers to obtain individual-level information about received doses of the qHPV vaccine and hospital records for 39 autoimmune diseases, 12 neurological diseases and venous thromboembolism. For each outcome, we estimated incidence rate ratios (RRs) with 95% confidence intervals (CIs) according to qHPV vaccination status.Results: Altogether 7384 boys received at least one dose of the qHPV vaccine at age 10-17 years. Overall, RRs were close to unity for the combined groups of autoimmune diseases (RR = 0.96; 95% CI: 0.71-1.28, n = 46 cases in qHPV-vaccinated boys) and neurological diseases (RR = 0.67; 0.41-1.10, n = 16), as well as for venous thromboembolism (RR = 0.88; 0.33-2.35, n = 4). After taking multiple testing into account, none of the 52 individual outcomes studied appeared to occur in excess among qHPV-vaccinated boys.Conclusions: Although additional large-scale epidemiological studies are warranted, our findings provide population-based reassurance that qHPV vaccination of 10-17-year-old boys is unlikely to be associated with an elevated risk of autoimmune diseases, neurological diseases or venous thromboembolism.

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.

SummaryBackground Atopic dermatitis (AD) is a prevalent disease with significant impact on physical health and quality of life. Staphylococcus aureus has been directly correlated to disease severity, and may also be a contributing causal factor in the pathogenesis of AD. Objectives The primary aim was to assess differences in S. aureus colonization in patients with AD with and without filaggrin gene mutations. The secondary aim was to assess disease severity in relation to S. aureus colonization. Exploratory analyses were performed to investigate S. aureus genetic lineages in relation to filaggrin gene (FLG) mutations and disease severity. Methods Adult patients with AD (n = 101) were included in the study. Bacterial swabs were taken from lesional skin, nonlesional skin and the nose. Swabs positive for S. aureus were characterized by spa and the respective clonal complex (CC) type assigned. Patients were characterized with respect to disease severity (Scoring Atopic Dermatitis) and FLG mutations (n = 88). Fisher's exact test was used to analyse differences in S. aureus colonization in relation to FLG mutations. Results Of the 101 patients included, 74 (73%) were colonized with S. aureus. Of the colonized patients, 70 (95%) carried only one CC type in all three different sampling sites. In lesional skin, S. aureus was found in 24 of 31 patients with FLG mutations vs. 24 of 54 wild-type patients (P = 0·0004). Staphylococcus aureusCC1 clonal lineage was more prevalent in patients with FLG mutations (n = 10) than in wild-type patients (n = 2) (P = 0·003). No specific bacterial lineage was linked to disease severity. Conclusions Increased S. aureus colonization in patients with AD with FLG mutations, and increased prevalence of CC1 in patients with FLG mutations, suggest that host–microbe interactions and clonal differences in S. aureus are important for colonization of AD skin.

Introduction: Safety, adherence and treatment satisfaction to interventions with dapagliflozin, metformin or exercise in individuals with prediabetes defined by the HbA1c criterion were studied in the randomized controlled PRE-D trial. Methods: 120 participants were randomized 1:1:1:1 to 13 weeks of either: (1) dapagliflozin (DAP, 10 mg daily); (2) metformin (MET, 1700 mg daily); (3) exercise (EXE, 5x30 min/week); or (4) control (CON, no treatment). Adverse events (AE) were collected during the entire study. Satisfaction with the interventions was assessed at 6 and 13 weeks using questionnaires. Adherence was assessed at 6 and 13 weeks by pill count in DAP and MET and each week by uploaded training data in EXE. Comparisons between groups were performed by ANOVA and chi-square tests. Results: At baseline, the median (Q1;Q3) HbA1c was 41 (39;43) mmol/mol (5.9 (5.7;6.1)%); age 62 (54;68) years, and 44% were men. Drop outs were 2 in DAP, 1 in MET, 3 in EXE and 2 in CON. One serious AE occurred in CON (cancer). 40% of the participants experienced at least one AE during the trial (15 in DAP, 22 in MET, 7 in EXE and 4 in CON (DAP vs. MET: P=0.111; MET vs. EXE: P Conclusion: In individuals with prediabetes, treatment with DAP is safe and did not result in more side-effects than treatment with MET. Adherence to all interventions was high, although the most preferred intervention was the EXE intervention. Disclosure H. Amadid: None. M.B. Blond: None. L. Bruhn: None. K.K. Clemmensen: None. C.T. Vainø: None. F. Persson: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Sanofi. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. M.E. Jørgensen: Research Support; Self; Amgen Inc., AstraZeneca, Danish Diabetes Association, Sanofi-Aventis. Stock/Shareholder; Self; Novo Nordisk A/S. K. Færch: Research Support; Self; Ascensia Diabetes Care, AstraZeneca, Unilever. Stock/Shareholder; Self; Novo Nordisk A/S.

Introduction: We assessed the effects of dapagliflozin, metformin or exercise on glucose metabolism in individuals with prediabetes. Methods: 120 participants were randomized to 13 weeks of either: 1) dapagliflozin (DAP, 10 mg once daily); 2) metformin (MET, 1700 mg daily); 3) exercise (EXE, 5x30 min/week); or 4) control (CON, no treatment). Participants were tested at baseline and after 6 and 13 weeks of intervention with oral glucose tolerance tests with 0, 30, 60, 120 min samples performed at baseline and at 13 weeks. Treatments were stopped the day before the last visit (two days before in EXE). Intention-to-treat analyses were conducted (baseline-adjusted). Results: 44% were men. At baseline, the median (Q1;Q3) age was 62 (54;68) years, BMI 30.8 (28.6;34.3) kg/m2, HbA1c 41 (39;43) mmol/mol (5.9 (5.7;6.1)%), fasting plasma glucose (FPG) 5.6 (5.2;5.8) mmol/L, and fasting serum insulin (FSI) 72 (47;99) pmol/L. HbA1c decreased in DAP at 6 weeks (Table 1). All groups showed reductions of around 1 mmol/mol at 13 weeks. MET, and to a lesser extend DAP, decreased FPG. FSI was reduced by 19-25% in all treatment groups, except for EXE at 13 weeks. The iAUCglucose increased by 66% in MET, and iAUCinsulin decreased somewhat in DAP and EXE. Conclusion: All treatments slightly improved HbA1c and fasting measures. Only DAP and EXE showed signs of improvements in postprandial glucose metabolism. Disclosure K. Færch: Research Support; Self; Ascensia Diabetes Care, AstraZeneca, Unilever. Stock/Shareholder; Self; Novo Nordisk A/S. M.B. Blond: None. H. Amadid: None. L.B. Nielsen: None. D. Vistisen: Stock/Shareholder; Self; Novo Nordisk A/S. K.K. Clemmensen: None. C.H. Pedersen: None. K. Karstoft: Employee; Self; Novo Nordisk A/S. M. Ried-Larsen: Other Relationship; Self; Novo Nordisk A/S. M.E. Jørgensen: Research Support; Self; Amgen Inc., AstraZeneca, Danish Diabetes Association, Sanofi-Aventis. Stock/Shareholder; Self; Novo Nordisk A/S. Funding Novo Nordisk Foundation; AstraZeneca

SummaryBackground It has been suggested that lifestyle factors such as smoking, being 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.

Summary 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

Summary Background Numerous risk factors have been suggested for hand eczema. This systematic review evaluates the association between tobacco smoking and hand eczema. Objective To review the literature systematically on the association between smoking and hand eczema. Methods The PubMed and EMBASE databases were searched up to 27 January 2015 for articles on the association between tobacco smoking and hand eczema, including human studies in English and German only. Experimental studies, studies on tobacco allergy, case reports, reviews and studies on second-hand smoking were excluded. Results Twenty articles were included. Among studies in occupational settings, three of seven found a statistically significant positive association between tobacco smoking and hand eczema prevalence rate, as did four of eight population-based studies. The association was stronger for studies in occupational settings than for population-based studies. No studies reported tobacco to be a clear protective factor for hand eczema. Two of five studies regarding severity found a positive association between smoking and hand eczema severity. Conclusion Overall, the data indicate that smoking may cause an increased frequency of hand eczema, particularly in high-risk occupations. However, data from studies controlling for other risk factors are conflicting, and few prospective studies are available. Studies controlling for other risk factors are needed, and information regarding the diagnosis of subclasses of hand eczema, as well as severity, may be important.

Summary 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

Summary Background Skin diseases are the most frequently recognized occupational diseases in Denmark. The prognosis for occupational contact dermatitis is often poor. Objectives To investigate the prognosis, assessed by eczema, job status and skin-related quality of life, among patients allergic to rubber chemicals and latex (ubiquitous allergens) and epoxy (nonubiquitous allergen), 2 years after recognition of occupational allergic contact dermatitis. Methods From a cohort of all patients recognized as having occupational dermatitis by the Danish National Board of Industrial Injuries in 2010, 199 patients with relevant rubber allergy (contact allergy to rubber chemicals or contact urticaria from latex) or epoxy allergy were identified. Follow-up consisted of a questionnaire covering current severity of eczema, employment, exposure and quality of life. Results The response rate was 75%. Clearance of eczema was reported by 11% of patients and 67% reported improvement. Overall 22% of patients with allergy to a nonubiquitous allergen had total clearance of eczema compared with 10% of cases allergic to ubiquitous allergens and 0% of those with contact urticaria (P = 0·116). Improvement was significantly more frequent in those who had changed jobs compared with those who had not (P = 0·01). Conclusions At follow-up, patients with contact urticaria had significantly poorer prognosis than those with contact allergy, and there was a trend towards a poorer prognosis for those with contact allergy to rubber chemicals than those with allergy to epoxy. A significant positive association between job change and improvement was found.

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

It has been suggested that lifestyle factors such as smoking, overweight and stress may influence the prevalence and severity of hand eczema.To investigate the association between lifestyle factors and hand eczema severity in a cohort of patients with work-related hand eczema.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.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).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.

Patch testing is mandatory for diagnosing contact dermatitis. It is, however, crucial that patients understand and remember the result of the test.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.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.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 age60 years (p0.01). Of patients with an additional contact allergy,36% remembered this correctly. Of patients allergic to natural rubber latex proteins, 50% remembered this correctly.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.

Summary Background Both atopic dermatitis and contact sensitization are common conditions; however, a definite understanding of the relationship between contact sensitization and atopic dermatitis has not been reached. Objectives In this descriptive study, we investigated the differences between positive patch test reactions in patients with and without atopic dermatitis in a patch test cohort, and explored the influence of disease severity. Patients/materials/methods Patch test results, information on atopic dermatitis and demographic variables were taken from a database, including all patients patch tested at Bispebjerg and Roskilde Hospitals from January 2009 to January 2013. Severe atopic dermatitis was defined as systemic therapy or hospitalization resulting from atopic dermatitis. All other patients with atopic dermatitis were defined as having mild/moderate disease. Results The study included 2221 patients: 293 patients with atopic dermatitis and 1928 without. Forty-one per cent of patients with and 46.2% of patients without atopic dermatitis had at least one positive patch test reaction (p = 0.092). More patients with severe atopic dermatitis than patients with non-severe atopic dermatitis had multiple positive patch test reactions (19.4% versus 10.0%, p = 0.046). Conclusions Overall, we found similar frequencies of positive patch test reactions in patients with and without atopic dermatitis. However, a higher frequency of multiple sensitizations was found in patients with severe atopic dermatitis.

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.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.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 evening50% 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.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.

Peritonsillar abscess (PTA) is a frequent complication to acute tonsillitis, in particular in adolescents and young adults. Smoking is most commonly initiated during adolescence and young adulthood. The study examines whether smoking increases the risk of PTA and whether smoking is associated with the bacterial findings in PTA. All patients with PTA admitted to the Ear-Nose-Throat Department at Aarhus University Hospital from January 2001 through December 2006 were included in the study. Age- and gender-stratified data on smoking habits in the Danish population and demographic data for Aarhus County for the same 6 years were obtained. Smoking status was available for 679 (80 %) of 847 patients with PTA. 247 (36 %) patients admitted to daily tobacco smoking. Age-stratified odds ratios of smokers compared to non-smokers, for developing PTA, were in the range of 1.9-4.7. Fusobacterium necrophorum and beta-hemolytic streptococci were equally distributed between smokers and non-smokers. Twenty nine percent of the higher incidence of PTA among males compared to females could be explained by a higher prevalence of smoking in males. After correcting for differences in smoking prevalence by gender, the risk of PTA was calculated to be 9.5 % higher among males than females. Smoking was associated with significantly increased risk of PTA in both males and females of all ages. No differences in the microbiological flora of smokers and non-smokers with PTA were found.

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.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.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.Both sales statistics and surveys have advantages and disadvantages. It may therefore be important to use both when estimating tobacco consumption.