Steno Diabetes Center North Jutland

Nursing staff are exposed to stressful work load which in turn is associated with poor physical and psychological health, sickness absence and job exit. The effort-reward imbalance (ERI) model is a validated approach to measure chronic psychosocial work stress by identifying nonreciprocity between occupational efforts spent and rewards received, and has been found to predict poor health. The aim of this cross-sectional study (n = 367 nurses and nurses aides) was first to test the psychometric properties of the Danish questionnaire measuring ERI, and secondly to analyse whether psychosocial work stress is associated with six indicators of poor self-rated health. Results derived from confirmatory factor analysis indicate satisfying psychometric properties. Elevated risks of poor self-rated health (odds ratios varying from 1.92 to 4.76) are observed in nursing staff characterized by high effort in combination with low reward. Effects are enhanced in those respondents who additionally exhibit a high level of work-related overcommitment. In conclusion, despite methodological limitations, this study contributes to the validation of the ERI questionnaire in Danish language. Furthermore, by documenting associations with poor self-rated health, it supports efforts of theory-guided prevention of work stress in health care professions.

BACKGROUND: Some 2.5% of fertile Danish women use sumatriptan, and the drug is also taken during pregnancy. Although sumatriptan reacts selectively in brain vessels, the possibility of reactions with placental blood flow and uterotonic activity cannot be ruled out. The aim of our study was to examine the association between sumatriptan exposure during pregnancy and the risk of preterm delivery and low birth weight. METHODS: Data from the Pharmaco-Epidemiological Prescription Database of North Jutland county regarding all women who had given birth in the county of North Jutland from 1991 to 1996 were linked to the Danish Medical Birth Registry. Women who were exposed to sumatriptan during pregnancy were identified (n = 34), and using logistic regression models their pregnancy outcome was compared with two groups of pregnant women: (1) healthy women (n = 15 955) and (2) migraine controls (n = 89), defined as migraine patients who did not redeem prescriptions for migraine treatment during pregnancy. RESULTS: The risk of preterm delivery was elevated among women exposed to sumatriptan compared with migraine controls (odds ratio [OR] 6.3, 95% confidence interval [CI] 1.2-32.0) and healthy women (OR 3.3, 95% CI 1.3-8.5). The odds ratio for having a newborn with a low birth weight was increased (OR 3.0, 95% CI 1.3-7.0) for all migraine patients who delivered at term (n=115) compared with the outcome of healthy pregnancies. CONCLUSIONS: We found that sumatriptan exposure during pregnancy was associated with an increased risk of preterm delivery and low birth weight. These findings may be due to drug exposure, but they may also reflect the impact of disease severity rather than the treatment itself, or confounding, or chance.

Type 2 diabetes (T2D) is associated with an increased risk of fracture, which has been reported in several epidemiological studies. However, bone mineral density in T2D is increased and underestimates the fracture risk. Common risk factors for fracture do not fully explain the increased fracture risk observed in patients with T2D. We propose that the pathogenesis of increased fracture risk in T2D is due to low bone turnover caused by osteocyte dysfunction resulting in bone microcracks and fractures. Increased levels of sclerostin may mediate the low bone turnover and may be a novel marker of increased fracture risk, although further research is needed. An impaired incretin response in T2D may also affect bone turnover. Accumulation of advanced glycosylation endproducts may also impair bone strength. Concerning antidiabetic medication, the glitazones are detrimental to bone health and associated with increased fracture risk, and the sulphonylureas may increase fracture risk by causing hypoglycemia. So far, the results on the effect of other antidiabetics are ambiguous. No specific guideline for the management of bone disease in T2D is available and current evidence on the effects of antiosteoporotic medication in T2D is sparse. The aim of this review is to collate current evidence of the pathogenesis, detection and treatment of diabetic bone disease.

The autonomic nervous system delicately regulates the function of several target organs, including the gastrointestinal tract. Thus, nerve lesions or other nerve pathologies may cause autonomic dysfunction (AD). Some of the most common causes of AD are diabetes mellitus and α-synucleinopathies such as Parkinson's disease. Widespread dysmotility throughout the gastrointestinal tract is a common finding in AD, but no commercially available method exists for direct verification of enteric dysfunction. Thus, assessing segmental enteric physiological function is recommended to aid diagnostics and guide treatment. Several established assessment methods exist, but disadvantages such as lack of standardization, exposure to radiation, advanced data interpretation, or high cost, limit their utility. Emerging methods, including high-resolution colonic manometry, 3D-transit, advanced imaging methods, analysis of gut biopsies, and microbiota, may all assist in the evaluation of gastroenteropathy related to AD. This review provides an overview of established and emerging assessment methods of physiological function within the gut and assessment methods of autonomic neuropathy outside the gut, especially in regards to clinical performance, strengths, and limitations for each method.

CONTEXT: Antithyroid drug (ATD) therapy in early pregnancy is associated with birth defects, but more data are needed to substantiate the risk associated with different types of ATD. Furthermore, the role of abnormal maternal thyroid function per se remains unclarified. OBJECTIVE: To evaluate the risk of birth defects associated with the use of ATD in an extended nationwide cohort and the role of abnormal maternal thyroid function in birth cohorts including stored maternal blood samples from early pregnancy. PARTICIPANTS: Danish pregnant women and their live-born children, including 1,243,353 children from a Nationwide Register-Based Cohort (NRBC), 1997 to 2016; 8830 children from the Danish National Birth Cohort (DNBC), 1997 to 2003; and 14,483 children from the North Denmark Region Pregnancy Cohort (NDRPC), 2011 to 2015. MAIN OUTCOME MEASURES: Birth defects diagnosed before 2 years of age. RESULTS: In the NRBC, altogether 2718 (0.2%) children had been exposed to ATD in early pregnancy. The overall frequency of birth defects was 6.7% (95% CI, 6.7% to 6.8%) in nonexposed children and higher after exposure to methimazole/carbimazole (9.6%; 95% CI, 8.2% to 11.2%) and propylthiouracil (8.3%; 95% CI, 6.7% to 10.3%). On the other hand, the frequency of maternal thyroid dysfunction in early pregnancy was similar in the random cohort and in cases of birth defect in the DNBC (12.4 vs 12.6%, P = 0.8) and the NDRPC (15.1 vs 15.4%, P = 0.8). CONCLUSIONS: Results corroborate an increased risk of birth defects associated with the use of ATD in early pregnancy and suggest that abnormal maternal thyroid function is not a major risk factor for birth defects.

OBJECTIVE Postpancreatitis diabetes mellitus (PPDM) is a type of secondary diabetes that requires special considerations for management. The main objective was to examine prescription patterns of glucose-lowering therapy among adults with PPDM compared with type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS In a Danish nationwide population-based cohort study, we identified all individuals with adult-onset diabetes in the period 2000–2018 and categorized them as having type 1 diabetes, type 2 diabetes, or PPDM. We ascertained diabetes incidence rates, clinical and demographic characteristics, and classifications and prescription patterns of glucose-lowering therapy and compared these parameters across diabetes subgroups. RESULTS Among 398,456 adults with new-onset diabetes, 5,879 (1.5%) had PPDM, 9,252 (2.3%) type 1 diabetes, and the remaining type 2 diabetes (96.2%). The incidence rate of PPDM was 7.9 (95% CI 7.7–8.1) per 100,000 person-years versus 12.5 (95% CI 12.2–12.7) for type 1 diabetes (incidence rate ratio 0.6 [95% CI 0.6–0.7]; P < 0.001). A sizeable proportion of patients with PPDM were classified as having type 2 diabetes (44.9%) and prescribed sulfonylureas (25.2%) and incretin-based therapies (18.0%) that can potentially be harmful in PPDM. In contrast, 35.0% of patients never received biguanides, which are associated with a survival benefit in PPDM. Increased insulin requirements were observed for patients with PPDM compared with type 2 diabetes (hazard ratio 3.10 [95% CI 2.96–3.23]; P < 0.001) in particular for PPDM associated with chronic pancreatitis (hazard ratio 4.30 [95% CI 4.01–4.56]; P < 0.001). CONCLUSIONS PPDM is a common type of secondary diabetes in adults but is often misclassified and treated as type 2 diabetes, although PPDM requires special considerations for management.

Abstract Objective Data on sex differences in acromegaly at the time of diagnosis vary considerably between studies. Design A nationwide cohort study including all incident cases of acromegaly (1978–2010, n = 596) and a meta‐analysis on sex differences in active acromegaly (40 studies) were performed. Method Sex‐dependent differences in prevalence, age at diagnosis, diagnostic delay, pituitary adenoma size, insulin‐like growth factor 1 (IGF‐I) and growth hormone (GH) concentrations were estimated. Results The cohort study identified a balanced gender distribution (49.6% females) and a comparable age (years) at diagnosis (48.2 CI95% 46.5–49.8 (males) vs. 47.2 CI95% 45.5–48.9 (females), p = 0.4). The incidence rate significantly increased during the study period ( R 2 = 0.42, p < 0.01) and the gender ratio (F/M) changed from female predominance to an even ratio (SR: 1.4 vs. 0.9, p = 0.03). IGF‐I SDS was significantly lower in females compared to males, whereas neither nadir GH nor pituitary adenoma size differed between males and females. In the meta‐analysis, the weighted percentage female was 53.3% (CI95% 51.5–55.2) with considerable heterogeneity ( I 2 = 85%) among the studies. The mean age difference at diagnosis between genders was 3.1 years (CI95% 1.9–4.4), and the diagnostic delay was longer in females by 0.9 years (CI95% −0.4 to 2.1). Serum IGF‐I levels were significantly lower in female patients, whereas nadir GH, and pituitary adenoma size were comparable. Conclusion There are only a minor sex differences in the epidemiology of acromegaly at the time of diagnosis except that female patients are slightly older and exhibit lower IGF‐I concentrations and a longer diagnostic delay.

BACKGROUND: Time-restricted eating (TRE) has been suggested to be a simple, feasible, and effective dietary strategy for individuals with overweight or obesity. We aimed to investigate the effects of 3 months of 10-h per-day TRE and 3 months of follow-up on bodyweight and cardiometabolic risk factors in individuals at high risk of type 2 diabetes. METHODS: ) with or without prediabetes and a habitual self-reported eating window (eating and drinking [except for water]) of 12 h per day or more every day and of 14 h per day or more at least 1 day per week. Individuals were randomly assigned 1:1 to 3 months of habitual living (hereafter referred to as the control group) or TRE, which was a self-selected 10-h per-day eating window placed between 0600 h and 2000 h. Randomisation was done in blocks varying in size and was open for participants and research staff, but outcome assessors were masked during statistical analyses. The randomisation list was generated by an external statistician. The primary outcome was change in bodyweight, assessed after 3 months (12 weeks) of the intervention and after 3 months (13 weeks) of follow-up. Adverse events were reported and registered at study visits or if participants contacted study staff to report events between visits. This trial is registered on ClinicalTrials.gov (NCT03854656). FINDINGS: Between March 12, 2019, and March 2, 2022, 100 participants (66 [66%] were female and 34 [34%] were male; median age 59 years [IQR 52-65]) were enrolled and randomly assigned (50 to each group). Of those 100, 46 (92%) in the TRE group and 46 (92%) in the control group completed the intervention period. After 3 months of the intervention, there was no difference in bodyweight between the TRE group and the control group (-0·8 kg, 95% CI -1·7 to 0·2; p=0·099). Being in the TRE group was not associated with a lower bodyweight compared with the control group after subsequent 3-month follow-up (-0·2 kg, -1·6 to 1·2). In the per-protocol analysis, participants who completed the intervention in the TRE group lost 1·0 kg (-1·9 to -0·0; p=0·040) bodyweight compared with the control group after 3 months of intervention, which was not maintained after the 3-month follow-up period (-0·4 kg, -1·8 to 1·0). During the trial and follow-up period, one participant in the TRE group reported a severe adverse event: development of a subcutaneous nodule and pain when the arm was in use. This side-effect was evaluated to be related to the trial procedures. INTERPRETATION: 3 months of 10-h per-day TRE did not lead to clinically relevant effects on bodyweight in middle-aged to older individuals at high risk of type 2 diabetes. FUNDING: Novo Nordisk Foundation, Aalborg University, Helsefonden, and Innovation Fund Denmark.

INTRODUCTION: Type 2 diabetes (T2D) is related to an increased fracture risk and low bone turnover. However, the mechanisms are not elucidated. In the present study we investigate the association between glycemic variability and bone turnover markers. METHODS: 100 participants with T2D and 100 age and gender matched controls were included in this cross-sectional study. All participants with T2D were equipped with a continuous glucose monitoring (CGM) sensor for 3 days (CGMS iPro Continuous Glucose Recorder; Medtronic MiniMed). The dawn glucose levels were defined as a morning period starting 1 h before breakfast ending 1 h post ingestion. On all participants serum (s)-C-terminal cross-linked telopeptide of type-I collagen (CTX), s-procollagen type 1 amino terminal propeptide (P1NP), and s-sclerostin were measured. RESULTS: Participants with T2D displayed significantly lower levels of the bone resorption marker s-CTX and the bone formation marker s-P1NP compared to controls. S-CTX was significantly negatively associated with the mean amplitude of glycemic excursions (MAGE) and the dawn glucose levels whereas s-P1NP only was significantly negatively associated with the dawn glucose levels while it was borderline significantly associated with MAGE (p = 0.05). S-CTX and s-P1NP were significantly lower among the 50% with the highest dawn glucose levels compared to the 50% lowest dawn glucose levels also after adjustment for age, gender, glycated hemoglobin A1c (HbA1c), and body mass index (BMI). CONCLUSION: We observed that the amplitude of glycemic excursions and rise in dawn glucose was negatively associated with bone turnover markers. Future research is needed to determine whether reduction of the amplitude of glycemic excursions increase bone turnover markers.

INTRODUCTION: The use of serious games is a popular approach to help children with Type 1 diabetes (T1D) learn how to self-manage. Many different game mechanisms exist. However, it is unclear which game mechanisms a serious game should include to teach self-management to children with T1D. Therefore, the aim of this scoping review is to map and describe the game mechanisms used in serious games that teach children with T1D how to self-manage and explain how they contribute to teaching self-management. METHODS: A systematic scoping review was conducted to map and describe the important game mechanisms published before 23 September 2020. A comprehensive search was performed in the PubMed, CINAHL, Embase, PsycINFO, Scopus, and Education Database. Relevant literature was selected, synthesized, and reported. RESULTS: Of the 800 articles identified, 18 were included in this systematic scoping review. The game mechanisms used in serious games that teach self-management included narrative contexts, feedback, avatars, simulations, goals, levels, and social interactions. DISCUSSION: This review identified 7 game mechanisms used in serious games that teach children how to self-manage. A serious game is most effective in teaching self-management when it is T1D-oriented and when multiple game mechanisms are combined. However, the most effective combination of game mechanisms has yet to be determined.

Childhood adverse events are risk factors for later bipolar disorder. We quantified the risks for a later diagnosis of bipolar disorder after exposure to adverse life events in children with and without parental psychopathology. This register-based population cohort study included all persons born in Denmark from 1980 to 1998 (980 554 persons). Adversities before age 15 years were: familial disruption; parental somatic illness; any parental psychopathology; parental labour market exclusion; parental imprisonment; placement in out-of-home care; and parental natural and unnatural death. We calculated risk estimates of each of these eight life events as single exposure and risk estimates for exposure to multiple life events. Main outcome variable was a diagnosis of bipolar disorder after the age of 15 years, analysed with Cox proportional hazard regression. Single exposure to most of the investigated adversities were associated with increased risk for bipolar disorder, exceptions were parental somatic illness and parental natural death. By far the strongest risk factor for bipolar disorder in our study was any mental disorder in the parent (hazard ratio 3.53; 95% confidence interval 2.73-4.53) and the additional effects of life events on bipolar risk were limited. An effect of early adverse life events on bipolar risk later in life was mainly observed in children without parental psychopathology. Our findings do not exclude early-life events as possible risk factors, but challenge the concept of adversities as important independent determinants of bipolar disorder in genetically vulnerable individuals.

AIMS: We examined cardiovascular outcomes associated with initiation of glucagon-like peptide-1 receptor agonist (GLP-1RA) vs. sodium-glucose co-transporter-2 inhibitor (SGLT-2i) treatment in a real-world setting among patients with type 2 diabetes. METHODS AND RESULTS: This Danish nationwide registry-based cohort study included patients with type 2 diabetes with a first-ever prescription of either GLP-1RA or SGLT-2i from 2013 through 2015 with follow-up until end of 2018. All analyses were standardized with respect to age, sex, diabetes duration, comorbidity, and comedication. The main outcome was a composite of cardiovascular death, myocardial infarction, and stroke. Furthermore, the components of the composite outcome and hospitalization for heart failure were evaluated. Standardized average 3-year risks of outcomes and differences thereof were estimated using doubly robust estimation combining cause-specific Cox regression with propensity score regression. We identified 8913 new users of GLP-1RA and 5275 new users of SGLT-2i. The standardized 3-year risk associated with initiating GLP-1RA and SGLT-2i, respectively, was as follows: composite cardiovascular outcome, 5.6% [95% confidence interval (CI): 5.2-6.1] vs. 5.6% (95% CI: 4.8-6.3); cardiovascular mortality, 1.6% (95% CI: 1.3-1.9) vs. 1.5% (95% CI: 1.1-1.8); hospitalization for heart failure, 1.7% (95% CI: 1.5-2.0) vs. 1.8% (95% CI: 1.2-2.5); myocardial infarction, 2.1% (95% CI: 1.8-2.4) vs. 2.1% (95% CI: 1.5-2.6); and stroke, 2.5% (95% CI: 2.2-2.9) vs. 2.6% (95% CI: 2.2-3.1). CONCLUSION: In this nationwide study of patients with type 2 diabetes, initiating GLP-1RA vs. SGLT-2i was not found to be associated with significant differences in cardiovascular risk.

OBJECTIVE: To study time-related changes in the prevalence and patient characteristics of acromegaly, as well as to assess the impact of changes in treatment on disease control. METHODS: A total of 107 patients with acromegaly were identified by healthcare registries and subsequently validated by patient chart review over a three-decade period (1992-2021). A systematic literature review focusing on the incidence and prevalence of acromegaly was performed identifying 31 studies. RESULTS: persons. The age at the first sign of acromegaly and the age at diagnosis significantly increased during the study period, whereas growth hormone and insulin-like growth factor I decreased. Incidentalomas constituted 32% of all cases diagnosed with acromegaly in the last decade. Primary surgery was used in 93% of all cases, and repeated surgery decreased from 24% to 10% during the three decades. The use of first-generation somatostatin analogues (21%-48%) and second-line medical treatment (4%-20%) increased with a concomitant improvement of biochemical disease control (58%-91%). CONCLUSION: The prevalence of acromegaly is higher than previously reported and the clinical presentation has shifted towards a milder phenotype. Modern treatment of acromegaly enables individualized treatment and disease control in the majority of patients.

Background: The incidence and prevalence of multiple endocrine neoplasia 2A (MEN2A) have only been reported once in a nationwide setting. However, it is unclear whether the figures are representative of other populations, as the major component of the syndrome, hereditary medullary thyroid carcinoma (MTC), has been reported as rare in the same country. We conducted a nationwide retrospective cohort study of MEN2A in Denmark from 1901 to 2014, aiming to describe the incidence and prevalence. Methods: This study included 250 unique MEN2A patients born or resident in Denmark before December 31, 2014. Patients were identified through the Danish RE arranged during T ransfection ( RET ) cohort, linkage of MEN2A pedigrees, the Danish MTC cohort, a nationwide collaboration of MEN2 centers, cross-checking of other relevant cohorts, and a systematic literature search. Results: The incidence from 1971 to 2000 was 28 (95% CI: 21–37) per million live births per year. Incidence for the specific mutations or for the overall MEN2A group did not change significantly from 1901 to 2014 ( P >0.05). Point prevalence at January 1, 2015, was 24 per million (95% CI: 20–28). Conclusion: The incidence and prevalence of MEN2A in Denmark seem higher than those reported in other countries. This is likely explained by the Danish C611Y founder effect. Also, our data indicate no significant change in MEN2A incidence during the last century. Keywords: multiple endocrine neoplasia 2A, incidence, prevalence, Denmark

Importance: Limited knowledge about interactions among health disorders impedes optimal patient care. Because comorbidities are common among patients 50 years and older with fractures, these fractures provide a useful setting for studying interactions among disorders. Objective: To define multimorbidity clusters at the time of fracture and quantify the interaction between multimorbidity and fracture in association with postfracture excess mortality. Design, Setting, and Participants: This nationwide cohort study included 307 870 adults in Denmark born on or before January 1, 1951, who had an incident low-trauma fracture between January 1, 2001, and December 31, 2014, and were followed up through December 31, 2016. Data were analyzed from February 1 to March 31, 2022. Main Outcomes and Measures: Fracture and 32 predefined chronic diseases recorded within 5 years before the index fracture were identified from the Danish National Hospital Discharge Register. Death was ascertained from the Danish Register on Causes of Death. Latent class analysis was conducted to identify multimorbidity clusters. Relative survival analysis was used to quantify excess mortality associated with the combination of multimorbidity and fractures at specific sites. Results: Among the 307 870 participants identified with incident fractures, 95 372 were men (31.0%; mean [SD] age at fracture, 72.3 [11.2] years) and 212 498 were women (69.0%; mean [SD] age at fracture, 74.9 [11.2] years). During a median of 6.5 (IQR, 3.0-11.0) years of follow-up, 41 017 men (43.0%) and 81 727 women (38.5%) died. Almost half of patients with fractures (42.9%) had at least 2 comorbidities. Comorbidities at fracture were categorized as low-multimorbidity (60.5% in men and 66.5% in women), cardiovascular (23.7% in men and 23.5% in women), diabetic (5.6% in men and 5.0% in women), malignant (5.1% in men and 5.0% in women), and mixed hepatic and/or inflammatory (5.1% in men only) clusters. These clusters distinguished individuals with advanced, complex, or late-stage disease from those with earlier-stage disease. Multimorbidity and proximal or lower leg fractures were associated with increased mortality risk, with the highest excess mortality found in patients with hip fracture in the malignant cluster (1-year excess mortality: 40.8% [95% CI: 38.1%-43.6%]). The combination of multimorbidity and fracture compounded the association with mortality, conferring much greater risk than either alone. Conclusions and Relevance: Concomitant illnesses were common and clustered into distinct multimorbidity clusters that were associated with excess postfracture mortality. The compound contribution of multimorbidity to postfracture excess mortality highlights the need for more comprehensive approaches in these high-risk patients. The analytical approach applied to fracture could also be used to examine other sentinel health events.

Abstract Rationale Sufficient levels of vitamin D seem to be essential for proper immune function, and low levels might be associated to disease activity in Rheumatoid Arthritis ( RA ). Most studies investigate only 25 OHD and not the physiologically active vitamin D metabolite, 1,25( OH ) 2 D. Objective To investigate associations between serum level of vitamin D metabolites and disease activity parameters in 160 inflammatory active and treatment naïve early RA patients. Serum level of vitamin D metabolites (25 OHD 2 , 25 OHD 3 and 1,25( OH ) 2 D) was measured by isotope dilution mass spectrometry and radio‐immunoassays at baseline. Disease characteristics were gender, number of tender joints, number of swollen joints, DAS 28‐ CRP , HAQ , VAS ‐scores, CRP , erosive status (Total Sharp Score; TSS ), ACPA and IgM‐ RF ‐status. Associations were evaluated using Spearman's and Wilcoxon rank‐sum tests. The study was registered in clinical trials; trial registration number: NCT 00209859. Findings Statistically significant inverse associations were found between the active metabolite 1,25( OH ) 2 D and DAS 28‐ CRP ( P = 0.004, rho = −0.23), HAQ ( P = 0.005, rho = −0.22), CRP ( P = 0.001, rho = −0.25), VAS patient‐pain ( P = 0.008, rho = −0.21), and a positive association was found to ACPA ‐status ( P = 0.04). Conclusion The vitamin D metabolite 1,25( OH ) 2 D was inversely associated with disease activity and positively associated with ACPA in treatment naïve and inflammatory active early RA . The results indicate that in RA , both the degree of inflammatory activity, and the diagnostic sensitivity and specificity might affect—or might be affected by the level of vitamin 1,25( OH ) 2 D.

Background Glucagon‐like peptide‐1 receptor agonists, such as liraglutide, reduce hyperglycaemia and induce weight loss and are used as a treatment in diabetes. However, common adverse effects include nausea, loss of appetite and prolonged gastric emptying. It is not known whether these changes are centrally generated or if liraglutide alters the enteric motility. Objective To investigate the effects of liraglutide on gastrointestinal function and symptoms. Methods A total of 48 adults with type 1 diabetes and confirmed distal symmetric polyneuropathy were randomised to receive liraglutide 1.8 mg/day or placebo for 26 weeks. Regional transit times and motility indexes were assessed with a wireless motility capsule, whereas symptoms were evaluated using the validated gastroparesis cardinal symptom index. Results Liraglutide treatment reduced large bowel transit time (31.7%, p = 0.04) and decreased motility index (6.1%, p = 0.04) compared to placebo, whereas the groups did not differ in gastric emptying or small‐bowel transit times. Liraglutide increased postprandial fullness with 29% ( p = 0.01). Increased small bowel transit time was associated with decreased bloating ( p = 0.008). Conclusion Liraglutide accelerates large bowel transit and decreases motility index, which may indicate better coordination of propulsive motility. This potentially improves the function of the enteric nervous system, leading to normalised colonic function and positive effects in type 1 diabetes.

OBJECTIVE: Abnormal thyroid function in pregnant women is a matter of concern. Knowledge on the occurrence of known and unidentified thyroid function abnormalities in a large unselected cohort of pregnant women is warranted as part of the debate on benefits and risks of routine testing. DESIGN: Cohort study. PARTICIPANTS: A total of 14 323 pregnant women in the North Denmark Region, who had a blood sample drawn as part of the prenatal screening program in early pregnancy (2011-2015). MEASUREMENTS: TSH, free thyroxine, thyroid peroxidase and thyroglobulin antibodies were measured in the stored blood samples using an automatic immunoassay (ADVIA Centaur XPT, Siemens Healthineers). Cohort-, method- and week-specific reference ranges were used for classification of maternal thyroid function, and a cut-off of 60 U/mL was used for thyroid autoantibodies. Information in Danish nationwide registers was used to identify diagnosed and treated maternal thyroid disease. RESULTS: Overall, 15.2% had thyroid function abnormalities in the early pregnancy and 14.9% were thyroid peroxidase and/or thyroglobulin antibody positive. Among women with known thyroid disease (n = 365), the frequency of abnormal thyroid function was 45.7%, and 62.8% in women (n = 172) who received current treatment in the pregnancy. When maternal thyroid disease was diagnosed in the years following pregnancy (n = 313), 46.7% had abnormal thyroid function and 54.3% were thyroid peroxidase and/or thyroglobulin antibody positive in the early pregnancy. CONCLUSION: Thyroid function abnormalities and thyroid autoantibodies were common in Danish pregnant women, particularly in women with known or later diagnosed thyroid disease, which raises concern about inadequately treated and unidentified abnormal thyroid function.

Background: Type 2 diabetes mellitus (T2D) is associated with an increased fracture risk. It is debated whether sodium-glucose cotransporter 2 (SGLT2) inhibitors influence fracture risk in T2D. We aimed to investigate the risk of major osteoporotic fractures (MOF) with SGLT2 inhibitors compared to glucagon-like peptide 1 (GLP-1) receptor agonists when used as add-on therapies to metformin. Methods: We conducted a population-based cohort study using Danish national health registries. Diagnoses were obtained from discharge diagnosis codes (ICD-10 and ICD-8-system) from the Danish National Patient Registry, and all redeemed drug prescriptions were obtained from the Danish National Prescription Registry (ATC classification system). Subjects treated with metformin in combination with either SGLT2 inhibitors or GLP-1 receptor agonists were identified and enrolled from 2012 to 2018. Subjects were then propensity-score matched 1:1 based on age, sex, and index date. Major osteoporotic fractures (MOF) were defined as hip, vertebral, humerus, or forearm fractures. A Cox proportional hazards model was utilized to estimate hazard rate ratios (HR) for MOF, and survival curves were plotted using the Kaplan-Meier estimator. Results: In total, 27,543 individuals treated with either combination were identified and included. After matching, 18,390 individuals were included in the main analysis (9,190 in each group). Median follow-up times were 355 [interquartile range (IQR) 126-780] and 372 [IQR 136-766] days in the SGLT2 inhibitor and GLP-1 receptor agonist group, respectively. We found a crude HR of 0.77 [95% CI 0.56-1.04] for MOF with SGLT2 inhibitors compared to GLP-1 receptor agonists. In the fully adjusted model, we obtained an unaltered HR of 0.77 [95% CI 0.56-1.05]. Results were similar across subgroup- and sensitivity analyses. Conclusion: These results suggest that SGLT2 inhibitors have no effect on fracture risk when compared to GLP-1 receptor agonists. This is in line with results from previous studies.

INTRODUCTION: A high proportion of people with diabetes experience gastrointestinal (GI) symptoms, which may be manifestations of diabetic autonomic neuropathy (DAN). The current treatment regime is ineffective and associated with major side effects. Transcutaneous vagal nerve stimulation (tVNS) is a new therapeutic option, which has been shown to increase GI motility and reduce inflammatory responses. As vagus is the main neuronal pathway for extrinsic coordination of GI secretion and motility, we hypothesise that tVNS will improve DAN-induced GI symptoms in subjects with diabetes. METHODS AND ANALYSIS: The DAN-VNS study is a randomised multicentre clinical trial investigating the effect of short-term, high intensity as well as long-term, medium-intensity tVNS on GI symptom alleviation in 120 subjects with diabetes. The primary outcome consists of changes from baseline in subjective ratings of symptom severity. Secondary outcomes include changes in gastric motility and GI transit time measured by MRI and wireless motility capsule. Moreover, cardiovascular and sudomotor function, glycaemic control, brain sensory processing and presence of low-grade inflammation will be investigated as secondary outcome measures. Lastly, 15 responders of tVNS treatment will be included in an explorative, randomised, cross-over study, in which the acute endocrine and metabolic response to short-term tVNS will be investigated. ETHICS AND DISSEMINATION: The study has been approved by the North Denmark Region Committee on Health Research Ethics (N-20190020). Results will be published in relevant international peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04143269.