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Background: Excessive energy intake and obesity lead to the metabolic syndrome (MetS). Dietary saturated fatty acids (SFAs) may be particularly detrimental on insulin sensitivity (SI) and on other components of the MetS.Objective: This study determined the relative efficacy of reducing dietary SFA, by isoenergetic alteration of the quality and quantity of dietary fat, on risk factors associated with MetS.Design: A free-living, single-blinded dietary intervention study.Subjects and Methods: MetS subjects (n = 417) from eight European countries completed the randomized dietary intervention study with four isoenergetic diets distinct in fat quantity and quality: high-SFA; high-monounsaturated fatty acids and two low-fat, high-complex carbohydrate (LFHCC) diets, supplemented with long chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs) (1.2 g per day) or placebo for 12 weeks. SI estimated from an intravenous glucose tolerance test (IVGTT) was the primary outcome measure. Lipid and inflammatory markers associated with MetS were also determined.Results: In weight-stable subjects, reducing dietary SFA intake had no effect on SI, total and low-density lipoprotein cholesterol concentration, inflammation or blood pressure in the entire cohort. The LFHCC n-3 PUFA diet reduced plasma triacylglycerol (TAG) and non-esterified fatty acid concentrations (P < 0.01), particularly in men.Conclusion: There was no effect of reducing SFA on SI in weight-stable obese MetS subjects. LC n-3 PUFA supplementation, in association with a low-fat diet, improved TAG-related MetS risk profiles. [ABSTRACT FROM AUTHOR]

Aims: To describe trends in the use of anti-obesity drugs in Norway during the period 2004-2022., Materials and Methods: We assessed the annual utilization of any available drug indicated for obesity recorded in the nationwide Norwegian Prescribed Drug Register for adults (age 18-79 years) from 1 January 2004 to 31 December 2022. Prevalence was stratified by sex and age group (18-29 years and 10-year age groups thereafter). Additional analyses were performed in individuals initiating treatment with an anti-obesity drug and on the cost of the anti-obesity drugs since 2017., Results: The prevalence of anti-obesity drug use decreased from 2009, when sibutramine and rimonabant were withdrawn from the market, and increased again after the approval of bupropion-naltrexone in 2017 and liraglutide in 2018. The use of the peripheral-acting anti-obesity drug orlistat decreased from 2004. In 2022, 1.04% of the adult Norwegian population (72.8% women) filled at least one prescription of bupropion-naltrexone, 0.91% used liraglutide (Saxenda; 74.2% women), and semaglutide without reimbursement was used by 0.68% (76.7% women). The prevalence increased with age, peaking in the age group 50 to 59 years, and decreased in older age groups. From 2017 to 2022, 2.8% of the adult residents initiated treatment with an anti-obesity drug. The total sale of those drugs increased from 1.1 million euros in 2017 to 91.8 million euros in 2022., Conclusions: The use of anti-obesity drugs in Norway has increased substantially in recent years, especially among women aged 40 to 59 years. Changes in availability and reimbursement have influenced the use of these drugs in recent years., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

South Asians (SAs) have a higher risk of developing type 2 diabetes (T2D) than white Europeans, especially following gestational diabetes mellitus (GDM). Despite similar blood glucose levels post-GDM, SAs exhibit more insulin resistance (IR) than Nordics, though the underlying mechanisms are unclear. This study aimed to assess markers of adipose tissue (AT) IR and liver fat in SA and Nordic women post-GDM. A total of 179 SA and 108 Nordic women in Norway underwent oral glucose tolerance tests 1-3 years post-GDM. We measured metabolic markers and calculated the AT IR index and non-alcoholic fatty liver disease liver fat (NAFLD-LFS) scores. Results showed that normoglycaemic SAs had less non-esterified fatty acid (NEFA) suppression during the test, resembling prediabetes/T2D responses, and higher levels of plasma fetuin-A, CRP, and IL-6 but lower adiponectin, indicating AT inflammation. Furthermore, normoglycaemic SAs had higher NAFLD-LFS scores, lower insulin clearance, and higher peripheral insulin than Nordics, indicating increased AT IR, inflammation, and liver fat in SAs. Higher liver fat markers significantly contributed to the ethnic disparities in glucose metabolism, suggesting a key area for intervention to reduce T2D risk post-GDM in SAs.

Background and Aims: The SARS-CoV-2 mRNA vaccines are associated with an increased risk of myocarditis. This association appears to be strongest in male adolescents and younger males and after the second dose. The aim was to evaluate the risk of myocarditis following SARS-CoV-2 mRNA booster vaccination in 12-to-39-year-olds., Methods: A multinational cohort study was conducted using nationwide register data in Denmark, Finland, Norway, and Sweden and comprising all 8.9 million individuals residing in each of the four countries. Participants were followed for an inpatient diagnosis of myocarditis. In each of the four countries, Poisson regression was used to estimate adjusted incidence rate ratios (IRRs) of myocarditis comparing vaccination schedules, with associated 95% confidence intervals (CIs). Country-specific results were combined in meta-analyses., Results: A total of 8.9 million residents were followed for 12 271 861 person-years and 1533 cases of myocarditis were identified. In 12-to-39-year-old males, the 28-day acute risk period following the third dose of BNT162b2 or mRNA-1273 was associated with an increased incidence rate of myocarditis compared to the post-acute risk period 28 days or more after the second dose [IRR 2.08 (95% CI 1.31-3.33) and 8.89 (2.26-35.03), respectively]. For females, the corresponding IRR was only estimable for BNT162b2, 3.99 (0.41-38.64). The corresponding absolute risks following the third dose of BNT162b2 and mRNA-1273 in males were 0.86 (95% CI 0.53-1.32) and 1.95 (0.53-4.99) myocarditis events within 28 days per 100 000 individuals vaccinated, respectively. In females, the corresponding absolute risks following the third dose of BNT162b2 were 0.15 (0.04-0.39) events per 100 000 individuals vaccinated. No deaths occurred within 30 days of vaccine-related cases., Conclusions: The results suggest that a booster dose is associated with increased myocarditis risk in adolescents and young adults. However, the absolute risk of myocarditis following booster vaccination is low., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

BackgroundSocioeconomic status in the risk of developing type 1 diabetes seems inconsistent. We investigated whether risk of childhood-onset type 1 diabetes differed by parental education or occupation in a nationwide cohort., Methods: This cohort study included all children born in Norway from 1974 to 2013. In individually linked data from nationwide population registries following children born in Norway up to 15 years of age, we identified 4647 with newly diagnosed type 1 diabetes during 15 381 923 person-years of follow-up., Results: Children of mothers with a master's degree had lower risk of type 1 diabetes than children of mothers with completed upper secondary education only (adjusted incidence rate ratio, aIRR=0.82 95% CI: 0.70 to 0.95). There was no difference between upper secondary and lower secondary maternal education (aIRR=0.98, 95% CI: 0.89 to 1.08). Paternal education was not significantly associated with type 1 diabetes, lower secondary compared with upper secondary aIRR 0.96 (0.88-1.05) and master compared with upper secondary aIRR 0.93 (0.83-1.05). While maternal elementary occupation was associated with a lower risk of type 1 diabetes, specific maternal or paternal occupations were not., Conclusions: Our results suggested inverse U-shaped associations between maternal socioeconomic status and risk of type 1 diabetes. Non-linear associations may be part of the reason why previous literature has been inconsistent., Competing Interests: Competing interests: PL-DR reports participation in a research project funded by LEO Pharma, all regulator mandated phase IV studies, all with funds paid to her institution (no personal fees) and with no relation to the work reported in this paper. All other authors declare no competing interests., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Estimate prevalence of gestational diabetes mellitus (GDM) and its treatment in Norway 2010-2020 and explore impact of new national GDM guidelines in 2017., Methods: We identified women giving birth in a nationwide cohort study using registers on births, prescriptions, education, primary and specialist care. For each year, we estimated prevalence of GDM overall, by BMI, age, education, and mother's birthplace; proportions of GDM pregnancies receiving pharmacological treatment; and distribution of the gestational week when GDM was diagnosed., Results: In 633,169 pregnancies, prevalence of GDM increased from 2.6 % in 2010 to 6.0 % in 2016, then stabilized. Similar patterns were seen across strata of BMI, age, education, and maternal birthplace, although prevalence was higher with higher BMI, higher age, lower education, and mothers born in Asia, Africa, or Middle East. The proportion of the GDM population pharmacologically treated increased from 11.6 % in 2010 to 13.6 % in 2016 and 31.6 % in 2020. GDM was diagnosed in recommended gestational week 24-28 in 19 % versus 45 % of GDM pregnancies in 2010 and 2020, respectively., Conclusions: Both the proportion diagnosed with GDM within recommended time of screening, and who received pharmacological treatment, increased substantially following new guidelines in 2017. Prevalence of GDM increased from 2010 to 2016, then plateaued., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [KF, ØK, PLDR and VH report participation in research projects funded by pharmaceutical companies (one on diabetes drug), all regulator mandated post-authorisation safety studies (PASS) unrelated to the submitted work, all with funds paid to the institution (no personal fees). KAW, LJK and HLG report no conflicts of interest.]., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To assess the risk of major congenital malformations with metformin versus insulin in pregnancies with type 2 diabetes., Research Design and Methods: This cohort study used four Nordic countries' nationwide registers of live and stillborn infants exposed to metformin or insulin during first trimester organogenesis. Main exclusion criteria were type 1 diabetes, polycystic ovary syndrome, fertility treatment, and exposure to other diabetes drugs. Adjusted risk ratios (RRs) and 95% CIs were estimated for any and cardiac malformations., Results: Of 3,734,125 infants in the source population, 25,956 were exposed to metformin or insulin in the first trimester, and 4,023 singleton infants were included. A malformation was diagnosed in 147 (4.7%) of 3,145 infants with exposure to any metformin (alone or in addition to insulin) and 50 (5.7%) of 878 infants with exposure to insulin alone (RR 0.84, 95% CI 0.46-1.54). Among 2,852 infants exposed to metformin alone and 293 infants exposed to metformin in addition to insulin 127 (4.4%) and 20 (6.8%), respectively, had a malformation. The adjusted risk was not increased for either metformin alone (0.83, 0.44-1.58) or both metformin and insulin (0.98, 0.56-1.69) versus insulin alone. Corresponding RRs for cardiac malformations were 1.01 (0.55-1.84) for any metformin, 0.92 (0.47-1.81) for metformin alone, and 1.72 (0.76-3.91) for both metformin and insulin., Conclusions: No evidence of an increased malformation risk with metformin versus insulin in the first trimester was found. Results should be interpreted with caution since information on glycemic control was missing., (© 2023 by the American Diabetes Association.)

Background: Whether the SARS-CoV-2 mRNA vaccines may cause a transient increased stroke risk is uncertain., Methods: In a registry-based cohort of all adult residents at December 27, 2020, in Norway, we linked individual-level data on COVID-19 vaccination, positive SARS-CoV-2 test, hospital admissions, cause of death, health care worker status, and nursing home resident status extracted from the Emergency Preparedness Register for COVID-19 in Norway. The cohort was followed for incident intracerebral bleeding, ischemic stroke, and subarachnoid hemorrhage within the first 28 days after the first/second or third dose of mRNA vaccination until January 24, 2022. Stroke risk after vaccination relative to time not exposed to vaccination was assessed by Cox proportional hazard ratio, adjusted for age, sex, risk groups, health care personnel, and nursing home resident., Results: The cohort included 4 139 888 people, 49.8% women, and 6.7% were ≥80 years of age. During the first 28 days after an mRNA vaccine, 2104 people experienced a stroke (82% ischemic stroke, 13% intracerebral hemorrhage, and 5% subarachnoid hemorrhage). Adjusted hazard ratios (95% CI) after the first/second and after the third mRNA vaccine doses were 0.92 (0.85-1.00) and 0.89 (0.73-1.08) for ischemic stroke, 0.81 (0.67-0.98) and 1.05 (0.64-1.71) for intracerebral hemorrhage, and 0.64 (0.46-0.87) and 1.12 (0.57-2.19) for subarachnoid hemorrhage, respectively., Conclusions: We did not find increased risk of stroke during the first 28 days after an mRNA SARS-CoV-2 vaccine.

Context: Serum soluble leptin receptor (sOb-R) may protect against future type 2 diabetes or serve as a marker for protective features, but how sOb-R is regulated is largely unknown., Objective: This work aimed to test how serum sOb-R is influenced by glucose, insulin, body fat, body mass index (BMI), food intake, and physical activity., Methods: We performed an epidemiological triangulation combining cross-sectional, interventional, and Mendelian randomization study designs. In 5 independent clinical studies (n = 24-823), sOb-R was quantified in serum or plasma by commercial enzyme-linked immunosorbent assay kits using monoclonal antibodies. We performed mixed-model regression and 2-sample Mendelian randomization., Results: In pooled, cross-sectional data, leveling by study, sOb-R was associated inversely with BMI (β [95% CI] -0.19 [-0.21 to -0.17]), body fat (-0.12 [-0.14 to -0.10), and fasting C-peptide (-2.04 [-2.46 to -1.62]). sOb-R decreased in response to acute hyperinsulinemia during euglycemic glucose clamp in 2 independent clinical studies (-0.5 [-0.7 to -0.4] and -0.5 [-0.6 to -0.3]), and immediately increased in response to intensive exercise (0.18 [0.04 to 0.31]) and food intake (0.20 [0.06 to 0.34]). In 2-sample Mendelian randomization, higher fasting insulin and higher BMI were causally linked to lower sOb-R levels (inverse variance weighted, -1.72 [-2.86 to -0.58], and -0.20 [-0.36 to -0.04], respectively). The relationship between hyperglycemia and sOb-R was inconsistent in cross-sectional studies and nonsignificant in intervention studies, and 2-sample Mendelian randomization suggested no causal effect of fasting glucose on sOb-R., Conclusion: BMI and insulin both causally decreased serum sOb-R levels. Conversely, intensive exercise and food intake acutely increased sOb-R. Our results suggest that sOb-R is involved in short-term regulation of leptin signaling, either directly or indirectly, and that hyperinsulinemia may reduce leptin signaling., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.)

Objective: To investigate the clinical outcomes of myocarditis associated with mRNA vaccines against the SARS-CoV-2 virus compared with other types of myocarditis., Design: Population based cohort study., Setting: Nationwide register data from four Nordic countries (Denmark, Finland, Norway, and Sweden), from 1 January 2018 to the latest date of follow-up in 2022., Participants: The Nordic myocarditis cohort; 7292 individuals aged ≥12 years who had an incident diagnosis of myocarditis as a main or secondary diagnosis, in a population of 23 million individuals in Denmark, Finland, Norway, and Sweden., Main Outcome Measures: Heart failure, or death from any cause within 90 days of admission to hospital for new onset myocarditis, and hospital readmission within 90 days of discharge to hospital for new onset myocarditis. Clinical outcomes of myocarditis associated with SARS-CoV-2 mRNA vaccination, covid-19 disease, and conventional myocarditis were compared., Results: In 2018-22, 7292 patients were admitted to hospital with new onset myocarditis, with 530 (7.3%) categorised as having myocarditis associated with SARS-CoV-2 mRNA vaccination, 109 (1.5%) with myocarditis associated with covid-19 disease, and 6653 (91.2%) with conventional myocarditis. At the 90 day follow-up, 62, nine, and 988 patients had been readmitted to hospital in each group (vaccination, covid-19, and conventional myocarditis groups, respectively), corresponding to a relative risk of readmission of 0.79 (95% confidence interval 0.62 to 1.00) and 0.55 (0.30 to 1.04) for the vaccination type and covid-19 type myocarditis groups, respectively, compared with the conventional myocarditis group. At the 90 day follow-up, 27, 18, and 616 patients had a diagnosis of heart failure or died in the vaccination type, covid-19 type, and conventional myocarditis groups, respectively. The relative risk of heart failure within 90 days was 0.56 (95% confidence interval 0.37 to 0.85) and 1.48 (0.86 to 2.54) for myocarditis associated with vaccination and covid-19 disease, respectively, compared with conventional myocarditis; the relative risk of death was 0.48 (0.21 to 1.09) and 2.35 (1.06 to 5.19), respectively. Among patients aged 12-39 years with no predisposing comorbidities, the relative risk of heart failure or death was markedly higher for myocarditis associated with covid-19 disease than for myocarditis associated with vaccination (relative risk 5.78, 1.84 to 18.20)., Conclusions: Compared with myocarditis associated with covid-19 disease and conventional myocarditis, myocarditis after vaccination with SARS-CoV-2 mRNA vaccines was associated with better clinical outcomes within 90 days of admission to hospital., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: no support from any organisation for the submitted work; AHu is supported by a postdoctoral research grant from the Lundbeck Foundation (grant No R322-2019-2800); AHv reports being a Scientific Advisory Board member for VAC4EU; LK reports speaker’s fees from Novo Nordisk, Novartis, AstraZeneca, Bayer, and Boehring, outside of the submitted work; PH reports being a member of an expert group, Future Rheumatology Advisory Board (2016 and 2017), funded by Pfizer; the Finnish Institute for Health and Welfare has a strategic policy of public private partnership, but none of the researchers of this report was involved with industry sponsored studies; OK reports participation in research projects funded by Novo Nordisk and LEO Pharma, all regulator mandated phase IV studies, all with funds paid to his institution (no personal fees), outside of the submitted work; HLG reports previous participation in research projects and clinical trials funded by Novo Nordisk, GSK, AstraZeneca, and Boheringer-Ingelheim, all related to diabetes and paid to her previous institution, Oslo University Hospital (no personal fees); HLG has received lecture fees and participated in advisory boards from several pharmaceutical companies before 2019 related to diabetes and metabolism; RL reports participation in a research project funded by Sanofi-Aventis, a regulator mandated phase IV study, with funds paid to his institution (no personal fees) (2011), outside of the submitted work; RL has received a lecture fee from Pfizer (2016), outside of the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

South Asian women have a higher risk of type 2 diabetes after gestational diabetes mellitus (GDM) than Nordic women; however, the mechanisms behind this difference remain unclear. We investigated insulin sensitivity, β-cell function, and hepatic insulin clearance in 179 South Asian and 108 Nordic women ∼17 months after GDM (mean age 35.3 years, BMI 29.1 kg/m2) by oral glucose tolerance test using deconvolution of C-peptide kinetics. Thirty-one percent of South Asian and 53% of Nordic participants were normoglycemic at the time of measurement. South Asian women had higher areas under the curve (AUCs) for glucose, prehepatic insulin, and peripheral insulin and lower insulin sensitivity, disposition index, and fasting hepatic insulin clearance than Nordic women. In the group with prediabetes or diabetes, South Asian women had similar AUCs for glucose and prehepatic insulin but a higher AUC for peripheral insulin, lower disposition index, and lower fasting hepatic insulin clearance than Nordic women. The waist-to-height ratio mediated ∼25-40% of the ethnic differences in insulin sensitivity in participants with normoglycemia. Overall, our novel data revealed that South Asian women with normoglycemia after GDM showed lower insulin secretion for a given insulin resistance and lower hepatic insulin clearance than Nordic women. South Asian women are at high risk of developing type 2 diabetes after GDM, and preventive efforts should be prioritized., (© 2022 by the American Diabetes Association.)

Background: Diabetes is a major public health issue. Because lifetime risk, life expectancy, and years of life lost are meaningful metrics for clinical decision making, we aimed to estimate these measures for type 2 diabetes in the high-income setting., Methods: For this multinational, population-based study, we sourced data from 24 databases for 23 jurisdictions (either whole countries or regions of a country): Australia; Austria; Canada; Denmark; Finland; France; Germany; Hong Kong; Hungary; Israel; Italy; Japan; Latvia; Lithuania; the Netherlands; Norway; Scotland; Singapore; South Korea; Spain; Taiwan; the UK; and the USA. Our main outcomes were lifetime risk of type 2 diabetes, life expectancy in people with and without type 2 diabetes, and years of life lost to type 2 diabetes. We modelled the incidence and mortality of type 2 diabetes in people with and without type 2 diabetes in sex-stratified, age-adjusted, and calendar year-adjusted Poisson models for each jurisdiction. Using incidence and mortality, we constructed life tables for people of both sexes aged 20-100 years for each jurisdiction and at two timepoints 5 years apart in the period 2005-19 where possible. Life expectancy from a given age was computed as the area under the survival curves and lifetime lost was calculated as the difference between the expected lifetime of people with versus without type 2 diabetes at a given age. Lifetime risk was calculated as the proportion of each cohort who developed type 2 diabetes between the ages of 20 years and 100 years. We estimated 95% CIs using parametric bootstrapping., Findings: Across all study cohorts from the 23 jurisdictions (total person-years 1 577 234 194), there were 5 119 585 incident cases of type 2 diabetes, 4 007 064 deaths in those with type 2 diabetes, and 11 854 043 deaths in those without type 2 diabetes. The lifetime risk of type 2 diabetes ranged from 16·3% (95% CI 15·6-17·0) for Scottish women to 59·6% (58·5-60·8) for Singaporean men. Lifetime risk declined with time in 11 of the 15 jurisdictions for which two timepoints were studied. Among people with type 2 diabetes, the highest life expectancies were found for both sexes in Japan in 2017-18, where life expectancy at age 20 years was 59·2 years (95% CI 59·2-59·3) for men and 64·1 years (64·0-64·2) for women. The lowest life expectancy at age 20 years with type 2 diabetes was observed in 2013-14 in Lithuania (43·7 years [42·7-44·6]) for men and in 2010-11 in Latvia (54·2 years [53·4-54·9]) for women. Life expectancy in people with type 2 diabetes increased with time for both sexes in all jurisdictions, except for Spain and Scotland. The life expectancy gap between those with and without type 2 diabetes declined substantially in Latvia from 2010-11 to 2015-16 and in the USA from 2009-10 to 2014-15. Years of life lost to type 2 diabetes ranged from 2·5 years (Latvia; 2015-16) to 12·9 years (Israel Clalit Health Services; 2015-16) for 20-year-old men and from 3·1 years (Finland; 2011-12) to 11·2 years (Israel Clalit Health Services; 2010-11 and 2015-16) for 20-year-old women. With time, the expected number of years of life lost to type 2 diabetes decreased in some jurisdictions and increased in others. The greatest decrease in years of life lost to type 2 diabetes occurred in the USA between 2009-10 and 2014-15 for 20-year-old men (a decrease of 2·7 years)., Interpretation: Despite declining lifetime risk and improvements in life expectancy for those with type 2 diabetes in many high-income jurisdictions, the burden of type 2 diabetes remains substantial. Public health strategies might benefit from tailored approaches to continue to improve health outcomes for people with diabetes., Funding: US Centers for Disease Control and Prevention and Diabetes Australia., Competing Interests: Declaration of interests SKP is currently a full-time employee of AstraZeneca. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The type 2 diabetes risk after gestational diabetes mellitus (GDM) is twice as high in South Asian compared to European women. Current guidelines differ regarding which test to use as a screening-tool post-GDM. We aimed to identify ethnic differences in the prevalence rates and early predictors for actionable HbA 1c (defined as prediabetes and diabetes) short time after GDM., Methods: This cross-sectional study, enrolling South Asian and Nordic women 1-3 years after a diagnosis of GDM, was undertaken at three hospitals in Norway. We performed a clinical and laboratory evaluation including an oral glucose tolerance test (OGTT). Medical records were used to retrieve data during pregnancy. Prediabetes was classified with HbA 1c alone or combined with OGTT glucose measurements according to the WHO, WHO-IEC, and ADA criteria (fasting plasma glucose (FPG) 6.1-6.9 mmol/L, FPG 6.1-6.9 mmol/L and/or HbA 1c 42-47 mmol/mol (6.0-6.4%), and FPG 5.6-6.9 mmol/L and/or HbA 1c 39-47 mmol/mol (5.7-6.4%)). Ethnic differences in prevalence and predictors of glucose deterioration were assed by χ 2 (Pearson) tests and logistic regression models., Results: We included 163 South Asian and 108 Nordic women. Actionable HbA 1c levels were highly prevalent and more so among South Asian than Nordic women (WHO-IEC-HbA 1c : 25.8% vs. 6.5% (p ≤ 0.001), ADA-HbA 1c : 58.3% vs. 22.2% (p ≤ 0.001)). Although adding OGTT-data gave higher combined prevalence rates of prediabetes and diabetes (WHO: 65.6% vs. 47.2% (p ≤ 0.05), WHO-IEC: 70.6% vs. 47.2% (p ≤ 0.001), ADA: 87.8% vs. 65.7% (p ≤ 0.001)), the excess risk in the South Asian women was best captured by the HbA 1c . Important predictors for glucose deterioration after GDM were: South Asian ethnicity, GDM before the index pregnancy, use of glucose-lowering drugs in pregnancy, higher age, and higher in-pregnancy fasting glucose levels., Conclusions: In women with GDM 1-3 year previously, we found high prevalence and significant ethnic differences in actionable ADA-HbA 1c levels, with South Asian ethnicity, GDM before the index pregnancy, and the use of glucose-lowering drugs in pregnancy as the most important risk factors. This study reinforces the importance of annual screening-preferably with HbA 1c measurements-to facilitate early intervention after GDM., (© 2022. The Author(s).)

Background: The Norwegian Institute of Public Health's statistics on immunisation against SARS-CoV-2 show that vaccination coverage for foreign-born persons living in Norway is lower than for persons born in Norway. As of January 2022, the difference was 18 percentage points (76 % versus 94 %). This difference is likely to be due to several factors, one of which may be that many of those who were immunised abroad have not had this registered in the Norwegian Immunisation Registry., Material and Method: In November 2021, the Norwegian Institute of Public Health conducted a public health survey in the county of Viken. Respondents were asked if they had been vaccinated against the coronavirus, if they were vaccinated in Norway or abroad, and if immunisation abroad had been reported to the Norwegian health service. They were also asked to specify their country of birth. The sample was drawn from the National Population Register. The survey was conducted online and the response rate was 41 % (n = 108 738)., Results: A total of 105 010 (97 %) of the respondents had had at least one dose of the coronavirus vaccine. Of these, 724 (<1 %) had only been vaccinated abroad. This applied to 392 (3 %) of the 13 286 foreign-born persons, 203 (52 %) of whom had reported their immunisation to the Norwegian health service., Interpretation: In this dataset, unregistered immunisation abroad explains only a small proportion of the difference in vaccination coverage between Norwegian-born and foreign-born persons.

Aims: We investigated the current extent of undiagnosed diabetes and prediabetes and their associated cardiovascular risk profile in a population-based study., Methods: All residents aged ≥20 years in the Nord-Trøndelag region, Norway, were invited to the HUNT4 Survey in 2017-2019, and 54% attended. Diagnosed diabetes was self-reported, and in those reporting no diabetes HbA1c was used to classify undiagnosed diabetes (≥48 mmol/mol [6.5%]) and prediabetes (39-47 mmol/mol [5.7%-6.4%]). We estimated the age- and sex-standardized prevalence of these conditions and their age- and sex-adjusted associations with other cardiovascular risk factors., Results: Among 52,856 participants, the prevalence of diabetes was 6.0% (95% CI 5.8, 6.2), of which 11.1% were previously undiagnosed (95% CI 10.1, 12.2). The prevalence of prediabetes was 6.4% (95% CI 6.2, 6.6). Among participants with undiagnosed diabetes, 58% had HbA1c of 48-53 mmol/mol (6.5%-7.0%), and only 14% (i.e., 0.1% of the total study population) had HbA1c >64 mmol/mol (8.0%). Compared with normoglycaemic participants, those with undiagnosed diabetes or prediabetes had higher body mass index, waist circumference, systolic blood pressure, triglycerides and C-reactive protein but lower low-density lipoprotein cholesterol (all p < 0.001). Participants with undiagnosed diabetes had less favourable values for every measured risk factor compared with those with diagnosed diabetes., Conclusions: The low prevalence of undiagnosed diabetes suggests that the current case-finding-based diagnostic practice is well-functioning. Few participants with undiagnosed diabetes had very high HbA1c levels indicating severe hyperglycaemia. Nonetheless, participants with undiagnosed diabetes had a poorer cardiovascular risk profile compared with participants with known or no diabetes., (© 2022 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Importance: Reports of myocarditis after SARS-CoV-2 messenger RNA (mRNA) vaccination have emerged., Objective: To evaluate the risks of myocarditis and pericarditis following SARS-CoV-2 vaccination by vaccine product, vaccination dose number, sex, and age., Design, Setting, and Participants: Four cohort studies were conducted according to a common protocol, and the results were combined using meta-analysis. Participants were 23 122 522 residents aged 12 years or older. They were followed up from December 27, 2020, until incident myocarditis or pericarditis, censoring, or study end (October 5, 2021). Data on SARS-CoV-2 vaccinations, hospital diagnoses of myocarditis or pericarditis, and covariates for the participants were obtained from linked nationwide health registers in Denmark, Finland, Norway, and Sweden., Exposures: The 28-day risk periods after administration date of the first and second doses of a SARS-CoV-2 vaccine, including BNT162b2, mRNA-1273, and AZD1222 or combinations thereof. A homologous schedule was defined as receiving the same vaccine type for doses 1 and 2., Main Outcomes and Measures: Incident outcome events were defined as the date of first inpatient hospital admission based on primary or secondary discharge diagnosis for myocarditis or pericarditis from December 27, 2020, onward. Secondary outcome was myocarditis or pericarditis combined from either inpatient or outpatient hospital care. Poisson regression yielded adjusted incidence rate ratios (IRRs) and excess rates with 95% CIs, comparing rates of myocarditis or pericarditis in the 28-day period following vaccination with rates among unvaccinated individuals., Results: Among 23 122 522 Nordic residents (81% vaccinated by study end; 50.2% female), 1077 incident myocarditis events and 1149 incident pericarditis events were identified. Within the 28-day period, for males and females 12 years or older combined who received a homologous schedule, the second dose was associated with higher risk of myocarditis, with adjusted IRRs of 1.75 (95% CI, 1.43-2.14) for BNT162b2 and 6.57 (95% CI, 4.64-9.28) for mRNA-1273. Among males 16 to 24 years of age, adjusted IRRs were 5.31 (95% CI, 3.68-7.68) for a second dose of BNT162b2 and 13.83 (95% CI, 8.08-23.68) for a second dose of mRNA-1273, and numbers of excess events were 5.55 (95% CI, 3.70-7.39) events per 100 000 vaccinees after the second dose of BNT162b2 and 18.39 (9.05-27.72) events per 100 000 vaccinees after the second dose of mRNA-1273. Estimates for pericarditis were similar., Conclusions and Relevance: Results of this large cohort study indicated that both first and second doses of mRNA vaccines were associated with increased risk of myocarditis and pericarditis. For individuals receiving 2 doses of the same vaccine, risk of myocarditis was highest among young males (aged 16-24 years) after the second dose. These findings are compatible with between 4 and 7 excess events in 28 days per 100 000 vaccinees after BNT162b2, and between 9 and 28 excess events per 100 000 vaccinees after mRNA-1273. This risk should be balanced against the benefits of protecting against severe COVID-19 disease.

Background: Levels of thyroid-stimulating hormone (TSH) are believed to reflect degree of disease in patients with hypothyroidism, and normalization of levels is the treatment goal. However, despite adequate levels of TSH after starting levothyroxine (LT4) therapy, 5-10% of hypothyroid patients complain of persisting symptoms with a significant negative impact on quality of life. This indicates that TSH is not an optimal indicator of intracellular thyroid hormone effects in all patients. Our aim was to investigate different effects of LT3 and LT4 monotherapy on other biomarkers of the thyroid signaling pathway, in addition to adverse effects, in patients with residual hypothyroid symptoms., Methods: Fifty-nine female hypothyroid patients, with residual symptoms on LT4 monotherapy or LT4/liothyronine (LT3) combination therapy, were randomly assigned in a non-blinded crossover study and received LT4 or LT3 monotherapy for 12 weeks each. Measurements, including serum analysis of a number of biochemical and hormonal parameters, were obtained at the baseline visit and after both treatment periods., Results: Free thyroxine (FT4) was higher in the LT4 group, while free triiodothyronine (FT3) was higher in the LT3 group. The levels of reverse triiodothyronine (rT3) decreased after LT3 treatment compared with LT4 treatment. Both low-density lipoprotein (LDL) and total cholesterol levels were reduced, while sex hormone-binding globulin (SHBG) increased after LT3 treatment compared with LT4 treatment. The median TSH levels for both treatment groups were within the reference range, however, lower in the LT4 group than in the LT3 group. We did not find any differences in pro-B-type natriuretic peptide (NT pro-BNP), handgrip strength, bone turnover markers, or adverse events between the two treatment groups., Conclusion: We have demonstrated that FT4, FT3, rT3, cholesterol, and SHBG show significantly different values on LT4 treatment compared with LT3 treatment in women with hypothyroidism and residual symptoms despite normal TSH levels. No differences in general or bone-specific adverse effects were demonstrated. This trial is registered with NCT03627611 in May 2018., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this study., (Copyright © 2022 Betty Ann Bjerkreim et al.)

Objective: To determine risk factors for SARS-CoV-2 infection and hospitalisation among children and adolescents., Design: Nationwide, population-based cohort study., Setting: Norway from 1 March 2020 to 30 November 2021., Participants: All Norwegian residents<18 years of age., Main Outcome Measures: Population-based healthcare and population registries were used to study risk factors for SARS-CoV-2 infection, including socioeconomic factors, country of origin and pre-existing chronic comorbidities. All residents were followed until age 18 years, emigration, death or end of follow-up. HRs estimated by Cox regression models were adjusted for testing frequency. Further, risk factors for admission to the hospital among the infected were investigated., Results: Of 1 219 184 residents, 82 734 (6.7%) tested positive by PCR or lateral flow tests, of whom 241 (0.29%) were admitted to a hospital. Low family income (adjusted HR (aHR) 1.26, 95% CI 1.23 to 1.30), crowded housing (1.27, 1.24 to 1.30), household size, age, non-Nordic country of origin (1.63, 1.60 to 1.66) and area of living were independent risk factors for infection. Chronic comorbidity was associated with a slightly lower risk of infection (aHR 0.90, 95% CI 0.88 to 0.93). Chronic comorbidity was associated with hospitalisation (aHR 3.46, 95% CI 2.50 to 4.80), in addition to age, whereas socioeconomic status and country of origin did not predict hospitalisation among those infected., Conclusions: Socioeconomic factors, country of origin and area of living were associated with the risk of SARS-CoV-2 infection. However, these factors did not predict hospitalisation among those infected. Chronic comorbidity was associated with higher risk of admission but slightly lower overall risk of acquiring SARS-CoV-2., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Soluble suppression of tumorigenesis-2 (sST2) and galectin (Gal)-3 are two biomarkers related to inflammation, metabolic disturbances and to myocardial fibrosis that characterize several cardiac pathological conditions. Increased circulating levels of these molecules have been associated with risk of cardiovascular death. Treatment with liraglutide, a glucagon-like peptide 1 analog, is associated with weight loss, improved glycemic control, and reduced cardiovascular risk. We wanted to assess (I) potential differences between subjects with prediabetes or type 2 diabetes mellitus (T2DM) and healthy controls in sST2 and Gal-3 circulating levels, and their relationship with glycemic control and markers of beta cell function and myocardial injury; (II) whether liraglutide treatment modulates these markers in subjects with prediabetes or early T2DM independently of weight loss; (III) whether baseline levels of any of these two molecules may predict the response to liraglutide treatment., Methods: Forty metformin-treated obese subjects (BMI ≥ 30) with prediabetes [impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) or both (n = 23)] or newly diagnosed T2DM (n = 17), were randomized to liraglutide or lifestyle counseling until achieving a comparable weight loss (7% of initial body weight). Thirteen subjects were enrolled as healthy controls for baseline sST2 and Gal-3 levels., Results: Baseline sST2 levels were comparable between controls and obese patients (p = 0.79) whereas Gal-3 levels were significantly higher in patients as compared to controls (p < 0.001). Liraglutide treatment, but not weight loss achieved by lifestyle counseling, decreased plasma sST2 levels (- 9%, beta = - 14.9, standard deviation 6.9, p = 0.037) while Gal-3 levels did not change. A reduction in serum hs-Troponin I was observed after intervention, due to a 19% (p = 0.29) increase in the lifestyle arm, and a 25% decrease (p = 0.033) in the liraglutide arm (between-group difference p = 0.083). Lower baseline Gal-3 levels predicted a better improvement in beta cell function after liraglutide treatment., Conclusions: Liraglutide-induced reduction in sST2 and possibly hs-TnI suggests that in obese patients with prediabetes or early T2DM this drug may have a positive effect on (cardiac) fibrosis, whereas plasma level of Gal-3 before liraglutide initiation may predict response to the drug in terms of beta cell function improvement. Trial registration Eudract: 2013-001356-36., (© 2022. The Author(s).)

Objective: The effects of levothyroxine (LT4)/liothyronine (LT3) combination therapy on quality of life (QoL) in hypothyroid patients former on LT4 monotherapy have been disappointing. We therefore wanted to test the effects of LT3 monotherapy on QoL in hypothyroid patients with residual symptoms despite thyroid stimulating hormone (TSH) values within the reference range., Design: Female hypothyroid patients with residual symptoms on LT4 monotherapy or combination LT4/LT3 therapy received LT3 and LT4 monotherapy, respectively for 12 weeks in a non-blinded randomized crossover study., Methods: Fifty-nine patients aged 18-65 years were included. QoL was assessed using one disease-specific questionnaire (ThyPRO) and two generic questionnaires (Fatigue Questionnaire and SF-36) at baseline and at the end of the two treatment periods. Clinical indices of cardiovascular health (resting heart rate and blood pressure), as well as thyroid tests, were assessed at baseline and at the end of the two treatment periods., Results: After 12 weeks of LT3 treatment, 12 of the 13 domains of the ThyPRO questionnaire (physical, mental and social domains) showed significant improvements. The most pronounced improvements were less tiredness (mean -21 ± 26; P <0.0001) and cognitive complaints (mean -20 ± 20; P <0.0001). LT4 monotherapy exerted minor effects on two domains only (cognitive complaints and impaired daily life). All three dimensions' scores in the Fatigue Questionnaire (physical, mental and total fatigue) improved after LT3 treatment compared to baseline ( P <0.001), and in the SF-36 questionnaire 7 of 8 scales showed significantly better scores after LT3 treatment compared to baseline. There were no differences in blood pressure or resting heart rate between the two treatment groups. TSH in patients on LT3 was slightly higher (median 1.33 mU/L (interquartile range (IQR) 0.47-2.26)) than in patients on LT4 (median 0.61 mU/L (IQR 0.25-1.20; P <0.018). Five patients on LT3 dropped out of the study due to subjectively reported side effects, compared to only one on LT4., Conclusions: LT3 treatment improved QoL in women with residual hypothyroid symptoms on LT4 monotherapy or LT4/LT3 combination therapy. Short-term LT3 treatment did not induce biochemical or clinical hyperthyroidism, and no cardiovascular adverse effects were recorded. Further studies are needed to assess the long-term safety and efficacy of LT3 monotherapy., Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03627611., Competing Interests: Authors SSH and EFE were employed by Pilestredet Park Specialist Center and LJO was employed by Balderklinikken. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2022 Bjerkreim, Hammerstad, Gulseth, Berg, Omdal, Lee-Ødegård and Eriksen.)

Background: Population-level trends in mortality among people with diabetes are inadequately described. We aimed to examine the magnitude and trends in excess all-cause mortality in people with diabetes., Methods: In this retrospective, multicountry analysis, we collected aggregate data from 19 data sources in 16 high-income countries or jurisdictions (in six data sources in Asia, eight in Europe, one from Australia, and four from North America) for the period from Jan 1, 1995, to Dec 31, 2016, (or a subset of this period) on all-cause mortality in people with diagnosed total or type 2 diabetes. We collected data from administrative sources, health insurance records, registries, and a health survey. We estimated excess mortality using the standardised mortality ratio (SMR)., Findings: In our dataset, there were approximately 21 million deaths during 0·5 billion person-years of follow-up among people with diagnosed diabetes. 17 of 19 data sources showed decreases in the age-standardised and sex-standardised mortality in people with diabetes, among which the annual percentage change in mortality ranged from -0·5% (95% CI -0·7 to -0·3) in Hungary to -4·2% (-4·3 to -4·1) in Hong Kong. The largest decreases in mortality were observed in east and southeast Asia, with a change of -4·2% (95% CI -4·3 to -4·1) in Hong Kong, -4·0% (-4·8 to -3·2) in South Korea, -3·5% (-4·0 to -3·0) in Taiwan, and -3·6% (-4·2 to -2·9) in Singapore. The annual estimated change in SMR between people with and without diabetes ranged from -3·0% (95% CI -3·0 to -2·9; US Medicare) to 1·6% (1·4 to 1·7; Lombardy, Italy). Among the 17 data sources with decreasing mortality among people with diabetes, we found a significant SMR increase in five data sources, no significant SMR change in four data sources, and a significant SMR decrease in eight data sources., Interpretation: All-cause mortality in diabetes has decreased in most of the high-income countries we assessed. In eight of 19 data sources analysed, mortality decreased more rapidly in people with diabetes than in those without diabetes. Further longevity gains will require continued improvement in prevention and management of diabetes., Funding: US Centers for Disease Control and Prevention, Diabetes Australia Research Program, and Victoria State Government Operational Infrastructure Support Program., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Context: Whether Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) differentially affect postprandial gastrointestinal hormones and β-cell function in type 2 diabetes remains unclear., Objective: We aimed to compare gastrointestinal hormones and β-cell function, assessed by an oral glucose tolerance test (OGTT) 5 weeks and 1 year after surgery, hypothesizing higher glucagon-like peptide-1 (GLP-1) levels and greater β-cell response to glucose after RYGB than after SG., Methods: This study was a randomized, triple-blind, single-center trial at a tertiary care center in Norway. The primary outcomes were diabetes remission and IVGTT-derived β-cell function. Participants with obesity and type 2 diabetes were allocated (1:1) to RYGB or SG. We measured gastrointestinal hormone profiles and insulin secretion as β-cell glucose sensitivity (β-GS) derived from 180-minute OGTTs., Results: Participants were 106 patients (67% women), mean (SD) age 48 (10) years. Diabetes remission rates at 1 year were higher after RYGB than after SG (77% vs 48%; P = 0.002). Incremental area under the curve (iAUC0-180) GLP-1 and β-GS increased more after RYGB than after SG, with 1-year between-group difference 1173 pmol/L*min (95% CI, 569-1776; P = 0.0010) and 0.45 pmol/kg/min/mmol (95% CI, 0.15-0.75; P = 0.0032), respectively. After surgery, fasting and postprandial ghrelin levels were higher and decremental AUC0-180 ghrelin, iAUC0-180 glucose-dependent insulinotropic polypeptide, and iAUC0-60 glucagon were greater after RYGB than after SG. Diabetes remission at 1 year was associated with higher β-GS and higher GLP-1 secretion., Conclusion: RYGB was associated with greater improvement in β-cell function and higher postprandial GLP-1 levels than SG., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Type 1 and type 2 diabetes mellitus incur an increased risk of fracture, with a generally higher risk among individuals with type 1 diabetes. The fracture risk among individuals with latent autoimmune diabetes of adulthood (LADA) is not known. The present cohort study aimed to estimate the risk of hip and forearm fracture among individuals with LADA, alongside type 1 and type 2 diabetes, using data from the second survey of the Trøndelag Health Study (HUNT2) in 1995-97. All inhabitants aged 20 years or older (N = 92,936) were invited to attend, of whom 65,234 (70%) participated. A total of 1972 (3%) reported to have diabetes; 1399 were found to have type 2 diabetes, 144 to have LADA, and 138 to have type 1 diabetes. All participants were followed prospectively with respect to hip- and forearm fractures by linkage to the local fracture registry. During a median follow-up of 16.2 years, 2695 persons with hip fractures and 3533 persons with forearm fractures were identified. There was an increased risk of hip fracture in women with type 2 diabetes (HR = 1.51, 95% CI 1.24-1.85) and LADA (HR = 2.15, 95% CI 1.25-3.72), whereas women with type 1 diabetes did not have a significantly increased risk (HR = 2.13, 95% CI 0.89-5.14). Among men, only LADA was associated with an increased risk of hip fracture (HR = 2.69, 95% CI 1.34-5.41). There was no statistically significant association between any of the diabetes types and forearm fracture. In women with type 2 diabetes, the highest risks of hip fracture were observed among those with highest HbA 1c level at baseline, longest time since diagnosis, and most visual and movement impairment. We found that individuals with LADA had an increased risk of hip fracture similar to that previously reported for individuals with type 1 diabetes, and no increased risk of forearm fracture., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Thyroid hormones are essential for the full thermogenic response of brown adipose tissue (BAT) and have been implicated in dermal temperature regulation. Nevertheless, persistent cold-intolerance exists among a substantial proportion of hypothyroid patients on adequate levothyroxine (LT4) substitution., Materials and Methods: To assess if skin temperature and activation of BAT during treatment with liothyronine (LT3) differs from that of LT4 treatment, fifty-nine female hypothyroid patients with residual symptoms on LT4 or LT4/LT3 combination therapy were randomly assigned in a non-blinded crossover study to receive monotherapy with LT4 or LT3 for 12 weeks each. Change in supraclavicular (SCV) skin temperature overlying BAT, and sternal skin temperature not overlying BAT, during rest and cold stimulation were assessed by infrared thermography (IRT). In addition, abundance of exosomal miR-92a, a biomarker of BAT activation, was estimated as a secondary outcome., Results: Cold stimulated skin temperatures decreased less with LT3 vs . LT4 in both SCV (mean 0.009°C/min [95% CI: 0.004, 0.014]; P <0.001) and sternal areas (mean 0.014°C/min [95% CI: 0.008, 0.020]; P <0.001). No difference in serum exosomal miR-92a abundance was observed between the two treatment groups., Conclusion: LT3 may reduce dermal heat loss. Thermography data suggested increased BAT activation in hypothyroid patients with cold-intolerance. However, this finding was not corroborated by assessment of the microRNA biomarker of BAT activation., Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03627611., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bjerkreim, Hammerstad, Gulseth, Berg, Lee-Ødegård, Rangberg, Jonassen, Budge, Morris, Law, Symonds and Eriksen.)

Introduction: We aimed to investigate whether the proportion of undiagnosed diabetes varies by socioeconomic status and healthcare consumption, in a Norwegian population screened with glycated hemoglobin (HbA 1c )., Research Design and Methods: In this cohort study, we studied age-standardized diabetes prevalence using data from men and women aged 40-89 years participating in four surveys of the Tromsø Study with available data on HbA 1c and self-reported diabetes: 1994-1995 (n=6720), 2001 (n=5831), 2007-2008 (n=11 987), and 2015-2016 (n=20 170). We defined undiagnosed diabetes as HbA 1c ≥6.5% (48 mmol/mol) and no self-reported diabetes. We studied the association of education, income and contact with a general practitioner on undiagnosed diabetes and estimated adjusted prevalence ratio (aPR) from multivariable adjusted (age, sex, body mass index) log-binomial regression., Results: Higher education was associated with lower prevalence of diagnosed and undiagnosed diabetes. Those with secondary and tertiary education had lower prevalence of undiagnosed diabetes (aPR for tertiary vs primary: 0.54, 95% CI: 0.44 to 0.66). Undiagnosed as a proportion of all diabetes was also significantly lower in those with tertiary education (aPR:0.78, 95% CI: 0.65 to 0.93). Household income was also negatively associated with prevalence of undiagnosed diabetes. Across the surveys, approximately 80% of those with undiagnosed diabetes had been in contact with a general practitioner the last year, similar to those without diabetes., Conclusions: Undiagnosed diabetes was lower among participants with higher education. The hypothesis that those with undiagnosed diabetes had been less in contact with a general practitioner was not supported., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: We aimed to investigate the effect of prebiotic inulin-type fructans (ITF) versus a control supplement on postprandial levels of glucagon-like peptide-1 and -2 (GLP-1 and -2), glucose and insulin in people with type 2 diabetes., Methods: Adult men and women with type 2 diabetes were randomised in a double-blind, placebo-controlled crossover study. The study participants received 16 g/d ITF and 16 g/d control supplement (maltodextrin) for 6 weeks each in two phases separated by a 4-week washout. A standardised mixed-meal test was performed before and after each intake period. The primary end point was changes in the GLP-1 response, and secondary end points were GLP-2, glucose and insulin responses. Data were analysed using mixed-model analysis., Results: A total of 29 participants were included in the study. Differences between and within the two treatments in estimated area under the curves were not significant. Yet, the predicted means for meal-induced GLP-1 response in plasma showed a 4.8% decline after the prebiotic treatment and an 8.6% increase after the control treatment (difference in changes between the treatments, p < 0.001). Fasting or postprandial glucose, insulin or GLP-2 levels were not changed., Conclusions: Our findings do not support that ITF improve incretin responses or glucose regulations in this population. Clinicaltrials.gov (NCT02569684)., (© 2021 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Aims: The type 2 diabetes risk following gestational diabetes mellitus (GDM) is high, particularly among South Asian women in Western countries. Our study aimed to advance the knowledge regarding the mechanisms behind suboptimal follow-up in the Nordic and South Asian women with previous GDM by comparing (1) their experiences, (2) health and disease perceptions and (3) barriers to and facilitators of health-promoting behaviours., Methods: This qualitative study was conducted in three hospital outpatient clinics in Norway, comprising six focus group interviews with 28 women 1-3 years after a pregnancy with GDM. The participants were purposively sampled and grouped according to their ethnicity. The data were analysed using thematic analysis, and a theoretical approach was applied to support the analysis and discuss the study's findings., Results: Five main themes were identified: lack of resilience, emotional distress, 'caught between a rock and a hard place', postpartum abandonment and insufficient guidance. The key determinants of the maintenance of unwanted health behaviours after GDM were consistent across the ethnic groups. Although the importance of a culturally sensitive approach was emphasised, it appeared secondary to the need for a more organised public healthcare during and after GDM., Conclusions: Women's real-life constraints, combined with the inadequate healthcare-service implementation, could explain the non-adherence to the lifestyle-changes guidelines essential for preventing diabetes post-GDM. We suggest promoting specific coping strategies and changing the healthcare service approach rather than relying on women's capacity to initiate the necessary changes., (© 2021 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Background: Diabetes prevalence is increasing in most places in the world, but prevalence is affected by both risk of developing diabetes and survival of those with diabetes. Diabetes incidence is a better metric to understand the trends in population risk of diabetes. Using a multicountry analysis, we aimed to ascertain whether the incidence of clinically diagnosed diabetes has changed over time., Methods: In this multicountry data analysis, we assembled aggregated data describing trends in diagnosed total or type 2 diabetes incidence from 24 population-based data sources in 21 countries or jurisdictions. Data were from administrative sources, health insurance records, registries, and a health survey. We modelled incidence rates with Poisson regression, using age and calendar time (1995-2018) as variables, describing the effects with restricted cubic splines with six knots for age and calendar time., Findings: Our data included about 22 million diabetes diagnoses from 5 billion person-years of follow-up. Data were from 19 high-income and two middle-income countries or jurisdictions. 23 data sources had data from 2010 onwards, among which 19 had a downward or stable trend, with an annual estimated change in incidence ranging from -1·1% to -10·8%. Among the four data sources with an increasing trend from 2010 onwards, the annual estimated change ranged from 0·9% to 5·6%. The findings were robust to sensitivity analyses excluding data sources in which the data quality was lower and were consistent in analyses stratified by different diabetes definitions., Interpretation: The incidence of diagnosed diabetes is stabilising or declining in many high-income countries. The reasons for the declines in the incidence of diagnosed diabetes warrant further investigation with appropriate data sources., Funding: US Centers for Disease Control and Prevention, Diabetes Australia Research Program, and Victoria State Government Operational Infrastructure Support Program., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Aims/hypothesis: Obesity and insulin resistance may be associated with elevated plasma concentration of branched-chain amino acids (BCAAs) and impaired BCAA metabolism. However, it is unknown whether the insulin-sensitising effect of long-term exercise can be explained by concomitant change in BCAAs and their metabolism., Methods: We included 26 sedentary overweight and normal-weight middle-aged men from the MyoGlu clinical trial, with or without dysglycaemia, for 12 weeks of supervised intensive exercise intervention, including two endurance and two resistance sessions weekly. Insulin sensitivity was measured as the glucose infusion rate (GIR) from a hyperinsulinaemic-euglycaemic clamp. In addition, maximum oxygen uptake, upper and lower body strength and adipose tissue depots (using MRI and spectroscopy) were measured, and subcutaneous white adipose tissue (ScWAT) and skeletal muscle (SkM) biopsies were harvested both before and after the 12 week intervention. In the present study we have measured plasma BCAAs and related metabolites using CG-MS/MS and HPLC-MS/MS, and performed global mRNA-sequencing pathway analysis on ScWAT and SkM., Results: In MyoGlu, men with dysglycaemia displayed lower GIR, more fat mass and higher liver fat content than normoglycaemic men at baseline, and 12 weeks of exercise increased GIR, improved body composition and reduced liver fat content similarly for both groups. In our current study we observed higher plasma concentrations of BCAAs (14.4%, p = 0.01) and related metabolites, such as 3-hydroxyisobutyrate (19.4%, p = 0.034) in dysglycaemic vs normoglycaemic men at baseline. Baseline plasma BCAA levels correlated negatively to the change in GIR (ρ = -0.41, p = 0.037) and [Formula: see text] (ρ = -0.47, p = 0.015) after 12 weeks of exercise and positively to amounts of intraperitoneal fat (ρ = 0.40, p = 0.044) and liver fat (ρ = 0.58, p = 0.01). However, circulating BCAAs and related metabolites did not respond to 12 weeks of exercise, with the exception of isoleucine, which increased in normoglycaemic men (10 μmol/l, p = 0.01). Pathway analyses of mRNA-sequencing data implied reduced BCAA catabolism in both SkM and ScWAT in men with dysglycaemia compared with men with normoglycaemia at baseline. Gene expression levels related to BCAA metabolism correlated positively with GIR and markers of mitochondrial content in both SkM and ScWAT, and negatively with fat mass generally, and particularly with intraperitoneal fat mass. mRNA-sequencing pathway analysis also implied increased BCAA metabolism after 12 weeks of exercise in both groups and in both tissues, including enhanced expression of the gene encoding branched-chain α-ketoacid dehydrogenase (BCKDH) and reduced expression of the BCKDH phosphatase in both groups and tissues. Gene expression of SLC25A44, which encodes a mitochondrial BCAA transporter, was increased in SkM in both groups, and gene expression of BCKDK, which encodes BCKDH kinase, was reduced in ScWAT in dysglycaemic men. Mediation analyses indicated a pronounced effect of enhanced SkM (~53%, p = 0.022), and a moderate effect of enhanced ScWAT (~18%, p = 0.018) BCAA metabolism on improved insulin sensitivity after 12 weeks of exercise, based on mRNA sequencing. In comparison, plasma concentration of BCAAs did not mediate any effect in this regard., Conclusion/interpretation: Plasma BCAA concentration was largely unresponsive to long-term exercise and unrelated to exercise-induced insulin sensitivity. On the other hand, the insulin-sensitising effect of long-term exercise in men may be explained by enhanced SkM and, to a lesser degree, also by enhanced ScWAT BCAA catabolism. Graphical abstract.

Background: Advanced age is the most important risk factor for death as a result of COVID-19, but there is a dearth of knowledge regarding the impact of chronic diseases. Using health registry data, we describe the disease profiles of persons who died after a confirmed infection with SARS-CoV-2 during the first three months of the pandemic in Norway., Material and Method: Data from the specialist health service (Norwegian Patient Registry, NPR) and the primary health service (Norwegian Registry for Primary Health Care, NRPHC) were linked to information on positive tests for SARS-CoV-2 from the Norwegian Surveillance System for Communicable Diseases (MSIS) and on deaths from the National Population Register. The data retrieval included the Norwegian population as of 1 March 2020 with data for confirmed infections, hospitalisations and deaths until 31 May 2020., Results: Of 8 412 persons with a confirmed SARS-CoV-2 infection, altogether 244 (2.9 %) died, whereof 133 (55 %) were men. Among those with a confirmed infection, the proportion who died varied from 0.2 % (age < 60 years) to 52 % (age ≥ 90 years). Altogether 92 (38 %) patients died in hospital. 25 (16 %) of those who died elsewhere had previously been hospitalised for COVID-19. The proportion with no registered chronic disease was 39 % in the age group < 70 years and 26 % in the age group ≥ 70 years. The disease distribution varied between those patients who had died in and outside of hospital, especially for diagnoses of diabetes, renal failure and dementia., Interpretation: Among those who had a SARS-CoV-2 infection confirmed during the first three months of the pandemic in Norway, only a small proportion died. The majority of those who died were 70 years or older and had at least one chronic disease, but the disease profile varied between patients who died in and outside of hospital. Health registry data can help provide a better overview of and advice to risk groups in the population during an ongoing pandemic.

Background: Cardiovascular diseases, cancer, type-2 diabetes and chronic obstructive pulmonary disease (COPD) were initially noted as the most common diseases among individuals who were hospitalised for COVID-19. However, the evidence base is weak. The objective of this study is to describe how selected diseases were distributed among adults with confirmed COVID-19 (COVID-19 positive tests) and among those hospitalised for COVID-19 compared to the general population., Material and Method: We used data from the Norwegian Patient Registry, the Norwegian Registry for Primary Health Care and the Norwegian Surveillance System for Communicable Diseases for adults from the age of 20 and older for the period 1 March 2020-13 May 2020., Results: Of all those who tested positive for COVID-19, 7 632 (94 %) were aged 20 years or older, and 1 025 (13.4 %) of these had been hospitalised. Among those hospitalised with COVID-19, there was a higher proportion of individuals with cardiovascular diseases (18.3 % versus 15.6 %), cancer (6.9 % versus 5.4 %), type-2 diabetes (8.6 % versus 5.2 %) and COPD (3.8 % versus 2.7 %) than in the general population as a whole after adjusting for age. The proportion of hospitalised patients with asthma, other chronic respiratory disease, cardiovascular disease, ongoing cancer treatment, complications related to hypertension, obesity and overweight, neurological disorders and cardiac and renal failure was also higher than in the general population. There were few differences between persons who had tested positive for COVID-19 and the general population in terms of underlying conditions., Interpretation: Among those hospitalised for COVID-19, there was a higher proportion of patients with underlying illnesses than in the general population. This may indicate that these patients tend to have a more severe course of disease or that they are more likely to be hospitalised compared to healthy individuals. The results must be interpreted with caution, since the sample of COVID-19 individuals is non-random.

Impaired insulin secretion and action are important for development of type 2 diabetes (T2D) and metabolic syndrome (MetS). Despite recognized heterogeneity of these glucometabolic disorders, few data are available of biological variation in insulin secretion and action among individuals with T2D and MetS. The aim of this study was to explore the inter-individual variations using gold standard methods in a cross-sectional study of two independent cohorts of phenotypically well-characterized subjects. Cohort I included 486 subjects with MetS, and cohort II 62 subjects with established T2D. First phase insulin secretion was defined as the incremental area under the curve 0-8 min (iAUC 0-8 min ) during an intravenous glucose tolerance test (IVGTT). Insulin sensitivity was measured as the insulin sensitivity index (S I ) modelled from IVGTT in cohort I, and in II as total glucose disposal (TGD) estimated from a euglycaemic-hyperinsulinaemic clamp. Variation is given as total range and, fold-variation between 5%- and 95%-percentile. The iAUC 0-8 min ranged from -60 to 3397 mUL -1 min -1 among subjects with MetS and from -263 to 1194 mUL -1 min -1 in subjects with T2D, representing a more than 10-fold variation. Insulin sensitivity ranged from S I 0.19 to 15.29 (mU/L) -1 min -1 among subjects with MetS and TGD 12.9-101.6 μmolkgFFM -1 min -1 in subjects with T2D, representing a 6.8 and 5.5-fold variation, respectively. The other components of MetS; BMI, waist-hip ratio, HDL-cholesterol, triglycerides and blood pressure (BP), showed a 1.4-4.7-fold variation. In conclusion, our data demonstrated extensive inter-individual variations in insulin secretion and sensitivity. These variations may be essential to take into account when planning clinical research and treatment in subjects with T2D and MetS.

Background: Children and adolescents are at lower risk of disease caused by SARS-CoV-2. We describe the incidence of confirmed infection and hospitalisation of children and adolescents under the age of 20 in Norway, and specifically among those with underlying conditions., Material and Method: The Norwegian Directorate of Health has collaborated with the Norwegian Institute of Public Health on the establishment of a data extraction system to monitor the coronavirus outbreak. Data from the specialist health service (Norwegian Patient Registry, NPR), and the primary health service (Norwegian Registry for Primary Health Care, NRPHC) are linked to data on positive SARS-CoV-2 tests from the Surveillance System for Communicable Diseases (MSIS). This covers all persons living in Norway as of 1 March 2020, with data on confirmed infection up to and including 13 May 2020 and on hospitalisations up to and including 30 April 2020., Results: Of 8 125 persons with confirmed SARS-CoV-2 in the whole population, 493 (6.1 %) were under 20 years old. The median age of the under-20s was 15 years, and 252 (51 %) were girls. 3 % were hospitalised. No deaths were registered among patients aged under 20 in Norway. We found a somewhat larger share with confirmed SARS-CoV-2 in the group with diseases of the neuromuscular system., Interpretation: Few children and adolescents have had SARS-CoV-2 confirmed, and only a very few have been hospitalised. Underlying conditions may result in a lower threshold for testing, and hence a higher incidence of confirmed infection in this group, although higher risk cannot be excluded.

Background and Aims: While excess energy intake and physical inactivity constitute the obvious causes of body fat accumulation, persistent organic pollutants (POPs) are novel factors that have been linked to cardiometabolic disorders. Major sources of POPs are animal fats including fatty fish. Given the putative protective effects of fish on cardiovascular disease, we explored whether high consumption of fatty fish increased serum concentrations of POPs., Methods and Results: Men and women aged 35-70 years with body mass index between 25 and 38 kg/m 2 and at least 1 cardiometabolic component were randomized to high intakes of fatty fish (mostly farmed salmon, ∼630 g/week; n = 45), high intakes of nuts (∼200 g/week; n = 42) or a control group following their usual diet but restricting fatty fish and nuts for 6 months (n = 44). Concentrations of 15 POPs (5 organochlorinated compounds, 2 dioxin-like polychlorinated biphenyls and 8 non-dioxin-like polychlorinated biphenyls) and cardiometabolic risk factors were measured at baseline and end of the study. Results showed that changes in concentrations of individual and classes of POPs did not differ between the dietary groups and controls (p > 0.05). Among cardiometabolic risk factors HDL-cholesterol increased in the fatty fish group compared to controls (+0.10 mmol/L, CI (0.05-0.20); p = 0.005) while no changes were observed in the group consuming nuts., Conclusion: Fatty fish consumption for 6 months did not increase the serum concentrations of POPs in individuals with overweight or obesity and metabolic risk. While this finding appears reassuring regarding short-term intakes of farmed salmon, long term variations in POPs in adipose stores require further study., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare. All authors had access to the data and have seen and approved the final submitted manuscript., (Copyright © 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: There is limited evidence linking type 2 diabetes (T2D) to influenza-related complications., Objectives: To test a set of research questions relating to pandemic influenza vaccination, hospitalization and mortality in people with and without T2D., Methods: In this population-based cohort study, we linked individual-level data from several national registers for all Norwegian residents aged 30 years or more as of January 2009. People with or without T2D at baseline (n = 2 992 228) were followed until December 2013. We used Cox regression to estimate adjusted hazard ratios (aHRs)., Results: Pandemic influenza hospitalization was more common in individuals with T2D (aHR = 2.46, 95% CI 2.04-2.98). The mortality hazard ratio associated with hospitalization for pandemic influenza was lower in people with T2D (aHR = 1.82, 95% CI 1.21-2.74) than in those without T2D (aHR = 3.89, 95% CI 3.27-4.62). The same pattern was observed when restricting to 90-day mortality (aHR = 3.89, 95% CI 1.25-12.06 amongst those with T2D and aHR = 10.79, 95% CI 7.23-16.10 amongst those without T2D). The rate of hospitalization for pandemic influenza was 78% lower in those vaccinated compared to nonvaccinated amongst people with T2D (aHR = 0.22, 95% CI 0.11-0.39), whilst the corresponding estimate for those without T2D was 59% lower (aHR = 0.41, 95% CI 0.33-0.52). Mortality was 25% lower in those vaccinated compared to nonvaccinated amongst people with T2D (aHR = 0.75, 95% CI 0.73-0.77), whilst the corresponding estimate for those without T2D was 9% (aHR = 0.91, 95% CI 0.90-0.92)., Conclusions: There may have been a lower threshold for pandemic influenza hospitalization for people with T2D, rather than more severe influenza infection. Our combined results support the importance of influenza vaccination amongst people with T2D, especially during pandemics., (© 2019 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Background: Obesity and type 2 diabetes (T2D) are associated with an increased risk of skeletal fractures despite a normal areal bone mineral density (aBMD) and low bone turnover, possibly due to reduced bone material strength. Roux-en-Y gastric bypass (RYGB) enables a substantial and persistent weight loss and resolution of obesity related comorbidities such as T2D. However, the procedure induces a decrease in aBMD and increased bone turnover and fracture rate. To our knowledge, changes in bone material strength after RYGB have not been explored. This study aimed to evaluate changes in factors influencing bone quality; bone material strength, aBMD and bone turnover markers, in a population with morbid obesity undergoing RYGB and whether these changes differed in participants with and without T2D. We also sought to assess factors associated with bone material strength and bone mineral density in obese subjects before and after RYGB., Methods: We examined 34 participants before and one year after RYGB, of whom 13 had T2D. Bone material strength index (BMSi) was evaluated by impact microindentation, aBMD and body composition by Dual energy X-ray absorptiometry, levels of bone turnover markers and calciotropic hormones were estimated from fasting serum samples. Participants with and without T2D were comparable before surgery, with the exception of glycosylated hemoglobin (HbA 1c )., Results: Preoperatively, BMSi was inversely associated with BMI, β unadjusted -1.1 (-1.9 to -0.28), R 2 =0.19, p=0.010, and this association remained significant after adjusting for age and gender. After RYGB the participants had lost a mean±SD of 33.9±10.9kg, 48.7±14.2 % of total body fat, increased physical activity, unchanged vitamin D levels, and all but one of the 13 participants with T2D were in diabetes remission. BMSi increased from 78.1±8.5 preoperatively to 82.0±6.4 one year after RYGB, corresponding to an increase of 4.0±9.8 in absolute units or 6.3±14.0 %, p=0.037. The increase was comparable in participants with and without T2D. In subjects with T2D, a larger decrease in HbA 1c was associated with a larger increase in BMSi β unadjusted -9.2 (-16.5 to -1.9), R 2 =0.47, p=0.019. Bone turnover markers (CTX-1 and PINP) increased by 195.1±133.5 % and 109.5±70.6 %, respectively. aBMD decreased by 3.9±5.5 % in the lumbar spine, 8.2±4.6 % in the femoral neck, 11.6±4.9 % in total hip and 9.4±3.8 % in total body., Conclusion: Our findings indicate that bone material strength improves despite an increase in bone turnover and a decrease in aBMD one year after RYGB. Trends were statistically comparable in participants with and without T2D. However, improved glucose control was associated with improved bone material strength in participants with T2D., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: For patients with obesity and type 2 diabetes, weight loss improves insulin sensitivity and β-cell function, and can induce remission of diabetes. The comparative efficacy of various bariatric procedures for the remission of type 2 diabetes has not been fully elucidated. We aimed to compare the effects of the two most common bariatric procedures, gastric bypass and sleeve gastrectomy, on remission of diabetes and β-cell function., Methods: We conducted a single-centre, triple-blind, randomised trial at Vestfold Hospital Trust (Tønsberg, Norway), in which patients (aged ≥18 years) with type 2 diabetes and obesity were randomly assigned (1:1) to receive gastric bypass or sleeve gastrectomy (the Oseberg study). Randomisation was performed with a computerised random number generator and a block size of 10. Treatment allocation was masked from participants, study personnel, and outcome assessors and was concealed with sealed opaque envelopes. Surgeons used identical skin incisions during both surgeries and were not involved in patient follow-up. The primary clinical outcome was the proportion of participants with complete remission of type 2 diabetes (HbA 1c of ≤6·0% [42 mmol/mol] without the use of glucose-lowering medication) at 1 year after surgery. The primary physiological outcome was disposition index (a measure of β-cell function) at 1 year after surgery, as assessed by an intravenous glucose tolerance test. Primary outcomes were analysed in the intention-to-treat and per-protocol populations. This trial is ongoing and closed to recruitment, and is registered with ClinicalTrials.gov, NCT01778738., Findings: Between Oct 15, 2012, and Sept 1, 2017, 1305 patients who were preparing for bariatric surgery were screened, of whom 319 consecutive patients with type 2 diabetes were assessed for eligibility. 109 patients were enrolled and randomly assigned to gastric bypass (n=54) or sleeve gastrectomy (n=55). 107 (98%) of 109 patients completed 1-year follow-up, with one patient in each group withdrawing after surgery (per-protocol population). In the intention-to-treat population, diabetes remission rates were higher in the gastric bypass group than in the sleeve gastrectomy group (risk difference 27% [95% CI 10 to 44]; relative risk [RR] 1·57 [1·14 to 2·16], p=0·0054); results were similar in the per-protocol population (risk difference 27% [95% CI 10 to 45]; RR 1·57 [1·14 to 2·15], p=0·0036). In the intention-to-treat population, disposition index increased in both groups (between-group difference 55 [-111 to 220], p=0·52); results were similar in the per-protocol population (between-group difference 21 [-214 to 256], p=0.86). In the gastric bypass group, ten of 54 participants had early complications and 17 of 53 had late side-effects. In the sleeve gastrectomy group, eight of 55 participants had early complications and 22 of 54 had late side-effects. No deaths occurred in either group., Interpretation: Gastric bypass was found to be superior to sleeve gastrectomy for remission of type 2 diabetes at 1 year after surgery, and the two procedures had a similar beneficial effect on β-cell function. The use of gastric bypass as the preferred bariatric procedure for patients with obesity and type 2 diabetes could improve diabetes care and reduce related societal costs., Funding: Morbid Obesity Centre, Vestfold Hospital Trust., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Diabetes in pregnancy and consequently the need for treatment with antidiabetic medication (ADM) has become increasingly prevalent. The prevalence and patterns of use of ADM in pregnancy from 2006 onward in seven different countries was assessed., Research Design and Methods: Data sources included individually linked data from the nationwide health registers in Denmark (2006-2016), Finland (2006-2016), Iceland (2006-2012), Norway (2006-2015), Sweden (2006-2015), state-wide administrative and claims data for New South Wales, Australia (2006-2012) and two US insurance databases: Medicaid Analytic eXtract (MAX; 2006-2012, public) and IBM MarketScan (2012-2015, private). The prevalence of ADM use was calculated as the proportion of pregnancies with at least one filled prescription of an ADM in the 90 days before pregnancy or within the three trimesters of pregnancy., Results: Prevalence of any ADM use in 5 279 231 pregnancies was 3% (n=147 999) and varied from under 2% (Denmark, Norway, and Sweden) to above 5% (Australia and US). Insulin was the most used ADM, and metformin was the most used oral hypoglycemic agent with increasing use over time in all countries. In 11.4%-62.5% of pregnancies with prepregnancy use, ADM (primarily metformin) was discontinued. When ADM treatment was initiated in late pregnancy for treatment of gestational diabetes mellitus, insulin was most often dispensed, except in the US, where glibenclamide was most often used., Conclusions: Prevalence and patterns of use of ADM classes varied between countries and over time. While insulin remained the most common ADM used in pregnancy, metformin use increased significantly over the study period., Competing Interests: Competing interests: CEC, GB, HK, LP, and IO are employees at the Centre for Pharmacoepidemiology, which receives grants from several entities (pharmaceutical companies, regulatory authorities and contract research organizations) for the performance of drug safety and drug utilization studies, unrelated to this work. HLG reports fees and grants from pharmaceutical companies in her previous position at Oslo University Hospital, unrelated to this work. SH-D reports receiving research grants to her institution from Eli Lilly, GlaxoSmithKline, and the National Institutes of Health and consulting fees from Roche unrelated to this work and having served as an epidemiologist with the North America AED pregnancy registry, which is funded by multiple companies. KFH reports receiving research grants to her institution from Eli Lilly, Pfizer, GlaxoSmithKline, and Boehringer-Ingelheim, unrelated to this work. BTB reports receiving grants to his institution from Eli Lilly, GlaxoSmithKline, Pacira, Baxalta, Pfizer, and Aetion unrelated to this work and having served on an expert panel for a postpartum hemorrhage quality improvement project that was conducted by the Association of Women’s Health, Obstetric, and Neonatal Nurses and funded by a grant from Merck for Mothers. All other authors have no conflicts of interest to declare., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Weight regain after bariatric surgery often starts after 1-2 y, but studies evaluating strategies to prevent weight regain are lacking. The aim of this intervention was to evaluate the efficacy of a 2-y-group-based lifestyle intervention starting approximately 2 y after Roux-en-Y gastric bypass (RYGB) compared with usual care on weight regain and related metabolic risk factors., Methods: A total of 165 patients with a mean of 21 months (range 14-32) after RYGB were randomized to a lifestyle intervention group (LIG) or a usual care group (UCG). Of the 165 participants 86% completed the study. The LIG was offered 16 group meetings over 2 y with focus on healthy diet, physical activity, and behavioural strategies to prevent weight regain, in addition to usual care., Results: Mean (SD) total weight loss at study start was 30.1 ± 8.2%, while weight regain during the intervention was 4.9 ± 7.4 and 4.6 ± 9.2% in the LIG and UCG, respectively (P = 0.84). There were no differences in metabolic risk factors between the groups. The LIG participants attended 8 ± 4 group meetings, with no difference in weight regain between participants with high compared to lower participation. In all the participants, a positive association between weight increase from nadir to study start and weight regain during the intervention was found. Participants who reported physical activity ≥ 150 min/wk had smaller % weight regain compared with less active participants (β = - 5.2 [SE 2.0, 95% CI - 9.1 to - 1.4])., Conclusion: We found no difference in weight regain between LIG and UCG.

Background: Roux-en-Y gastric bypass (RYGB) is a common surgical procedure for treatment of morbid obesity. RYGB induces considerable and sustained weight loss, and remission of obesity related-comorbidities. While studies have suggested negative effects of RYGB on bone health, long-term data are lacking. We aimed to evaluate the prevalence of aBMD below the expected range for age, osteopenia, osteoporosis and low-energy fractures in a defined patient cohort 10 years after RYGB. Secondly, we wanted to identify factors associated with increased risk of aBMD z-score or t-score of -1.1 or lower 10 years after RYGB., Methods: Patients undergoing RYGB surgery from June 2004 to December 2006 at the Department of Morbid Obesity and Bariatric Surgery, Oslo University Hospital, a tertiary referral centre for treatment of morbid obesity, were invited to a 10 year follow-up. Follow-up visits included morning fasting blood samples, clinical examination, anthropometric measures and dual energy X-ray absorptiometry (DXA)., Results: Out of 194 patients eligible for the study, 124 attended the 10 year follow-up and 122 (63%) were examined with DXA. Mean (SD) age was 50.3 (9.0) years, 118 (97%) were of Caucasian ethnicity, 94 were females (77%), of whom 41 (44%) were postmenopausal. Secondary hyperparathyroidism (SHPT) was noted in 37 participants (31%) and vitamin D deficiency (value below 50 nmol/L) and insufficiency (value below 75 nmol/L) in 40 (33%) and 91 (75%), respectively. Among the 63 participants who were premenopausal females or males 49 years or younger the prevalence of areal bone mineral density (aBMD) in the lower range of normal (z-score -1.1- to -1.9) was 30% (n = 19) and aBMD below the expected range for age (z-score ≤ -2.0) was noted in 8% (n = 5). Among the 59 participants who were postmenopausal females or males 50 years or older, the prevalence of osteopenia (t-score -1.1 to -2.4) was 51% (n = 30) and osteoporosis (t-score ≤ -2.5) was 27% (n = 16). The bone resorption markers CTX-1 and PINP were higher in participants with aBMD z-score or t-score of -1.1 or lower compared to participants with aBMD z-score or t-score of -1.0 or higher. Preoperative hypothyroidism, or higher age, postmenopausal status, BMI < 35 kg/m 2 , SHPT or higher PINP levels at 10 year follow-up were independently associated with aBMD z-score or t-score of -1.1 or lower 10 years after RYGB. Eighteen participants (15%) reported a clinical low-energy fracture after RYGB. In addition, vertebral fracture assessment by DXA revealed that 10 participants (8%) had experienced at least one moderate to severe morphometric vertebral fracture., Conclusion: Ten years after RYGB 27% of postmenopausal females and males 50 years or older were osteoporotic, and 8% of premenopausal females and males 49 years or younger exhibited aBMD below the expected range for age. The prevalence of fragility fractures was high. SHPT, higher age, postmenopausal status or higher PINP levels at 10 years and preoperative hypothyroidism were all independent risk factors for aBMD z-score or t-score of -1.1 or lower 10 years after RYGB., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Bone marrow adipose tissue (BMAT) has been postulated to mediate skeletal fragility in type 2 diabetes (T2D) and obesity. Roux-en-Y gastric bypass (RYGB) induces a substantial weight loss and resolution of comorbidities. However, the procedure induces increased bone turnover and fracture rates. No previous study has evaluated biopsy-measured BMAT fraction preoperatively and after RYGB. In this study, we aimed to investigate BMAT fraction of the hip in participants with and without T2D preoperatively and 1 year after RYGB and explore factors associated with BMAT change. Patients with morbid obesity scheduled for RYGB were examined preoperatively and 1 year after RYGB. Forty-four participants were included and preoperative examinations were possible in 35. Of these, 33 (94%) met for follow-up, 2 were excluded, and BMAT estimation was not possible in 1. Eighteen (60%) of the participants were females and 11 (37%) had T2D. Preoperative BMAT fraction was positively associated with glycosylated hemoglobin and negatively associated with areal bone mineral density (aBMD). After RYGB, BMAT fraction decreased from 40.4 ± 1.7% to 35.6 ± 12.8%, p = 0.042, or with mean percent change of 10.7% of preoperative BMAT fraction. Change in BMAT fraction was positively associated with change in body mass index (BMI) and total body fat. In females, we observed a mean percent reduction of 22.4 ± 19.6%, whereas in males BMAT increased with a mean percent of 6.8 ± 37.5%, p = 0.009. For males, changes in estradiol were associated with BMAT change; this was not observed for females. In participants with and without T2D, the mean percent BMAT reduction was 5.8 ± 36.9% and 13.5 ± 28.0%, respectively, p = 0.52. We conclude that a high BMAT seems to be associated with lower aBMD and poorer glycemic control in obese subjects. After RYGB, we observed a significant decrease in BMAT. The reduction in BMAT did not differ between participants with and without T2D, but appeared sex specific. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc., (© 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.)

Objective: Severe hypoglycemia is the most serious acute complication for people with type 1 diabetes (T1D). Approximately 25% of people with T1D have impaired ability to recognize impending hypoglycemia, and nocturnal episodes are feared., Approach: We have investigated the use of non-invasive sensors for detection of hypoglycemia based on a mathematical model which combines several sensor measurements to identify physiological responses to hypoglycemia. Data from randomized single-blinded euglycemic and hypoglycemic glucose clamps in 20 participants with T1D and impaired awareness of hypoglycemia was used in the analyses., Main Results: Using a sensor combination of sudomotor activity at three skin sites, ECG-derived heart rate and heart rate corrected QT interval, near-infrared and bioimpedance spectroscopy; physiological responses associated with hypoglycemia could be identified with an F1 score accuracy up to 88%., Significance: We present a novel model for identification of non-invasively measurable physiological responses related to hypoglycemia, showing potential for detection of moderate hypoglycemia using a wearable sensor system.

Introduction: Bariatric surgery is increasingly recognised as an effective treatment option for subjects with type 2 diabetes and obesity; however, there is no conclusive evidence on the superiority of Roux-en-Y gastric bypass or sleeve gastrectomy. The Oseberg study was designed to compare the effects of gastric bypass and sleeve gastrectomy on remission of type 2 diabetes and β-cell function., Methods and Analysis: Single-centre, randomised, triple-blinded, two-armed superiority trial carried out at the Morbid Obesity Centre at Vestfold Hospital Trust in Norway. Eligible patients with type 2 diabetes and obesity were randomly allocated in a 1:1 ratio to either gastric bypass or sleeve gastrectomy. The primary outcome measures are (1) the proportion of participants with complete remission of type 2 diabetes (HbA1c≤6.0% in the absence of blood glucose-lowering pharmacologic therapy) and (2) β-cell function expressed by the disposition index (calculated using the frequently sampled intravenous glucose tolerance test with minimal model analysis) 1 year after surgery., Ethics and Dissemination: The protocol of the current study was reviewed and approved by the regional ethics committee on 12 September 2012 (ref: 2012/1427/REK sør-øst B). The results will be disseminated to academic and health professional audiences and the public via publications in international peer-reviewed journals and conferences. Participants will receive a summary of the main findings., Trial Registration Number: NCT01778738;Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)