Background: Historically, life expectancy in persons with type 1 diabetes (T1D) has been shorter than the general population, but earlier studies did not stratify patients according to cardiorenal complications. Methods: T1D persons were identified in the Swedish National Diabetes Registry (n=45,575) and compared with matched controls from the general population (n=220,141) . Mortality rates from 2002 to 20were estimated in persons with T1D overall and after stratification for prevalent cardiovascular and renal disease. Results: In persons with T1D, mean age was 32.4 years and 44.9% were women. Age- and sex- adjusted mortality rates decreased over time in both groups but remained significantly higher in those with T1D during 2017 to 2019. In T1D persons ≥45 years without previous renal or cardiovascular complications (approximately 50% of persons in this age group) similar standardized mortality rates were observed, over time compared with controls, with slightly lower mortality in T1D persons during the last period, 5.55 (95% CI 4.51-6.60) vs. 7. (95% CI 6.75-7.40) deaths per 1,000 person years (Figure) . Conclusion: Excess mortality persisted over time in persons with T1D, largely in patients with cardiorenal complications. Improved secondary prevention with a focus on differentiated treatment is needed to close the gap in mortality for persons with T1D. Disclosure S. Hallström: None. M.O. Wijkman: None. J. Ludvigsson: Advisory Panel; Dompé. Research Support; Diamyd Medical. M.A. Pfeffer: Consultant; AstraZeneca, Boehringer Ingelheim and Eli Lilly Alliance, Corvidia Therapeutics, GlaxoSmithKline plc., Lexicon Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Peerbridge, Sanofi. Research Support; Novartis Pharmaceuticals Corporation. Other Relationship; DalCor Pharmaceuticals, National Heart, Lung, and Blood Institute. A. Rosengren: None. M. Lind: Consultant; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk. Research Support; Eli Lilly and Company, Novo Nordisk. Funding ALF [ALFGBG-717211] and [ALFGBG-966173], grants from the Novo Nordisk foundation, Swedish Heart and Lung Foundation [20180589], [20210679], Swedish Research Council [2018-02527] [VRREG 2019-00193], and the Gothenburg Society of Medicine.

ObjectiveThe aim of the study was to investigate all-cause and disease-specific mortality in a large population-based cohort of oral glucocorticoid (GC) users.MethodsThis was a retrospective, matched cohort study. Information on dispensed prescriptions was obtained from the Swedish Prescribed Drug Register. The cause of death was obtained from the Swedish Cause-of-Death Registry. Patients receiving prednisolone ≥5 mg/day (or equivalent dose of other GC) for ≥21 days between 2007-2014 were included. For each patient, one control subject matched for age and sex was included. The study period was divided into 3-month periods and patients were divided into groups according to a defined daily dose (DDD) of GC used per day. The groups were: Non-users (0 DDD per day), low-dose users (>0 but <0.5 DDD per day), medium-dose users (0.5-1.5 DDD per day) and high-dose users (>1.5 DDD per day). Hazard ratios (HRs), unadjusted and adjusted for age, sex and comorbidities, were calculated using a time-dependent Cox proportional hazard model.ResultsCases (n=223 211) had significantly higher all-cause mortality compared to controls (HR adjusted for age, sex and comorbidities 2.08, 95% confidence interval 2.04 to 2.13). After dividing the cases into subgroups, adjusted HR was 1.31 (1.28 to 1.34) in non-users, 3.64 (3.51 to 3.77) in low-dose users, 5.43 (5.27 to 5.60) in medium-dose users and, 5.12 (4.84 to 5.42) in high-dose users. The highest adjusted hazard ratio was observed in high-dose users for deaths from sepsis 6.71 (5.12 to 8.81) and pulmonary embolism 7.83 (5.71 to 10.74).ConclusionOral GC users have an increased mortality rate compared to the background population, even after adjustment for comorbidities. High-dose users have an increased risk of dying from sepsis, and pulmonary embolism compared to controls. Whether the relationship between GC exposure and the excess mortality is causal remains to be elucidated.

Background Historically, the incidence of cardiovascular disease and mortality in persons with Type I diabetes (TID) has been increased compared to the general population. Contemporary studies on time trends of mortality and cardiovascular disease are sparse. Methods In this observational study, TID persons were identified in the Swedish National Diabetes Registry (n=45,575) and compared with matched controls from the general population (n=220,141). Incidence rates from 2002 to 2019 were estimated with respect to mortality and cardiovascular disease in persons with TID overall and when stratified for prevalent cardiovascular and renal disease relative to controls. Findings Mean age in persons with TID was 32.4 years and 44.9% (20,446/45,575) were women. Age- and sex-adjusted mortality rates declined over time in both groups but remained significantly higher in those with TID compared to controls during 2017-2019, 7.62 (95% CI 7.16; 8.08) vs. 2.23 (95% CI 2.13; 2.33) deaths per 1,000 person years. Myocardial infarction, heart failure and stroke decreased over time in both groups, with persistent excess risks in the range of 3.4 -5.0 times from 2017 to 2019 in those with TID. TID persons >= 45 years without previous renal or cardiovascular complications had standardized mortality rates similar or even lower than controls 5.55 (4.51; 6.60) vs.7.08 (6.75; 7.40) respectively in the last time period. Interpretation Excess mortality persisted over time in persons with TID, largely in patients with cardiorenal complications. Improved secondary prevention with a focus on individualized treatment is needed to dose the gap in mortality for individuals with TID. Copyright (C) 2022 The Authors. Published by Elsevier Ltd.

Abstract Objective. Long-term oral glucocorticoid (GC) use is associated with increased mortality in patients with rheumatoid arthritis and inflammatory bowel disease. The aim of the study was to investigate whether there is excess mortality among oral GC users, regardless of the underlying disease. Methods. This was a retrospective case-control study. Information on dispensed prescriptions was obtained from the Swedish Prescribed Drug Register. Patients receiving ≥5 mg prednisolone (or equivalent dose of other GC) daily for ≥21 days between 2007-2014 were included. For each patient, a control person, matched for age and sex, was included. The cause of death was obtained from the Swedish Cause-of-Death Registry. Hazard ratio (HR) for mortality was calculated by using Cox proportional hazard model and by the log-rank test. The GC users were divided into four groups according to the length of GC treatment: 1) single-occasion users 2) occasional users (&lt;300 tablets/year); 3) medium-term users (&gt; 300 tablets/year for ≤ 2 consecutive years); and 4) long-term users (&gt;300 tablets/year for &gt; 2 consecutive years). Results. Of 1,585,335 inhabitants in Western Sweden, 223,211 GC users (women 55.6%) were identified for the analysis. The mean age was 48 ± 24 years. Median follow-up time was 3.6 years for GC users and 3.9 years for matched controls. The overall HR for death in oral GC users was 2.26 (95% CI 2.21-2.31). After exclusion of patients with malignant neoplasm, the HR for death was 1.41 (95% CI 1.38-1.45); 1.33 (95% CI 1.27-1.38) in single-occasion GC users (n=112,196), 1.36 (95% CI 1.30-1.42) in occasional users (n=63,862), 1.89 (95% CI 1.79-1.99) in medium-term users (n=19,129) and 1.67 (95% CI 1.51-1.84) in long-term users (n=7,191). The highest HRs were observed for deaths from heart failure (HR 1.71, 95% CI 1.63-1.80), sepsis (HR 1.71, 95% CI 1.51-1.94), and pulmonary embolism (HR 1.87, 95% CI 1.58-2.21). Conclusion. GC users have excess mortality compared to the background population. This illustrates the importance of surveillance for patients on oral GC treatment where adverse effects should be monitored and, when indicated, appropriately treated.

OBJECTIVE:Glucocorticoids (GCs) are a cornerstone in treating various common and uncommon diseases. The aim of this study was to estimate the prevalence of GC use in terms of doses associated with risk of tertiary adrenal insufficiency in adults and children, and treatment indications.METHODS:This was a retrospective cohort study. Information on dispensed prescriptions was obtained from the Swedish Prescribed Drug Register. Patients with prescriptions of prednisolone (or equivalent dose of other GCs) ≥5 mg daily for ≥21 days between 2007 and 2014 were included. Information on concurrent diseases was obtained from the Swedish National Patient Register and the Västra Götaland Regional Healthcare Database.RESULTS:Of 1 585 335 inhabitants in Västra Götaland County, 223 211 were included in the study (women 55.6%). Mean age was 48 ± 24 years. Period prevalence of oral GC use during the 8-year study period was 14.1%. The highest prevalence (27.4%) was in men aged 80-89 years and lowest (7.5%) in men 10-19 years of age. The period prevalence in children 0-9 years of age was 10.6%. COPD and asthma were the most common indications for treatment (17.2%) followed by allergy (12.5%) and malignant neoplasms (11.5%). Allergy was the most frequent indication (20.5%) in children and adolescents.CONCLUSION:Between 2007 and 2014, every seventh inhabitant in western Sweden received a GC prescription at doses associated with risk of developing tertiary adrenal insufficiency. These findings illustrate the importance of awareness of the potential development of tertiary adrenal insufficiency in both paediatric and adult patients.