Patients with type 2 diabetes who had five risk-factor variables within the target ranges appeared to have little or no excess risk of death, myocardial infarction, or stroke, as compared with the general population. (Funded by the Swedish Association of Local Authorities and Regions and others.).

BACKGROUNDLong-term trends in excess risk of death and cardiovascular outcomes have not been extensively studied in persons with type 1 diabetes or type 2 diabetes. METHODSWe included patients registered in the Swedish National Diabetes Register from 1998 through 2012 and followed them through 2014. Trends in deaths and cardiovascular events were estimated with Cox regression and standardized incidence rates. For each patient, controls who were matched for age, sex, and county were randomly selected from the general population. RESULTSAmong patients with type 1 diabetes, absolute changes during the study period in the incidence rates of sentinel outcomes per 10,000 person-years were as follows: death from any cause, −31.4 (95% confidence interval [CI], −56.1 to −6.7); death from cardiovascular disease, −26.0 (95% CI, −42.6 to −9.4); death from coronary heart disease, −21.7 (95% CI, −37.1 to −6.4); and hospitalization for cardiovascular disease, −45.7 (95% CI, −71.4 to −20.1). Absolute changes per 10,000 person-years among patients with type 2 diabetes were as follows: death from any cause, −69.6 (95% CI, −95.9 to −43.2); death from cardiovascular disease, −110.0 (95% CI, −128.9 to −91.1); death from coronary heart disease, −91.9 (95% CI, −108.9 to −75.0); and hospitalization for cardiovascular disease, −203.6 (95% CI, −230.9 to −176.3). Patients with type 1 diabetes had roughly 40% greater reduction in cardiovascular outcomes than controls, and patients with type 2 diabetes had roughly 20% greater reduction than controls. Reductions in fatal outcomes were similar in patients with type 1 diabetes and controls, whereas patients with type 2 diabetes had smaller reductions in fatal outcomes than controls. CONCLUSIONSIn Sweden from 1998 through 2014, mortality and the incidence of cardiovascular outcomes declined substantially among persons with diabetes, although fatal outcomes declined less among those with type 2 diabetes than among controls. (Funded by the Swedish Association of Local Authorities and Regions and others.) a bs tr ac t

Type 1 diabetes mellitus (T1DM), also known as autoimmune diabetes, is a chronic disease characterized by insulin deficiency due to pancreatic β-cell loss and leads to hyperglycaemia. Although the age of symptomatic onset is usually during childhood or adolescence, symptoms can sometimes develop much later. Although the aetiology of T1DM is not completely understood, the pathogenesis of the disease is thought to involve T cell-mediated destruction of β-cells. Islet-targeting autoantibodies that target insulin, 65 kDa glutamic acid decarboxylase, insulinoma-associated protein 2 and zinc transporter 8 - all of which are proteins associated with secretory granules in β-cells - are biomarkers of T1DM-associated autoimmunity that are found months to years before symptom onset, and can be used to identify and study individuals who are at risk of developing T1DM. The type of autoantibody that appears first depends on the environmental trigger and on genetic factors. The pathogenesis of T1DM can be divided into three stages depending on the absence or presence of hyperglycaemia and hyperglycaemia-associated symptoms (such as polyuria and thirst). A cure is not available, and patients depend on lifelong insulin injections; novel approaches to insulin treatment, such as insulin pumps, continuous glucose monitoring and hybrid closed-loop systems, are in development. Although intensive glycaemic control has reduced the incidence of microvascular and macrovascular complications, the majority of patients with T1DM are still developing these complications. Major research efforts are needed to achieve early diagnosis, prevent β-cell loss and develop better treatment options to improve the quality of life and prognosis of those affected.

Swedish Heart and Lung Foundation.

Word count: Background: Risk of cardiovascular disease (CVD) and mortality for patients with versus without type 2 diabetes mellitus (T2DM) appears to vary by age of T2DM diagnosis, but few population studies have analyzed mortality and CVD outcomes associations across the full age range. Methods: Using the Swedish National Diabetes Registry (NDR), everyone with T2DM registered in the NDR between 1998, and, 2012 were included. Controls were randomly selected from the general population matched for age, sex, and county. The analysis cohort comprised 318,083 patients with T2DM matched with just under 1•6 million controls. Participants were followed from 1998 to 2013 for CVD outcomes and to 2014 for mortality. Outcomes of interest were total mortality, CV mortality, non-CV mortality, coronary heart disease, acute myocardial infarction, stroke, heart failure, and atrial fibrillation. We also examined life expectancy by age of diagnosis. We conducted the primary analyses using Cox proportional hazards models in those with no prior cardiovascular disease and repeated the work in the entire cohort. Results: Over a median follow-up period of 2.52 years, T2DM patients diagnosed under 40 years or less had the highest excess risk for most outcomes relative to controls with adjusted HR [95% CI] of 2•05 [1•81 to 2•83] for total mortality, 2•72 [2•13 to 3•48] for CV related mortality, 1•95 [1•68-2•25] for non-CV mortality, 4•77 [3•86-5•89] for HF and 4•33 [3•82-4•91] for CHD. All risks attenuated progressively with each increasing decade at diagnostic age; by the time T2DM was diagnosed above 80 years, the adjusted HRs for CVD and non-CVD mortality were below one, with excess risks for other CVD outcomes substantially attenuated. Moreover, survival in those diagnosed beyond 80 was the same as controls, whereas it was beyond a decade less when T2DM was diagnosed in adolescence. Finally, HRs for most outcomes were numerically greater in younger women with T2DM. 4 Conclusions: Age at diagnosis of T2DM is prognostically important for survival and cardiovascular risks, with implications for determining timing and intensity of risk factor interventions for clinical decision making and for guideline-directed care. These observations amplify support for preventing / delaying T2DM onset in younger individuals.

Aim To study the characteristics and outcome among cardiac arrest cases with COVID-19 and differences between the pre-pandemic and the pandemic period in out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA). Method and results We included all patients reported to the Swedish Registry for Cardiopulmonary Resuscitation from 1 January to 20 July 2020. We defined 16 March 2020 as the start of the pandemic. We assessed overall and 30-day mortality using Cox regression and logistic regression, respectively. We studied 1946 cases of OHCA and 1080 cases of IHCA during the entire period. During the pandemic, 88 (10.0%) of OHCAs and 72 (16.1%) of IHCAs had ongoing COVID-19. With regards to OHCA during the pandemic, the odds ratio for 30-day mortality in COVID-19-positive cases, compared with COVID-19-negative cases, was 3.40 [95% confidence interval (CI) 1.31–11.64]; the corresponding hazard ratio was 1.45 (95% CI 1.13–1.85). Adjusted 30-day survival was 4.7% for patients with COVID-19, 9.8% for patients without COVID-19, and 7.6% in the pre-pandemic period. With regards to IHCA during the pandemic, the odds ratio for COVID-19-positive cases, compared with COVID-19-negative cases, was 2.27 (95% CI 1.27–4.24); the corresponding hazard ratio was 1.48 (95% CI 1.09–2.01). Adjusted 30-day survival was 23.1% in COVID-19-positive cases, 39.5% in patients without COVID-19, and 36.4% in the pre-pandemic period. Conclusion During the pandemic phase, COVID-19 was involved in at least 10% of all OHCAs and 16% of IHCAs, and, among COVID-19 cases, 30-day mortality was increased 3.4-fold in OHCA and 2.3-fold in IHCA.

ObjeCtiveTo investigate the long term effects of continuous subcutaneous insulin infusion (insulin pump therapy) on cardiovascular diseases and mortality in people with type 1 diabetes. DesignObservational study. PartiCiPants 18 168 people with type 1 diabetes, 2441 using insulin pump therapy and 15 727 using multiple daily insulin injections. Main OutCOMe MeasuresCox regression analysis was used to estimate hazard ratios for the outcomes, with stratification of propensity scores including clinical characteristics, risk factors for cardiovascular disease, treatments, and previous diseases. results Follow-up was for a mean of 6.8 years until December 2012, with 114 135 person years. With multiple daily injections as reference, the adjusted hazard ratios for insulin pump treatment were significantly lower: 0.55 (95% confidence interval 0.36 to 0.83) for fatal coronary heart disease, 0.58 (0.40 to 0.85) for fatal cardiovascular disease (coronary heart disease or stroke), and 0.73 (0.58 to 0.92) for all cause mortality. Hazard ratios were lower, but not significantly so, for fatal or non-fatal coronary heart disease and fatal or non-fatal cardiovascular disease. Unadjusted absolute differences were 3.0 events of fatal coronary heart disease per 1000 person years; corresponding figures were 3.3 for fatal cardiovascular disease and 5.7 for all cause mortality. When lower body mass index and previous cardiovascular diseases were excluded, results of subgroup analyses were similar to the results from complete data. A sensitivity analysis of unmeasured confounders in all individuals showed that an unmeasured confounders with hazard ratio of 1.3 would have to be present in >80% of the individuals treated with multiple daily injections versus not presence in those treated with pump therapy to invalidate the significantly lower hazard ratios for fatal cardiovascular disease. Data on patient education and frequency of blood glucose monitoring were missing, which might have influenced the observed association. COnClusiOnAmong people with type 1 diabetes use of insulin pump therapy is associated with lower cardiovascular mortality than treatment with multiple daily insulin injections.

S. (2018) Excess mortality and cardiovascular disease in young adults with type 1 diabetes in relation to age at onset: a nationwide, registerbased cohort study. Lancet, 392(10146), pp. 477-486. There may be differences between this version and the published version. You are advised to consult the publisher's version if you wish to cite from it. Abstract word count: 258 words 26Evidence before this study 27 People with type 1 diabetes are at 2-to 5-fold increased risk of death and 3-to 7-fold increased risk 28 of coronary heart disease. Several risk factors, notably glycemic control, affect survival in type 1 29 diabetes. The importance of age at disease onset, however, remains weakly studied. Guidelines do 30 not articulate any specific recommendations in relation to age at disease onset, only duration. We 31 did a systematic search in PubMed for articles published between Jan 1, 1960, and April 15, 2018. 32Our search terms included "type 1 diabetes", "age at diagnosis", "age at disease onset", "childhood 33 onset", "late onset", "debut age", "mortality", "cardiovascular disease", "coronary artery disease", 34 "myocardial infarction". We searched articles by title and abstract to identify relevant studies. 35Studies were also sought within reference lists of eligible studies. We considered studies that 36 evaluated association between age at onset/diagnosis of type 1 diabetes and cardiovascular disease 37 and survival. Studies using diabetes free controls as comparator were of primary interest, as such 38 studies addresses the excess risk conferred by diabetes. 40Added value of this study 41 By studying 27,195 individuals with type 1 diabetes and 135,178 matched controls, we demonstrate 42 a ubiquitous inverse association between age at diagnosis and risk of mortality and cardiovascular 43 disease, independent of diabetes duration. Patients with type 1 diabetes with disease onset before 44 10 years of age experienced a 30-fold increased risk of CHD and AMI. Women with onset of type 1 45 diabetes before 10 years of age displayed a 60-and 90-fold increased risk of CHD and AMI, 46 respectively. The difference in risk levels between those with onset at age 0-10 years and 25-30 47 years was up to 5-fold (AMI and CHD). Although absolute risks were low in this young cohort, 48 developing T1D before 10 years of age resulted in a loss of 17.7 and 14.2 life years for women and 49 men, respectively, whereas years of life lost were around 9-10 years with later age at diagnosis. 51Implications of all the available evidence 52 Age at disease onset appears an important determinant of survival and, in particular of, 53 cardiovascular disease in type 1 diabetes. These findings suggest that more patients with earlier 54 onset type 1 diabetes be offered cardioprotective medications (statins, BP medications) sooner than 55 currently practiced. A greater effort towards improved glycaemia control in such individual would 56 also be beneficial. Abstract 61 Background 62We compared individuals with type 1 diabetes (T1D) to match...