Mortality and Cardiovascular Disease in Type 1 and Type 2 Diabetes
Aidin Rawshani, M.D., Araz Rawshani, M.D., Ph.D., Stefan Franzén, Ph.D., Björn Eliasson, M.D., Ph.D., Ann-Marie Svensson, Ph.D., Mervete Miftaraj, M.Sc., Darren K. McGuire, M.D., M.H.Sc., Naveed Sattar, M.D., Ph.D., Annika Rosengren, M.D., Ph.D., and Soffia Gudbjörnsdottir, M.D., Ph.D.
N Engl J Med 2017; 376:1407-1418April 13, 2017DOI: 10.1056/NEJMoa1608664
BACKGROUND
Long-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.
METHODS
We 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.
RESULTS
Among 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.
CONCLUSIONS
In 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.)
From the article
Diabetes mellitus is a complex and heterogeneous group of chronic meta-bolic diseases that are characterized by hyperglycemia. Type 1 diabetes occurs predominantly in young people (diagnosis at 30 years of age or younger) and is generally thought to be precipitated by an immune-associated destruc-tion of insulin-producing pancreatic beta cells, leading to insulin deficiency and an absolute need for exogenous insulin replacement.1 Type 2 diabetes is a progressive metabolic disease that is characterized by insulin resistance and even-tual functional failure of pancreatic beta cells.2 The prevalence of type 2 diabetes has been in-creasing dramatically over the past few decades,3 with projections of an even greater growth over coming decades.4
Landmark studies such as the Diabetes Control and Complications Trial, United Kingdom Prospective Diabetes Study, Collaborative Atorva-statin Diabetes Study, and several others have shown the importance of glucose-lowering ther-apy, statin use, blood-pressure control, and multi-factorial intervention in reducing the risk of cardiovascular outcomes among patients with diabetes.5-18 These trial results and the clinical application of their findings, along with lifestyle interventions (including smoking cessation), are likely to have improved outcomes in patients with diabetes during the past two decades. We set out to investigate the long-term trends (1998 through 2014) in all-cause mortality and the incidence of major diabetes-related cardiovascular complica-tions, as compared with contemporary trends in the general population.
Discussions
Our analysis of Swedish nationwide registry data from 1998 to 2014 showed marked reductions in mortality and in the incidence of cardiovascular complications among adults with either type 1 diabetes or type 2 diabetes. The reduction in the rate of fatal outcomes did not differ significantly factors are gradually decreasing, with improved control in patients with type 1 diabetes and those with type 2 diabetes.
Heart failure has been a somewhat neglected complication of diabetes.23,35 Hospitalizations for heart failure did not decline significantly among either patients with type 1 diabetes or their matched controls. However, patients with type 2 diabetes had a greater event-rate reduction than controls. These findings are somewhat surpris-ing, because rates of hospitalization for coronary heart disease and acute myocardial infarction, as well as the number of persons with hyperten-sion and the rate of macroalbuminuria (risk pre-dictors for heart failure), have decreased to a greater degree among patients with type 1 dia-betes than among those with type 2 diabetes. These observations suggest that other processes, less well appreciated and therefore less well treated, that contribute to heart-failure risk are not affected by contemporary clinical care for patients with type 1 diabetes.
Some limitations of our study should be noted. First, classification of diabetes type was not based on detection of islet autoantibodies or measurement of C-peptide levels. However, we believe that misclassification is unlikely to have biased our findings. The epidemiologic definitions that we used have been validated as accurate in 97% of cases, as reported previously.36 (See the Supple-mentary Appendix for a more detailed discussion of this issue.37) Second, we cannot exclude the possibility that secular trends, such as evolving diagnostic thresholds or admissions criteria, could have influenced the changes in event rates that we have reported. Third, our results are model-dependent and could change slightly with differ-ent approaches to the data. Finally, correction for multiple testing was not performed, and thus caution is needed with respect to the interpretation of significance tests.
In conclusion, we report a decline in all-cause mortality and the incidence of cardiovascular complications among patients with type 1 dia-betes or type 2 diabetes in the Swedish NDR. The reduction in fatal outcomes did not differ significantly between patients with type 1 diabe-tes and controls, and the reduction in such out-comes was smaller among patients with type 2 diabetes than among controls. Nonfatal out-comes decreased more rapidly among patients with either type of diabetes than among controls, but the event rates of all outcomes studied remained significantly higher among patients with diabetes.
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