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Excess Mortality among Persons with Type 2 Diabetes



Mauro Tancredi, M.D., Annika Rosengren, M.D., Ann-Marie Svensson, Ph.D., Mikhail Kosiborod, M.D., Aldina Pivodic, M.Sc., Soffia Gudbjörnsdottir, M.D., Ph.D., Hans Wedel, Ph.D., Mark Clements, M.D., Ph.D., Sofia Dahlqvist, and Marcus Lind, M.D., Ph.D.
N Engl J Med 2015; 373:1720-1732October 29, 2015DOI: 10.1056/NEJMoa1504347
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BACKGROUND
The excess risks of death from any cause and death from cardiovascular causes among persons with type 2 diabetes and various levels of glycemic control and renal complications are unknown. In this registry-based study, we assessed these risks according to glycemic control and renal complications among persons with type 2 diabetes.

METHODS
We included patients with type 2 diabetes who were registered in the Swedish National Diabetes Register on or after January 1, 1998. For each patient, five controls were randomly selected from the general population and matched according to age, sex, and county. All the participants were followed until December 31, 2011, in the Swedish Registry for Cause-Specific Mortality.

RESULTS
The mean follow-up was 4.6 years in the diabetes group and 4.8 years in the control group. Overall, 77,117 of 435,369 patients with diabetes (17.7%) died, as compared with 306,097 of 2,117,483 controls (14.5%) (adjusted hazard ratio, 1.15; 95% confidence interval [CI], 1.14 to 1.16). The rate of cardiovascular death was 7.9% among patients versus 6.1% among controls (adjusted hazard ratio, 1.14; 95% CI, 1.13 to 1.15). The excess risks of death from any cause and cardiovascular death increased with younger age, worse glycemic control, and greater severity of renal complications. As compared with controls, the hazard ratio for death from any cause among patients younger than 55 years of age who had a glycated hemoglobin level of 6.9% or less (≤52 mmol per mole of nonglycated hemoglobin) was 1.92 (95% CI, 1.75 to 2.11); the corresponding hazard ratio among patients 75 years of age or older was 0.95 (95% CI, 0.94 to 0.96). Among patients with normoalbuminuria, the hazard ratio for death among those younger than 55 years of age with a glycated hemoglobin level of 6.9% or less, as compared with controls, was 1.60 (95% CI, 1.40 to 1.82); the corresponding hazard ratio among patients 75 years of age or older was 0.76 (95% CI, 0.75 to 0.78), and patients 65 to 74 years of age also had a significantly lower risk of death (hazard ratio, 0.87; 95% CI, 0.84 to 0.91).

CONCLUSIONS
Mortality among persons with type 2 diabetes, as compared with that in the general population, varied greatly, from substantial excess risks in large patient groups to lower risks of death depending on age, glycemic control, and renal complications. (Funded by the Swedish government and others.)
Supported by grants from the Swedish government (under the Avtal om Läkarutbildning och Medicinsk Forskning [Agreement for Medical Education and Research]), the Swedish Society of Medicine, the Health and Medical Care Committee of the Regional Executive Board, Region Västra Götaland, Sweden, the Swedish Heart and Lung Foundation, and Diabetes Wellness and grants (2013-5187 and 2013-4236) from the Swedish Research Council.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
This article was updated on October 29, 2015, at NEJM.org.
We thank all the data-collecting clinicians and staff at the National Diabetes Register, and Joseph W. Murphy for editorial assistance with an earlier version of the manuscript.

SOURCE INFORMATION
From the Department of Molecular and Clinical Medicine, University of Gothenburg (M.T., A.R., S.G., M.L.), Center of Registers in Region Västra Götaland (A.-M.S.), Statistiska Konsultgruppen (A.P.), and Nordic School of Public Health (H.W.), Gothenburg, and the Department of Medicine, NU Hospital Group, Trollhättan and Uddevalla (M.T., S.D., M.L.) — all in Sweden; Saint Luke’s Mid America Heart Institute (M.K.) and Children’s Mercy Hospital (M.C.), University of Missouri–Kansas City School of Medicine, Kansas City; and the University of Kansas School of Medicine, Kansas City (M.C.).
Address reprint requests to Dr. Lind at the Department of Medicine, Uddevalla Hospital, 451 80 Uddevalla, Sweden, or at lind.marcus@telia.com.
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Stacey Kaltman, PhD
Photograph by Welton Doby III
Stacey Kaltman, PhD
Occupation
Clinical Psychologist, Georgetown University
Focus
Psychosocial Behavioral Medicine
ADA Research Funding

Innovation Grant