TY - JOUR
T1 - The association of severe hypoglycemia with incident cardiovascular events and mortality in adults with type 2 diabetes
AU - Lee, Alexandra K.
AU - Warren, Bethany
AU - Lee, Clare J.
AU - McEvoy, John W.
AU - Matsushita, Kunihiro
AU - Huang, Elbert S.
AU - Sharrett, A. Richey
AU - Coresh, Josef
AU - Selvin, Elizabeth
N1 - Funding Information:
and participants of the ARIC study for their important contributions. Cancer incidence datahavebeenprovidedbytheMarylandCancer Registry, Center for Cancer Surveillance and Control, Department of Health and Mental Hygiene, Baltimore, MD. Funding. The ARIC study has been funded in whole or in part with federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health & Human Services, under contract numbers HHSN268201700001I, HHSN268201700003I, HHSN268201700005I, HHSN268201700004I, and HHSN2682017000021. This research was supported by National Institutes of Health grants (National Heart, Lung, and Blood Institute grant T32-HL-007024 to A.K.L. and B.W. and National Institute of Diabetes and Digestive and Kidney Diseases grants 1K23-DK-107921 to C.J.L., K24-DK-105340 and P30-DK-092949 to E.S.H., and K24-DK-106414 and R01-DK-089174 to E.S.) and by the Agency for Healthcare Research and Quality (grant R01-HS-018542 to E.S.H.). Studies on cancer in ARIC are also supported by the National Cancer Institute (U01-CA-164975).
Funding Information:
The authors acknowledge the State of Maryland, the Maryland Cigarette Restitution Fund, and the National Program of Cancer Registries (NPCR) of the Centers for Disease Control and Prevention (CDC) for the funds that helped support the availability of the cancer registry data. Duality of Interest. No potential conflicts of interest relevant to this article were reported. Author Contributions. A.K.L. conceived and designedthestudy,conductedstatisticalanalyses, and wrote the manuscript. B.W. and K.M. assisted withstatisticalanalysesandmadecriticalrevisions to the manuscript for important intellectual content. C.J.L., J.W.M., E.S.H., A.R.S., and J.C. made critical revisions to the manuscript for important intellectual content. E.S. helped to conceive and design the study, provided guidance for the statistical analysis, and made critical revisions to the manuscript for important intellectual content. E.S. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Prior Presentation. Parts of this study were presented in abstract form at the American Heart Association Epidemiology and Prevention Life-style and Cardiometabolic Health Scientific Sessions, Portland, OR, 7–10 March 2017.
Publisher Copyright:
© 2017 by the American Diabetes Association.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - OBJECTIVE There is suggestive evidence linking hypoglycemia with cardiovascular disease, but fewdata have been collected in a community-based setting. Information is lacking on individual cardiovascular outcomes and cause-specific mortality. RESEARCH DESIGN AND METHODS We conducted a prospective cohort analysis of 1,209 participants with diagnosed diabetes from the Atherosclerosis Risk in Communities (ARIC) study (analytic baseline, 1996-1998). Severe hypoglycemic episodes were identified using first position ICD-9 codes fromhospitalizations, emergency department visits, andambulance calls through 2013. Cardiovascular events and deaths were captured through 2013. We used adjusted Cox regressionmodelswith hypoglycemia as a time-varying exposure. RESULTS There were 195 participants with at least one severe hypoglycemic episode during a median fellow-up of 15.3 years. After severe hypoglycemia, the 3-year cumulative incidence of coronary heart disease was 10.8% and of mortality was 28.3%. After adjustment, severe hypoglycemia was associated with coronary heart disease (hazard ratio [HR] 2.02, 95% CI 1.27-3.20), all-causemortality (HR 1.73, 95%CI 1.38-2.17), cardiovascular mortality (HR 1.64, 95% CI 1.15-2.34), and cancer mortality (HR 2.49, 95% CI 1.46-4.24). Hypoglycemia was not associated with stroke, heart failure, atrial fibrillation, or noncardiovascular and noncancer death. Results were robust within subgroups defined by age, sex, race, diabetes duration, and baseline cardiovascular risk. CONCLUSIONS Severe hypoglycemia is clearly indicative of declining health and is a potentmarker of high absolute risk of cardiovascular events and mortality.
AB - OBJECTIVE There is suggestive evidence linking hypoglycemia with cardiovascular disease, but fewdata have been collected in a community-based setting. Information is lacking on individual cardiovascular outcomes and cause-specific mortality. RESEARCH DESIGN AND METHODS We conducted a prospective cohort analysis of 1,209 participants with diagnosed diabetes from the Atherosclerosis Risk in Communities (ARIC) study (analytic baseline, 1996-1998). Severe hypoglycemic episodes were identified using first position ICD-9 codes fromhospitalizations, emergency department visits, andambulance calls through 2013. Cardiovascular events and deaths were captured through 2013. We used adjusted Cox regressionmodelswith hypoglycemia as a time-varying exposure. RESULTS There were 195 participants with at least one severe hypoglycemic episode during a median fellow-up of 15.3 years. After severe hypoglycemia, the 3-year cumulative incidence of coronary heart disease was 10.8% and of mortality was 28.3%. After adjustment, severe hypoglycemia was associated with coronary heart disease (hazard ratio [HR] 2.02, 95% CI 1.27-3.20), all-causemortality (HR 1.73, 95%CI 1.38-2.17), cardiovascular mortality (HR 1.64, 95% CI 1.15-2.34), and cancer mortality (HR 2.49, 95% CI 1.46-4.24). Hypoglycemia was not associated with stroke, heart failure, atrial fibrillation, or noncardiovascular and noncancer death. Results were robust within subgroups defined by age, sex, race, diabetes duration, and baseline cardiovascular risk. CONCLUSIONS Severe hypoglycemia is clearly indicative of declining health and is a potentmarker of high absolute risk of cardiovascular events and mortality.
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U2 - 10.2337/dc17-1669
DO - 10.2337/dc17-1669
M3 - Article
C2 - 29127240
AN - SCOPUS:85038891949
VL - 41
SP - 104
EP - 111
JO - Diabetes Care
JF - Diabetes Care
SN - 1935-5548
IS - 1
ER -