Observational Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Oct 15, 2016; 7(18): 449-461
Published online Oct 15, 2016. doi: 10.4239/wjd.v7.i18.449
Impact of diabetes mellitus on risk of cardiovascular disease and all-cause mortality: Evidence on health outcomes and antidiabetic treatment in United States adults
Longjian Liu, Barbara Simon, Jinggaofu Shi, Arshpreet Kaur Mallhi, Howard J Eisen
Longjian Liu, Jinggaofu Shi, Arshpreet Kaur Mallhi, Department of Epidemiology and Biostatistics, Drexel University Dornsife School of Public Health, Philadelphia, PA 19104, United States
Barbara Simon, Division of Endocrinology, Drexel University College of Medicine, Philadelphia, PA 19102, United States
Howard J Eisen, Division of Cardiology, Drexel University College of Medicine, Philadelphia, PA 19102, United States
Author contributions: All the authors contributed to this manuscript.
Supported by A grant from the Drexel-AmeriHealth Faculty Initiatives, No. 282573.
Institutional review board statement: The NHIS, NHIS-Mortality Linked File and MEPS have been approved by the Institutional Review Board of the United States CDC NCHS, and are publicly available through the NCHS (http://www.cdc.gov/nchs/nhis.htm).
Informed consent statement: The current report used data from the National Center for Health Statistics (NCHS) of the United States Centers for Disease Control and Prevention CDC). All informed consents were conducted by the NCHS while the study was carried. No further informed consent forms were requested by using the dataset (https://www.cdc.gov/nchs/nhis/).
Conflict-of-interest statement: We have no conflict of interest to report.
Data sharing statement: Data used in the present study were public use data files provided by the United States CDC NCHS. Those who are interested may apply for and download from NCHS website.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Longjian Liu, MD, PhD, MSc, FAHA, Department of Epidemiology and Biostatistics, Drexel University Dornsife School of Public Health, 3215 Market ST, Philadelphia, PA 19104, United States. longjian.liu@drexel.edu
Telephone: +1-267-3596049 Fax: +1-267-3596201
Received: March 28, 2016
Peer-review started: March 28, 2016
First decision: May 26, 2016
Revised: August 1, 2016
Accepted: August 17, 2016
Article in press: August 18, 2016
Published online: October 15, 2016

To examine the epidemic of diabetes mellitus (DM) and its impact on mortality from all-cause and cardiovascular disease (CVD), and to test the effect of antidiabetic therapy on the mortality in United States adults.


The analysis included a randomized population sample of 272149 subjects ages ≥ 18 years who participated in the National Health Interview Surveys (NHIS) in 2000-2009. Chronic conditions (hypertension, DM and CVD) were classified by participants’ self-reports of physician diagnosis. NHIS-Mortality Linked Files, and NHIS-Medical Expenditure Panel Survey Linkage Files on prescribed medicines for patients with DM were used to test the research questions. χ2, Poisson and Cox’s regression models were applied in data analysis.


Of all participants, 22305 (8.2%) had DM. The prevalence of DM significantly increased from 2000 to 2009 in all age groups (P < 0.001). Within an average 7.39 (SD = 3) years of follow-up, male DM patients had 1.56 times higher risk of death from all-cause (HR = 1.56, 95%CI: 1.49-1.64), 1.72 times higher from heart disease [1.72 (1.53-1.93)], 1.48 times higher from cerebrovascular disease [1.48 (1.18-1.85)], and 1.67 times higher from CVD [1.67 (1.51-1.86)] than subjects without DM, respectively. Similar results were observed in females. In males, 10% of DM patients did not use any antidiabetic medications, 38.1% used antidiabetic monotherapy, and 51.9% used ≥ 2 antidiabetic medications. These corresponding values were 10.3%, 40.4% and 49.4% in females. A significant protective effect of metformin monotherapy or combination therapy (except for insulin) on all-cause mortality and a protective but non-significant effect on CVD mortality were observed.


This is the first study using data from multiple linkage files to confirm a significant increased prevalence of DM in the last decade in the United States. Patients with DM have significantly higher risk of death from all-cause and CVD than those without DM. Antidiabetic mediations, specifically for metformin use, show a protective effect against all-cause and CVD mortalities.

Keywords: Epidemic of diabetes mellitus, Cardiovascular disease, Pharmacoepidemiologic profiles, United States

Core tip: The study is one of the first projects to use a 10-years nationally linked dataset. The results highlight a new epidemic of diabetes in the United States. It addresses the impact of diabetes on cardiovascular disease and all-cause mortality. The study is also one of the first studies to explore the association between glucose lowering drug use and health outcomes using health survey data from the real-world.