Acute Myocardial Infarction Is a Risk Factor for New Onset Diabetes in Patients with Coronary Artery Disease

RESEARCH ARTICLE Acute Myocardial Infarction Is a Risk Factor for New Onset Diabetes in Patients with Coronary Artery Disease Chul Soo Park1,2, Woo Baek Chung1,2, Yun Seok Choi1,2, Pum Joon Kim1,3, Jong Min Lee1,4, Ki-Hyun Baek1,7, Hee Yeol Kim1,5, Ki Dong Yoo1,6, Ki-Ho Song1,7, Wook Sung Chung1,3, Ki Bae Seung1,3, Man Young Lee1,2, Hyuk-Sang Kwon1,7* a11111 1 Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea, 2 Cardiovascular Center and Cardiology Division, Yeouido St. Mary’s Hospital, The Catholic University of Korea, Seoul, Republic of Korea, 3 Cardiovascular Center and Cardiology Division, Seoul St. Mary’s Hospital, Catholic University of Korea, Seoul, Republic of Korea, 4 Cardiovascular Center and Cardiology Division, Uijeongbu St. Mary’s Hospital, The Catholic University of Korea, Uijeongbu, Republic of Korea, 5 Cardiovascular Center and Cardiology Division, Bucheon St. Mary’s Hospital, The Catholic University of Korea, Bucheon, Republic of Korea, 6 Cardiovascular Center and Cardiology Division, St. Vincent Hospital, The Catholic University of Korea, Suwon, Republic of Korea, 7 Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary’s Hospital, The Catholic University of Korea, Seoul, Republic of Korea * Abstract OPEN ACCESS Citation: Park CS, Chung WB, Choi YS, Kim PJ, Lee JM, Baek K-H, et al. (2015) Acute Myocardial Infarction Is a Risk Factor for New Onset Diabetes in Patients with Coronary Artery Disease. PLoS ONE 10(8): e0136354. doi:10.1371/journal.pone.0136354 Objective Editor: Stephan Henrik Schirmer, Universitätsklinikum des Saarlandes, GERMANY Methods Received: May 20, 2015 Accepted: August 1, 2015 Published: August 21, 2015 Copyright: © 2015 Park et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: The authors have no support or funding to report. Competing Interests: The authors have declared that no competing interests exist. To test the hypothesis that acute myocardial infarction (AMI) might accelerate development of new onset diabetes in patients with coronary artery disease independent of known risk factors. We conducted a retrospective cohort study within COACT (CathOlic medical center percutAneous Coronary inTervention) registry. From a total of 9,127 subjects, 2,036 subjects were diabetes naïve and followed up for at least one year with both index and follow-up laboratory data about diabetes. Cox proportional hazard model was used to derive hazard ratios (HRs) and 95% confidence interval (CI) for new onset diabetes associated with AMI in univariate and multivariate analysis after adjusting several covariates. Results The overall hazard for diabetes was higher in AMI compared to non-AMI patients (p by log rank <0.01) with HR of 1.78 and 95% CI of 1.37–2.32 in univariate analysis. This association remained significant after adjusting covariates (HR, 1.54; 95% CI, 1.14–2.07; p<0.01). AMI was an independent predictor for higher quartile of WBC count in multivariate ordinal logistic regression analysis (OR, 6.75; 95% CI, 5.53–8.22, p<0.01). In subgroup analysis, the diabetogenic effect of AMI was more prominent in the subgroup without MetS compared to MetS patients (p for interaction<0.05). Compared to the reference group of non-AMI PLOS ONE | DOI:10.1371/journal.pone.0136354 August 21, 2015 1 / 12 Acute Myocardial Infarction and New Onset Diabetes +nonMetS, the group of AMI+non-MetS (HR, 2.44; 95% CI, 1.58–3.76), non-AMI+MetS (HR, 3.42; 95% CI, 2.34–4.98) and AMI+MetS (HR, 4.12; 95% CI, 2.67–6.36) showed higher HR after adjusting covariates. However, the hazard was not different between the non-AMI+MetS and AMI+non-MetS groups. Conclusions AMI patients have a greater risk of new-onset diabetes when compared to non AMI patients, especially those with mild metabolic abnormalities. Introduction Diabetes mellitus is an important risk factor for coronary heart disease [1], and it is associated with higher prevalence of coronary heart disease and an unfavorable prognosis [2]. While there are broad evidences that diabetes showed worse outcomes after coronary revascularization procedures [3–6], there is a paucity of data regarding the incidence and risk factors for developing new-onset diabetes in patients with coronary artery disease. Although recent data have shown that cardiovascular drugs such as statins [7] and beta blockers [8] are related with diabetes development, it has become clear that systemic inflammation largely contributes to its development [9–11]. Since Dutta et al. [12] revealed that acute myocardial infarction (AMI) triggered system-wide activity of innate immune cells leading to acceleration of remote area atherosclerosis in an animal model, this finding has also been demonstrated in humans using 18F-FDG positron emission tomography [13, 14]. Furthermore, AMI accelerated non-culprit coronary lesion atherosclerosis [15]. Therefore, we hypothesized that after AMI, the patients might have higher risk of newonset diabetes compared with non AMI patients by activated systemic inflammatory response. Materials and Methods Study Population and Assessment We used the COACT (CathOlic medical center percutAneous Coronary inTervention) registry, a large observational registry of demographic, clinical, and procedural data, including clinical outcomes of “all-comer” patients who underwent percutaneous coronary intervention with drug eluting stent implantation at any of the eight affiliated hospitals of the Catholic University of Korea between January 2004 and December 2009. Of the 9,127 patients enrolled in this registry, 4,527 were diabetes naïve at index admission. Diabetes naïve was defined as a patient with no self-reported or documented history of diabetes and proved glycated hemoglobin (HbA1c) < 6.5% or fasting blood glucose (FBG) <126 mg/dl at index admission. The patients with previous revascularization, with previous MI, whose follow up duration was less than 1 year before censoring, whose laboratory data of HbA1c and FBG were missing, who were taking steroid, who were receiving dialysis, and cancer patients treated during the follow up, were excluded. Thus, the data of total 2,036 subjects were available for analysis (S1 Table). All of the laboratory and clinical parameter data were obtained from careful review of patients’ medical records at index admission. This study protocol complied with the principles of the Declaration of Helsinki (revised in 2000). The Institutional Review Board of Yeouido Saint Mary's Hospital, The Catholic University of Korea, Seoul, Korea approved this study (No. SC15RISI0005) and waived the need (...truncated)