Impact of Cytomegalovirus Disease on New-Onset Type 2 Diabetes Mellitus: Population-Based Matched Case-Control Cohort Study

Abstract

Background: A latent cytomegalovirus (CMV) cause chronic inflammation through undesirable inflation of cell-mediated immune response. CMV immunoglobulin G has been associated with cardiovascular disease and type 1 diabetes mellitus. We evaluated impact of CMV diseases on new-onset type 2 diabetes mellitus (T2DM).

Methods: From the Korean Health Insurance Review and Assessment Service claim database of entire population with 50 million, we retrieved 576 adult case group with CMV diseases diagnosed with International Statistical Classification of Diseases and Related-Health Problems 10th Revision (ICD-10) B25 code between 2010 and 2014 after exclusion of patients with T2DM to 2006. The 2,880 control patients without T2DM from 2006 to cohort entry point were selected between 2010 and 2014 by age, sex matching with case group. The subjects without new-onset T2DM were followed until 2015. T2DM, hypertension (HTN), dyslipidemia (DYS), and end-stage renal disease (ESRD) were coded as ICD-10.

Results: The frequency of new-onset T2DM in case group was significantly higher than that in control (5.6% vs. 2.2%, P<0.001). The group with T2DM (n=95) had higher incidence of CMV diseases than the group without T2DM (n=3,361) (33.7% vs. 16.2%, P<0.001). In multivariate regression model adjusted by age, sex, lower income, HTN, and DYS, the incidence rate (IR) of T2DM in case group was significantly higher than that in the control group (IR per 1,000, 19.0 vs. 7.3; odds ratio, 2.1; 95% confidence interval, 1.3 to 3.2). The co-existence of HTN, DYS, and ESRD with CMV diseases did not influence the IR of T2DM.

Conclusion: CMV diseases increase the patients' risk of developing T2DM.

Keywords: Cytomegalovirus; Diabetes mellitus, type 2; Disease; Population.

Fig. 1. The process of subject selection by case and control group. T2DM, type 2 diabetes mellitus; CMV, cytomegalovirus; ICD-10, International Statistical Classification of Diseases and Related-Health Problems 10th Revision; HIRA, the Korean Health Insurance Review and Assessment Service. aIf patients were died before event occurrence, they were censored.

Fig. 2. Kaplan-Meier curve for new-onset type 2 diabetes mellitus (T2DM) incidence according to cytomegalovirus (CMV) disease. (A) Comparison of patients with and without CMV diseases. (B) Comparison of three groups including refractory and non-refractory CMV diseases (P value of log-lank test).