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 coexistence 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.

Association Between Cytomegalovirus End-organ Diseases andModerate-to-Severe Dementia: A Population-Based Cohort Study

“…This did not include the codes for congenital CMV infection (P35. 1) or cytomegaloviral mononucleosis (B27.1) [14,17]. Furthermore, a dementia diagnosis for RID registration using a unique V800 and V810 code was consistent with the ICD-10 codes: AD ( The solid organ transplantation (SOT) recipients had V005 (kidney), V013 (liver), V015 (heart), and/or V277 (lung) codes according to the transplant organ for RID registration, which are consistent with the Z94 codes in the ICD-10 (Z94.0, Z94.1, Z94.2, Z94.3, and Z94.4 for the kidney, heart, lung, heart and lung, and liver, respectively).…”

Association Between Cytomegalovirus End-organ Diseases and Moderate-to-Severe Dementia: A Population-Based Cohort Study

“…All medical institutions present claims on diseases diagnosed using the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) codes, World Health Organization (WHO) [16,17]. Rare incurable diseases (RIDs) including human immunodeficiency virus-1 (HIV-1) infection, CMV end-organ diseases, cancer, and moderate-to-severe dementia are controlled by the Korean NHIS [14][15][16]18]. Patients with RIDs receive significant health coverage by paying 5% of their healthcare costs.…”

“…The V104 code is consistent with the specific B25 codes in the ICD-10, including those for all types of CMV tissue-invasive end-organ diseases, such as cytomegaloviral pneumonitis (B25.0), cytomegaloviral hepatitis (B25.1), cytomegaloviral pancreatitis (B25.2), other cytomegaloviral diseases (B25.8), and cytomegaloviral diseases, unspecified (B25.9) [17]. This did not include the codes for congenital CMV infection (P35.1) or cytomegaloviral mononucleosis (B27.1) [14,17]. Furthermore, a moderate-to-severe dementia diagnosis for RID registration using a unique V800 and V810 code was consistent with the ICD-10 codes: AD (early or presenile onset or type 2 The solid organ transplantation (SOT) recipients had V005 (kidney), V013 (liver), V015 (heart), and/or V277 (lung) codes according to the transplant organ for RID registration, which are consistent with the Z94 codes in the ICD-10 (Z94.0, Z94.1, Z94.2, Z94.3, and Z94.4 for the kidney, heart, lung, heart and lung, and liver, respectively).…”

“…Body mass index (BMI) was calculated as weight/height × height (kg/m 2 ) and categorised as <25 and ≥25 kg/m 2 . Low income status was defined as the lower 25th percentile of annual household income, based on data from the 2010 South Korean Population and Housing Census [14].…”

“…The Republic of Korea has high rates of CMV seropositivity [13]. Moreover, our country strictly applies the registration of CMV tissue-invasive end-organ diseases and moderate-to-severe dementia using the national health insurance system [14,15]. Therefore, confirming an association between CMV tissue-invasive end-organ diseases that present with active virus replication and severe tissue inflammation through reactivation of primary or past latent infection and moderate-to-severe dementia with cognitive impairment severe enough to interfere with social and occupational functioning and daily living could provide clearer evidence of CMV causality in dementia than previous studies that were based on known seroprevalence.…”