Type I Diabetes Mellitus Increases the Cardiovascular Complications of Influenza Virus Infection

Abstract

People with diabetes mellitus are susceptible to both cardiovascular disease and severe influenza A virus infection. We hypothesized that diabetes also increases risks of influenza-associated cardiac complications. A murine type 1 (streptozotocin-induced) diabetes model was employed to investigate influenza-induced cardiac distress. Lung histopathology and viral titres revealed no difference in respiratory severity between infected control and diabetic mice. However, compared with infected control mice, infected diabetic mice had increased serum cardiac troponin I and creatine-kinase MB, left ventricular structural changes and right ventricular functional alterations, providing the first experimental evidence of type I diabetes increasing risks of influenza-induced cardiovascular complications.

Keywords: cardiac; comorbid; in vivo; influenza A virus; murine model; type 1 diabetes mellitus; vascular.

Figure 1

The pulmonary severity of IAV is not increased in T1DM versus control male C57BL/6J mice at six days post-infection. (A) Percentage of original body weight over infection course in IAV- or mock-infected mice with and without T1DM. (B) Arterial oxygen saturation percentage in IAV- or mock-infected mice with and without T1DM. (C) Lung IAV viral copy number in IAV- or mock-infected mice with and without T1DM. (D) Total lung histopathology scores in IAV- or mock-infected mice with and without T1DM. Data are pooled from two experiments, the initial containing six mice per group and the repeat containing 3 mice per group. Statistical outliers were removed by ROUTS test (Q=1%). For graph (A), each data point represents the mean ± SEM of at least n=9 mice per group, for graphs (B, C), each data point represents one mouse with median ± IQR of at least n=5 per group, and for graph (D), each data point represents one mouse with mean ± SEM of at least n=9 mice per group. Statistical analysis was performed as described in “Methods”, being performed on untransformed data for graphs (B, C) as transforming did not achieve closer-to-normal distribution.

Figure 2

Increased markers of cardiac damage, and changes in left ventricular structure in IAV-infected T1DM versus control male C57BL/6J mice at six days post-infection. (A) Serum cardiac troponin I (CTNI) (ng/ml) in IAV- or mock-infected mice with and without T1DM. (B) Serum creatine kinase MB (CK-MB) (ng/ml) in IAV- or mock-infected mice with and without T1DM. (C) IAV viral copy number present in hearts of IAV- or mock-infected mice with and without T1DM. (D) Echocardiogram-derived left ventricular mass index in IAV-infected mice with and without T1DM. Data are pooled from two experiments, the initial containing six mice per group and the repeat containing 3 mice per group. Statistical outliers were removed by ROUTS test (Q=1%). Each data point represents one mouse with at least n=6 per group and mean ± SEM for graphs (A, B), and median ± IQR for graphs (C, D). Statistics were performed on log-transformed data for LV mass index as these showed the closest to normal distribution, but on untransformed data for graph (C) as transformation did not achieve closer-to-normal distribution. Statistical analysis was performed as described in “Methods” with *P<0.05; **P<0.01.