Statistical methods

In the epidemiologic study, we used independent t-tests for continuous variables and chi-square tests for categorical variables to evaluate differences in demographic characteristics and underlying comorbidities between two cohorts. The Kaplan–Meier method with a Log rank test was performed to compare the risk of outcomes between two cohorts. We used multivariable Cox proportional hazards regressions to identify independent predictors of the outcomes and evaluate their effects. Stratified analyses according to age, sex, underlying comorbidities, and follow-up period were also conducted. All patients were right-censored to a new-onset outcome, date of death, or end of follow-up date, which is December 31, 2017. We used SAS 9.4 (SAS Institute Inc., Cary, NC, USA) to perform statistical analyses and STATA 14.0 (Stata Corp., College Station, TX, USA) to display Kaplan–Meier curves.

In the animal study, we used Prism (Version 7.01, S GraphPad Software, Inc., CA, USA) to perform statistical analyses. Data were presented as the mean ± standard error of the mean. Differences in pathophysiological scores between two groups of rats were evaluated using independent t-tests. Hormone values and glucose levels were analyzed using one-way analysis of variance for repeated measures. A two-tailed p value of <0.05 was considered statistically significant.