Visit-to-visit glucose variability is associated with echocardiographic variables in people with type 2 diabetes: epidemiological and mendelian randomization approaches

BACKGROUND: This study aimed to examine the associations between visit-to-visit variability in fasting plasma glucose (FPG) and HbA1c with echocardiographic variables in patients with type 2 diabetes using epidemiologic and Mendelian randomization (MR) methods. METHODS: From January 2001 to December 2020, 2,326 (1,233 men and 1,093 women) subjects with type 2 diabetes who underwent echocardiography assessment were enrolled in the diabetes care management program of a medical center in Taiwan. The echocardiographic variables included those for cardiac structural, cardiac systolic, and diastolic function. Variability in FPG and HbA1c within one-year prior echocardiographic measurements was calculated using coefficient of variation (CV). A two-stage multivariable regression analysis was used to assess the causal relationship among FPG-CV, HbA1c-CV, and echocardiographic variables using 22 SNPs for FPG and 14 SNPs for HbA1c as instrumental variables. RESULTS: A total of 2,326 participants were included, with a mean age of 64.5 years and 53.0% were men. Epidemiologic and MR analyses show the significant associations between left atrium diameter (LAD), left ventricular systolic diameter (LVSd), left ventricular mass (LVM), left ventricular ejection fraction (LVEF), E, and E/e' ratio with FPG variability. Significant associations between HbA1c variability and echocardiographic variables including LAD, E/e', and deceleration time identified in the epidemiologic approach became non-significant in the MR analysis when controlling for covariates. CONCLUSIONS: Our epidemiologic and MR studies demonstrated that visit-to-visit variability of FPG in patients with type 2 diabetes was independently associated with the left cardiac structure as well as systolic and diastolic function.