Higher HbA_1c variability is associated with increased arterial stiffness in individuals with type 1 diabetes

Background: Both long-term glycaemic variability and arterial stiffness have been recognized as cardiovascular risk factors. This study aims to investigate whether an association between these phenomena exists in individuals with type 1 diabetes.

Methods: This cross-sectional study included 673 adults (305 men, 368 women) with type 1 diabetes and combined available retrospective laboratory data on HbA_1c from the preceding 10 years with outcome data on arterial stiffness and clinical variables from a comprehensive study visit. HbA_1c variability was calculated as adjusted standard deviation (adj-HbA_1c-SD), coefficient of variation (HbA_1c-CV) and average real variability (HbA_1c-ARV). As measures of arterial stiffness, carotid-femoral pulse wave velocity (cfPWV; n = 335) and augmentation index (AIx; n = 653) were assessed using applanation tonometry.

Results: The study population had a mean age of 47.1 (± 12.0) years and a median duration of diabetes of 31.2 (21.2-41.3) years. The median number of HbA_1c assessments per individual was 17 (12-26). All three indices of HbA_1c variability were significantly correlated with both cfPWV and AIx after adjustment for sex and age (p < 0.001). In separate multivariable linear regression models, adj-HbA_1c-SD and HbA_1c-CV were significantly associated with cfPWV (p = 0.032 and p = 0.046, respectively) and AIx (p = 0.028 and p = 0.049, respectively), even after adjustment for HbA_1c-mean. HbA_1c-ARV was not associated with cfPWV or AIx in the fully adjusted models.

Conclusions: An association independent of HbA_1c-mean was found between HbA_1c variability and arterial stiffness, suggesting a need to consider multiple HbA_1c metrics in studies assessing cardiovascular risk in type 1 diabetes. Longitudinal and interventional studies are needed to confirm any causal relationship and to find strategies for reducing long-term glycaemic variability.