Abstract
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.