Time-varying parameters of glycemic control and glycation in relation to arterial stiffness in patients with type 1 diabetes

BACKGROUND: A substantial proportion of type 1 diabetes (T1D) patients free from known cardiovascular disease (CVD) show premature arterial stiffening, with age, blood pressure, and HbA1c—as gold standard of glycemic control—as main predictors. However, the relationship of arterial stiffness with other time-varying parameters of glycemic control and glycation has been far less explored. This study investigated the relationship of arterial stiffness with several short- and long-term parameters of glycemic control and glycation in patients with T1D, such as advanced glycation end-products (AGEs) and continuous glucose monitoring (CGM)-derived parameters. METHODS: Cross-sectional study at a tertiary care centre including 54 patients with T1D free from known CVD. Arterial stiffness was assessed with carotid-femoral pulse wave velocity (cf-PWV). Current level and 10-year history of HbA1c were evaluated, and skin AGEs, urinary AGEs, and serum soluble AGE-receptor (sRAGE) concentrations. CGM for 7 days was used to determine time in range, time in hyper- and hypoglycemia, and glycemic variability. RESULTS: Cf-PWV was associated with current HbA1c (r(s) = + 0.28), mean 10-years HbA1c (r(s) = + 0.36), skin AGEs (r(s) = + 0.40) and the skin AGEs-to-sRAGE ratio (r(s) = + 0.40), but not with urinary AGE or serum sRAGE concentrations; and not with any of the CGM-parameters. Multiple linear regression for cf-PWV showed that the model with the best fit included age, T1D duration, 24-h mean arterial pressure and mean 10-years HbA1c (adjusted R(2) = 0.645, p < 0.001). CONCLUSIONS: Longer-term glycemic exposure as reflected by current and mean 10-years HbA1c is a key predictor of arterial stiffness in patients with T1D, while no relationship was found with any of the short-term CGM parameters. Our findings stress the importance of early and sustained good glycemic control to prevent premature CVD in patients with T1D and suggest that HbA1c should continue to be used in the risk assessment for diabetic complications. The role of skin glycation, as a biomarker for vascular aging, in the risk assessment for CVD is an interesting avenue for further research.