Endocrine Abstracts

Background: In patients with type 1 diabetes (T1D), arterial stiffness is a potential alternative biomarker for cardiovascular (CV) risk as it has recently shown important prognostic value in the development of CVD that is independent from traditional risk factors. Glycemic control by means of HbA1c is a main determinant of arterial stiffness progression, however the relationship with continuous glucose monitoring (CGM)-derived parameters such as time in range (TIR) has not been explored yet.

Aims: Evaluate arterial stiffness and its determinants in T1D patients who are still free from known CVD, and investigate its relationship with new CGM-derived parameters of glycemic control.

Methods: Cross-sectional study, in which adult T1D patients with a disease duration (DD) of at least 10 years and without known CVD were enrolled. The STENO T1D risk engine was used to estimate 10-years CV event risk, with 3 groups: low (< 10%), moderate (10-20%), and high CV event risk (20%). Current level and 10-years history of HbA1c was collected, as well as advanced glycation end products (AGEs; AGEreader). Patients were equipped with a CGM sensor (Dexcom G5) for 7 days, to determine TIR, time in hyper- and hypoglycaemia, and parameters of glycemic variability. Arterial stiffness was evaluated with carotid-femoral pulse wave velocity (cfPWV) (SphygmoCor). Ambulatory blood pressure monitoring, duplex carotid ultrasound and coronary artery calcium scoring was performed; and information on renal function and the presence of microvascular complications was also retrieved. Levels of physical activity (DynaPort MoveMonitor) and exercise capacity were evaluated as well. Pearson (r) and Spearman (rs) correlations, and multiple linear regression were used to investigate associations. Independent samples t-test and one-way ANOVA or their non-parametric alternatives were used to compare variables between two or more groups, respectively.

Results: 54 patients (M/F: 32/22; age: 46 ± 9.5 yrs; DD: 27 ± 8.8 yrs; HbAc1: 7.8 ± 0.83%) were included. According to the STENO 10-year CV event risk score, 20 patients (37%) were at low, 20 patients (37%) at moderate, and 14 patients (26%) at high risk. Median cfPWV was 8.3 [6.8-10.1] m/s, with approximately 25% of patients showing increased aortic stiffness, i.e. cfPWV > 10 m/s or above the 90^th percentile of age-and BP-matched reference values. cfPWV was strongly associated with the STENO score (r=+0.75), increasing in each higher STENO group (P < 0.01); and showed moderate to good individual correlations with the traditional risk factors age (rs=+0.69), disease duration (rs=+0.41) and 24-hour MAP (rs=+0.45). cfPWV was significantly associated with current HbA1c (rs=+0.28), mean 10-years HbA1c (rs=+0.36) and AGEs (+0.40), but not with any of the CGM-derived parameters. cfPWV was also negatively associated with VO2max and level of physical activity. Regressions models for cfPWV showed the following: (1) The STENO score explained 57% of variation (R²= 0.566, P < 0.001); (2) Sedentary time showed additional predictive value improving the fit of the model (R²= 0.698, P < 0.05); (3) Only one alternative model that did not include the STENO score achieved better fit (R²= 0.675, P < 0.001) including age, disease duration, mean 10-years HbA1c and 24 hours-MAP. CONCLUSION: This study demonstrates that a substantial proportion (~25%) of T1D patients who are still free from CVD show premature arterial stiffening, which was found to be highly associated with the STENO score. The present study also provides arguments that HbA1c should not be completely replaced by TIR, as long-term glycemic control reflected by HbA1c and AGEs was a main determinant of arterial stiffness, while no relationship was found with any of the CGM-derived parameters. Furthermore, physical inactivity showed an additional negative impact on arterial stiffness, while no relationship was found with any of the CGM-derived parameters. Furthermore, physical inactivity showed an additional negative impact on arterial stiffness. Future studies should investigate if evaluation of arterial stiffness could be implemented in clinical practice and which patients benefit the most from its assessment, so that adequate preventive measures can be taken.

Key words: Type 1 diabetes, Arterial stiffness, Glycemic control, Continuous glucose monitoring, Time in range.