Highlight
This longitudinal observational study shows that higher continuous glucose monitoring-derived time in range (TIR) is significantly associated with less progression of arterial stiffness measured by brachial-ankle pulse wave velocity (baPWV) over 5 years in patients with type 2 diabetes (T2D). Notably, this association is independent of glycemic control measured by HbA1c levels. Other CGM metrics, including coefficient of variation, had no significant longitudinal association with arterial stiffness. These findings support the clinical utility of TIR as a complementary metric to HbA1c in cardiovascular risk stratification in T2D.
Study Background
Type 2 diabetes is a major global health burden characterized by hyperglycemia and increased risk of macrovascular complications, including cardiovascular disease (CVD). Arterial stiffness, frequently assessed by pulse wave velocity (PWV), is a recognized surrogate marker for vascular aging and atherosclerotic risk predicting cardiovascular events and mortality.
Conventionally, HbA1c is used to monitor glycemic control, but it does not capture glucose variability or acute glycemic excursions that may contribute to vascular dysfunction. Continuous glucose monitoring (CGM) technologies provide dynamic glucose profiles, enabling measurement of parameters such as time in range (TIR; percentage of time glucose stays within euglycemic target range) and coefficient of variation (CV; a measure of glycemic variability). Emerging cross-sectional data have suggested associations between CGM metrics and arterial stiffness, but longitudinal evidence has been lacking.
Study Design
This exploratory, multicenter prospective cohort study evaluated 348 type 2 diabetes patients without prior symptomatic cardiovascular disease. Participants underwent CGM assessment and baPWV measurement at baseline and follow-ups at approximately 2 years (104 weeks) and 5 years (260 weeks).
Patients were dichotomized by median baseline values of CGM metrics (especially TIR and CV) and HbA1c. The primary endpoint was the longitudinal change in arterial stiffness assessed by baPWV over follow-up. Mixed-effects models for repeated measures were applied to analyze associations between baseline CGM metrics and changes in baPWV, with adjustments for traditional atherosclerotic risk factors and HbA1c.
Key Findings
Over the study period, median baPWV increased significantly, indicating progressive arterial stiffening (median increase: 60.1 cm/s at 104 weeks and 130.3 cm/s at 260 weeks; p < 0.001).
Crucially, patients with higher baseline TIR exhibited significantly less progression in baPWV compared to those with lower TIR, with a significant interaction between TIR group and time in multivariable models (p = 0.013). This association remained robust even after controlling for HbA1c, indicating that TIR conveys additional information on vascular changes beyond average glycemic exposure.
Conversely, baseline CV, other CGM-derived metrics, and HbA1c alone did not predict longitudinal baPWV changes, suggesting that glycemic variability and HbA1c may be less sensitive markers of arterial stiffness progression than TIR.
These results highlight that maintaining glucose within target ranges consistently (higher TIR) could confer vascular benefits by slowing arterial stiffening in T2D patients with no overt cardiovascular disease.
Expert Commentary
The study addresses an important gap in understanding the prognostic value of CGM metrics for vascular function in diabetes. The use of baPWV as a noninvasive, reproducible measure of arterial stiffness strengthens clinical relevance. The independent association of TIR with arterial stiffening progression emphasizes the potential of TIR as a valuable glycemic target complementary to HbA1c, particularly for cardiovascular risk management.
However, limitations include the observational design, which precludes direct causal inference, and potential confounders not fully accounted for despite multivariable adjustments. The study cohort’s exclusion of patients with prior symptomatic cardiovascular disease may limit generalizability to higher risk populations. Furthermore, the threshold for TIR was median-based rather than clinically predefined targets, which warrants further investigation.
Mechanistically, continuous exposure to glucose levels within range may reduce oxidative stress and endothelial dysfunction that drive arterial stiffening. The lack of association with glycemic variability (CV) contrasts with some previous reports, suggesting the need for larger studies to clarify the roles of different glycemic parameters in vascular health.
Conclusion
This prospective cohort study demonstrates that higher CGM-derived time in range is independently associated with attenuated progression of arterial stiffness over five years in type 2 diabetes patients without prior cardiovascular disease. TIR may offer additional prognostic value beyond HbA1c measurement for cardiovascular risk assessment and management in diabetes care.
These findings underscore the clinical importance of CGM metrics in comprehensive glycemic evaluation. Future interventional studies are needed to determine whether improving TIR directly translates into reduced cardiovascular events and to define optimal TIR targets for vascular protection.
Funding and Clinical Trials Registration
The study was supported by [Funding sources if available]. Clinical trials registration information was not specified in the source document.
References
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- American Diabetes Association. 10. Cardiovascular Disease and Risk Management: Standards of Medical Care in Diabetes—2024. Diabetes Care. 2024;47(Suppl 1):S183-S194.
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- Nasrallah M, Inzucchi SE. Role of continuous glucose monitoring in diabetes management. J Clin Endocrinol Metab. 2018;103(3):1135-1143.
- Blacher J, Safar ME. Pulse wave velocity and cardiovascular events: prospects for improving risk prediction. J Hypertens. 2019;37(1):9-11.