Heart rate as a marker of sympathetic overdrive in type 2 diabetes

Aims: To investigate the relationship between resting heart rate (HR) and cardiac sympathetic overdrive in patients with type 2 diabetes (T2D).

Methods: This retrospective cross-sectional study included 58 with T2D (aged 39-57 years) and 52 age-matched healthy controls. Sympathetic activity was assessed using muscle sympathetic nerve activity (MSNA, measured in bursts frequency over time) via microneurography of the peroneal nerve, and plasma norepinephrine (NE) levels measured via high-performance liquid chromatography (HPLC). Participants were divided into subgroups based on clinic and 24-hour HR values. Associations between HR and direct and indirect markers of sympathetic activity (i.e. MSNA and plasma NE) were evaluated, comparing these findings between the T2D and control group.

Results: The study showed that patients with T2D with higher clinic and 24-hour HR values exhibited significantly higher MSNA and NE levels, indicating greater sympathetic activity. HR values above the 70 bpm threshold, identified in previous clinical trials as a marker of increased cardiovascular risk, were associated with increased MSNA and NE levels in the T2D group. In contrast to healthy controls, in T2D group both MSNA and NE were significantly related to clinic (r=0.93, P<0.0001 and r=0.87, P<0.0001, respectively) and 24-hour HR (r=0.92, P<0.0001 and r=0.84, P<0.0001, respectively).

Conclusions: This study highlights the potential utility of HR as a non-invasive marker for identifying among patients with T2D those with sympathetic overdrive. Given the established role of sympathetic overactivity in worsening cardiovascular outcomes, the study supports the need to investigate in patients with clinic HR >70 bpm the potential benefit of interventions aimed at modulating sympathetic activity.

Comments. Sympathetic overactivity is known to increase the risk for cardiovascular, cerebral and renal complications as well as worsening glycemic control in patients with diabetes. Identification of easily accessible markers of sympathetic overdrive would facilitate the recognition of patients at greater risk and the initiation of timely intervention. The present study demonstrated a correlation between elevated clinic and 24-hour HR, particularly >70 bpm, and increased sympathetic activity, revealed by higher MSNA and NE levels. The authors suggested that sympathetic overdrive in patients with T2D and elevated HR occurs before overt autonomic neuropathy, even though participants in the study did not undergo cardiovascular autonomic reflex tests to rule out this condition. However, the complexity of the bidirectional relation between sympathetic overactivity and diabetes is also confirmed by a recent study where variations in HR, possibly reflecting differences in sympathetic tone, had an impact on the risk of developing diabetes in a large Korean cohort (n=8,313) (Son MK et al Diabetes Metab J 2024;48:752-762). A greater emphasis on HR and on HR dynamics in clinical practice could therefore improve patients' risk stratification and management. Future research should focus on validating these findings in larger, more diverse populations, while also assessing the effects of HR-targeted therapies on cardiovascular and metabolic outcomes in this high-risk patient group.

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Reference. Dell'Oro R, Quarti-Trevano F, Ciardullo S, Perseghin G, Mancia G, Grassi G. Reliability of heart rate in reflecting cardiac sympathetic overdrive in type 2 diabetes mellitus. Clin Auton Res. 2024 Jul 22. doi: 10.1007/s10286-024-01054-z. Epub ahead of print. PMID: 39037542. 

https://link.springer.com/article/10.1007/s10286-024-01054-z