Insulin Dosing Is Associated With Cardiac Sympathetic Predominance Independent of Glycemic Profiles in Type 1 Diabetes Under Free-Living Conditions

Abstract

While insulin activates the sympathetic nervous system in experimental settings, whether therapeutic insulin administration is associated with cardiac sympathetic predominance under free-living conditions remains unclear. This prospective observational study investigated the association between insulin dosing and cardiac autonomic balance in adults with type 1 diabetes managed exclusively with insulin therapy. Participants underwent continuous heart rate variability (HRV) and glucose monitoring over 4 consecutive days during routine daily activities. Cardiac sympathetic predominance was assessed using the low-frequency power to high-frequency power (LF/HF) ratio derived from HRV analysis, and associations were evaluated using generalized estimating equations. A higher last bolus insulin dose was associated with an increased LF/HF ratio during the early sleep phase. A higher basal insulin dose was also associated with an increased LF/HF ratio during the late sleep phase. These associations persisted after adjustment for mean glucose and mean absolute glucose change during the corresponding sleep phases. Under free-living conditions, higher insulin doses were associated with dose-dependent increases in cardiac sympathetic predominance, independent of glycemic profiles. These findings suggest that insulin dosing may be linked to cardiac autonomic regulation in individuals with type 1 diabetes, highlighting the importance of considering cardiac autonomic balance and potential cardiovascular risk when optimizing insulin therapy. Article Highlights The relationship between therapeutic insulin administration and cardiac autonomic balance under free-living conditions remains unclear. We examined whether insulin dosing was associated with cardiac sympathetic predominance during daily life in adults with type 1 diabetes managed with insulin therapy. Higher last bolus and basal insulin doses were associated with increased cardiac sympathetic predominance during the early and late sleep phases, respectively, independent of glycemic profiles. These findings suggest that insulin dosing patterns may be linked to cardiac autonomic balance, with potential implications for optimizing insulin therapy in type 1 diabetes.