Metabolic and sympathovagal effects of bolus insulin glulisine versus basal insulin glargine therapy in people with type 2 diabetes: A randomized controlled study.

Aim This study compares the effects of two different insulin regimens-basal versus bolus insulin-on metabolic and cardiovascular autonomic function in Japanese participants with type 2 diabetes. Methods Participants were randomly assigned to groups for therapy with insulin glulisine (IGlu) or insulin glargine (IGla). The primary efficacy endpoint was glycemic variability, including M-values, mean of glucose levels, and a blood glucose profile of seven time points before and after the intervention. The secondary endpoints included pleiotropic effects, including endothelial and cardiac autonomic nerve functions. Results Blood glucose levels at all time points significantly decreased in both groups. Post-lunch, post-dinner, and bedtime blood glucose levels were significantly lower in the IGlu group than in the IGla group. Nadir fasting blood glucose levels at the endpoint were significantly lower in the IGla group than in the IGlu group. M-value and mean blood glucose levels were significantly decreased from baseline in both groups, though the former was significantly lower in the IGlu group than in the IGla group. IGla, but not IGlu, was found to elevate 24-hour parasympathetic tone, especially during nighttime, and it decreased 24-hour sympathetic nerve activity, especially at dawn. Conclusions Both IGlu and IGla regimens reduced glucose variability, with IGlu bringing a greater reduction in M-value. IGla, but not IGlu, increased parasympathetic tone during nighttime and decreased sympathetic nerve activity at dawn. These findings shed light on the previously unrecognized role of nighttime basal insulin supplementation on sympathovagal activity in type 2 diabetes.