Short term optimization of glycaemic control using insulin improves sympatho-vagal tone activities in patients with type 2 diabetes

Published:October 03, 2019DOI:



      Diabetic cardiac autonomic neuropathy (CAN) is potentially life threatening and its severity might further be aggravated by poor glycaemic control. A decrease in Heart rate variability (HRV) is the earliest finding of CAN even at the sub clinical stage. While intensive glycaemic control prevents the development of CAN in patients with type 1 diabetes, it is not known whether the intensification of glycaemic control using insulin would improve cardiovascular autonomic functions in type 2 diabetes patients. This study aimed to determine the short term effects of optimizing glycaemic control using insulin on the HRV in type 2 diabetes patients.


      We conducted a single arm open label clinical trial. Participants were poorly controlled non-insulin treated type 2 diabetes mellitus patients (HbA1c ≥ 7%). The intervention lasted 60 days and consisted in the intensification of glycaemic control through the initiation of a basal plus insulin regimen with titration of insulin to protocol defined glycaemic targets which were; fasting glycaemia: 0.70–1.30 g/L and post prandial glycaemia <1.80 g/L. Long term HRV measurement was done using a 24-h ambulatory electrocardiographic (ECG) recording on day 0 and day 60. Wilcoxon signed rank test was used to compare differences in HRV parameters before and after the intervention.


      A total of 29 (14 males and 15 females) consenting type 2 diabetes mellitus patients without clinical signs of CAN were enrolled and allocated to intervention (14 males and 15 females). The median age was 52 [43–59] years, and duration of diabetes 3.0 [0.6–6.7] years. The intervention induced a reduction in HbA1c from 10.1 [9.1–11.9]% to 6.7 [5.9–6.9]% (p < 0.001) without severe hypoglycaemic events. Concerning HRV parameters, there was a significant improvement in markers of the parasympathetic tone (PNN50: 5.7 [3.6–10.3]% to 8.1 [3.1–16.9]%, p = 0.008) and sympathetic tone (SDNN: 102.01 [90.45–111.05] ms to 122.40 [91.70–135.95] ms, p = 0.01).


      The optimization of glycaemic control using a basal plus insulin regimen while inducing a significant reduction in glycated hemoglobin, significantly improves 24-h ambulatory ECG derived sympathetic and parasympathetic activities. This suggests that tight glycaemic control using insulin may revert cardiac autonomic neuropathy in type 2 diabetes mellitus patients.



      Bpm (beats per minutes), HbA1c (glycated hemoglobin), HR (heart rate), HRV (heart rate variability), HF (high frequency), LF (low frequency), ms (milliseconds), PNN 50 (percentage of normal to normal intervals differing by more than 50 ms), RMSSD (root-mean-square of successive differences), SDNN (standard deviation of all normal R-R intervals), SDANN (standard deviation of average normal to normal R-R intervals), T2DM (type 2 diabetes mellitus)
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