Cardiac autonomic dysfunction in type 2 diabetes - effect of hyperglycemia and disease duration

Abstract

Heart rate variability (HRV) is reduced in diabetes mellitus (DM) patients, suggesting dysfunction of cardiac autonomic regulation and an increased risk for cardiac events. The aim of this paper was to examine the associations of blood glucose level (BGL), glycated hemoglobin (HbA1c), and duration of diabetes with cardiac autonomic regulation assessed by HRV analysis. Resting electrocardiogram (ECG), recorded over 20 min in supine position, and clinical measurements of 189 healthy controls and 93 type 2 DM (T2DM) patients were analyzed. HRV was assessed using several time-domain, frequency-domain, and non-linear methods. HRV parameters showed a clear difference between healthy controls and T2DM patients. Hyperglycemia was associated with increase in mean heart rate and decrease in HRV, indicated by negative correlations of BGL and HbA1c with mean RR interval and most of the HRV parameters. Duration of diabetes was strongly associated with decrease in HRV, the most significant decrease in HRV was found within the first 5-10 years of the disease. In conclusion, elevated blood glucose levels have an unfavorable effect on cardiac autonomic function and this effect is pronounced in long-term T2DM patients. The most significant decrease in HRV related to diabetes and thus presence of autonomic neuropathy was observed within the first 5-10 years of disease progression.

Keywords: HbA1c; blood glucose; cardiac autonomic neuropathy; duration; heart rate variability; hyperglycemia.

Figure 1

RR interval time series (bold line showing the removed trend) and AR spectrum estimates for healthy control subject (A), T2DM patient diagnosed 6 years prior to measurement (B), and T2DM patient diagnosed 13 years prior to measurement (C).

Figure 2

Box plots of selected HRV associations with BGL (A), HbA1c (B), and duration of diabetes (C). On each box, the central mark is the median, the edges of the box are the 25th and 75th percentiles, and the whiskers extend to the most extreme parameter values excluding outliers. Significant differences between all the “boxes” (A,B) or between successive “boxes” (C) were tested using the Mann–Whitney U test (***p ≤ 0.001; **p ≤ 0.01; *p ≤ 0.05).

Figure 3

Box plots of most significant associations between clinical characteristics, BGL, HbA1c, and duration of diabetes (***p ≤ 0.001; **p ≤ 0.01; *p ≤ 0.05). Descriptions as in Figure 2.

Figure 4

Polynomial least squares surface fits for the associations of mean RR (top) and total power (bottom) with BGL and disease duration.