Painful Diabetic Neuropathy Is Associated With Greater Autonomic Dysfunction Than Painless Diabetic Neuropathy

OBJECTIVE

Although a clear link between diabetic peripheral neuropathy (DPN) and autonomic neuropathy is recognized, the relationship of autonomic neuropathy with subtypes of DPN is less clear. This study aimed to investigate the relationship of autonomic neuropathy with painless and painful DPN.

RESEARCH DESIGN AND METHODS

Eighty subjects (20 healthy volunteers, 20 with no DPN, 20 with painful DPN, 20 with painless DPN) underwent detailed neurophysiological investigations (including conventional autonomic function tests [AFTs]) and spectral analysis of short-term heart rate variability (HRV), which assesses sympathovagal modulation of the heart rate. Various frequency-domain (including low frequency [LF], high frequency [HF], and total power [TP]) and time-domain (standard deviation of all normal-to-normal R-R intervals [SDNN] and root mean square of successive differences [RMSSD]) parameters were assessed.

RESULTS

HRV analysis revealed significant differences across the groups in LF, HF, TP, SDNN, and RMSSD (ANOVA P < 0.001). Subgroup analysis showed that compared with painless DPN, painful DPN had significantly lower HF (3.59 ± 1.08 [means ± SD] vs. 2.67 ± 1.56), TP (5.73 ± 1.28 vs. 4.79 ± 1.51), and SDNN (2.91 ± 0.65 vs. 1.62 ± 3.5), P < 0.05. No significant differences were seen between painless DPN and painful DPN using an AFT.

CONCLUSIONS

This study shows that painful DPN is associated with significantly greater autonomic dysfunction than painless DPN. These changes are only detected using spectral analysis of HRV (a simple test based on a 5-min electrocardiogram recording), suggesting that it is a more sensitive tool to detect autonomic dysfunction, which is still under-detected in people with diabetes. The greater autonomic dysfunction seen in painful DPN may reflect more predominant small fiber involvement and adds to the growing evidence of its role in the pathophysiology of painful DPN.Diabetic neuropathy is one of the most frequent complications of diabetes. The prevalence of some form of neuropathy has been reported to be as high as 66% in type 1 diabetes and 59% in type 2 diabetes (1). It is the source of great distress, disability, and premature death. It is the main initiating factor for foot ulceration and the most common cause of nontraumatic lower-limb amputation in the Western world (2). It is also one of the more poorly understood complications of diabetes.Although a clear relationship between diabetic peripheral neuropathy (DPN) and cardiac autonomic neuropathy (CAN) has been recognized, the nature of the relationship of CAN with painless or painful neuropathy was less clear. Recently, there has been some evidence that at the level of the peripheral nerve, local autonomic dysfunction has an important role to play in the generation of pain (3). However, clinical studies looking to see if this translates into more generalized autonomic neuropathy have shown mixed and often opposite results (4,5). Part of the reason for this may be that all of these studies used conventional autonomic function tests (AFTs), which tend to detect autonomic dysfunction only at more advanced stages (6).Over recent years, a number of different techniques have been developed that are more sensitive measures of autonomic function and are therefore able to detect subclinical abnormalities (7). One such technique is spectral analysis of heart rate variability (HRV). Short-term HRV analysis is relatively quick and simple to carry out because it is based on a 2- to 5-min resting electrocardiogram (ECG) recording. The recording is able to detect autonomic dysfunction in subjects in whom conventional AFTs are still normal (8).The aim of this study was to determine if there are differences in autonomic function between painful and painless DPN using spectral analysis of HRV.