Do high proinsulin and C-peptide levels play a role in autonomic nervous dysfunction? Power spectral analysis in patients with non-insulin-dependent diabetes and nondiabetic subjects

Background Immunoreactive insulin has been shown to predict the development of parasympathetic autonomic neuropathy. It is possible that constituents of immunoreactive insulin could explain this association. In this cross-sectional study, the relationship of specific insulin, C-peptide, and proinsulin with autonomic nervous dysfunction was evaluated in 57 NIDDM patients and 108 control subjects. Methods and Results The frequency-domain analysis of heart rate variability was determined by using spectral analysis from stationary regions of registrations while the subjects breathed spontaneously in a supine position. Total power was divided into three frequency bands: low (0 to 0.07 Hz), medium (MFP, 0.07 to 0.15 Hz), and high (HFP, 0.15 Hz to 0.50 multiplied by the frequency equal to the mean RR interval). In NIDDM patients, total power, the three frequency bands (P < .001 for each), and the MFP/HFP ratio (P = .016), which expresses sympathovagal balance, were reduced compared with control subjects. Fasting proinsulin (r(s) = -.324, P = .014 for diabetics and r(s) = -.286, P = .003 for control subjects), C-peptide (r(s) = -.492, P < .001 for diabetics and r(s) = -.304, P = .001 for control subjects), and total immunoreactive insulin (r(s) = -.291, P = .028 for diabetics and r(s) = -.228, P = .017 for control subjects) were inversely related to MFP/HFP. For proinsulin and C-peptide the results did not change after controlling for the effects of age, body mass index, and fasting glucose. Conclusions Both proinsulin and C-peptide levels were significantly associated with the sympathovagal balance of autonomic nervous function in NIDDM patients and control subjects, but this study cannot determine whether these compounds are directly involved in autonomic nervous dysfunction.