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
Jp. Toyry et al., 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, Circulation, 96(4), 1997, pp. 1185-1191
Background Immunoreactive insulin has been shown to predict the develo
pment of parasympathetic autonomic neuropathy. It is possible that con
stituents of immunoreactive insulin could explain this association. In
this cross-sectional study, the relationship of specific insulin, C-p
eptide, and proinsulin with autonomic nervous dysfunction was evaluate
d in 57 NIDDM patients and 108 control subjects. Methods and Results T
he frequency-domain analysis of heart rate variability was determined
by using spectral analysis from stationary regions of registrations wh
ile the subjects breathed spontaneously in a supine position. Total po
wer 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 su
bjects) were inversely related to MFP/HFP. For proinsulin and C-peptid
e 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 s
ubjects, but this study cannot determine whether these compounds are d
irectly involved in autonomic nervous dysfunction.