Power spectral analysis of heart rate variability during hyperinsulinemia in nondiabetic offspring of type 2 diabetic patients - Evidence for possible early autonomic dysfunction in insulin-resistant subjects

Sympathetic activation has been considered as a link between insulin resist ance, hyperinsulinemia, and hypertension. However, little is known about th e association between insulin sensitivity and autonomic regulation or about the effect of acute hyperinsulinemia on cardiac sympathovagal balance. The aim of this study was to investigate heart rate variability (HRV) during t he euglycemic-hyperinsulinemic clamp in nondiabetic offspring of patients w ith type 2 diabetes. We studied 35 nondiabetic offspring of patients with t ype 2 diabetes and 19 control subjects. Probands were chosen from a 10-year follow-up study of patients with well-characterized type 2 diabetes accord ing to their fasting C-peptide level (selected from both ends of the distri bution) and from control subjects to form three groups: 1) a group includin g subjects who were offspring of type 2 diabetic patients with low C-peptid e levels (deficient insulin secretion group [IS group], n = 17), 2) a group including subjects who were offspring of type 2 diabetic patients with hig h C-peptide levels (insulin-resistant group [IR group], n = 18), and 3) a c ontrol group without a history of type 2 diabetes in first-degree relatives (n = 19). HRV was assessed at baseline and at the steady state during the euglycemic-hyperinsulinemic clamp. Rates of whole-body glucose uptake (M va lue) were lower in the IR group than in the IS group and the control group (41 +/- 3 vs. 54 +/- 2 vs. 60 +/- 4 mmol kg(-1) min(-1), P < 0.01 and P < 0 .01, respectively). In all groups, heart rate increased significantly durin g hyperinsulinemia. In the IR group, insulin infusion increased total power of HRV [from 7.70 +/- 0.15 to 8.05 +/- 0.15 ln(ms(2)), P < 0.01] and the l ow frequency-to-high frequency ratio (from 0.62 +/- 0.14 to 1.14 +/- 0.18, P < 0.01) and decreased power of the high frequency spectral component (fro m 5.73 < 0.17 to 5.43 +/- 0.16 ln(ms(2)), P < 0.05), whereas in other group s, changes in HRV were not significant. We conclude that the HRV response t o acute hyperinsulinemia in the offspring of type 2 diabetic probands was l ikely to be modulated by the type 2 diabetic phenotype of the parent. In in sulin-resistant subjects, autonomic dysfunction may be an earlier defect th an hitherto acknowledged.