Diabetic cardiac autonomic neuropathy (CAN) is associated with a high risk of cardiovascular events. Previous studies have shown that strict glycemic control slows the deterioration of CAN as assessed by standard autonomic function tests but fails to show reversibility. The aim of this study was to evaluate the effect of glycemic control on early and advanced CAN in type I diabetic patients using power spectral analysis of heart rate variability (HRV). Ten patients with early and 13 patients with advanced CAN were enrolled in a program of intensified insulin treatment. Standard autonomic function tests and 24-hour time and frequency domain HRV parameters were obtained at baseline, 3, 6, and 12 months. Hemoglobin A1C decreased from 9.5 +/- 0.4% to 8.4 +/- 0.5% (p = 0.02) in the early CAN group, and from 9.3 +/- 0.4% to 8.2 +/- 0.5% (p = 0.006) in the advanced CAN group. In general, both time and frequency domain HRV indexes tended to improve in patients with early CAN but continued to deteriorate in patients with advanced CAN. The low- and high-frequency power increased in patients with early CAN (229 +/- 95 to 626 +/- 563 ms2 and 62 +/- 30 to 183 +/- 168 ms2, respectively). The high-frequency power significantly improved at 12 months over baseline (p = 0.04), indicating increased parasympathetic tone. By contrast, these parameters continued to deteriorate in patients with advanced CAN (65 +/- 32 to 46 +/- 8 ms2 and 193 +/- 75 to 144 +/- 33 ms2, respectively). Autonomic function tests showed no significant change in both groups. These data show that a reversible metabolic component of CAN exists in patients with early CAN. Power spectral analysis of HRV allows early identification of potential reversibility as early as 1 year after the institution of strict glycemic control.