Effects of Treatment With the Antioxidant α-Lipoic Acid on Cardiac Autonomic Neuropathy in NIDDM Patients: A 4-month randomized controlled multicenter trial (DEKAN Study)

Dan Ziegler; Helmut Schatz; Frank Conrad; F Arnold Gries; Heinz Ulrich; The DEKAN Study Group; Gerhard Reichel

doi:10.2337/diacare.20.3.369

Original Articles

Effects of Treatment With the Antioxidant α-Lipoic Acid on Cardiac Autonomic Neuropathy in NIDDM Patients: A 4-month randomized controlled multicenter trial (DEKAN Study)

Dan Ziegler, MD,
Helmut Schatz, MD,
Frank Conrad, PHD,
F Arnold Gries, MD,
Heinz Ulrich, MD,
The DEKAN Study Group and
Gerhard Reichel, MD

Diabetes-Forschungsinstitut an der Heinrich-Heine-Universität, Ruhr-Universität Bochum Düsseldorf
ASTA Medica AG, Ruhr-Universität Bochum Frankfurt am Main
Paracelsus-Klinik Zwickau
Medizinische Universitätsklinik Bcrgmannsheil, Ruhr-Universität Bochum Germany

Address correspondence and reprint requests to Dan Ziegler, MD, Diabetes-Forschungsinstitut an der Heinrich-Heine-Universität, Auf'm Hennekamp 65, 40225 Düsseldorf, Germany.

Diabetes Care 1997 Mar; 20(3): 369-373. https://doi.org/10.2337/diacare.20.3.369

Abstract

OBJECTIVE To evaluate the efficacy and safety of oral treatment with the antioxidant alpha-lipoic acid (ALA) in NIDDM patients with cardiac autonomic neuropathy (CAN), assessed by heart rate variability (HRV).

RESEARCH DESIGN AND METHODS In a randomized, double-blind placebo-controlled multicenter trial (Deutsche Kardiale Autonome Neuropathie [DEKAN] Study), NIDDM patients with reduced HRV were randomly assigned to treatment with daily oral dose of 800 mg ALA (n = 39) or placebo (n = 34) for 4 months. Parameters of HRV at rest included the coefficient of variation (CV), root mean square successive difference (RMSSD), and spectral power in the low-frequency (LF; 0.05–0.15 Hz) and high-frequency (HF; 0.15–0.5 Hz) bands. In addition, cardiovascular autonomic symptoms were assessed.

RESULTS Seventeen patients dropped out of the study (ALA n = 10; placebo n = 7). Mean blood pressure and HbA₁ levels did not differ between the groups at baseline and during the study, but heart rate at baseline was higher in the group treated with ALA (P < 0.05). RMSSD increased from baseline to 4 months by 1.5 ms (−37.6 to 77.1) [median (minimum-maximum)] in the group given ALA and decreased by −0.1 ms (−19.2 to 32.8) in the placebo group (P < 0.05 for ALA vs. placebo). Power spectrum in the LF band increased by 0.06 bpm² (−0.09 to 0.62) in ALA, whereas it declined by −0.01 bpm² (−0.48 to 1.86) in placebo (P < 0.05 for ALA vs. placebo). Furthermore, there was a trend toward a favorable effect of ALA versus placebo for the CV and HF band power spectrum (P = 0.097 and P = 0.094 for ALA vs. placebo). The changes in cardiovascular autonomic symptoms did not differ significantly between the groups during the period studied. No differences between the groups were noted regarding the rates of adverse events.

CONCLUSIONS These findings suggest that treatment with ALA using a well-tolerated oral dose of 800 mg/day for 4 months may slightly improve CAN in NIDDM patients.