Am. J. Respir. Crit. Care Med., Volume 163, Number 6, May 2001, 1314-1319

A Novel Pathophysiologic Phenomenon in Cachexic Patients with Chronic Obstructive Pulmonary Disease
The Relationship between the Circadian Rhythm of Circulating Leptin and the Very Low-Frequency Component of Heart Rate Variability

NORIAKI TAKABATAKE, HIDENORI NAKAMURA, OSAMU MINAMIHABA, MINORU INAGE, SUMITO INOUE, SHIGERU KAGAYA, MICHIYASU YAMAKI, and HITONOBU TOMOIKE

First Department of Internal Medicine, and Department of Laboratory Medicine, Yamagata University School of Medicine, Yamagata, Japan

Cachexic patients with chronic obstructive pulmonary disease (COPD) show abnormalities of the autonomic nervous system (ANS), neuroendocrine function, and energy expenditure. Leptin has been implicated in the regulation of ANS, neuroendocine function, and thermogenesis in humans. We assessed the physiologic significance of the circadian rhythm of circulating leptin using power spectrum analysis of heart rate variability (HRV) in nine cachexic male patients with COPD, eight noncachexic patients with COPD, and seven healthy control subjects. A diurnal pattern of 24-h leptin levels was present in both the control subjects (analysis of variance [ANOVA]; F = 7.80, p < 0.0001) and noncachexic COPD patients (F = 9.29, p < 0.0001), but was strikingly absent in the cachexic COPD patients (F = 2.09, p = NS). Analysis of HRV demonstrated that the diurnal rhythm of 24-h very low frequency (VLF; 0.003 to 0.04 Hz) showed significantly identical fluctuations with those of 24-h leptin levels, in all of the three groups (r = 0.388, p < 0.0001). Because VLF has been considered to reflect neuroendocrine and thermoregulatory influences, these data may suggest that the loss of circadian rhythm of circulating leptin has clinical importance in the pathophysiologic features in cachexic patients with COPD.

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