Increases in leptin levels, sympathetic drive, and weight gain in obstructive sleep apnea

Patients with obstructive sleep apnea (OSA) are frequently obese and are predisposed to weight gain. They also have heightened sympathetic drive. We reasoned that noradrenergic activation of beta(3)-receptors on adipocytes would inhibit leptin production, predisposing to obesity in sleep apnea. We therefore tested the hypothesis that obesity and predisposition to weight gain in OSA are associated with low levels of plasma leptin. We prospectively studied 32 male patients (43 +/- 2 yr) with OSA who were newly diagnosed and never treated and who were free of any other diseases. Control measurements were obtained from 32 similarly obese closely matched male subjects (38 +/- 2 yr). Leptin levels were 13.7 +/- 1.3 and 9.2 +/- 1.2 ng/ml in patients with OSA and controls, respectively (P = 0.02). Weight gain over the year before diagnosis was 5.2 +/- 1.7 and 0.5 +/- 0.9 kg in sleep apnea patients and similarly obese control subjects, respectively (P = 0.04). Muscle sympathetic activity was 46 +/- 4 and 30 +/- 4 bursts/min in patients with OSA (n = 16) and control subjects (n = 18), respectively (P = 0.01). Plasma leptin levels are elevated in newly diagnosed otherwise healthy patients with untreated sleep apnea beyond the levels seen in similarly obese control subjects without sleep apnea. Higher leptin levels in OSA, independent of body fat content, suggest that OSA is associated with resistance to the weight-reducing effects of leptin.