EFFECT OF FAT DISTRIBUTION ON THE PHARMACOKINETICS OF CORTISOL IN OBESITY

Objective: Patients with predominantly upper body obesity are at great er risk for developing diabetes mellitus, hyperlipidemia, hypertension , and cardiovascular disease. Little is known about the mechanisms inv olved in the regulation of regional body distribution, It has been acc epted that the accumulation of fat into adipose tissue depends on regi onal metabolic regulation of adipocytes and that glucocorticoids play a role in this mechanism. The aim of the present study is to investiga te how the pharmacokinetics of cortisol correlate to intraabdominal an d subcutaneous fat distribution in obese patients. Methods: A group of 24 obese patients (13 males and 11 females) were submitted to a CT sc an for intraabdominal and subcutaneous fat area evaluation. A 30-min c ortisol infusion (0.25 mg/kg) was administered and plasma cortisol was measured over 6 hours. Results: Patients with larger intraabdominal f at areas were found to have a higher cortisol clearance than those wit h lower intraabdominal fat areas. Cortisol clearance (both, absolute a nd body-weight corrected) showed a statistically significant correlati on with intraabdominal fat area, either expressed by waist-hip ratio o r obtained by computerized tomography. Conclusions: These findings ind icate a more effective clearance capability for cortisol in patients w ith central obesity resulting in lowered cortisol plasma levels despit e an increased cortisol secretion observed in this patient group.