Twenty obese volunteers were investigated before and after
weight loss. Patients underwent hyperinsulinemic-euglycemic clamps with simultaneous adipose microdialysis and oral
cortisone acetate administration. Changes in
glucocorticoid secretion and metabolism were assessed using 24-h urine collections.
RESULTS: Before
weight loss, fat mass correlated with
glucocorticoid secretion rate (total fat, r = 0.46, P < 0.05; trunk fat, r = 0.52, P < 0.05); however,
glucocorticoid secretion rate was inversely related to
insulin sensitivity (r = -0.51, P < 0.05).
Hyperinsulinemia failed to suppress adipose tissue interstitial fluid
glycerol release (180 +/- 50 micromol [basal] vs. 153 +/- 10 micromol [steady state], NS). After oral
cortisone (25 mg),
cortisol concentrations within adipose interstitial fluid increased (4.3 +/- 1.1 vs. 14.2 +/- 2.6 nmol/l, P < 0.01), but
glycerol concentrations did not change. After
weight loss,
insulin sensitivity increased. Consistent with
insulin sensitization, adipose tissue interstitial fluid
glycerol concentrations fell under hyperinsulinemic conditions (186 +/- 16 vs. 117 +/- 9 micromol, P < 0.05).
Glucocorticoid secretion decreased (11,751 +/- 1,520 vs. 7,464 +/- 937 microg/24 h, P < 0.05) as did 5alphaR activity (5alpha-
tetrahydrocortisol-to-
tetrahydrocortisol ratio 1.41 +/- 0.16 vs. 1.12 +/- 0.17, P < 0.005).
CONCLUSIONS: