Insulin resistance induced by hydrocortisone is increased in patients with abdominal obesity.
Glucocorticoids hypersensitivity may be involved in the development of abdominal obesity and insulin resistance. Eight normal weight and eight obese women received on two occasions a 3-h intravenous infusion of saline or hydrocortisone (HC) (1.5 microg x kg(-1) x min(-1)). Plasma cortisol, insulin, and glucose levels were measured every 30 min from time(-30) (min) (time(-30)) to time(240). Free fatty acids, adiponectin, and plasminogen activator inhibitor-1 (PAI-1) levels were measured at time(-30), time(180), and time(240). At time(240), subjects underwent an insulin tolerance test to obtain an index of insulin sensitivity (K(ITT)). Mean(30-240) cortisol level was similar in control and obese women after saline (74 +/- 16 vs. 75 +/- 20 microg/l) and HC (235 +/- 17 vs. 245 +/- 47 microg/l). The effect of HC on mean(180-240) insulin, mean(180-240) insulin resistance obtained by homeostasis model assessment (HOMA-IR), and K(ITT) was significant in obese (11.4 +/- 2.0 vs. 8.2 +/- 1.3 mU/l, P < 0.05; 2.37 +/- 0.5 vs. 1.64 +/- 0.3, P < 0.05; 2.81 +/- 0.9 vs. 3.32 +/- 1.02%/min, P < 0.05) but not in control women (3.9 +/- 0.6 vs. 2.8 +/- 0.5 mU/l; 0.78 +/- 0.1 vs. 0.49 +/- 0.1; 4.36 +/- 1.1 vs. 4.37 +/- 1.2%/min). In the whole population, the quantity of visceral fat, estimated by computerized tomography scan, was correlated with the increment of plasma insulin and HOMA-IR during HC infusion [Delta mean(30-240) insulin (r = 0.61, P < 0.05), Delta mean(30-240) HOMA-IR (r = 0.66, P < 0.01)]. The increase of PAI-1 between time(180) and time(240) after HC was higher in obese women (+25%) than in controls (+12%) (P < 0.05), whereas no differential effect between groups was observed for free fatty acids or adiponectin. A moderate hypercortisolism, equivalent to that induced by a mild stress, has more pronounced consequences on insulin sensitivity in abdominally obese women than in controls. These deleterious effects are correlated with the amount of visceral fat.
Darmon
Patrice
P
Endocrinology and Nutrition Department, Hôpital Nord, Marseille, France. pdarmon@ap-hm.fr
Dadoun
Frédéric
F
Boullu-Ciocca
Sandrine
S
Grino
Michel
M
Alessi
Marie-Christine
MC
Dutour
Anne
A
D050153:Abdominal Fat / Q000187:drug effects / Q000378:metabolism*; D052242:Adiponectin / Q000097:blood; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage* / Q000097:blood; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D012044:Regression Analysis; D012965:Sodium Chloride / Q000008:administration & dosage; D013315:Stress, Psychological / Q000378:metabolism*
D052242:Adiponectin; D000893:Anti-Inflammatory Agents; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D017395:Plasminogen Activator Inhibitor 1; D012965:Sodium Chloride; D006854:Hydrocortisone