title: Insulin resistance induced by hydrocortisone is increased in patients with abdominal obesity.
abstract: 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.
authors.affiliation: Endocrinology and Nutrition Department, Hôpital Nord, Marseille, France. pdarmon@ap-hm.fr
authors.forename: Patrice
authors.initials: P
authors.lastname: Darmon
authors.forename: Frédéric
authors.initials: F
authors.lastname: Dadoun
authors.forename: Sandrine
authors.initials: S
authors.lastname: Boullu-Ciocca
authors.forename: Michel
authors.initials: M
authors.lastname: Grino
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Alessi
authors.forename: Anne
authors.initials: A
authors.lastname: Dutour
mesh_terms: 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*
chemical_list: 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