title: Gender differences in non-glycemic responses to improved insulin sensitivity by pioglitazone treatment in patients with type 2 diabetes.
abstract: Excess cortisol and GH induce insulin resistance, a central feature of type 2 diabetes (T2D). To study whether the insulin sensitizer pioglitazone affects basal cortisol levels and the GH-IGF-I axis in patients with T2D. Forty-eight patients with T2D (men/women = 28:20, age 61 ± 1 years, BMI 31 ± 0.6 kg/m(2)) were treated for 26 weeks with pioglitazone 30-45 mg daily in addition to their preexisting therapy. Insulin, proinsulin, HbA(1c), IGF-I, IGFBP-1, and basal cortisol were analyzed before and after treatment. Pioglitazone decreased proinsulin/insulin ratio and HbA(1c) decreased (HbA(1c) from 7.8 ± 0.2 to 6.6 ± 0.2% in men and from 7.6 ± 0.2 to 6.1 ± 0.2% in women, p < 0.001 in both). There was a redistribution of fat but no change in waist circumference. IGF-I and adiponectin increased (p ≤ 0.001) in both genders. IGFBP-1 increased but significantly only for the whole group (p = 0.033). Triglycerides decreased significantly in women only (p = 0.015). Before treatment, women had lower basal cortisol (p = 0.045). Basal cortisol increased in women (from 390 ± 26 to 484 ± 32 nmol/L, p = 0.020) but not in men and did not differ between genders at week 26. ΔIGFBP-1 correlated with Δcortisol (r = 0.458; p = 0.049) and Δadiponectin (r = 0.600; p = 0.005) in women only. In addition to the known effect of improving insulin sensitivity, pioglitazone increased IGF-I regardless of gender and in women also increased basal cortisol. Increased IGF-I may contribute to improved insulin sensitivity after treatment. There seems to be gender differences in treatment responses to pioglitazone on lipid metabolism and basal cortisol, perhaps correcting different mechanisms of insulin resistance between genders.
authors: Department of Molecular Medicine and Surgery, Karolinska Institutet, 17176, Stockholm, Sweden, lisa.arnetz@ki.se.
authors: Lisa
authors: L
authors: Arnetz
authors: Mozhgan
authors: M
authors: Dorkhan
authors: Michael
authors: M
authors: Alvarsson
authors: Kerstin
authors: K
authors: Brismar
authors: Neda Rajamand
authors: NR
authors: Ekberg
mesh_terms: D052242:Adiponectin / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance / Q000502:physiology*; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D012737:Sex Factors; D018709:Statistics, Nonparametric; D045162:Thiazolidinediones / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
chemical_list: D052242:Adiponectin; D006442:Glycated Hemoglobin; D006854:Hydrocortisone; D007004:Hypoglycemic Agents; D018970:Insulin-Like Growth Factor Binding Protein 1; D007334:Insulin-Like Growth Factor I; D000077205:Pioglitazone; D045162:Thiazolidinediones; D014280:Triglycerides; C499918:ADIPOQ protein, human; C032231:IGFBP1 protein, human