title: Improved Insulin Sensitivity during Pioglitazone Treatment Is Associated with Changes in IGF-I and Cortisol Secretion in Type 2 Diabetes and Impaired Glucose Tolerance.
abstract: Background. Hypercortisolism and type 2 diabetes (T2D) share clinical characteristics. We examined pioglitazone's effects on the GH-IGF-I and HPA axes in men with varying glucose intolerance. Methods. 10 men with T2D and 10 with IGT received pioglitazone 30-45 mg for 12 weeks. OGTT with microdialysis in subcutaneous adipose tissue and 1 μg ACTH-stimulation test were performed before and after. Glucose, insulin, IGF-I, IGFBP1, and interstitial measurements were analyzed during the OGTT. Insulin sensitivity was estimated using HOMA-IR. Results. HOMA-IR improved in both groups. IGF-I was initially lower in T2D subjects (P = 0.004) and increased during treatment (-1.4 ± 0.5 to -0.5 ± 0.4 SD; P = 0.007); no change was seen in IGT (0.4 ± 39 SD before and during treatment). Fasting glycerol decreased in T2D (P = 0.038), indicating reduced lipolysis. Fasting cortisol decreased in T2D (400 ± 30 to 312 ± 25 nmol/L; P = 0.041) but increased in IGT (402 ± 21 to 461 ± 35 nmol/L; P = 0.044). Peak cortisol was lower in T2D during treatment (599 ± 32 to 511 ± 43, versus 643 ± 0.3 to 713 ± 37 nmol/L in IGT; P = 0.007). Conclusions. Pioglitazone improved adipose tissue and liver insulin sensitivity in both groups. This may explain increased IGF-I in T2D. Pioglitazone affected cortisol levels in both groups but differently, suggesting different mechanisms for improving insulin sensitivity between T2D and IGT.
authors: Department of Molecular Medicine and Surgery, D2:04, Karolinska Institutet and Karolinska University Hospital, 17176 Stockholm, Sweden.
authors: Lisa
authors: L
authors: Arnetz
authors: Neda
authors: N
authors: Rajamand Ekberg
authors: Charlotte
authors: C
authors: Höybye
authors: Kerstin
authors: K
authors: Brismar
authors: Michael
authors: M
authors: Alvarsson
references: J Clin Invest. 1989 Jul;84(1):205-13
references: 2661589
references: Clin Endocrinol (Oxf). 2007 Apr;66(4):459-65
references: 17371460
references: Acta Endocrinol (Copenh). 1991 Jun;124(6):620-9
references: 2068892
references: N Engl J Med. 2004 Sep 9;351(11):1106-18
references: 15356308
references: Int J Obes Relat Metab Disord. 1996 Apr;20(4):291-302
references: 8680455
references: Clin Endocrinol Metab. 1984 Mar;13(1):113-43
references: 6202444
references: J Clin Endocrinol Metab. 1999 Mar;84(3):838-43
references: 10084558
references: Diabet Med. 1999 May;16(5):373-83
references: 10342336
references: Diabetes Care. 2005 Jan;28(1):120-5
references: 15616244
references: Acta Endocrinol (Copenh). 1984 Dec;107(4):563-70
references: 6083690
references: Clin Chim Acta. 2005 Sep;359(1-2):53-64
references: 15939412
references: Am J Physiol. 1988 Nov;255(5 Pt 1):E737-42
references: 3189543
references: J Clin Endocrinol Metab. 1995 Sep;80(9):2646-52
references: 7545695
references: Diabetes. 1996 Dec;45(12):1661-9
references: 8922349
references: Diabetes Care. 2004 Jul;27(7):1660-7
references: 15220243
references: Monogr Endocrinol. 1979;12:535-46
references: 386091
references: Clin Chem. 2006 Apr;52(4):746-9
references: 16469860
references: Diabetes Metab Rev. 1996 Oct;12(3):195-215
references: 8959385
references: Diabetes. 1999 Jan;48(1):10-4
references: 9892216
references: Eur J Endocrinol. 2004 Aug;151(2):173-8
references: 15296471
references: Eur J Endocrinol. 1999 Jan;140(1):51-5
references: 10037252
references: Diabetes. 1999 Aug;48(8):1572-8
references: 10426375
references: J Clin Endocrinol Metab. 1999 Oct;84(10):3648-55
references: 10523009
references: Growth Regul. 1993 Mar;3(1):11-3
references: 7683515
references: Clin Nutr. 2009 Dec;28(6):597-603
references: 19773097
references: Evid Rep Technol Assess (Summ). 2005 Aug;(128):1-11
references: 16194123
references: Biochem Biophys Res Commun. 1986 Dec 30;141(3):1157-61
references: 2434081
references: Metabolism. 1992 Jan;41(1):22-7
references: 1538640
references: Metabolism. 1990 Mar;39(3):251-8
references: 2407926
references: Diabetes Res Clin Pract. 1999 Apr;44(1):21-6
references: 10414936
references: Diabetes Obes Metab. 2005 Sep;7(5):525-35
references: 16050945
references: Acta Physiol Scand. 1986 Aug;127(4):547-51
references: 3092579
references: Diabetes. 2003 Feb;52(2):283-90
references: 12540598
references: J Clin Endocrinol Metab. 1999 Nov;84(11):4172-7
references: 10566668
references: Diabetes Care. 2006 Aug;29(8):1909-14
references: 16873801