%0 Journal Article
%T Improved Insulin Sensitivity during Pioglitazone Treatment Is Associated with Changes in IGF-I and Cortisol Secretion in Type 2 Diabetes and Impaired Glucose Tolerance
%A Lisa Arnetz
%A Neda Rajamand Ekberg
%A Charlotte H£¿ybye
%A Kerstin Brismar
%A Michael Alvarsson
%J ISRN Endocrinology
%D 2013
%R 10.1155/2013/148497
%X 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¨C45£¿mg for 12£¿weeks. OGTT with microdialysis in subcutaneous adipose tissue and 1£¿¦Ìg 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 ( ) and increased during treatment ( to SD; ); no change was seen in IGT ( SD before and during treatment). Fasting glycerol decreased in T2D ( ), indicating reduced lipolysis. Fasting cortisol decreased in T2D ( to £¿nmol/L; ) but increased in IGT ( to £¿nmol/L; ). Peak cortisol was lower in T2D during treatment ( to , versus to £¿nmol/L in IGT; ). 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. 1. Introduction Type 2 diabetes (T2D) is a significant public health issue due to its prevalence and complications. Obesity, particularly abdominal obesity, is a major risk factor for the disease. Central features of T2D include hyperglycemia, insulin resistance, and progressive ¦Â-cell failure. According to a theory developed by Bj£¿rntorp et al., there are also disturbances in the central hormone axes, with activity increased in the hypothalamus-pituitary-adrenal (HPA) axis and decreased in the growth hormone (GH) insulin-like growth factor I (IGF-I) and LH-testosterone axes [1]. As T2D develops via an insidious phase of impaired glucose tolerance (IGT) [2], it is of importance to understand the pathogenesis of both conditions in order to improve treatment options and prevent progression of IGT to T2D. Of the end products produced by the central hormone axes, IGF-I and cortisol have the greatest effects on insulin sensitivity. IGF-I is produced mainly in the liver [3] and has effects highly comparable to those of insulin [4]. Its production is dependent on GH, insulin, and nutritional status [5]. Cortisol has anti-insulin effects on glucose metabolism, increasing gluconeogenesis and decreasing glucose uptake [6]. However, chronic elevation of glucocorticoid levels as well as hyperinsulinemia result in the
%U http://www.hindawi.com/journals/isrn.endocrinology/2013/148497/