Objective To investigate the concordance/discordance of IGF-1 and peak stimulated GH in identifying subjects with reduced GH secretion and to determine the physiological significance of any discordance in obese subjects. underwent GH stimulation testing and overnight frequent blood sampling. The association of IGF-1 and peak stimulated GH with parameters of endogenous YH249 GH secretion was assessed. Results 60 of obese subjects had normal IGF-1 and peak stimulated GH while 8.4% of obese subjects had reduced IGF-1 and GH secretion. Discordance rate for IGF-1 and peak GH was 31.6%. Subjects with both low IGF-1 and low peak GH had the highest cIMT while subjects with both normal IGF-1 and peak GH had the lowest cIMT. YH249 Subjects with reduction in either IGF-1 or peak GH had intermediate cIMT (P=0.02). IGF-1 and peak stimulated GH were associated with maximum and mean overnight serum GH and GH AUC as well as maximum peak YH249 mass and median pulse mass. Peak stimulated GH but not IGF-1 was also associated with nadir overnight serum GH concentration and basal GH secretion. Conclusion Peak stimulated GH and IGF-1 demonstrate significant discordance in identification of subjects with reduced GH secretion in obesity. Subjects with reduction of either IGF-1 or peak GH had higher cIMT compared to subjects with both normal IGF-1 and peak GH. Subjects with reductions in both IGF-1 and peak GH had the highest cIMT. Peak GH compared to IGF-1 has broader associations with various Rabbit Polyclonal to DMGDH. parameters of endogenous GH secretion which support its utility in identifying YH249 those with reduced GH secretion. Keywords: GH IGF-1 GH stimulation test GHRH-Arginine deconvolution analyses AutoDecon frequent sampling carotid intima-media thickness Introduction Endogenous [1-3] and stimulated GH secretion [4 5 are reduced in obesity. Unlike the unequivocal effects of obesity to significantly lower GH however the effects of obesity on IGF-1 have been more controversial. While some studies have demonstrated reduced total IGF-1 levels in obesity [6 YH249 7 other studies have demonstrated normal total IGF-1 in obesity [8 9 This discrepancy as to the effects of obesity on total IGF-1 may be secondary to the changes in IGF binding proteins bioactive IGF-1 IGF-II and/or the hyperinsulinemia associated with obesity among other possibilities. Nonetheless the reduced GH secretion in obesity is associated with pathophysiological sequelae including dyslipidemia sub-clinical inflammation and increased carotid intima-media thickness (cIMT) [10-12]. Furthermore we recently demonstrated normalization of GH/IGF-1 using a hypothalamic GH releasing hormone analog tesamorelin in obese subjects with reduced GH secretion results in improvement in these cardiovascular disease risk markers including cIMT  suggesting a true physiologic role of the GH-IGF-1 axis in mediating some of the co-morbidities associated with YH249 obesity. We hypothesize that reductions in IGF-1 and peak stimulated GH in obesity may represent different aspects of physiological GH secretion. To better understand the relationship between the potential reduction of IGF-1 in obesity and the reduced GH in obesity we evaluated the concordance and discordance rate of IGF-1 and peak stimulated GH utilizing a standard stimulation testing paradigm with GH releasing hormone (GHRH) and arginine in the same patients. In addition we assessed the physiological significance of the reductions in IGF-1 and peak stimulated GH by measuring cIMT as a measure of cardiovascular disease risk. Furthermore we assessed the relationship of both IGF-1 and peak stimulated GH to parameters of endogenous GH secretion in obesity. While previous studies have assessed the relationship between IGF-1 and measures of endogenous GH secretion in otherwise healthy older men  and in adults with and without acromegaly  this is the first study to our knowledge to simultaneously assess in the same patients the relationships between both IGF-1 and peak stimulated GH to endogenous GH secretion parameters in obesity. Materials and Methods Study subjects New data and extended analyses from two previously completed clinical studies are reported in this manuscript. In the first study a total of 138 normal weight and obese men and women age 18-55y were recruited at the Massachusetts General Hospital between November 2007 and March 2009. All 138 subjects underwent GHRH-arginine stimulation test.