INVESTIGATOR INITIATED STUDY OF THE EFFECTS OF ANDROGEN THERAPY ON CARBOHYDRA

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 这是一项研究者发起的开放标签研究，旨在研究补充睾酮对12名患有腹部肥胖和空腹胰岛素水平升高的老年性腺功能减退（睾酮水平<300 ng/dL）男性的睾酮水平升高至正常生理范围上限的影响。 本研究的主要目的是确定在该人群中补充睾酮对中心脂肪组织（腹部VAT、SAT和肝脏脂肪）和外周骨骼肌脂肪（通过MRI和MR光谱法测定肌细胞内脂质和肌细胞间脂肪）的影响。 第二个目的是确定补充睾酮对肝脏葡萄糖输出和外周葡萄糖处理（Rd）、脂联素、载脂蛋白B水平和基础代谢率（REE，R/Q）的影响，这些与DEXA测定的骨骼肌质量变化有关。 受试者将被分配每天早晨接受10 g经皮睾酮（Androgel），持续20周。 如果我们的假设，即安道生治疗，以产生睾酮水平在正常生理范围内的老年人，肥胖男性性腺功能减退症显着减少脂肪组织和改善胰岛素敏感性得到证实，该研究的结果将确定是否改善胰岛素敏感性的主要网站是中央（肝脏或腹内脂肪）与外周（肌细胞内）脂肪储存网站。 无论如何，通过减少脂肪储存来改善胰岛素敏感性将对代谢综合征的治疗具有重要意义，以降低由于糖尿病并发症和加速动脉粥样硬化导致的严重发病率和死亡的风险。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is an investigator-initiated open-label, study to investigate the effects of supplemental testosterone to increase testosterone levels to the upper normal physiological range in 12 older hypogonadal (testosterone levels <300 ng/dL) men with abdominal obesity and elevated fasting insulin levels. Primary purpose of this study is to determine the effects of supplemental testosterone in this population on central adipose tissue (abdominal VAT, SAT, and hepatic fat) and peripheral skeletal muscle fat (intramyocellular lipids and intermyocellular fat by MRI and MR spectroscopy). The secondary purpose is to determine the effects of supplemental testosterone on hepatic glucose output and peripheral glucose disposal (Rd), adiponectin, apoprotein B levels, and basal metabolic rate REE, R/Q) as related to changes in skeletal muscle mass by DEXA. Subjects will be assigned to receive 10 g of transdermal testosterone (Androgel) every morning for 20 weeks. If our hypothesis that andogen therapy to produce testosterone levels in the upper normal physiologic range in older, obese men with hypogonadism significantly reduces adipose tissue and improve insulin sensitivity is substantiated, the results of the study will identify whether the primary site for improving insulin sensitivity is central (liver or intrabdominal fat) versus peripheral (intramyocellilar) adipose storages sites. Regardless, that insulin sensitivity is improved by decreasing fat stores would have important implications for the treatment of the Metabolic Syndrome to reduce risks for serious morbidity and death due to complications of diabetes and accelerated atherosclerosis.