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利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这是一项由研究人员发起的开放标签研究，旨在调查补充睾酮对12名患有腹型肥胖和空腹胰岛素水平升高的老年性腺功能低下(睾酮水平和300 ng/dL)男性的睾酮水平提高到正常上限生理范围的影响。这项研究的主要目的是确定补充睾酮对该人群中央脂肪组织(腹部VAT、SAT和肝脏脂肪)和外周骨骼肌脂肪(MRI和MR波谱显示的肌内脂肪和肌间脂肪)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置(RD)、脂联素、载脂蛋白B水平和基础代谢率(REE，R/Q)的影响，以及与DEXA骨骼肌质量变化有关的情况。受试者将被分配到每天早上接受10克的透皮睾酮(安卓凝胶)，持续20周。 如果我们的假设得到证实，即雄激素疗法在性腺功能减退的老年肥胖男性中产生的睾酮水平处于较高的正常生理范围内，显著减少脂肪组织并改善胰岛素敏感性，研究结果将确定改善胰岛素敏感性的主要部位是中枢(肝脏或腹内脂肪)还是外周(肌细胞内)脂肪储存部位。无论如何，通过减少脂肪储备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，以降低糖尿病并发症和加速动脉粥样硬化引起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.