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.
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