Effects Of Androgen Deficiency on Glucose Homeostasis

最近，我们与约翰霍普金斯大学的合作者一起，一直在研究性腺功能减退对胰岛素抵抗和代谢综合征的影响。前列腺癌患者接受雄激素剥夺治疗作为治疗的一部分，不仅会出现胰岛素抵抗，而且超过50%的患者还会发展为代谢综合征。这显然会使他们面临中风和心脏病发作的风险，因此前列腺癌的治疗将增加他们的死亡率和发病率。这是一个新的和不断发展的感兴趣的领域，其他小组刚刚出现的数据证实了我们的发现。我们目前正在制定一项方案，对前列腺癌患者进行前瞻性研究(其中一些人将接受前列腺癌切除手术，一些人将接受雄激素剥夺治疗，另一些人将同时接受两者)，并对他们进行纵向跟踪。我们希望确定，1)胰岛素抵抗出现的时间和原因，以及在哪一组中，2)在一个亚群中进行治疗以减轻胰岛素抵抗(二甲双胍、吡格列酮、exendin-4或GLP-1)并跟踪结果，3)使用葡萄糖钳量化胰岛素抵抗的程度，以及，4)试图确定雄激素剥夺导致胰岛素抵抗的作用机制。如果雄激素治疗继续作为前列腺癌的一种治疗方法，将需要对雄激素缺乏患者采取适当的管理策略。

Recently, in conjunction with collaborators at Johns Hopkins, we have been studying the effects of hypogonadism on insulin resistance and the metabolic syndrome. Patients with prostate cancer who undergo androgen deprivation therapy as part of their treatment become not only insulin resistant but more than 50% also develop the metabolic syndrome. This clearly puts them at risk for strokes and heart attacks and therefore the treatment for the prostate cancer will increase their mortality and morbidity. This is a new and evolving field of interest and data is just now appearing from other groups confirming our findings. We are currently divising a protocol to carry out a prospective study of prostate cancer patients (some of whom will have cancer-removal surgery of the prostate, some of who will receive androgen deprivation therapy and some of whom will receive both) and follow them longitudinally. We wish to determine, 1) when and why insulin resistance manifests itself and in which group, 2) introduce therapy in a subpopulation to lessen insulin resistance ( metformin, pioglitazone, exendin-4, or GLP-1) and follow outcomes, 3) quantify the degree of insulin resistance using glucose clamps, and, 4) attempt to define the mechanism of action by which androgen deprivation leads to insulin resistance. If androgen therapy continues to be a treatment for prostate cancer, proper management strategies of androgen deprived patients will be required.