Diamond M P, Grainger D, Diamond M C, Sherwin R S, Defronzo R A
Department Obstetrics and Gynecology, Hutzel Hospital/Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
J Clin Endocrinol Metab. 1998 Dec;83(12):4420-5. doi: 10.1210/jcem.83.12.5333.
The frequent coexistence of hyperandrogenism and insulin resistance is well established; however, whether a cause and effect relationship exists remains to be established. In this study we tested the hypothesis that short-term androgen administered to women would induce insulin resistance. To test this hypothesis, regularly menstruating, nonobese women were studied before and during methyltestosterone administration (5 mg tid for 10-12 days) by the hyperglycemic (n=8) and euglycemic, hyperinsulinemic (n=7) clamp techniques. Short-term methyltestosterone administration had no significant effects on the fasting levels of glucose, insulin, c-peptide, glucagon, or glucose turnover. During the hyperglycemic clamp studies, the mean glucose level during the final hour was 203+/-2 and 201+/-1 mg/dL in the methyltestosterone and control studies, respectively. The insulin response to this hyperglycemic challenge was slightly but not significantly greater during methyltestosterone treatment (first phase 59+/-8 vs. 50+/-8 microU/mL in controls; second phase 74+/-9 vs. 67+/-9 microU/mL in controls; total insulin response 133+/-16 vs. 117+/-15 microU/mL in controls). In spite of this, glucose uptake was reduced from the control study value of 10.96+/-1.11 to 7.3+/-0.70 mg/kg/min by methyltestosterone (P < 0.05). The ratio of glucose uptake per unit of insulin was also significantly reduced from a control study value of 14.3+/-1.4 to 9.4+/-1.3 mg/kg/min per microU/mL x 100 during methyltestosterone administration. In the euglycemic hyperinsulinemic clamp studies, insulin was infused at rates of 0.25 and 1.0 mU/kg/min to achieve insulin levels of approximately 25 and 68 microU/mL, respectively. During low-dose insulin infusion, rates of endogenous hepatic glucose production were equivalently suppressed from basal values of 2.37+/-0.29 and 2.40+/-0.27 mg/kg/min to 0.88+/-0.25 and 0.77+/-0.26 mg/kg/min in the methyltestesterone and control studies respectively. Whole body glucose uptake during low-dose insulin infusion was minimally affected. During the high-dose insulin infusion, endogenous hepatic glucose production was nearly totally suppressed in both groups. However, whole body glucose uptake was reduced from the control value of 6.11+/-0.49 mg/kg/min to 4.93+/-0.44 mg/kg/min during methyltestosterone administration (P < 0.05). Our data demonstrate that androgen excess leads to the development of insulin resistance during both hyperglycemic and euglycemic hyperinsulinemia. These findings provide direct evidence for a relationship between hyperandrogenemia and insulin resistance, and its associated risk factors for cardiovascular disease.
高雄激素血症与胰岛素抵抗常常并存，这一点已得到充分证实；然而，两者之间是否存在因果关系仍有待确定。在本研究中，我们检验了一个假设，即对女性进行短期雄激素给药会诱发胰岛素抵抗。为验证这一假设，我们通过高血糖钳夹技术（n = 8）和正常血糖、高胰岛素钳夹技术（n = 7），对月经规律、非肥胖女性在服用甲基睾酮（5 mg，每日三次，共10 - 12天）之前及期间进行了研究。短期服用甲基睾酮对空腹血糖、胰岛素、C肽、胰高血糖素或葡萄糖代谢率水平均无显著影响。在高血糖钳夹研究中，甲基睾酮组和对照组在最后一小时的平均血糖水平分别为203±2和201±1 mg/dL。甲基睾酮治疗期间，对这种高血糖刺激的胰岛素反应略有增加，但无显著差异（第一阶段：甲基睾酮组59±8 μU/mL，对照组50±8 μU/mL；第二阶段：甲基睾酮组74±9 μU/mL，对照组67±9 μU/mL；总胰岛素反应：甲基睾酮组133±16 μU/mL，对照组117±15 μU/mL）。尽管如此，甲基睾酮使葡萄糖摄取量从对照组的10.96±1.11降至7.3±0.70 mg/kg/min（P < 0.05）。每单位胰岛素的葡萄糖摄取率在甲基睾酮给药期间也从对照组的14.3±1.4显著降至9.4±1.3 mg/kg/min per μU/mL×100。在正常血糖高胰岛素钳夹研究中，分别以0.25和1.
