Peiris A N, Mueller R A, Struve M F, Smith G A, Kissebah A H
J Clin Endocrinol Metab. 1987 Jan;64(1):162-9. doi: 10.1210/jcem-64-1-162.
The importance of androgenic activity in mediating the effects of obesity and body fat topography on splanchnic insulin metabolism and peripheral insulin sensitivity was studied in 19 nonhirsute premenopausal women with a wide range of ideal body weight [percent ideal body weight (% IBW), 78-202%] and body fat distribution pattern [waist to hip girth ratio (WHR), 0.67-0.91]. Turnover kinetics of peripheral plasma C-peptide and insulin were measured, and estimates of pancreatic insulin production (PIP) and the hepatic extraction fraction (HEF) were calculated. The peripheral insulin sensitivity index (M/I) was determined during an euglycemic insulin clamp study. Androgenic activity was assessed by estimating the plasma level of sex hormone-binding globulin (SHBG) and percentage of free testosterone (% FT). After iv glucose stimulation, PIP ranged from 40-254 mU/min X m2 and correlated highly with % IBW (r = 0.78; P less than 0.01). Insulin HEF ranged from 5-69% of the pancreatic production and was inversely proportional to WHR (r = -0.60; P less than 0.01). Increasing WHR also correlated with the diminution in M/I (r = -0.47; P less than 0.05), which, in turn, correlated with the decline in the HEF of insulin (r = 0.60; P less than 0.01). Since PIP, HEF, and M/I correlated with SHBG and % FT, and since the degree of androgenic activity correlated with % IBW and WHR, partial regression analysis was performed. After adjusting for the effects of SHBG and % FT, the relationship between % IBW and PIP remained unaltered, whereas the correlation between WHR and HEF or M/I and their relationship to each other were either markedly reduced or became insignificant. Thus, in premenopausal women, the increase in pancreatic insulin production with increasing weight is independent of the degree of androgenic activity. On the other hand, the decline in hepatic insulin extraction and diminution in peripheral insulin sensitivity with upper body fat localization are in part mediated by increased androgenic activity. This association may account for the pronounced hyperinsulinemia and insulin resistance characteristic of this form of obesity.
在19名非多毛的绝经前女性中，研究了雄激素活性在介导肥胖及体脂分布对内脏胰岛素代谢和外周胰岛素敏感性影响方面的重要性。这些女性的理想体重范围较广[理想体重百分比（%IBW），78 - 202%]，体脂分布模式[腰臀围比（WHR），0.67 - 0.91]。测量外周血浆C肽和胰岛素的转换动力学，并计算胰腺胰岛素生成（PIP）和肝脏提取分数（HEF）的估计值。在正常血糖胰岛素钳夹研究期间测定外周胰岛素敏感性指数（M/I）。通过估计性激素结合球蛋白（SHBG）的血浆水平和游离睾酮百分比（%FT）来评估雄激素活性。静脉注射葡萄糖刺激后，PIP范围为40 - 254 mU/min×m²，且与%IBW高度相关（r = 0.78；P < 0.01）。胰岛素HEF范围为胰腺生成量的5 - 69%，且与WHR成反比（r = -0.60；P < 0.01）。WHR增加也与M/I降低相关（r = -0.47；P < 0.05），而M/I又与胰岛素HEF下降相关（r = 0.60；P < 0.01）。由于PIP、HEF和M/I与SHBG和%FT相关，且雄激素活性程度与%IBW和WHR相关，因此进行了偏回归分析。在调整SHBG和%FT的影响后，%IBW与PIP之间的关系保持不变，而WHR与HEF之间或M/I与它们彼此之间的相关性要么显著降低，要么变得不显著。因此，在绝经前女性中，随着体重增加胰腺胰岛素生成增加与雄激素活性程度无关。另一方面，上半身脂肪堆积导致的肝脏胰岛素提取减少和外周胰岛素敏感性降低部分是由雄激素活性增加介导的。这种关联可能解释了这种肥胖形式所特有的明显高胰岛素血症和胰岛素抵抗。
