超重或肥胖的男性2型糖尿病患者性激素水平的研究

目的 观察超重或肥胖的男性2型糖尿病患者性激素水平及胰岛素抵抗、糖脂代谢的变化.方法 选择男性2型糖尿病患者112例,根据体重指数分为体重正常组(50例)和超重或肥胖组(62例).所有患者测定血糖、血脂、胰岛素及性激素水平,包括睾酮、性激素结合球蛋白(SHBG)、孕激素、催乳素、黄体生成素、卵泡刺激素、雌二醇、脱氢表雄酮,并计算得出游离睾酮、生物活性睾酮.比较两组性激素水平、糖脂代谢及胰岛素抵抗相关指标的差异.结果 与体重正常组相比,超重或肥胖组空腹血糖、HbA1c、尿酸、空腹胰岛素和餐后胰岛素水平显著升高(f=-4.58～-2.35,P均＜0.05);总睾酮、SHBG水平显著降低(t=2.17,2.06,P均＜0.05).Pearson相关性分析发现,体重指数、腰围与总睾酮(r =-0.40,-0.41,P均＜0.01)、SHBG(r =-0.33,-0.42,P均＜0.01)呈显著负相关.总胆固醇和甘油三酯与总睾酮(r =-0.28,-0.24,P均=0.01)、SHBG(r =-0.27,-0.37,P均≤0.01)呈负相关;空腹胰岛素、餐后胰岛素、稳态模型评估-胰岛素抵抗指数(HOMA-IR)与总睾酮(r=-0.30-0.21,P均=0.01)、SHBG水平(r=-0.29-0.20,P均≤0.05)呈负相关.结论 超重或肥胖的男性2型糖尿病患者常存在性腺功能减退症,并与胰岛素抵抗和脂代谢异常密切相关.     

血游离脂肪酸与不稳定心绞痛病人胰岛素抵抗的关系

目的探讨无糖尿病的不稳定心绞痛患者血浆游离脂肪酸(freefattyacids,FFA)与胰岛素抵抗(insulinresistance,IR)的关系。方法不稳定心绞痛组为经冠状动脉造影确诊不稳定型心绞痛的无糖尿病患者42例,对照组为经冠状动脉造影排除了冠心病患者30例,行75g葡萄糖口服耐量试验,分别测定空腹、餐后30min、120min血糖、胰岛素及FFA水平。结果伴IR患者在不稳定心绞痛组26例(26/42),对照组为12例(12/30),(P=0.066);在不稳定心绞痛组,伴IR患者空腹和餐后120min,FFA分别为(0.63±0.16)mmol/L和(0.16±0.07)mmol/L;高于无IR患者,空腹和餐后120min值为(0.48±0.21)mmol/L和(0.07±0.06)mmol/L(P<0.05);稳态模型评估胰岛素抵抗(homeostasismodelassay-insulinresistanceindex,HOMA-IR)增高(0.50±0.20与0.36±0.22,P<0.05),胰岛素敏感指数(insulinsensitivityindex,HOMA-ISI)降低(-1.96±0.20与-1.71±0.22,P<0.05);不稳定心绞痛组和对照组伴IR患者比较,FFA明显高于对照组,分别为[(0.63±0.16)mmol/L与(0.48±0.22)mmol/L,P<0.05,(0.16±0.07)mmol/L与(0.08±0.03)mmol/L,P<0.01]。相关分析显示HOMA-IR与体重指数呈正相关(r=0.51,P<0.01);餐后30minFFA与HOMA-IR呈正相关(r=0.44,P<0.05);餐后120minFFA分别与空腹胰岛素(r=0.55,P<0.05)、餐后120min血糖呈正相关(r=0.432,P<0.05);游离脂肪酸曲线下面积(FFAAUC)与HOMA-IR(r=0.492,P<0.05)、体重指数(r=0.94,P<0.0001)、腰围(r=0.41,P<0.05)、臀围(r=0.40,P<0.05)和餐后120min胰岛素(r=0.90,P<0.0001)呈正相关。多重逐步回归分析显示,HOMA-IR与体重指数、餐后120minFFA呈正相关。结论FFA与无糖尿病的不稳定心绞痛患者胰岛素抵抗存在密切关系,餐后120minFFA有可能作为评价这类患者胰岛素抵抗的间接辅助诊断指标。     

年龄依赖性胰岛素抵抗与睾酮水平的相关性

目的探讨健康男性年龄对胰岛素抵抗的影响和胰岛素抵抗与睾酮的关系。方法在北京、上海、西安和重庆四城市调查20～78岁健康男性1080例,同时测定空腹血糖、胰岛素、总睾酮、雌二醇、黄体生成激素(LH)、卵泡刺激激素(FSH)和性激素结合球蛋白(SHBG),计算稳态模型胰岛素抵抗指数(HOMA-IR)、游离睾酮(cFT)、睾酮分泌指数(TSI)和游离睾酮指数(FTI),将空腹血糖、胰岛素和HOMA-IR与其他检验结果进行相关分析。结果空腹血糖、胰岛素和HOMA-IR与年龄(r=0.1644、0.1536和0.1587;均为P<0.01)、LH(r=0.1909、0.1310和0.1920;均为P<0.01)和FSH(r=0.1 704、0.1543和0.1907;均为P<0.01)呈显著正相关,与总睾酮(r=-0.0825、-0.2187和-0.1619;P>0.05、P<0.01和P<0.01)、cFT(r=0.1238、-0.1 567和-0.1346;P<0.01、P<0.01和P<0.05)和TSI(r=-0.2143、-0.2098和-0.2488;均为P<0.01)呈显著负相关。结论健康男性随年龄增长伴有空腹血糖、胰岛素和HOMA-IR的逐渐升高,年龄依赖性雄激素水平降低对这种胰岛素抵抗的变化可能起着重要作用。     

雄激素及其受体与老年男性冠状动脉粥样硬化性心脏病的相关性研究

目的 观察老年男性冠状动脉粥样硬化性心脏病(冠心病)患者性激素及雄激素受体水平的变化及相关性. 方法 横断面调查老年男性539例,其中健康人(对照组)400例,年龄62～92岁,平均(71.4±5.2)岁;冠心病患者139例,年龄60～88岁,平均(73.6±6.4)岁.测定总睾酮、游离睾酮、脱氢表雄酮硫酸酯(DHEAS)、性激素结合球蛋白(SHBG)、雌二醇、黄体生成素(LH)、卵泡刺激素(FSH)水平,同时采用流式细胞术检测外周血雄激素受体(AR)水平. 结果 老年男性冠心病患者DHAES、总睾酮、SHBG、游离睾酮、AR荧光强度均低于对照组(均为P<0.01),而FSH、E2高于对照组(均为P<0.01).年龄与总睾酮、游离睾酮呈负相关(r分别为-0.28、-0.17,P<0.01和P<0.05);与E2、SHBG呈正相关(r分别为0.33、0.14,P<0.01和P<0.05).AR荧光强度与收缩压呈负相关(r=-0.12,P<0.01).Logistic回归分析显示,总睾酮(OR=1.065,95%CI:1.012～1.121,P<0.05)、SHBG(OR=0.994,95%CI:0.990～0.998,P<0.01)和AR(OR=0.971,95%CI:0.956～0.986,P<0.01)与老年男性冠心病相关. 结论 老年男性冠心病患者存在低水平的DHEAS、总睾酮、SHBG、游离睾酮、AR,同时存在高水平的FSH、E2;低水平总睾酮、SHBG和AR可能是老年男性冠心病独立的危险因素.     

血清性激素结合球蛋白与男性2型糖尿病患者下肢血管病变的关系

目的探讨男性2型糖尿病(T2DM)患者血清性激素结合球蛋白(SHBG)水平与下肢血管病变的关系。方法 170例T2DM患者根据下肢血管超声结果分为T2DM患者无下肢血管病变组(A组)86例和T2DM患者下肢血管病变组(B组)84例,并选取80例同期来院体检的男性健康者为对照组(NC组)。采用电化学发光法检测各组空腹血清SHBG,检测空腹血糖(FPG)、血脂、糖化血红蛋白(Hb A1c)、餐后2 h血糖(2 h PG)、胰岛素,分析上述指标与T2DM患者下肢血管病变的关系。结果 3组血清SHBG水平依次为:NC组[(59.49±12.98)μg/L]>A组[(45.69±14.01)μg/L]>B组[(31.14±10.03)μg/L(P<0.01,P<0.05)];相关分析显示,血清SHBG与病程、体重指数(BMI)、腰臀比、总胆固醇(TC)、甘油三酯(TG)、Hb A1c、胰岛素抵抗指数(HOMA-IR)负相关(r值分别为-0.071、-0.439、-0.310、-0.202、-0.213、-0.142、-0.395,P<0.05或P<0.01),与LDL-C、2 h PG正相关(r=0.248,0.441;P<0.05)。回归分析显示,血清SHBG水平是男性T2DM患者下肢血管病变的主要影响因素之一(P<0.05)。结论低SHBG水平与男性T2DM患者下肢血管病变的发生密切相关。     

肝癌患者胰岛素抵抗与糖代谢障碍的关系探讨

目的探讨原发性肝癌患者胰岛素抵抗和胰岛素分泌指数的变化。方法测定45例健康体检者和50例原发性肝癌患者空腹血糖、空腹胰岛素、空腹乳酸和服糖后血糖水平,并采用稳态模式评估法计算胰岛素抵抗指数和胰岛素分泌指数。结果原发性肝癌患者空腹乳酸(6.4±0.5mmol/L)、空腹胰岛素(16.2±6.4hUI/ml)、胰岛素抵抗指数(3.5±1.1)及服糖后血糖含量(8.7±2.4mmol/L)均明显高于正常对照组(2.8±0.3mmol/L、11.3±4.3hUI/ml、2.0±0.9、4.9±1.8mmol/L,P0.01);肝癌患者胰岛素分泌指数(210±20)明显低于正常对照组(400±34)(P0.01),空腹血糖(4.9±1.7mmol/L)与正常对照组(4.1±0.3mmol/L)比较无显著性差异(P0.05)。结论原发性肝癌患者存在糖代谢紊乱,并与胰岛素抵抗有关。     

血清雄激素水平与男性动脉粥样硬化的关系

目的研究男性冠心病患者血清雄激素水平及颈动脉内膜—中膜厚度的变化,以及血清雄激素对血清脂蛋白、血糖、胰岛素抵抗的影响,探讨血清雄激素水平与男性动脉粥样硬化的关系。方法选择经冠状动脉造影证实的男性冠心病病人91例(冠心病组),根据血管病变情况分为单支病变组(n=30)、两支病变组(n=33)和三支病变组(n=28),同时选择冠状动脉造影正常男性43例作为对照组。入选病例均测定血清总睾酮、游离睾酮、去氢表雄酮,血清总胆固醇、甘油三酯、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、脂蛋白a和空腹血糖、空腹胰岛素,以稳态模型评估胰岛素抵抗指数,超声测量颈动脉内膜—中膜厚度。结果冠心病组与对照组比较,血清总胆固醇、低密度脂蛋白、脂蛋白a、空腹胰岛素、空腹血糖、稳态模型评估胰岛素抵抗指数及颈动脉内膜—中膜厚度显著增高(P<0.05),血清高密度脂蛋白胆固醇、游离睾酮显著降低(P<0.001);游离睾酮冠心病各亚组与对照组比差异有显著性(P<0.001);颈动脉内膜—中膜厚度冠心病各亚组均高于对照组(P<0.001),单支病变组低于两支及三支病变组(P<0.01);空腹胰岛素及稳态模型评估胰岛素抵抗指数:冠心病各亚组均显著高于对照组(P<0.01),且三支病变组显著高于单支病变组。Pearson相关分析表明,内膜—中膜厚度与游离睾酮、高密度脂蛋白胆固醇呈显著负相关(r值均小于-0.5,P<0.001),与空腹胰岛素、稳态模型评估胰岛素抵抗指数、低密度脂蛋白胆固醇、脂蛋白a呈显著正相关(r值均大于0.5,P<0.001)。结论男性冠心病患者血清游离睾酮水平下降,游离睾酮通过影响血脂、血糖、胰岛素抵抗等因素参与男性动脉粥样硬化的形成。     

多囊卵巢综合征患者肥胖和高雄激素血症与胰岛素抵抗的相关性

收集多囊卵巢综合征(PCOS)患者101例,招募30名正常健康志愿者。根据血清雄激素水平及稳态模型评估的胰岛素抵抗指数(HOMA-IR)水平分层分析肥胖、高雄激素和胰岛素抵抗的关系。结果显示,101例PCOS患者中39.8％患者体重正常,24.5％超重,35.7％肥胖。将PCOS患者分为正常雄激素组(睾酮＜0.51 μg/L)和高雄激素组(睾酮≥0.51 μg/L),两组体重指数(BMI)、空腹血糖(FPG)、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)及HOMA-IR均无统计学差异。将PCOS患者分为非胰岛素抵抗组(HOMA-IR＜2.29)和胰岛素抵抗组(HOMA-IR≥2.29),两组血清睾酮水平无统计学差异,胰岛素抵抗组的BMI、FPG、TG、TC、LDL-C明显高于非胰岛素抵抗组(P＜0.05或P＜0.01),HDL-C明显低于非胰岛素抵抗组(P＜0.01)。HOMA-IR与BMI显著相关(P＜0.01),而与血清睾酮水平无显著相关性,提示PCOS患者体重增加与HOMA-IR的相关性独立于血清睾酮水平。     

高尿酸血症与老年糖调节受损患者代谢性指标的相关性

目的探讨高尿酸(UA)血症与老年糖调节受损(IGR)患者代谢性指标的相关性。方法选取120例老年IGR患者,按血尿酸浓度(高尿酸血症的诊断标准:男性UA420μmol/L,女性UA360μmol/L)分为高UA组(50例)和正常组(70例),测量2组患者的体重指数(BMI)、空腹血糖(FPG)、空腹胰岛素(FINS)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、糖化血红蛋白(Hb A1c)、甘油三酯(TG)、总胆固醇(TC)、血UA、胰岛素抵抗指数(HOMA-IR)、胰岛素敏感指数(ISI)并进行统计分析。结果高UA组的BMI〔(27.83±2.76)vs.(24.42±2.41)kg/m2,t=7.191,P0.01〕、TC〔(6.68±2.37)vs.(5.59±2.41)mmol/L,t=2.460,P0.05〕、TG〔(3.64±2.25)vs.(1.82±1.31)mmol/L,t=5.577,P0.01〕、HOMA-IR(3.11±1.24 vs.2.58±0.87,t=2.753,P0.01)、ISI(-4.09±2.53 vs.-2.52±1.86,t=3.919,P0.01)、UA〔(474.28±227.36)vs.(263.19±186.51)μmol/L,t=1.393,P0.05〕水平均高于正常组。高UA组的Hb A1c(5.90%±0.61%vs.6.16%±0.72%,t=5.576,P0.01)低于正常组。高UA组患者的UA与TG(r=0.289)、TC(r=0.317)、LDL(r=0.365)、HOMA-IR(r=0.416)水平正相关(P0.05),而与Hb A1c呈显著负相关(r=-0.298,P0.05)。结论 IGR老年患者的TG、TC、LDL、HOMA-IR浓度越高,Hb A1c越低,则血UA浓度越高。     

非酒精性脂肪性肝病患者血清视黄醛结合蛋白4的变化及临床意义

目的观察非酒精性脂肪性肝病(NAFLD)患者视黄醇结合蛋白4(RBP4)的变化及其临床意义。方法收集2016年7月至2018年6月上海市第八人民医院收治的80例NAFLD患者(NAFLD组),另选取健康体检者72例(健康对照组)。80例NAFLD患者中单纯NAFLD患者30例,伴ALT异常的NAFLD患者50例。检测所有研究对象的ALT、AST、TG、TC、FBG、空腹胰岛素水平及RBP4水平,观察NAFLD患者ALT异常、肝纤维化程度、胰岛素抵抗程度与RBP4的相关性。计量资料组间比较采用独立样本t检验,计数资料组间比较采用χ2检验,两变量间的相关性采用Pearson相关系数分析。结果NAFLD组患者的AST、ALT、TG、TC、FBG、HOMA-IR、NAFLDFS水平均显著高于健康对照组(t值分别为8.016、8.581、4.997、10.080、4.877、6.989、5.639,P值均<0.01);RBP4水平显著高于健康对照组[(533.95±197.21)ngl/ml vs(249.09±58.78)ngl/mL,t=11.791,P<0.05]。肝纤维化危险组的FBG、HOMA-IR、RBP4高于无肝纤维化组[FBG:(7.05±2.12)mmol/L vs(5.05±0.33)mmol/L,t=-4.644,P<0.01;HOMA-IR(3.88±1.76)vs(2.36±1.72),t=-4.725,P<0.01;RBP4:(588.23±133.33)ngl/ml vs(463.40±103.20)ngl/mL,t=-4.721,P<0.01]。伴ALT异常NAFLD患者的血清ALT水平显著高于单纯NAFLD患者[ALT:(106.79±59.56)U/L vs(26.90±8.21)U/L,t=-7.081,P<0.01];但RBP4无明显差异[RBP4:(509.80±118.76)ngl/mL vs(520.44±139.93)ngl/mL,t=-0.348,P=0.729]。Pearson相关性分析结果显示,RBP4与HOMA-IR、NAFLDFS呈显著正相关(r值分别为0.430、0.464,P值均<0.01);与ALT(r=-0.061,P=0.593)无相关。结论NAFLD患者存在RBP4高表达,且在胰岛素抵抗、肝纤维化程度高的NAFLD患者中表现更为明显。血清RBP4能在一定程度上反映NAFLD患者胰岛素抵抗、肝纤维化的严重程度。     

Correlation of plasma insulin and insulin-like growth factor-I with indices of androgen transport and metabolism in women with polycystic ovary syndrome

OBJECTIVE: Polycystic ovary syndrome (PCOS) is said to be associated with hyperinsulinaemia. Insulin stimulates androgen production by ovarian tissue in vitro and previous studies have identified a positive correlation of insulin with androstenedione. The aim of the present study was to discover whether insulin levels correlate with clinical presentation and with markers of androgen transport and metabolism in women with PCOS. DESIGN: Within-group analysis of clinical and biochemical characteristics of a consecutive series of women with PCOS, focusing on correlations of plasma insulin with clinical presentation and androgens. Insulin levels were also compared with a control group of normal women. PATIENTS: Forty-seven women who presented with hirsutism, cycle abnormalities or both, with ultrasound proven PCOS, were recruited. Mean age was 26.6 +/- 0.7 years (mean +/- SEM), BMI 27.3 +/- 1.2 kg/m2. MEASUREMENTS: Plasma insulin levels were measured at 30-minute intervals for 3 hours following a 75 g glucose load. Blood was also taken for measurement of testosterone (T), androstenedione (A), free testosterone (fT), sex hormone binding globulin (SHBG) and insulin-like growth factor-I (IGF-I). Androsterone glucoronide (AG), a marker of peripheral androgen metabolism, was also measured. RESULTS: Neither basal insulin nor the sum of insulin measurements during the glucose tolerance test (sumINS) in women with PCOS were significantly different from a control group with normal ovaries. Within the PCOS group, basal insulin was greater in women with irregular cycles or amenorrhoea than in those with regular ovulatory menses (8.0 +/- 1.1 vs 3.1 +/- 1.5 mU/l, P less than 0.01) despite similarly raised androgen levels. Both basal insulin and sumINS correlated with BMI in women with PCO (r = 0.37, P less than 0.05 and r = 0.64, P less than 0.01 respectively) but not in controls. There was no significant correlation between insulin or IGF-I levels and T, A or AG despite a positive correlation of AG (but no other androgen) with BMI. SHBG showed an inverse correlation and fT correlated positively with sumINS (r = -0.51, P less than 0.01; r = 0.39, P less than 0.05). Regression analysis of each of the androgens on the other variables demonstrated no significant relationship between insulin and androgens. CONCLUSIONS: These data suggest that, in vivo, the major effect of insulin on androgen secretion is mediated by changes in SHBG rather than by direct stimulation of ovarian androgen production. Higher insulin concentrations in anovulatory compared with ovulatory women with hyperandrogenaemia may indicate that insulin resistance in the ovary contributes to the mechanism of anovulation in PCOS.     

Increased levels of serum advanced glycation end-products in women with polycystic ovary syndrome

OBJECTIVE: Women with polycystic ovary syndrome (PCOS) carry a number of cardiovascular risk factors and are considered to be at increased risk for atherosclerosis. Elevated concentrations of advanced glycation end-products (AGE), which exert their effects through interaction with specific receptors (RAGE), have been implicated in the cellular and tissue damage during atherosclerotic processes. DESIGN/PATIENTS: We investigated serum AGE levels in 29 young women with PCOS as well as the expression of their receptor, RAGE, in circulating monocytes and compared them levels with 22 healthy control women. MEASUREMENTS/RESULTS: Women with PCOS had higher levels of serum AGE proteins compared to healthy individuals (9.81 +/- 0.16 vs. 5.11 +/- 0.16, P < 0.0001), and increased RAGE expression was observed in monocytes of PCOS women compared to controls (30.91 +/- 10.11 vs. 7.97 +/- 2.61, P < 0.02). A positive correlation was observed between AGE proteins and testosterone (T) levels (r = 0.73, P < 0.0001). The correlation between AGE proteins and T levels remained high (partial correlation coefficient = 0.61, P = 0.0001) after controlling for body mass index (BMI), insulin levels and the area under the curve for glucose (AUCGLU) during an oral glucose tolerance test (OGTT). A positive correlation was also observed between AGE proteins and the free androgen index (FAI) (r = 0.58, P < 0.0001), waist-to-hip ratio (WHR) (r = 0.31, P < 0.02), insulin (r = 0.46, P < 0.001), homeostasis model assessment (HOMA) (r = 0.47, P < 0.0001), AUCGLU (r = 0.52, P < 0.002) and RAGE (r = 0.59, P < 0.01). A negative correlation was observed between AGE proteins and glucose/insulin ratio (GLU/INS) (r = -0.35, P < 0.01), and the quantitative insulin sensitivity check index (QUICKI) (r =-0.50, P < 0.01). In multiple regression analysis T was the only independent predictor of AGE levels (P < 0.0001, b = 0.044) between BMI, insulin, SHBG and AUCGLU (adjusted R2 = 0.59, F = 44.41, P < 0.0001). CONCLUSION: These data clearly demonstrate, for the first time, that PCOS women without overt hyperglycaemia have increased AGE levels and elevated RAGE expression when compared with controls.     

DECREASED SEX HORMONE BINDING GLOBULIN (SHBG) AND INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN (IGFBP-1) IN EXTREME OBESITY

Obesity may be characterized by abnormal sex steroid secretion and reduced sex hormone binding globulin (SHBG) which in turn is related to fat distribution and insulin secretion. Recent in-vitro and in-vivo evidence suggests that insulin is the common mechanism regulating the secretion of SHBG and insulin-like growth factor small binding protein (IGFBP-1). IGFBP-1 appears not only to be a carrier for insulin growth factors (IGFs) but also to play an active role in growth processes, independent of growth hormone secretion. We have examined the possible relationship between fasting insulin, SHBG, testosterone, IGF-1, IGFBP-1 and fat distribution in 25 extremely obese, menstruating women (mean weight 107 +/- 3 kg) with normal glucose tolerance. Fat distribution was assessed from measurements of the waist to hip ratio (W/H). The obese women showed an elevated fasting insulin (mean +/- SEM; 21 +/- 2 mumol/l), a normal IGF-1, but reduced IGFBP-1 (14.6 +/- 2 micrograms/l); in 15 women IGFBP-1 levels were undetectable by the present assay. In addition, SHBG levels were reduced in the obese women (24 +/- 2 nmol/l) but total testosterone values (1.9 +/- 0.1 nmol/l) were normal. The elevated fasting insulin levels were positively correlated with increasing upper segment obesity as expressed by a rising W/H ratio (P less than 0.01, r2 = 0.306) and inversely correlated with SHBG (P less than 0.01, r2 = 0.483). Similarly, reduced SHBG values showed an inverse correlation with increasing W/H ratio (P less than 0.001, r2 = 0.383). No correlation was found between IGFBP-1 and W/H ratio but a strong positive correlation was seen between IGFBP-1 and SHBG (P less than 0.001, r2 = 0.466). Furthermore, an equally significant inverse correlation was found between IGFBP-1 and insulin levels (P less than 0.001, r2 = 0.474).(ABSTRACT TRUNCATED AT 250 WORDS)     

Decreased hepatic insulin extraction in upper body obesity: relationship to unbound androgens and sex hormone binding globulin

Hyperinsulinemia is a well-recognized entity of simple obesity. It is demonstrated that hyperinsulinemia is associated with upper body fat and fat cell hypertrophy. Androgen excess and lower levels of sex hormone binding globulin (SHBG) may produce fat cell hypertrophy and hyperinsulinemia as well. We measured serum insulin and C-peptide levels during an OGTT in two groups of obese premenopausal women to determine whether the hyperinsulinemia is due to hypersecretion or due to a diminished hepatic extraction of insulin. In this study, we found no correlation between the insulin and C-peptide levels or their ratio and the degree of obesity. However, a significant correlation was found between the waist-to-hip circumference ratio (WHR), used as an index of body fat distribution, and the areas of insulin (r = 0.55; P less than 0.001) and C-peptide (r = 0.51; P less than 0.001). SHBG and free androgen index (FAI) were also significantly related to these areas. The peripheral C-peptide/insulin molar ratio has been assumed to reflect changes in hepatic insulin extraction while the corrected C-peptide response reflects beta-cell function. WHR was negatively related to this ratio (r = -0.44; P less than 0.005) and SHBG showed a positive correlation (r = 0.34; P less than 0.05). Stepwise multiple regression analysis revealed that the 2-h insulin and C-peptide values and both curve areas can be explained up to 40-80% by sex hormones and anthropometric variables. Also the C-peptide/insulin molar ratio is dependent in a first step on WHR (r2 = 0.23; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

不同糖调节受损人群血糖波动与氧化应激的相关性分析

目的 采用动态血糖监测系统研究不同糖调节受损人群的血糖波动与氧化应激的相关性.方法 2008年1月至7月选取北京地区稳定人群66名,根据美国糖尿病学会(ADA)2003年标准分为正常糖耐量组(13例),糖尿病前期组(17例),2型糖尿病组(36例);所有受试对象均行72 h动态血糖临测,选取平均血糖波动幅度评价血糖波动情况;其间第48～72小时留取24 h尿,采用酶联免疫吸附法检测8-异前列腺素F2α(8-isoPGF2α)评价氧化应激水平.2型糖尿病组给予"重组赖脯胰岛素25"强化治疗12周,其间定期随访、指导生活方式干预并调整胰岛素用量.对干预前、后血糖波动、氧化应激和各项代谢指标的变化行方差分析,并对其影响因素行相关分析及多元逐步回归分析.结果 (1)基线时2型糖尿病组24 h尿游离8-isoPGF2α分泌率(8-isoPGF2α/Cr)为(1706±477)pg/mg,与糖尿病前期组[(216±65)pg/mg]和正常糖耐量组[(269±60)pg/mg]比较升高690%和534%,差异有统计学意义(F=27.304,P<0.05);2型糖尿病组平均血糖波动幅度(MAGE)为6.04 mmol/L,与糖尿病前期组[(2.7±1.2)mmol/L]和正常糖耐量组[(1.7±0.5)mmol/L]比较升高124%和249%,差异有统计学意义(F=67.729,P均<0.05).(2)2型糖尿病组经"重组赖脯胰岛素25"干预后,24 h尿8-isoPGF2α/Cr、MAGE、糖化血红蛋白、甘油三酯与干预前比较分别降低34.53%,31.81%,18.50%,28.79%,差异有统计学意义(F值分别为6.108、18.378、39.322、5.942,P均<0.05);此外,收缩压、舒张压、空腹血糖、餐后2 h血糖与干预前比较显著下降(F值分别为7.879、11.684、38.952、61.207,P均<0.01).(3)Pearson相关分析显示24 h尿8-isoPGF2α/Cr与MAGE呈显著相关(r=0.593,P<0.01);与空腹血糖(r=0.415,P<0.01)、餐后2 h 血糖(r=0.472,P<0.01)、高密度脂蛋白胆固醇(r=-0.307,P<0.01)、甘油三酯(r=0.296,P<0.01)、收缩压(r=0.268,P<0.05)显著相关;而与糖化血红蛋白无相关(r=0.186,P>0.05).(4)以24 h尿8-isoPGF2α/Cr为因变量,以上述与其有相关性的变量为自变量进行多元逐步同门分析,只有MAGE和高密度脂蛋白胆固醇进入最终方程(决定系数r2分别为0.354、0.346,P均<0.01);偏相关分析与卜述结果 一致.结论 (1)2型糖尿病组与正常糖耐昔组、糖尿病前期组比较血糖波动幅度大,氧化应激水平高;(2)2型糖尿病氧化应激活化程度与血糖波动和部分血脂代谢相关;(3)经胰岛素强化干预后,血糖波动幅度下降,氧化应激反应减轻.     

Plasma total and glycosylated corticosteroid-binding globulin levels are associated with insulin secretion.

In humans, steroid hormones circulate in the blood mainly bound to specific steroid transport proteins, namely corticosteroid-binding globulin (CBG) for cortisol and sex hormone-binding globulin (SHBG) for testosterone and estradiol. The binding activities of these proteins are believed to modulate the biodisposal of steroids to target cells. It has been shown in vitro that insulin is a potent inhibitor of both CBG and SHBG secretion by a human hepatoblastoma cell (HepG2) line. To further investigate this potential effect of insulin in vivo, we prospectively studied three groups of lean subjects, obese subjects, and obese subjects with glucose intolerance, all of whom were otherwise healthy. The three groups were comparable in sex and age, and in the two obese groups, body mass index, waist to hip ratio, and blood pressure were similar. Plasma total CBG concentrations (38.2 +/- 5.4 vs. 31.7 +/- 4.05 mg/L; P = 0.016) and glycosylated CBG levels (37.3 +/- 5.2 vs. 31 +/- 3.9 mg/L; P = 0.018) were significantly increased in obese subjects with glucose intolerance. Plasma CBG correlated positively with fasting glucose levels (r = 0.49; P = 0.002), hemoglobin A1c levels (r = 0.35; P = 0.03), and area under the curve of glucose after an oral glucose tolerance test (r = 0.45; P = 0.005) and correlated negatively with the insulin response to i.v. glucose (AIRg; -0.38, P = 0.02) as well as to oral glucose (r = -0.40; P = 0.01) challenge tests. CBG levels did not covariate with insulin sensitivity. Multiple linear regression analysis showed that only AIRg contributed to the variability of the CBG concentration (P = 0.03), explaining 41% of its variance. Morning cortisol levels did not differ between the groups and did not correlate to any of the glucose or insulin metabolism parameters. Because carbohydrate chains influence the biological activity and half-life of glycoproteins, we analyzed the migration profile of CBG by Western blot and the interaction of CBG with lectin, Con A. The results indicated that the CBG mol wt and interaction with Con A did not differ between lean and obese patients. These data favor the hypothesis that the inhibitory effect of insulin on CBG liver secretion might be relevant in vivo and therefore contribute to decrease CBG levels in obese patients with enhanced insulin secretion. In both men and women, SHBG levels correlated negatively with fasting glucose (r = -0.55; P < 0.0001) and hemoglobin A1c (r = -0.38; P = 0.02) and positively with insulin sensitivity (S(I); r = 0.65; P = 0.003 and r = 0.63; P = 0.007 in men and women, respectively), but not with insulin secretion. The disposition index (S(I) x AIRg) was significantly decreased in the obese, glucose-intolerant subjects, suggesting that AIRg was inadequate for their degree of insulin resistance. The disposition index correlated positively with plasma SHBG levels (r = 0.52; P = 0.001) and negatively with plasma CBG levels (r = -0.54; P = 0.001). Our data suggest that CBG is a marker of insulin secretion in a similar way as SHBG is a marker of insulin sensitivity. As high plasma CBG levels have been associated with increased incidence of type 2 diabetes, this important issue merits further investigations.     

The biological variation of testosterone and sex hormone-binding globulin (SHBG) in polycystic ovarian syndrome: implications for SHBG as a surrogate marker of insulin resistance

This study was designed to assess the biological variability of total testosterone and SHBG in polycystic ovarian syndrome (PCOS) and to determine the use of SHBG as a surrogate marker of insulin resistance in PCOS. Fasting blood samples were collected at 4-d intervals on 10 consecutive occasions from 12 PCOS patients and 11 age- and weight-matched controls. Duplicate samples were analyzed for SHBG, testosterone, and insulin in a single batch, and insulin resistance was calculated by the homeostasis model assessment method (HOMA-IR). The PCOS group had higher testosterone (mean +/- SD, 3.9 +/- 0.8 vs. 3.2 +/- 1.3 nmol/liter; P = 0.001), lower SHBG (28.6 +/- 17.1 vs. 57.6 +/- 30.2 nmol/liter; P = 0.001), and greater HOMA-IR (5.85 +/- 5.3 vs. 1.67 +/- 0.63 U; P = 0.001) than the controls. In contrast to HOMA-IR (1.09 vs. 0.48 U; P = 0.001), the intraindividual variation in SHBG was lower in the PCOS group (mean, 3.4 vs. 6.3 nmol/liter; P = 0.041). The index of individuality for SHBG and testosterone in PCOS was 0.49 and 0.69, respectively. This study shows that for patients with PCOS, SHBG is an integrated marker of insulin resistance that may be of use to identify insulin-resistant individuals for targeted treatment with insulin-sensitizing agents. However, SHBG and testosterone concentrations measured in isolation are inherently unsuitable for use as tests to detect hyperandrogenemia.     

Serum inhibin B in polycystic ovary syndrome: regulation by insulin and luteinizing hormone

Inhibin B is a product of the granulosa cells of growing preantral and antral follicles. Despite the large ovarian volume and increased follicle number typically detected in women with polycystic ovary syndrome (PCOS), previous studies demonstrate that inhibin B is not elevated as would be expected in PCOS, but is inversely correlated with body mass index (BMI). We therefore hypothesized that inhibin B levels in women with PCOS are regulated by a factor related to BMI. Thus, LH, sex steroids, and metabolic parameters were measured in 50 anovulatory PCOS subjects in pools constituted from equal aliquots of serum drawn every 10 min for 4 h and were correlated with inhibin B. Based on the results of these correlative studies, inhibin B regulation by human chorionic gonadotropin (hCG) and insulin was tested directly. In PCOS subjects, inhibin B correlated inversely with BMI (r = -0.413; P < 0.004) and fasting insulin (r = -0.409; P < 0.004). Inhibin B also correlated directly with pool LH (r = 0.419; P < 0.003), LH pulse amplitude (r = 0.512; P < 0.0001), and SHBG (r = 0.429; P < 0.003). The relationships demonstrated for inhibin B were not demonstrated for inhibin A, nor were they evident in normal subjects. To determine whether the correlations represent regulation of inhibin B, i.e. stimulation of inhibin B by LH or suppression by insulin, two interventional studies were performed. In the first study hCG (5000 U) was administered to PCOS subjects (n = 15) to mimic the effects of LH. Inhibin B was not increased, but was significantly reduced 24 h after hCG administration (223.8 +/- 21.3 vs. 152.4 +/- 15.9 pg/ml; P < 0.0005). In the second study, diazoxide (100 mg every 8 h) was administered for 3 d to PCOS subjects (n = 9). Inhibin B increased (85.4 +/- 12.4 to 136.6 +/- 18.8 pg/ml; P < 0.05) in association with a decrease in the insulin area under the curve (104 +/- 29 to 83 +/- 22 nmol/liter.min; P < 0.05) induced by diazoxide. In PCOS subjects, inhibin B demonstrated significant relationships with BMI and factors related to BMI, including LH, insulin, and SHBG. Although LH was associated with inhibin B, hCG administration suppressed inhibin B secretion after 24 h, whereas short-term insulin suppression increased inhibin B. These findings suggest that both increased LH and insulin may account for the relative suppression of inhibin B in patients with PCOS.