Elevated fasting insulin is associated with cardiovascular and metabolic risk in women with polycystic ovary syndrome

AimsPCOS is associated with various immediate and long term health complications. The aim of this study was to investigate the association of serum fasting insulin concentration with cardiovascular and metabolic risk factors in women with polycystic ovary syndrome.MethodsA total of 349 women, 249 women with polycystic ovary syndrome and 100 age-matched healthy controls, were recruited in this case-control study. Fasting insulin and various other biochemical, hormonal and clinical parameters were measured in all participants. The correlation of insulin with cardiometabolic risk factors was evaluated in PCOS women with normal and high serum insulin concentration.ResultsFasting Insulin, BMI, WHR, FAI, LH: FSH, HOMA, QUICKI were significantly higher in PCOS women compared with healthy controls (p < 0.01). Fasting insulin showed a positive correlation with more cardiovascular and metabolic risk factors in PCOS compared to controls. The BMI, BAI, LAP, HOMA IR, QUICKI and FAI were significantly higher (all p < 0.05) in PCOS patients with higher insulin levels than with PCOS women with normal levels.ConclusionFasting insulin is an important determinant in the pathogenesis of obesity and hyperandrogenism in PCOS. It is associated with an increased risk of cardiovascular and metabolic disorders in women with PCOS.     

Plasma leptin concentrations and obesity in relation to insulin resistance syndrome components among school children in Taiwan--The Taipei Children Heart Study

OBJECTIVE: Leptin, an adipose tissue-derived product of the obesity (OB) gene, is an important regulator of energy metabolism and may be associated with the occurrence of insulin resistance and diabetes in humans. The purpose of this study was to evaluate the association of plasma leptin concentration with obesity and the components of insulin resistance syndrome (IRS) among school children in Taiwan. METHODS: After multistage sampling of 85 junior high schools in Taipei, we randomly selected 1,264 children (617 boys and 647 girls) aged 12-16y. Obesity measurements included body mass index (BMI) and waist-to-hip circumference ratio (WHR). We calculated an IRS summary score for each individual by adding the quartile ranks from the distribution of systolic blood pressure (BP), serum triglyceride (TG), HDL-cholesterol (inverse), and insulin levels. RESULTS: Boys had a higher BMI and WHR, BP and IRS score and lower leptin, insulin, TG and HDL-C levels than girls. BMI, WHR and plasma leptin levels were significantly associated with the IRS summary score and each of its components in both genders. Children with higher plasma leptin levels (> 75th percentiles) have significantly higher BP, TG, insulin levels and IRS score than children with low leptin levels. The associations between plasma leptin level and the IRS components and score were still significant after adjusting for BMI in boys, but less so in girls. In both genders, after adjusting for WHR, plasma leptin levels were still significantly associated with the IRS components and summary score (P< 0.001). The final model that included the standard covariates, BMI and leptin, but not WHR, was the most predictive of the IRS summary score among school children. CONCLUSIONS: Insulin resistance syndrome in childhood, characterized by high blood pressure, dyslipidemia, and hyperinsulinemia, may be an early marker of cardiovascular risk. From the present BMI and leptin in combination are the most predictive markers of insulin resistance syndrome among school children in Taiwan.     

Relation of weight and rate of increase in weight during childhood and adolescence to body size, blood pressure, fasting insulin, and lipids in young adults. The Minneapolis Children's Blood Pressure Study

BACKGROUND: Weight gain is of concern during early development because adult obesity and its cardiovascular consequences appear to have their origins during childhood. Insulin resistance is known to be related to obesity. Thus, weight gain beginning in childhood may influence the development of insulin-induced cardiovascular risk during adulthood. METHODS AND RESULTS: We monitored 679 individuals from 7.7+/-0.1 years of age with repeated measures of height, weight, and systolic blood pressure (SBP) until 23.6+/-0.2 years of age, when blood samples were obtained for measurements of insulin and lipids. Initial childhood weight, body mass index (BMI), and height were significantly correlated with young adult weight, BMI, and height and with fasting insulin, lipids, and SBP. The increases in weight and BMI but not height during childhood were significantly related to the young adult levels of insulin, lipids, and SBP. CONCLUSIONS: These data suggest that weight gain in excess of normal growth during childhood is a determinant of adult cardiovascular risk. The finding in multiple linear regression analysis that weight gain during childhood rather than the childhood weight at 7.7 years of age is significantly related to young adult risk factors suggests that a reduction in weight gain could reduce subsequent levels of cardiovascular risk.     

Coronary heart disease risk factors in adult premenopausal white women with polycystic ovary syndrome compared with a healthy female population

Our specific aim was to determine whether coronary heart disease (CHD) risk factors in polycystic ovary syndrome (PCOS) patients were independent of their higher body mass index (BMI) and centripetal obesity. In adult, premenopausal, white women, CHD risk factors were compared between 488 patients with well-defined PCOS and 351 healthy free-living population controls from the Princeton Follow-up Study (PFS). After excluding women with irregular menses (putative PCOS phenotypes), comparisons were also made between the 261 PFS women with a history of regular menses and the 488 women with PCOS. Fasting lipids, insulin, glucose, homeostasis model assessment of insulin resistance (HOMA-IR), HOMA insulin secretion, blood pressure, BMI, and waist circumference were measured. Compared with both the full cohort of 351 PFS women and the subgroup of 261 PFS women with regular menses, women with PCOS had higher BMI, waist circumference, total and low-density lipoprotein cholesterol, triglyceride, systolic blood pressure, diastolic blood pressure, insulin, glucose, and HOMA-IR (all Ps ≤ .005). After adjusting for age and BMI, women with PCOS, compared with the 351 and 261 PFS women, had lower high-density lipoprotein cholesterol (P < .0001, .0008) and higher systolic blood pressure (P = .0002, < .0001), insulin (P = .017, .039), HOMA-IR (P = .013, .032), and HOMA insulin secretion (P = .022, .037). The small subgroup of PCOS women with normal BMI (<25 kg/m²) (36/488, 7%) also had higher age-adjusted insulin, glucose, and HOMA-IR (all Ps < .005) than the subgroup of PFS women with BMI less than 25 kg/m² (123/261, 47%). Increased CHD risk factors and high HOMA-IR in PCOS cannot be exclusively attributed to their preponderant centripetal obesity. Identification of women with clinical features of PCOS should alert the clinician to potentially increased risk for CHD and prompt CHD risk factor testing.     

The cardiovascular risk of young women with polycystic ovary syndrome: an observational, analytical, prospective case-control study

To evaluate the cardiovascular risk of polycystic ovary syndrome (PCOS), we investigated lipid profile, metabolic pattern, and echocardiography in 30 young women with PCOS and 30 healthy age- and body mass index (BMI)-matched women. PCOS women had higher fasting glucose and insulin levels, homeostasis model assessment score of insulin sensitivity, total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels, and TC/high density lipoprotein cholesterol (HDL-C) ratio and lower HDL-C levels than controls. Additionally, PCOS women had higher left atrium size (32.0 +/- 4.9 vs. 27.4 +/- 2.1 mm; P < 0.0001) and left ventricular mass index (80.5 +/- 18.1 vs. 56.1 +/- 5.4 g/m(2); P < 0.0001) and lower left ventricular ejection fraction (64.4 +/- 4.1 vs. 67.1 +/- 2.6%; P = 0.003) and early to late mitral flow velocity ratio (1.6 +/- 0.4 vs. 2.1 +/- 0.2; P < 0.0001) than controls. When patients and controls were grouped according to BMI [normal weight (BMI, >18 and <25 kg/m(2)), overweight (BMI, 25.1-30 kg/m(2)), and obese (BMI, >30 kg/m(2))], the differences between PCOS women and controls were maintained in overweight and obese women. In normal weight PCOS women, a significant increase in left ventricular mass index and a decrease in diastolic filling were observed, notwithstanding no change in TC, LDL-C, HDL-C, TC/HDL-C ratio, and TG compared with controls. In conclusion, our data show the detrimental effect of PCOS on the cardiovascular system even in young women asymptomatic for cardiac disease.     

Relationship between androgen levels and blood pressure in young women with polycystic ovary syndrome

The role of testosterone on the development of hypertension is controversial, especially in women with polycystic ovary syndrome (PCOS) who have higher prevalence of obesity and insulin resistance than women without PCOS. Little is known about the association between serum testosterone level and blood pressure in young women with PCOS. In the 151 young Taiwanese women with PCOS enrolled in this cross-sectional study, we measured the body mass index, waist circumference, blood pressure, fasting glucose, fasting insulin, lipid profile, and hormone profiles. The free androgen index, total testosterone, and sex hormone-binding globulin, but not the level of dehydroepiandrosterone sulfate, significantly correlated with both systolic blood pressure (SBP) and diastolic blood pressure (DBP). In multiple linear regression models adjusted for age, body mass index, and other anthropometric, metabolic, and hormonal variables, the level of serum free androgen index or total testosterone, but not the sex hormone-binding globulin, were independently related to SBP and DBP. The age- and body mass index-adjusted least-square mean of serum-free androgen index levels were significantly different between the highest quartile and other quartiles of the SBP and DBP levels. The high bioavailable testosterone levels (free androgen index: >or=19%) in women with PCOS increased the risk of elevated blood pressure (SBP >or=130 mm Hg and/or DBP >or=85 mm Hg) with an odds ratio of 3.817 (P=0.029; 95% CI: 1.14 to 12.74) after adjustment for age, anthropometric measures, and metabolic profiles. Our results suggest that the characteristic hyperandrogenemia in young women with PCOS was associated with an elevated SBP and DBP independent of age, insulin resistance, obesity, or dyslipidemia.     

Obesity, free testosterone, and cardiovascular risk factors in adolescents with polycystic ovary syndrome and regularly cycling adolescents

Adolescent girls with polycystic ovary syndrome (PCOS) have increased levels of factors constituting the metabolic syndrome: centripetal obesity, hypertension, hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-C), and hyperinsulinemia. Given the strong association reported between early, persistent obesity and development of metabolic syndrome 10 years later in girls, we speculated that if adolescent girls without PCOS had obesity measures similar to girls with PCOS, they would exhibit similar metabolic syndrome-cardiovascular disease risk factors. Within this context, we compared 37 adolescent girls with PCOS and 2 samples of normal, regularly cycling adolescent girls (controls) of similar ages, selected from the Cincinnati Clinic of the National Heart, Lung, and Blood Institute Growth and Health Study. The first sample included 157 controls selected using a stratified random sample based on age. As expected, girls with PCOS had higher body mass index (BMI), waist circumference, insulin, systolic blood pressure (SBP) and diastolic blood pressure, triglycerides (TGs), lower HDL-C, and higher low-density lipoprotein cholesterol (LDL-C) and free testosterone (FT) than controls. A second sample consisted of girls matched one to one with girls with PCOS for BMI and age. Comparisons of group differences were not significant for insulin, lipids, or blood pressure; girls with PCOS had a trend toward higher values for waist circumference (median, 92.7 vs 87.5 cm; P = .07) and much higher median FT (4.25 vs 1.42 ng/mL, P = .0001). After matching for BMI and age, by conditional regression analysis, we showed that the groups were not differentiated (P > .15) by insulin, HDL-C, LDL-C, TG, SBP, or diastolic blood pressure, but were differentiated by higher FT (P = .0024) and waist circumference (P = .0024) in PCOS than in controls. Prospective longitudinal analyses of NHGS controls showed that changes in BMI from ages 9 to 10 years to ages 15 to 16 years were positively associated with changes in waist circumference (P < .0001), LDL-C (P = .01), TG (P = .008), and SBP (P = .002). These findings suggest that if adolescent girls achieve adiposity equal to girls with PCOS, they then acquire major components of the metabolic syndrome, and excluding high FT and waist circumference, comparable increased cardiovascular disease risk.     

Adiposity indices in the prediction of metabolic abnormalities associated with cardiovascular disease in non-diabetic adults

Background and Aims

The prevalence of insulin resistance and cardiovascular disease (CVD) increases with degree of obesity. Whether measurements of generalized and abdominal obesity differ in the ability to predict changes associated with increased CVD risk is widely debated. We compared the prevalence of metabolic abnormalities in 275 women and 204 men stratified by categories of body mass index (BMI) and waist circumference (WC), and assessed the ability of these adiposity indices in combination with metabolic risk variables to predict insulin resistance.

Methods and Results

Healthy, non-diabetic volunteers underwent measurements of BMI, WC, blood pressure, fasting plasma glucose (FPG), lipoprotein concentrations, and direct quantification of insulin-mediated glucose uptake. Insulin resistance was defined as the top tertile of steady-state plasma glucose (SSPG) concentrations. BMI and WC were highly correlated (P < 0.001) in both women and men. Abnormal SSPG and triglyceride concentrations were associated with increasing adiposity by either index in both genders. Among women, abnormal FPG and high density lipoprotein cholesterol (HDL-C) concentrations were associated with increasing BMI and WC. In men, abnormal HDL-C was associated with increasing BMI only. Elevated systolic blood pressure (SBP) was associated with increasing BMI in both genders. The odds of insulin resistance were greatest in women with elevated FPG and triglycerides (4.5-fold). In men, the best predictors were BMI and SBP, and WC and HDL-C (3-fold).

Conclusion

BMI is at least comparable to WC in stratifying individuals for prevalence of metabolic abnormalities associated with increased CVD risk and predicting insulin resistance.     

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。     

Relationship of left ventricular mass to insulin sensitivity and body mass index in healthy individuals

OBJECTIVE: The objective of this study was to investigate the contribution of insulin resistance, hyperinsulinaemia and obesity, independently of other major factors, to changes in left ventricular mass a cardiovascular risk indicator, in a healthy population without co-morbid states such as diabetes or hypertension. METHODS AND RESULTS: This cross-sectional relational study was perfomed in 153 healthy subjects, comprising 76 men and 77 women with ages ranging from 23 to 67 years. All of them were normotensive and had a normal oral glucose tolerance test, none had cardiovascular disease and none were taking any medication. Weight, height and waist circumference were measured and BMI was calculated. A blood sample was drawn in the fasting state: plasma glucose, insulin, serum total and high density lipoprotein (HDL), low density lipoprotein cholesterol and triglycerides were measured. Insulin resistance was determined by the 'Homeostasis Assessment Model' (HOMA-IR). Subjects were studied by echocardiography. The left ventricular mass was calculated by using the anatomically validated formula of Devereux et al. RESULTS: Left ventricular mass significantly and positively correlated with BMI, age, systolic and diastolic blood pressure and fasting blood glucose. The correlation of left ventricular mass with fasting blood glucose was not maintained after controlling for BMI. BMI, fasting blood glucose, HOMA-IR, systolic and diastolic blood pressure showed significant differences with higher values for people with left ventricular hypertrophy. The logistic regression analysis showed a strong association between left ventricular hypertrophy and BMI (p < 0.05). CONCLUSION: Insulin resistance and fasting insulin is not associated with left ventricular hypertrophy in healthy people, independent of obesity. Obesity appears to be an independent risk factor for left ventricular hypertrophy.     

多囊卵巢综合征患者胰岛素抵抗与糖脂代谢及性激素的研究

目的通过高胰岛素正葡萄糖钳夹试验评估多囊卵巢综合征(PCOS)患者的胰岛素抵抗,探讨伴胰岛素抵抗PCOS患者糖脂代谢及性激素水平特点。方法将2017年7月至2019年2月就诊于遵义医科大学附属医院内分泌科住院及门诊的73例PCOS患者和体重指数及年龄匹配的27名健康女性行高胰岛素正葡萄糖钳夹试验,根据葡萄糖代谢率、体重指数和稳态模型评估的胰岛素抵抗指数(HOMA-IR)分组,分析PCOS患者糖脂代谢及性激素指标的变化及差异。结果在PCOS组中,糖调节受损者占3.23%(1/31),血脂代谢异常者占9.68%(3/31);而在PCOS合并胰岛素抵抗组中,糖调节受损者占7.14%(3/42),血脂代谢异常者达47.62%(20/42),5例患者被诊断为代谢综合征,占11.90%。相关分析显示,葡萄糖代谢率与体重指数、腰臀比、收缩压、空腹血糖、空腹胰岛素、HOMA-IR、皮质醇、三酰甘油、总胆固醇、低密度脂蛋白胆固醇(LDL-C)、游离雄激素指数(FAI)和谷氨酰转肽酶(GGT)呈负相关(P<0.05),与高密度脂蛋白胆固醇(HDL-C)呈正相关(P=0.028);HOMA-IR与体重指数、腰臀比、收缩压、空腹血糖、空腹胰岛素、HbA1C、LDL-C呈正相关(P<0.05),与葡萄糖代谢率和HDL-C呈负相关(P<0.05);体重指数与腰臀比、收缩压、空腹血糖、空腹胰岛素、HOMA-IR、三酰甘油和LDL-C呈正相关(P<0.05),与葡萄糖代谢率、HDL-C和性激素结合球蛋白(SHBG)呈负相关(P<0.01)。多元线性逐步回归分析表明,体重指数、总胆固醇、三酰甘油和皮质醇是影响葡萄糖代谢率的重要因素,空腹血糖、空腹胰岛素和收缩压是HOMA-IR的重要影响因素,葡萄糖代谢率、HOMA-IR、HDL-C和SHBG仍然是影响体重指数的重要影响因素。结论FAI、SHBG和皮质醇可能参与到PCOS患者的胰岛素抵抗发生中,存在胰岛素抵抗的PCOS患者更容易发生代谢紊乱。     

Asymmetrical dimethylarginine, inflammatory and metabolic parameters in women with polycystic ovary syndrome before and after metformin treatment

CONTEXT: Insulin resistance plays a significant role in the pathogenesis of the polycystic ovary syndrome (PCOS) and represents a link to the unfavorable cardiovascular risk profile frequently found in affected patients. The endogenous nitric oxide synthase inhibitor asymmetrical dimethyl-L-arginine (ADMA) is associated with atherosclerosis and represents an independent marker for cardiovascular morbidity and mortality. OBJECTIVE: We investigated ADMA levels among other cardiovascular, metabolic, and hormonal parameters in women with PCOS and the effects of metformin treatment on these parameters. DESIGN: A cross-sectional study and clinical trial were performed. PATIENTS AND PARTICIPANTS: Women with PCOS (n = 83) compared with a control group of healthy women (n = 39) were studied. INTERVENTIONS: In a subgroup of patients with PCOS (n = 21), the effect of metformin was assessed after 6 months of treatment. MAIN OUTCOME MEASURES: ADMA, intima media thickness (IMT), metabolic and hormonal parameters, and markers of inflammation were investigated. RESULTS: ADMA levels were significantly higher in the PCOS group compared with controls (0.57 +/- 0.15 vs. 0.50 +/- 0.11; P = 0.024). Androgens, C-reactive protein, fasting C-peptide, area under the curve (AUC) insulin, AUC glucose, homeostatic assessment of insulin resistance, fasting insulin, glycosylated hemoglobin, cholesterol, low-density lipoprotein cholesterol, triglycerides, and IMT were significantly higher in women with PCOS compared with controls. In PCOS patients ADMA was found to be positively correlated with body mass index (BMI), waist to hip ratio, parameters of insulin sensitivity, hyperandrogenemia (free testosterone, free androgen index), and IMT. Treatment with metformin ameliorated hyperandrogenemia and decreased ADMA levels (0.53 +/- 0.06 vs. 0.46 +/- 0.09, P = 0.013). Decrease in ADMA levels subsequent to metformin treatment did not correlate with change in BMI or metabolic parameters. CONCLUSIONS: ADMA amd parameters of insulin sensitivity are elevated in women with PCOS and the degree of insulin resistance confers the greatest influence on ADMA level. Metformin treatment led to improvement of hormonal and metabolic parameters and decreased ADMA levels possibly independent of BMI and metabolic changes.     

The polycystic ovary syndrome per se is not associated with increased chronic inflammation

OBJECTIVE: The syndrome of polycystic ovaries (PCOS) is a known risk factor for type 2 diabetes. It is not known, however, whether the increase in diabetes risk is related to endocrine abnormalities associated with PCOS such as hyperandrogenemia, or whether it is a consequence of the anthropometric or metabolic alterations frequently observed in PCOS women. DESIGN: Since markers of inflammation are supposed to predict type 2 diabetes, interleukin-6 (IL-6) and C-reactive protein (CRP) in combination with parameters of obesity, insulin resistance and hyperandrogenism were determined in 57 PCOS women and in 20 age-matched healthy controls. In addition, the C-174G IL-6 promoter polymorphism was analyzed as a determinant in influencing IL-6, obesity, and androgen levels in women. RESULTS: Neither CRP nor IL-6 were significantly elevated in lean or obese PCOS women compared with age-matched lean or obese controls. In PCOS patients, variables of body composition (body mass index (BMI), waist to hip ratio, dual-energy X-ray-absorptiometry fat mass) and of insulin resistance were correlated with IL-6 or CRP, while parameters of hyperandogenism were not. Multivariate linear regression analysis revealed that obesity is the dominant force, thus explaining 18% and 24% of the IL-6 or CRP levels, respectively, in PCOS women. No association of IL-6 or BMI to a certain genotype at C-174G could be demonstrated in 50 PCOS patients. The heterozygous GC genotype, however, was associated with lower androstendione levels. Metformin treatment of 9 obese, insulin-resistant PCOS patients over a period of 6 months caused a significant decrease in body weight, body fat mass and total testosterone, but showed no significant decline in IL-6 or CRP concentrations. CONCLUSIONS: In PCOS women, plasma levels of IL-6 and CRP were not increased when compared with age- and BMI-matched controls. BMI was, however, the parameter most strongly related to IL-6 and CRP in PCOS; thus PCOS-related endocrine abnormalities do not appear to activate inflammatory parameters thereby enhancing the risk of diabetes. In PCOS, the type 2 diabetes risk may, therefore, be confined to those with obesity and/or metabolic alterations rather than affecting all women suffering from the syndrome.     

60岁及以上非糖尿病人群代谢紊乱集簇与血清铁蛋白水平的关系

目的探讨60岁及以上人群代谢紊乱集簇与血清铁蛋白水平的关系。方法2008年6至7月人选上海市闵行区汀川社区60岁以上非糖尿病老年人3416名,测定血压、血脂、血糖、空腹胰岛素、尿白蛋白／肌酐比值、血清铁蛋白,采用稳态模型评价胰岛素抵抗指数和胰岛β细胞功能,计算胰岛素敏感指数及处置指数。根据上述结果将糖耐量正常者分为4组：胰岛素敏感＋胰岛素分泌减退组（SF2组,n=514）;胰岛素敏感＋胰岛素分泌正常组（SF,组,n=1049）;胰岛素抵抗＋胰岛素分泌减退组（SF,组,n=17）;胰岛素抵抗＋胰岛素分泌正常组（SF4组,n=516）。另根据代谢综合征诊断标准将全部研究对象分为代谢紊乱0组分组（MS0组,n=1564）、代谢紊乱1组分组（MS1组,n=1603）、代谢紊乱2组分组（MS2组,n=170）、代谢紊乱93组分组（MS3组,n=79）。各胰岛功能组及代谢紊乱组分别进行血清铁蛋白水平相关性分析。计数资料比较采用X^2检验,组间比较采用方差分析（Bonferroni法）。血清铁蛋白与各指标的相关性研究采用Spearman相关分析和多元逐步回归分析。结果随着代谢紊乱组分数目增加,血清铁蛋白、体质指数、体脂含量、收缩斥、舒张压、空腹血糖、总胆固醇、甘油三酯、尿白蛋白／肌酐比值、空腹胰岛素、胰岛素抵抗指数逐渐升高,胰岛素敏感指数及处置指数逐渐下降。高甘油三酯组、肥胖组患者血清铁蛋白水平分别高于正常甘油三酯组、正常体质量组。各代谢紊乱组（高甘油三酯、高胆同醇、高血压和肥胖组）中男性铁蛋白水平均高于女性。Spearman相关分析显示,空腹血糖、2h血糖、空腹胰岛素、体质指数、甘油三酯、总胆㈨醇、胰岛素抵抗指数、胰岛β细胞功能与血清铁蛋白呈显著正相关（P〈0．01）,胰岛素处置指数、胰岛素敏感指数与血清铁蛋白呈显著负相关（P〈0．01）。多元逐步回归分析显示,胰岛素抵抗指数、总胆固醇、体质指数、甘油三酯是影响老年代谢紊乱者血清铁蛋白水平的独立危险因素。结论60岁及以上人群血清铁蛋白升高与代谢紊乱集簇显著相关,血脂异常、肥胖和胰岛素抵抗是该年龄段人群血清铁蛋白升高的主要危险因素。     

Overexpression of the phosphoprotein enriched in diabetes gene product (Ped/pea-15) in women with polycystic ovary syndrome

OBJECTIVE: To evaluate Ped/pea-15 (phosphoprotein enriched in diabetes) expression in polycystic ovary syndrome (PCOS) women. DESIGN AND PATIENTS: Thirty PCOS women were studied and compared with other 30 age- and body mass index (BMI)-matched women, considered as the control group. Both patients and controls were divided according to BMI. All subjects underwent endocrine and metabolic investigation and Ped/pea-15 expression was evaluated by western blot analysis. Insulin resistance was assessed by HOMA model and insulin sensitivity index (ISI) composite. RESULTS: Insulin resistance, evaluated by HOMA-R and ISI composite, was significantly higher in PCOS women and in obese controls than in normal weight controls. Ped/pea-15 expression (%) was higher in PCOS women than in controls (440.4 +/- 220.7 vs. 163.0 +/- 45.5; P < 0.001; range 145.5-987% and 97-281%, respectively), and was positively correlated with insulin, BMI, total testosterone, HOMA index, and family history (P < 0.001). In patients with PCOS univariate analysis of variance showed no effect of BMI variation (P = 0.13) on Ped/pea-15 expression levels. On multiple linear regression analysis, the major determinants of Ped/pea-15 overexpression were family history, insulin, and PCOS status independent of BMI. CONCLUSION: These preliminary data (1) highlight the overexpression of Ped/pea-15 in PCOS compared to normal controls, independent of obesity; (2) suggest that Ped/pea-15 overexpression might be an early component of the metabolic syndrome in PCOS; and (3) support the hypothesis that Ped/pea-15 represents a possible useful tool to assess the presence of a genetic condition associated with insulin resistance in PCOS.     

Low serum 25-hydroxyvitamin D concentrations are associated with insulin resistance and obesity in women with polycystic ovary syndrome.

Insulin resistance (IR) and central obesity are common features of the polycystic ovary syndrome (PCOS). Vitamin D is thought to play a role in the pathogenesis of type 2 diabetes by affecting insulin metabolism. The aim of our study was to investigate the effect of 25-hydroxyvitamin D (25-OH-VD) on metabolic parameters and IR in PCOS. In 120 untreated PCOS patients (median age 28 years) levels of 25-OH-VD (radioimmunoassay method provided by DiaSorin), calcium and anorganic phosphate were measured. In addition, endocrine and metabolic variables were evaluated and a glucose tolerance test was performed to assess indices of IR. In the entire PCOS cohort, 25-OH-VD concentrations were negatively correlated with body mass index (r=-0.2765), body fat (r=-0.2490), HOMA-IR (r=-0.1947), hyperinsulinemia (r=-0.1892) and leptin levels (r=-0.2834), and positively correlated with HDL cholesterol (r=0.2630) (all p<0.05). Subgroup analysis of lean, overweight and obese women revealed significant higher 25-OH-VD levels in lean women. Differences remained significant when women were divided according to their 25-OH-VD levels. Women with hypovitaminosis D (<9 ng/ml) had higher mean BMI, indices of IR and leptin levels compared to women with normal serum levels (all p<0.05). Analysis of vitamin D and biochemical endocrine PCOS features revealed a significant correlation only between 25-OH-VD and sex hormone-binding globulin as well as the free androgen index. In conclusion, in PCOS women, low 25-OH-VD levels are associated with obesity and insulin resistance but not with PCOS per se.     

Glucose-to-insulin ratio rather than sex hormone-binding globulin and adiponectin levels is the best predictor of insulin resistance in nonobese women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS), the main androgen disorder in women, has been suggested to be associated with a high risk of developing cardiovascular disease and type 2 diabetes. In many PCOS patients, overweight or central obesity is generally associated with increases in fasting insulin levels, insulin resistance, and glucose intolerance, and has been identified as a target for new therapeutic strategy, including early change in lifestyle. Early biochemical marker(s) for identifying at-risk patients will be useful for prevention studies. The main goal of the present study was to search for such tool(s). We investigated 16 nonobese PCOS women by performing euglycemic hyperinsulinemic clamp and measuring insulin levels during fasting and oral glucose tolerance test, as well as the serum concentrations of SHBG, leptin, and adiponectin, the newly identified adipose factors. Eight of the 16 patients had a steady-state glucose disposal rate less than 8.5 mg/kg.min, the lowest normal value for nonobese control women. These insulin-resistant patients had significant higher body mass index (BMI) and waist-to-hip ratio (WHR), and lower high-density lipoprotein cholesterol and SHBG levels. As expected, glucose disposal correlated negatively with BMI (P = 0.01), WHR (P = 0.01), and fasting insulin level (P = 0.003). On stepwise regression analysis, however, the glucose-to-insulin ratio (GIR) emerged as the strongest independent parameter to appraise insulin resistance (R(2) = 0.61). SHBG level correlated positively with GIR (P < 0.001) and negatively with BMI (P = 0.003) but did not correlate with either insulin response during the glucose tolerance test or plasma leptin and/or adiponectin levels. In contrast, BMI was the only independent predictive parameter of SHBG (P = 0.003, R(2) = 0.73). Interestingly, plasma adiponectin levels were positively associated with glucose disposal rate (P = 0.043) and negatively with WHR (P = 0.024), waist circumference being the best predictor of adiponectin level (P < 0.01). Leptin level correlated only with BMI (r = 0.62, P = 0.01). This study confirmed that insulin resistance, despite the lack of obesity as such, is clearly present in many PCOS women, and demonstrated that GIR is the best predictor for insulin resistance. It was also shown that adiponectin level is a good indicator of abdominal fat mass and is associated to insulin resistance. Finally, low SHBG levels in PCOS are intimately associated with BMI, suggesting that some signal(s) from the adipose tissue, independent of adiponectin and leptin, may regulate liver production of SHBG.     

Plasma homocysteine levels in polycystic ovary syndrome and congenital adrenal hyperplasia

The purpose of this study was to determine whether polycystic ovary syndrome (PCOS) and nonclassic 21-hydroxylase deficiency (CAH) are related to hyperhomocysteinemia, and to investigate if there is a correlation between homocysteine levels and insulin sensitivity in women with PCOS and CAH. Fifty patients with PCOS, 50 patients with CAH and 25 control women were included in the study. Blood samplings were performed in the early follicular phase for measuring hormone profile, Vitamin B(12), folate, homocysteine levels and fasting blood glucose. Ovulatory status was assessed with timed serum progesterone measurements. Homeostasis model assessment-insulin resistance (HOMA-IR) was calculated as a measure of insulin resistance. Mean homocysteine levels were found as (8.9 + 1.9 micromol/l and 17.7 + 3.6 micromol/l) in the normal group and PCOS respectively (p<0.001), but there was no statistical significance between nonclassic 21-hydroxylase deficiency (9.0 + 2.2 micromol/l) and control group. Most of the patients in PCOS group (35 of 50) were significantly insulin resistant. However, there was no insulin resistant patient in CAH or control group. When we compare the two subgroups of PCOS women, the patients with insulin resistance had significantly higher homocysteine levels than the ones who were not insulin resistant. There were positive correlations among serum homocysteine, insulin and androgen levels in PCOS patients. There were no correlations among these parameters in CAH and control groups. Increased homocysteine levels may contribute to increased cardiovascular disease risk in patients with PCOS. The reason for hyperhomocysteinemia seems to be related to insulin resistance but not high androgen levels.     

藏族多囊卵巢综合征患者胰岛素抵抗的研究

目的：探讨藏族人群多囊卵巢综合征（POS）与胰岛素抵抗的关系。方法：将30例POS患者的血压、体重指数（BMI）、血脂、血糖和胰岛素水平与30例正常对照组比较。结果：POS患者的BMI（P〈0.01）、血压（P〈0．05）、总胆固醇（P〈0.01）、甘油三酯（P〈0.05）、低密度脂蛋白（P〈0．05）水平高于对照组，高密度脂蛋白（P〈0．0001）低于对照组。空腹胰岛素（P〈0．0001）和餐后2h血糖（P〈0．0001）也高于对照组。POS组的胰岛素抵抗指数（HOMA-IR值）高于对照组（P〈0.01）。结论：藏族POS患者呈现动脉粥样硬化危险因素聚集（肥胖、血脂异常、高血压、高血糖）。     

多囊卵巢综合征患者非酒精性脂肪性肝病的发病情况及特点分析

目的探讨多囊卵巢综合征（PCOS）患者非酒精性脂肪性肝病（NAFLD）的发生情况和临床特点。方法对306例PCOS患者行基础内分泌、口服糖耐量试验及胰岛素释放试验、肝功、血脂、肝脏超声等检查。分析NAFLD的发病情况及特点。结果 NAFLD发生率为30.7%（94/306）;NAFLD发病率随体质量指数（BMI）和年龄的增加而升高。PCOS合并NAFLD者空腹血糖、空腹胰岛素、口服葡萄糖2h后血糖及胰岛素水平、稳态模型评估（HOMA-IR）、谷丙转氨酶（ALT）、谷草转氨酶（AST）、TC、TG、LDL-C、BMI、腰围、腰臀比,均显著高于不合并NAFLD者（P均〈0.05）;而量化胰岛素敏感指数（QUICK）、HDL-C则显著低于不合并NAFLD者（P均〈0.05）。PCOS合并NAFLD者胰岛素抵抗、腹型肥胖、糖耐量异常、糖尿病、肝功异常、血脂异常、高血压病及代谢综合征的患病率显著高于不合并NAFLD者（P〈0.05）。结论 PCOS伴NAFLD发病率较高;其发病率与BMI和年龄呈正相关;PCOS伴NAFLD多存在胰岛素抵抗、代谢异常;超重及腹型肥胖是PCOS患者NAFLD的主要危险因素。