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ABSTRACT: Alterations in the phenotypes of macrophages in adipose tissue play a key role in inflammation and insulin resistance (IR). The phenotypes of macrophages in subcutaneous adipose tissue (SAT) and the relationship between proinflammation markers and IR in women with polycystic ovary syndrome (PCOS) remain unclear. The objectives of this study are to characterize the gene expression of macrophage markers and cytokines in the SAT of PCOS women and to estimate their relationships with circulating levels of cytokines and IR.
The cross-sectional study involves 16 PCOS women and 18 normal control women. Cytokines and macrophage markers in the circulation and SAT were determined using ELISA, quantitative PCR, or immunofluorescence staining. IR was estimated using the homeostasis model assessment (HOMA-IR).
The gene expression levels of CD11c along with TNF α and leptin in SAT remained significantly higher in PCOS women than in normal women (P<0.05). However, no significant differences were found in CD68 mRNA expression in SAT between women with and without PCOS (P>0.05). Furthermore, CD11c mRNA abundance provided a stronger contribution to models predicting serum levels of TNFα (sTNFα) than did CD68 mRNA abundance. Lastly, increased sTNFα was associated with increased HOMA-IR in PCOS women, and this association was independent of both overall and visceral adiposity.
The high expression level of CD11c mRNA in SAT was proved to be an important feature in PCOS women. Furthermore, CD11c mRNA abundance made a stronger contribution to models predicting sTNFα in which existing proinflammatory properties might significantly contribute to the pathogenesis of IR in PCOS women.
European Journal of Endocrinology 09/2012; 167(5):705-13. · 3.42 Impact Factor
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ABSTRACT: An ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC/Q-TOF-MS) method coupled with a principal component analysis (PCA) was developed and applied toward identifying donkey-hide gelatin, bovine-hide gelatin, pig-hide gelatin, tortoise shell glue, and deerhorn glue. The UPLC-MS data of the trypsin digested samples were subjected to principal component analysis (PCA) in order to classify these five gelatins. Additionally, marker peptides given by the loadings plot of PCA were identified based on a comparison of recorded LC-MS data with a previously reported database of the corresponding gelatin variants. The results from this study indicate that the proposed method is reliable, and it has been successfully applied to the identification of variants of gelatins commonly used in Traditional Chinese Medicine (TCM).
Journal of pharmaceutical and biomedical analysis 03/2012; 62:191-5. · 2.45 Impact Factor
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ABSTRACT: Modulation of sex steroid pre-receptor in adipose tissue is important for the development of metabolic diseases, but its roles in the pathogenesis of polycystic ovary syndrome (PCOS) has not been fully characterized. Herein we compared the expression of key sex steroid converting enzymes in the subcutaneous adipose tissue (SAT) between patients with PCOS and the matched controls. Most of the sex steroid converting enzymes were highly expressed in the SAT, except 17α-hydroxylase (CYP17A1). Compared with the controls, PCOS patients showed significantly higher levels of 3β-hydroxysteroid dehydrogenase1-2 (3β-HSD1-2), aldo-keto reductase 1C 1-3 (AKR1C1-3) and leptin, but lower level of P450 aromatase and 5α-reductase 1. Interestingly, leptin was positively correlated to AKR1C2 expression and negatively to 5α-reductase1 as well as peroxisome proliferator-activated receptor γ (PPARγ). In summary, the expression of enzymes synthesizing testosterone and enzymes inactivating DHT and progesterone was higher in SAT of PCOS patients compared to controls. Correlation analysis indicated that increased leptin expression may be negatively related to local DHT level. These data suggested that sex steroid converting enzymes expression was different in SAT of PCOS patients that might contribute to abnormal testosterone and leptin level of PCOS patients.
The Journal of steroid biochemistry and molecular biology 02/2012; 132(1-2):120-6. · 2.66 Impact Factor
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ABSTRACT: The pathogenic factors that account for the development of diabetes condition in Chinese women with polycystic ovary syndrome (PCOS) remain elusive.
To clarify the pathogenic features by evaluating the levels of insulin sensitivity and β cell function in these women with PCOS, either separately or by using of a disposition indexes (DIs).
Cross-sectional study involving 137 Chinese women with PCOS and 123 normal women were examined by anthropometry, lipid profile, sex hormone, high-sensitivity C reactive protein, oral glucose tolerance tests and insulin tolerance tests.
After controlling for BMI status, the Matsuda Index was significantly lower in women with PCOS in comparison to those of normal women (p<0.000). The early phase of insulin secretion (insulinogenic index) remained significantly lower in lean women with PCOS(LP) than those of both lean and obese women of control group (p=0.007, and p = 0.01, respectively). The mean HOMA-F values were significantly lower (p =0.045) in obese women with PCOS (OP) than those of BMI-matched women. Further, all DIs derived from non-fasting state indexes in women with PCOS were significantly lower than those of BMI-matched control women (p<0.001 for all). Lastly, DIs derived from fasting states indexes in OP were significantly lower than those of LP.
Early impaired β cell function was detected in both LP and OP. However, more serious primary defect in insulin action was detected in LP compared to OP. These findings imply that early screening and intervention for PCOS would be therapeutic for Chinese women.
International journal of clinical and experimental pathology 01/2012; 5(8):777-86. · 1.89 Impact Factor
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ABSTRACT: Menopause is associated with central obesity, dyslipidemia, hypertension and insulin resistance, which are also shown in the patients with excess of glucocorticoids. However, the interaction of hypothalamic-pituitary-adrenal (HPA) axis activity and menopause has not been fully understood. In this study, 55 healthy non-obese women were recruited, and then divided into two groups, premenopausal group (n = 24) and postmenopausal group (n = 31). HPA axis function was evaluated by using dexamethasone suppression test (DST; 0.25 mg), and adrenocorticotrophic hormone (ACTH)-stimulation test. Moreover, 25 mg cortisone acetate test was applied to evaluate the hepatic 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity. We found that hepatic 11β-HSD1 activity and adrenal response to ACTH were increased in the postmenopausal group compared with the premenopausal group, whereas the negative feedback effect of dexamethasone did not show significant difference between pre- and postmenopausal women. These findings suggest that the adrenal sensitivity to ACTH and hepatic 11β-HSD1 activity are increased. The increased cortisol conversion and/or synthesis may be contributed to the dysmetabolic features in the postmenopausal women.
Gynecological Endocrinology 07/2011; 27(10):794-9. · 1.58 Impact Factor
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ABSTRACT: Adiponectin, an abundant adipokine with insulin-sensitizing properties, exists in different multimeric forms, including low-molecular weight, medium-molecular weight, and high-molecular weight (HMW) species. Alterations in the distribution of adiponectin multimers and the relationship between adiponectin multimers and insulin resistance (IR) in women with polycystic ovary syndrome (PCOS) remain unclear. The objective of this study was to compare adiponectin multimerization status and estimate insulin sensitivity in Chinese women with PCOS compared with age- and body mass index (BMI)-matched controls.
Cross-sectional study involving 64 Chinese women with PCOS and 59 normal women. Circulating total adiponectin and its multimeric forms were determined by ELISA, and IR was estimated using the homeostasis model assessment IR index (HOMA-IR).
After controlling for BMI status, levels of both total and HMW adiponectin were significantly lower in women with PCOS compared with normal women (P<0.05). Furthermore, HMW adiponectin provided a stronger contribution to models predicting IR than total adiponectin. Lastly, decreased HMW adiponectin was associated with increased HOMA-IR in both normal and PCOS women, and this association was independent of both overall adiposity and visceral adiposity.
Levels of both total and HMW adiponectin were decreased in Chinese women with PCOS compared with normal control women, and the differences in HMW adiponectin persisted after controlling for BMI. Furthermore, HMW adiponectin is a stronger predictor of IR than total adiponectin in both women with PCOS and normal women.
European Journal of Endocrinology 09/2010; 163(3):399-406. · 3.42 Impact Factor
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ABSTRACT: Isolated hyperglycemia is associated with atherosclerosis in individuals with type 2 diabetes, but the relationship between postchallenge glucose excursion and atherosclerosis is less clear. This study examines the relationships between postchallenge glucose spikes (PGS), carotid intima-media thickness (IMT), and traditional risk factors for atherosclerosis in individuals with type 2 diabetes.
A total of 474 individuals with type 2 diabetes who were within the highest or lowest IMT distribution quartile were included. The Student's t-test, one-way analysis of variance (ANOVA), single variate and multivariate analyses were implemented to study the data. An additional healthy control group (n=896) was selected during routine health examination. They were Han nationality and unrelated to the diabetic patients.
(1) Compared with subjects of healthy control group, the subjects with type 2 diabetes had significantly higher levels of body mass index (BMI), waist-to-hip ratio (WHR), systolic blood pressure, triglyceride, total cholesterol, low density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), 120 min postchallenge glucose (PG120), hemoglobin A1c (HbA1c) and IMT (P < or = 0.01) and relatively lower levels of high density lipoprotein cholesterol (HDL-C) (P < or = 0.05). (2) According to the IMT which was measured by B-mode ultrasonography, the patients of type 2 diabetes could be divided into two subgroups: one was the subgroup of IMT > or = P(75) and another was the subgroup of IMT < or = P(25). Compared with subjects of IMT > or = P(25) subgroup, subjects being in the IMT > or = P(75) subgroup exhibited significantly increased age, WHR, diabetes duration, systolic blood pressure, total cholesterol, triglyceride, LDL-C, and significantly decreased HDL-C levels. And among all the plasma glucose variables, except for FPG and PG30, all the other variables (include PG60, PG120, PG180, PGS, HbA1C, under area curve of glucose) showed a significant increase in the IMT>/=P(75) subgroup. (3) A multivariate logistic regression analysis was performed to establish which were independently related with carotid IMT, and the results showed the PGS was identified as the strongest determinant of IMT from all the atherosclerosis risk factors. (4) PGS is significantly correlated to a variety of atherosclerosis risk factors.
This study identified several important associations between PGS and known risk factors for atherosclerosis and suggested that PGS is independently related to carotid IMT. Wide postchallenge glucose excursions may contribute to the development of atherosclerosis in individuals with type 2 diabetes, independent of other risk factors.
Atherosclerosis 11/2009; 210(1):302-6. · 3.79 Impact Factor
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Yaomin Hu, Wei Liu,
Yawen Chen,
Ming Zhang,
Lihua Wang,
Huan Zhou,
Peihong Wu,
Xiangyu Teng,
Ying Dong,
Jia wen Zhou,
Hua Xu,
Jun Zheng,
Shengxian Li,
Tao Tao,
Yumei Hu,
Yun Jia
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ABSTRACT: The aim of this study is to assess the validity of combined use of fasting plasma glucose (FPG) and glycated hemoglobin A1c (HbA1c) as screening tests for diabetes and impaired glucose tolerance (IGT) in high-risk subjects. A total of 2,298 subjects were included. All subjects underwent a 75-g oral glucose tolerance test (OGTT) and HbA1c measurement. Receiver operating characteristic curve (ROC curve) analysis was used to examine the sensitivity and specificity of FPG and HbA1c for detecting diabetes and IGT, which was defined according to the 1999 World Health Organization (WHO) criteria. (1) Based on the ROC curve, the optimal cut point of FPG related to diabetes diagnosed by OGTT was 6.1 mmol/l that was associated with a sensitivity and specificity of 81.5 and 81.0%, respectively; The optimal cut point of HbA1c related to diabetes diagnosed by OGTT was 6.1%, which was associated with a sensitivity and specificity of 81.0 and 81.0%, respectively; The screening model using FPG > or = 6.1 mmol/l or HbA1c > or = 6.1% had sensitivity of 96.5% for detecting undiagnosed diabetes; the screening model using FPG > or = 6.1 mmol/l and HbA1c > or = 6.1% had specificity of 96.3% for detecting undiagnosed diabetes. (2) Based on the ROC curve, the optimal cut point of FPG related to IGT diagnosed by OGTT was 5.6 mmol/l that was associated with a sensitivity and specificity of 64.1 and 65.4%, respectively; The optimal cut point of HbA1c related to IGT diagnosed by OGTT was 5.6%, which was associated with a sensitivity and specificity of 66.2 and 51.0%, respectively; The screening model using FPG > or = 5.6 mmol/l or HbA1c > or = 5.6% had sensitivity of 87.9% for detecting undiagnosed IGT; The screening model using FPG > or = 5.6 mmol/l and HbA1c > or = 5.6% had specificity of 82.4% for detecting undiagnosed IGT. Compared with FPG or HbA1c alone, the simultaneous measurement of FPG and HbA1c (FPG and/or HbA1C) might be a more sensitive and specific screening tool for identifying high-risk individuals with diabetes and IGT at an early stage.
Acta Diabetologica 09/2009; 47(3):231-6. · 2.78 Impact Factor
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ABSTRACT: This systematic review attempted to summarize the associations between the Asn291Ser variant in the lipoprotein lipase (LPL) gene and dyslipidemia, the risk of type 2 diabetes mellitus (T2DM), and coronary heart disease (CHD). In addition, the relationships between the Asn291Ser variant and other metabolic diseases such as obesity and high blood pressure were also investigated in this systematic review. We systematically reviewed the literature by means of a meta-analysis. Twenty-one articles, including 19,246 white subjects, were selected for this meta-analysis. The summary standardized mean difference (SMD) of plasma triglyceride (TG) for carriers compared with noncarriers of the Asn291Ser variant was 3.23 (P < 0.00001). The summary SMD of plasma HDL-cholsterol (HDL-C) for carriers compared with noncarriers of the Asn291Ser variant was -3.42 (P < 0.0001). The summary SMD of the association of the Asn291Ser variant with plasma TG increased with increasing age and weight gain. Significant interactions between the LPL Asn291Ser variant and fasting glucose, T2DM, and CHD were seen (P = 0.02, 0.04, and 0.01, respectively). No significant interactions were seen between the LPL Asn291Ser variant and body mass index, waist-hip ratio, and blood pressure (P > 0.05). This meta-analysis indicates that the Asn291Ser variant in the LPL gene is a risk factor for dyslipidemia, characterized by hypertriglyceridemia and low HDL-C levels. And the Asn291Ser variant in the LPL gene predisposes to more severe dyslipidemia with increasing age and weight gain. Also, this meta-analysis shows that the LPL Asn291Ser variant is associated with CHD and T2DM.
The Journal of Lipid Research 09/2006; 47(9):1908-14. · 5.56 Impact Factor
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ABSTRACT: To extract the important physiological factors related to diabetes from an oral glucose tolerance test (OGTT) by mathematical modeling, highly informative but convenient protocols are required. Current models require a large number of samples and extended period of testing, which is not practical for daily use. The purpose of this study is to make model assessments possible even from a reduced number of samples taken over a relatively short period. For this purpose, test values were extrapolated using a support vector machine. A good correlation was found between reference and extrapolated values in evaluated 741 OGTTs. This result indicates that a reduction in the number of clinical test is possible through a computational approach.
