The relation of serum adiponectin and leptin levels to metabolic syndrome in women before and after the menopause

INTRODUCTION: It is well known that there is a higher prevalence of cardiovascular risk factors and metabolic syndrome (MS) in postmenopausal women. Recently it has become evident that adiponectin and leptin secreted by adipose tissue may be involved in the pathophysiology of MS. The aim of the study: was to assess the effects of the menopause on the relationships between adiponectin and leptin and different cardiovascular and metabolic risk factors. MATERIALS AND METHODS: A total of 56 postmenopausal women and 75 premenopausal subjects were enrolled in this study. We measured blood pressure, BMI, waist circumference and WHR, triglycerides (TG), high density lipoprotein cholesterol (cHDL) levels and fasting glucose and applied the oral glucose tolerance test (OGTT). Women were categorised as having 0, 1, 2, 3 or more risk factors. The presence of at least 3 abnormalities was defined as MS. Serum was assayed for adiponectin and leptin by the radioimmunoassay (RIA) method. RESULTS: A decline in adiponectin was related to an increased number of MS variables in postmenopausal and premenopausal women. Postmenopausal women with MS had significantly lower adiponectin concentrations than premenopausal women with MS. Serum adiponectin concentrations were inversely correlated to leptin in postmenopausal women. In premenopausal women no clear relationships were found between serum leptin and the number of metabolic disturbances. In contrast to young women, postmenopausal women showed an increase in leptin secretion with a growing number of MS elements. Compared to premenopausal women with MS, postmenopausal women with MS had higher levels of leptin. We found associations between leptin and different risk factors, mainly in the postmenopausal group. When the presence of MS was used as a dependent variable (yes/no) and adiponectin, leptin and menopause status as independent factors, adiponectin and leptin remained significant variables related to MS. CONCLUSION: The significant role of adiponectin in the pathophysiology of MS in premenopausal and postmenopausal women is confirmed in this study. Leptin is correlated with several MS components but this adipocytokine appears to play a role only in postmenopausal women.     

Plasma adiponectin concentration in healthy pre- and postmenopausal women: relationship with body composition, bone mineral, and metabolic variables

The aim of the current investigation was to determine the possible relationships of fasting adiponectin level with body composition, bone mineral, insulin sensitivity, leptin, and cardiorespiratory fitness parameters in 153 women. Subjects were classified as premenopausal (n = 42; 40.8 +/- 5.7 yr) if they had regular menstrual periods, early postmenopausal (n = 49; 56.7 +/- 3.6 yr) if they had been postmenopausal for more than >1 yr but <7 yr (5.5 +/- 1.3 yr), and postmenopausal (n = 62; 72.2 +/- 4.5 yr) if they had been postmenopausal for >7 yr. All women studied had a body mass index (BMI) <30 kg/m(2). Adiponectin values were higher (P < 0.05) in middle-aged (12.0 +/- 5.1 microg/ml) and older (15.3 +/- 7.3 microg/ml) postmenopausal women compared with middle-aged premenopausal women (8.4 +/- 3.2 microg/ml). Mean plasma adiponectin concentration in the total group of women (n = 153) was 12.2 +/- 6.3 microg/ml and was positively related (P < 0.05) to age, indexes of overall obesity (BMI, body fat mass), and cardiorespiratory fitness (PWC) values. In addition, a negative association (P < 0.05) between adiponectin with central obesity (waist-to-hip and waist-to-thigh ratio), fat-free mass, bone mineral (bone mineral content, total and lumbar spine bone mineral density), and leptin and insulin resistance (insulin, fasting insulin resistance index) values was observed. However, multivariate regression analysis revealed that only age, fasting insulin resistance index, and leptin were independent predictors of adiponectin concentration. In conclusion, circulating adiponectin concentrations increase with age in normal-weight middle-aged and older women. It appears that adiponectin is independently related to age, leptin, and insulin resistance values in women across the age span and menstrual status.     

Relationship of plasma leptin and adiponectin concentrations with menopausal status in Tunisian women

To evaluate the effect of menopausal status and body mass index (BMI) on circulating leptin and adiponectin concentrations and investigate whether there is an influence of menopausal transition on the relationships of these adipokines and leptin to adiponectin (L/A) ratio with lipid profile and insulin resistance in a sample of Tunisian women. One hundred ninety-six premenopausal (mean age 35.3 ± 7.6 years) and 180 postmenopausal women (mean age 53.4 ± 6.2 years) were included in the study. Participants were stratified into obese and normal weight groups based upon their baseline BMI. Fasting glucose, HDL-cholesterol (HDL-C), triglycerides (TG), total cholesterol (TC), insulin, leptin, and adiponectin concentrations were measured. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Premenopausal women had significantly higher leptin and L/A ratio and lower adiponectin levels than postmenopausal women. Menopause had no effect on the mean values of BMI, insulin or HOMA-IR, HDL-C, and TG. Using a multiple linear regression model, menopausal status was identified, as significant independent predictor for leptin and adiponectin levels. Irrespective of the menopausal status, obese women exhibited higher leptin and L/A ratio and lower adiponectin levels compared to those with normal weight. Comparison between the two menopausal stages in obese and normal weight groups showed that leptin and L/A ratio decreased, while adiponectin increased from pre- to postmenopausal stage only in obese group. The L/A ratio correlated better with lipid profile and HOMA-IR in postmenopausal stage. The present study showed a significant interaction between menopause and BMI on leptin and adiponectin secretion. Menopausal transition affects the relationships of these adipokines with lipids and insulin resistance.     

Relatively high levels of serum adiponectin in obese women, a potential indicator of anti-inflammatory dysfunction: relation to sex hormone-binding globulin

It is unclear whether serum adiponectin concentrations diminish linearly with increasing adiposity and, if not, which factors codetermine this association. These issues were investigated cross-sectionally in 1188 men and women, representative of middle-aged and elderly Turkish adults. Serum total adiponectin was assayed by ELISA. Serum adiponectin values in men, though declining significantly in transition from the bottom to the mid tertile of body mass index (BMI) and waist circumference (WC), were similar in the two respective upper tertiles. In women, serum adiponectin concentrations were not significantly different in any tertile of these indices, were significantly correlated with BMI or WC within the low tertiles and not within the two higher tertiles. In a linear regression analysis for WC (or BMI) in a subset of the sample in which serum sex hormone-binding globulin (SHBG) was available and which additionally comprised adiponectin, fasting insulin and other confounders, only insulin and, in women SHBG, were significantly associated, but not adiponectin. In linear regression analyses for covariates of adiponectin in two models comprising 12 variables, insulin and SHBG concentrations were significantly associated in both genders though not BMI. Whereas in men HDL-cholesterol and CRP were covariates of adiponectin (both p<0.01), SHBG and apolipoprotein B positively associated in women (p<0.001), independent of BMI and fasting insulin levels. CONCLUSIONS: Relationship between excess adiposity and adiponectin levels is inconsistent in Turkish adults. Independently from obesity and hyperinsulinemia, serum adiponectin discloses significant relationship with inflammatory markers and HDL only in men, not in women in whom it is influenced by SHBG, with consequent attenuation of its anti-inflammatory activities.     

The Relationship between Serum Ferritin Levels and Insulin Resistance in Pre- and Postmenopausal Korean Women: KNHANES 2007–2010

BackgroundSerum ferritin levels increase in postmenopausal women, and they are reported to be linked to major health problems. Here, we investigated the association between serum ferritin levels and insulin resistance (IR) in postmenopausal women.MethodsA total of 6632 healthy Korean women (4357 premenopausal and 2275 postmenopausal) who participated in the Korean National Health and Nutrition Examination Survey (KNHANES) in 2007–2010 were enrolled in the study. Serum ferritin values were divided into six groups for the premenopausal and postmenopausal groups. IR and obesity indices were evaluated according to the six serum ferritin groups. Statistical analysis was carried out using SAS software, version 9.2 (SAS Institute Inc., Cary, NC, USA).ResultsThe association between the IR indices and ferritin groups had a higher level of statistical significance in the postmenopausal group than in the premenopausal group. In addition, for the postmenopausal group, the estimates increased significantly in the sixth ferritin group compared to those in the first ferritin group. However, the association between the obesity indices and ferritin levels was not significantly different between the premenopausal and postmenopausal groups.ConclusionElevated serum ferritin levels were associated with an increased risk of insulin resistance in postmenopausal women.     

Adiponectin is inversely associated with intramyocellular and intrahepatic lipids in obese premenopausal women

Adiponectin, an adipokine secreted by adipocytes, exerts beneficial effects on glucose and lipid metabolism and has been found to improve insulin resistance by decreasing triglyceride content in muscle and liver in obese mice. Adiponectin is found in several isoforms and the high-molecular weight (HMW) form has been linked most strongly to the insulin-sensitizing effects. Fat content in skeletal muscle (intramyocellular lipids, IMCL) and liver (intrahepatic lipids, IHL) can be quantified noninvasively using proton magnetic resonance spectroscopy ((1)H-MRS). The purpose of our study was to assess the relationship between HMW adiponectin and measures of glucose homeostasis, IMCL and IHL, and to determine predictors of adiponectin levels. We studied 66 premenopausal women (mean BMI 31.0 ± 6.6 kg/m(2)) who underwent (1)H-MRS of calf muscles and liver for IMCL and IHL, computed tomography (CT) of the abdomen for abdominal fat depots, dual-energy X-ray absorptiometry (DXA) for fat and lean mass assessments, HMW and total adiponectin, fasting lipid profile and an oral glucose tolerance test (homeostasis model assessment of insulin resistance (HOMA(IR)), glucose and insulin area under the curve). There were strong inverse associations between HMW adiponectin and measures of insulin resistance, IMCL and IHL, independent of visceral adipose tissue (VAT) and total body fat. IHL was the strongest predictor of adiponectin and adiponectin was a predictor of HOMA(IR). Our study showed that in premenopausal obese women HMW adiponectin is inversely associated with IMCL and IHL content. This suggests that adiponectin exerts positive effects on insulin sensitivity in obesity by decreasing intracellular triglyceride content in skeletal muscle and liver; it is also possible that our results reflect effects of insulin on adiponectin.     

Adiponectin is associated with bone mineral density in perimenopausal women.

The aim of the current investigation was to investigate any potential effect of fasting plasma adiponectin concentration on bone tissue, and to find possible relationships of fasting plasma adiponectin level with different body composition, insulin sensitivity and physical performance parameters in a group of healthy perimenopausal women. Twenty-one premenopausal and 17 early postmenopausal women participated in this study. The women were matched for body mass index (BMI) and level of mean daily energy expenditure. Women had similar adiponectin (8.4 +/- 3.9 vs. 9.9 +/- 5.4 microg/ml) and leptin values (12.0 +/- 7.7 vs. 14.0 +/- 8.2 ng/ml) before and after menopause. Significant relationships were observed between plasma adiponectin and bone mineral content, total bone mineral density (BMD) and lumbar spine BMD values (r > - 0.36; p < 0.05). Furthermore, adiponectin had a significant negative association with total BMD (beta = - 1.228; p = 0.004) and lumbar spine BMD (beta = - 0.312; p = 0.005) independent of the influence that other measured body compositional, hormonal or physical performance factors may exert on BMD. Adiponectin was also significantly related to waist-to-hip ratio (WHR) (beta = - 2.300; p = 0.002) and fasting insulin resistance index (FIRI) (beta = - 0.006; p = 0.007) in separate regression models. No relationship was observed between leptin and measured bone, physical performance and insulin resistance values. Leptin significantly correlated to BMI (beta = 0.018; p = 0.034), lean body mass (beta = 0.025; p = 0.024) and fat mass (beta = 0.019; p = 0.001) in separate regression models. In conclusion, the results of present study show that circulating adiponectin appears to exert an independent effect on BMD in perimenopausal women and may represent a link between adipose tissue and bone mineral density.     

Insulin Resistance Distribution and Cut-Off Value in Koreans from the 2008-2010 Korean National Health and Nutrition Examination Survey

BackgroundWe sought to identify the distribution and cut-off value of the ‘homeostasis model assessment of insulin resistance’ (HOMA-IR) according to gender and menopausal status for metabolic syndrome in Koreans.MethodsData were from the Korean National Health and Nutrition Examination Survey in 2008–2010. The subjects included adults aged 20 years or older. We excluded participants who had diabetes or fasting serum glucose ≥ 7 mmol/L. Finally, 11,121 subjects (4,911 men, 3,597 premenopausal women, 2,613 postmenopausal women) were enrolled. The modified Adult Treatment Panel III criteria were used to define metabolic syndrome.ResultsThe mean HOMA-IR was 2.11 (2.07–2.15) for men, 2.0 (1.97–2.04) for premenopausal women, and 2.14 (2.2–2.19) for postmenopausal women. The first cut-off values in men, premenopausal women, and postmenopausal women were 2.23 (sensitivity 70.6%, specificity 66.9%), 2.39 (sensitivity 72.3%, specificity 76.4%), and 2.48 (sensitivity 51.9%, specificity 80.2%), respectively. Based on the first HOMA-IR cut-off value, the prevalence of metabolic syndrome was 22.9% in men, 13.7% in premenopausal women, and 51.6% in postmenopausal women. The second cut-off value was around 3.2 in all three groups. Based on the second HOMA-IR cut-off value, the prevalence of metabolic syndrome was 50.8% in men, 42.5% in premenopausal women, and 71.6% in postmenopausal women.ConclusionIn conclusion, the first cut-off values for HOMA-IR were 2.2–2.5 and the second cut-off value was 3.2 in Korea. The distribution of HOMA-IR showed differences according to gender and menopausal status. When we apply HOMA-IR, we should consider gender, menopausal status, and the prevalence of metabolic syndrome.     

Molecular forms of adiponectin: Comparative evaluation of their correlations with parameters of carbohydrate and lipid metabolism

Interrelationship between total, multimer (MM) and oligomer (OM) adiponectin blood concentrations with some metabolic parameters has been investigated in 49 men and 49 women (mean age of 57.3 ± 10.1 years). We have found negative correlations between total blood adiponectin and its MM form content with body mass index, waist circumference, the insulin resistance index HOMA, with blood concentrations of insulin, glucose, free fatty acids, triglycerides and also positive correlations with high density lipoprotein cholesterol content. There was a poor correlation between OM adiponectin concentration with any parameter studied. According to the regression analysis, concentration of total adiponectin but not its MM form was an independent determinant of the HOMA index in women and free fatty acid concentration in men. In the group of men with the low level of adiponectin its MM form but not total adiponectin reversely correlated with the HOMA index and was its independent determinant. Thus, correlation between blood adiponectin concentration and metabolic parameters is associated with its MM rather than OM form. Study of the role of adiponectin in development of metabolic disorders may be limited to determination of total blood adiponectin concentration except a group of male patients characterized by a low level of this adipokine. In these patients concentrations of the MM form should be determined.     

Adiponectin multimers and metabolic syndrome traits: relative adiponectin resistance in African Americans

African Americans (AAs) tend to have lower total adiponectin levels compared to European Americans (EA); however, it is not known whether race affects adiponectin multimer distribution and their relationships to metabolic traits. We measured total adiponectin, high molecular weight (HMW), low molecular weight (LMW) (i.e., hexamer), and trimer adiponectin in 132 normoglycemic premenopausal women (75 AAs, 57 EAs), together with measures of total and abdominal fat, plasma lipids, insulin sensitivity (S(i)), and genetic admixture estimates. We found that lower total adiponectin in AAs was explained by reduced LMW, and trimer forms because levels of HMW did not differ between races. In EAs, HMW was highly correlated with multiple metabolic syndrome traits. In contrast, the LMW and trimer forms were most highly correlated with metabolic traits in AAs, including abdominal adiposity, lipids, and S(i). At similar levels of visceral adiposity, AAs exhibited significantly lower LMW adiponectin than EAs. Similarly, at comparable levels of HMW and LMW adiponectin, AAs were more insulin resistant than their EA counterparts. In conclusion, (i) serum adiponectin is lower in AAs predominantly as a result of reduced concentrations of LMW and trimers multimeric forms; (ii) LMW and trimer, not HMW, are most broadly correlated with metabolic traits in AAs. Thus, HMW adiponectin may exert less bioactivity in explaining the metabolic syndrome trait cluster in populations of predominant African genetic background.     

Exenatide once weekly treatment maintained improvements in glycemic control and weight loss over 2 years

Background

Latinos in the United States have a higher prevalence of type 2 diabetes than non-Latino whites, even after controlling for adiposity. Decreased adiponectin is associated with insulin resistance and predicts T2DM, and therefore may mediate this ethnic difference. We compared total and high-molecular-weight (HMW) adiponectin in Latino versus white individuals, identified factors associated with adiponectin in each ethnic group, and measured the contribution of adiponectin to ethnic differences in insulin resistance.

Methods

We utilized cross-sectional data from subjects in the Latinos Using Cardio Health Actions to reduce Risk study. Participants were Latino (n = 119) and non-Latino white (n = 60) men and women with hypertension and at least one other risk factor for CVD (age 61 ± 10 yrs, 49% with T2DM), seen at an integrated community health and hospital system in Denver, Colorado. Total and HMW adiponectin was measured by RIA and ELISA respectively. Fasting glucose and insulin were used to calculate the homeostasis model insulin resistance index (HOMA-IR). Variables independently associated with adiponectin levels were identified by linear regression analyses. Adiponectin's contribution to ethnic differences in insulin resistance was assessed in multivariate linear regression models of Latino ethnicity, with logHOMA-IR as a dependent variable, adjusting for possible confounders including age, gender, adiposity, and renal function.

Results

Mean adiponectin levels were lower in Latino than white patients (beta estimates: -4.5 (-6.4, -2.5), p < 0.001 and -1.6 (-2.7, -0.5), p < 0.005 for total and HMW adiponectin), independent of age, gender, BMI/waist circumference, thiazolidinedione use, diabetes status, and renal function. An expected negative association between adiponectin and waist circumference was seen among women and non-Latino white men, but no relationship between these two variables was observed among Latino men. Ethnic differences in logHOMA-IR were no longer observed after controlling for adiponectin levels.

Conclusions

Among patients with CVD risk, total and HMW adiponectin is lower in Latinos, independent of adiposity and other known regulators of adiponectin. Ethnic differences in adiponectin regulation may exist and future research in this area is warranted. Adiponectin levels accounted for the observed variability in insulin resistance, suggesting a contribution of decreased adiponectin to insulin resistance in Latino populations.     

Leptin expression in breast nipple aspirate fluid (NAF) and serum is influenced by body mass index (BMI) but not by the presence of breast cancer.

While obesity is a known risk factor for postmenopausal breast cancer, the molecular mechanisms involved are unclear. Systemic levels of leptin, the product of the ob (obesity) gene, are increased in obese individuals (body mass index, BMI, over 25) and are higher in women than men. Leptin has been found to stimulate the growth of breast cancer cells in vitro. Our goal was to determine whether leptin was 1) present in nipple aspirate fluid (NAF), and 2) whether NAF leptin levels were associated with a) levels in serum, b) obesity, and c) breast cancer. We collected and evaluated NAF specimens from 83 subjects and serum specimens from 49 subjects. NAF leptin was detectable in 16/41 (39 %) of premenopausal and 21/42 (50 %) postmenopausal subjects. NAF leptin was significantly lower (p = 0.042) in premenopausal than postmenopausal women with a BMI < 25, but not in those with a higher BMI. NAF leptin was significantly associated with BMI in premenopausal (p = 0.011) but not in postmenopausal women. Serum leptin was associated with BMI in both premenopausal and postmenopausal women (p = 0.0001 for both). NAF and serum leptin were associated in premenopausal (p = 0.02) but not postmenopausal women. Neither NAF nor serum leptin was associated with premenopausal or postmenopausal breast cancer. Our findings include that 1) leptin is present in the breast and detectable in a subset of NAF samples, 2) NAF leptin in premenopausal but not postmenopausal women parallels serum leptin levels, and 3) neither NAF nor serum levels of leptin were associated with premenopausal or postmenopausal breast cancer.     

Relationship of plasma adiponectin with sex hormone and insulin-like growth factor levels

Objective: Recent studies have suggested that a relationship between adiponectin and sex hormone, prolactin, and insulin‐like growth factor levels could be important for breast cancer risk and insulin sensitivity. Therefore, we assessed the relationship of adiponectin with plasma concentrations of estrone; estradiol; estrone sulfate; testosterone; androstenedione; dehydroepiandrosterone (DHEA); dehydroepiandrosterone sulfate (DHEAS); sex hormone binding globulin (SHBG); prolactin; insulin‐like growth factor (IGF‐1); its binding protein, IGF binding protein 3 (IGFBP‐3); c‐peptide; and IGF binding protein 1 (IGFBP‐1) among 360 postmenopausal women not taking postmenopausal hormones from the Nurses’ Health Study. Research Methods and Procedures: Multivariate models were adjusted for physical activity, alcohol consumption, age at blood draw, age at first birth/parity, fasting status, and time of day of blood draw; a separate model was additionally adjusted for BMI at blood draw. Results: Estrogens were inversely associated with adiponectin levels; however, except for free estradiol, these associations were substantially attenuated after adjustment for BMI. Free estradiol levels were 27% lower among women in the top vs. bottom quartile of adiponectin levels. No consistent associations were observed for the androgens, prolactin, IGF‐1, and IGFBP‐3. However, SHBG, c‐peptide, and IGFBP‐1 were strongly and independently associated with adiponectin levels (r = 0.29, ?0.30, 0.24, respectively). Conclusion: With the exceptions of SHBG, c‐peptide, and IGFBP‐1, the studied analytes were modestly associated with adiponectin and the associations were, in large part, mediated by body fat.     

Lipid and lipoprotein profile in menopausal transition. Effects of hormones, age and fat distribution.

The behavior of lipoproteins during the menopausal transition and their relationship with sex hormones and body fat distribution is still unclear. Our aim was to evaluate atherogenic IDL, LDL, Lp(a) and antiatherogenic HDL lipoproteins in four groups of women: premenopausal (n = 20), menopausal transition women with menstrual bleeding (n = 31), menopausal transition women with 3 to 6 months amenorrhea (n = 36), and postmenopausal women (n = 30). We also measured their FSH, LH and estradiol levels along with BMI and waist circumference. Menopausal transition and postmenopausal women showed higher values of waist circumference (p < 0.0032), LDL-cholesterol (p < 0.002), IDL-cholesterol (p < 0.002) and apoprotein B (p < 0.0001) than premenopausal women. Total-cholesterol (p < 0.0001), triglycerides (p < 0.004), IDL-cholesterol and Lp(a) were higher in menopausal transition women with amenorrhea and in postmenopausal women in comparison with premenopausal women. After adjustment according to age and waist circumference, multiple regression analysis showed the increase in total-cholesterol and LDL-cholesterol to be linearly associated to menopausal status and estradiol concentration, whereas Lp(a) was only related to menopausal status. Age was found to be an independent variable in relation to apoprotein B concentration changes. The effect of menopausal status on TG levels did not remain in the model when age, waist and BMI were included (beta = 0.05, p = 0.356). HDL-cholesterol levels were the same in all the groups. Menopause, age and the increase in abdominal fat distribution were three independent and significant factors impairing lipoprotein profiles from the beginning of the menopausal transition.     

C-Reactive Protein, Waist Circumference, and Family History of Heart Attack are Independent Predictors of Body Iron Stores in Apparently Healthy Premenopausal Women

Ferritin levels have been associated with metabolic syndrome and insulin resistance. The aim of the present study was to evaluate the prediction of ferritin levels by variables related to cardiometabolic disease risk in a multivariate analysis. For this aim, 123 healthy women (72 premenopausal and 51 posmenopausal) were recruited. Data were collected through procedures of anthropometric measurements, questionnaires for personal/familial antecedents, and dietary intake (24-h recall), and biochemical determinations (ferritin, C reactive protein (CRP), glucose, insulin, and lipid profile) in blood serum samples obtained. Multiple linear regression analysis was used and variables with no normal distribution were log-transformed for this analysis. In premenopausal women, a model to explain log-ferritin levels was found with log-CRP levels, heart attack familial history, and waist circumference as independent predictors. Ferritin behaves as other cardiovascular markers in terms of prediction of its levels by documented predictors of cardiometabolic disease and related disorders. This is the first report of a relationship between heart attack familial history and ferritin levels. Further research is required to evaluate the mechanism to explain the relationship of central body fat and heart attack familial history with body iron stores values.     

Circulating High-Molecular-Weight (HMW) Adiponectin Level Is Related with Breast Cancer Risk Better than Total Adiponectin: A Case-Control Study

The level of total adiponectin, a mixture of different adiponectin forms, has been reported associated with breast cancer risk with inconsistent results. Whether the different forms play different roles in breast cancer risk prediction is unclear. To examine this, we measured total and high molecular weight (HMW) adiponectin in a case-control study (1167 sets). Higher circulating HMW adiponectin was negatively associated with breast cancer risk after adjusting for menopausal status and family history of breast cancer (P=0.024). We analyzed the relationship between adiponectin and breast cancer risk in 6 subgroups. Higher circulating HMW adiponectin was also negatively associated with breast cancer risk (P=0.020, 0.014, 0.035) in the subgroups of postmenopausal women, negative family history of breast cancer, BMI>=24.0. Total adiponectin was positively associated with breast cancer (P=0.028) in the subgroup of BMI<=24.0. Higher HMW/total adiponectin ratio was negatively associated with breast cancer (P=0.019) in the subgroup of postmenopausal women. Interestingly, in the subgroup of women with family history of breast cancer, higher circulating total and HMW adiponectin were positively associated with breast cancer risk (P=0.034, 0.0116). This study showed different forms of circulating adiponectin levels might play different roles in breast cancer risk. A higher circulating HMW adiponectin is associated with a decreased breast cancer risk, especially in postmenopausal, without family history of breast cancer or BMI>=24.0 subgroups, whereas higher circulating HMW adiponectin levels is a risk factor in women with a family history of breast cancer. Further investigation of different forms of adiponectin on breast cancer risk is needed.     

Contributions of total and regional fat mass to risk for cardiovascular disease in older women

The aim of this study was to determine whether trunk fat mass, measured by dual-energy X-ray absorptiometry (DEXA), is predictive of insulin resistance and dyslipidemia, independently of arm and leg fat mass, in postmenopausal women. Total and regional body composition was measured by DEXA in 166 healthy, postmenopausal women (66 +/- 4 yr). Four primary markers of insulin resistance and dyslipidemia were assessed: 1) area under the curve for the insulin (INS(AUC)) response to an oral glucose tolerance test (OGTT), 2) product of the OGTT glucose and insulin areas (INS(AUC)xGLU(AUC)), 3) serum triglycerides (TG), and 4) high-density lipoprotein (HDL)-cholesterol. Trunk fat mass was the strongest independent predictor of each of the primary dependent variables. In multivariate regression models, trunk fat mass was associated with unfavorable levels of INS(AUC), INS(AUC)xGLU(AUC), TG, and HDL-C, whereas leg fat mass was favorably associated with each of these variables. Thus trunk fat is a strong independent predictor of insulin resistance and dyslipidemia in postmenopausal women, whereas leg fat appears to confer protective effects against metabolic dysfunction.     

Plasma homocysteine levels increase in women during psychological stress.

Homocysteine is an amino acid that has been strongly associated with vascular disease. Plasma homocysteine concentrations are known to vary with dietary patterns and to decrease with exogenous estrogen use, but no other behavioral factors have been examined as potential modifiers of this risk factor. Because psychological stress has also been implicated in the development of cardiovascular disease, the purpose of this study was to test the hypothesis that acute psychological stress induces elevations in plasma homocysteine concentrations. A secondary aim was to test potential differences in response between premenopausal and postmenopausal women. Thirty-four healthy women, one-half of whom were naturally postmenopausal with no hormone replacement, participated in this study. The psychological stressors included standard mental arithmetic and speech stressors. Blood samples were taken prior to, during, and after the stressors, and heart rate and blood pressure were also monitored. Results indicated significant elevations in plasma homocysteine during acute psychological stress, with a return to baseline concentrations during recovery. The pattern of findings for blood pressure and heart rate was similar, suggesting that the rise in homocysteine concentrations may have been sympathetically-mediated. No effects of menopausal status or endogenous estrogens were found. The findings provide preliminary evidence that plasma homocysteine may be an important factor in the relationship between psychological stress and risk for heart disease.     

Mental stress induces sustained elevation of blood pressure and lipid peroxidation in postmenopausal women

Mental stress is thought to underlie cardiovascular events, but there is information on oxidative stress induced by mental stress in association with cardiovascular responses in women. Using a sensitive assay for plasma 4-hydroxy-2-nonenal (HNE), as a marker for oxidative stress, we addressed the relation between pressor responses and oxidative stress induced by mental or physical stress in premenopausal and postmenopausal women. Healthy subjects (7 postmenopausal and 8 premenopausal women, in early and late follicular phases) were subjected to mental and physical stress evoked by a Color Word Test (CWT) and isometric handgrip, respectively. The CWT induced a rapid elevation of diastolic blood pressure (DBP), at a higher level in the postmenopausal than in the premenopausal women (p<0.01), and this higher DBP was sustained during the CWT and recovery (p<0.01). The CWT induced a significant elevation in plasma noradrenaline in premenopausal women in the early follicular phase and in postmenopausal women (p<0.05). Plasma nitric oxide metabolites were higher in postmenopausal than in the premenopausal women in the late follicular phase (p<0.05), but did not change during exposure to the two types of stress in either group. Plasma HNE was increased during recovery from the CWT, but not the handgrip, in postmenopausal women (2.4 times, p<0.05). There was a significant difference in the time course of the CWT-induced HNE response between the postmenopausal and premenopausal women (p<0.05). These findings suggest that mental, but not physical, stress causes sustained diastolic blood pressure elevation in postmenopausal women, accompanied by heightened oxidative stress.     

Adiponectin represents an independent cardiovascular risk factor predicting serum HDL-cholesterol levels in type 2 diabetes

Low levels of high-density lipoprotein (HDL)-cholesterol represent an independent cardiovascular risk factor and, besides reduced physical activity, mechanisms leading to decreased HDL-cholesterol levels are not known. We aimed to test the hypothesis, that adiponectin provides a missing link between type 2 diabetes and low levels of HDL-cholesterol, independent from common metabolic risk factors. 523 patients with type 2 diabetes were investigated for adiponectin serum levels and parameters of lipid metabolism. Even after correction for age, gender, BMI and fasting insulin concentration, serum levels of adiponectin were highly significant (P<0.0001) and positively (regression analysis: r=0.86) associated with HDL-cholesterol levels in type 2 diabetes. CONCLUSION: adiponectin seems to predict HDL-cholesterol levels in patients with diabetes mellitus type 2. Low levels of adiponectin are associated with low levels of HDL-cholesterol independently from common metabolic risk factors and therefore represent an independent cardiovascular risk factor in type 2 diabetes. Thus, adiponectin is a potentially new drug target in the treatment of dyslipidaemia.