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The adipokine profile of metabolically benign obese and at-risk normal weight postmenopausal women: the Women's Health Initiative Observational Study.

ABSTRACT: OBJECTIVE:Nearly, a third of obese individuals, termed metabolically benign obese, have a low burden of adiposity-related cardiometabolic abnormalities, whereas a substantial proportion of normal-weight individuals possess risk factors. METHODS:In cross-sectional analyses of 699 normal weight and 1,294 overweight/obese postmenopausal women enrolled in a nested case-control stroke study ancillary to the Women's Health Initiative Observational Study, we compared levels of adiponectin, leptin, and resistin among metabolically benign normal weight, at-risk normal weight, metabolically benign obese, and at-risk obese women using components of the ATP III definition of the metabolic syndrome (metabolically benign: ?1 of the four components; at-risk phenotype: ?2 components or diabetes). RESULTS:Overall, 382/699 normal-weight women (54.6%) and 328/1,194 overweight/obese women (27.5%) were metabolically benign. Among normal-weight women, at-risk women had higher leptin and lower adiponectin levels compared to metabolically benign women; multivariate-adjusted odds ratios were significant for having leptin (OR: 2.51; 95% CI: 1.28-5.01) and resistin (1.46; 1.03-2.07) in the top tertile and adiponectin in the bottom tertile (2.64; 1.81-3.84). Compared to metabolically benign overweight/obese women, at-risk obese women had higher odds of having leptin in the top tertile (1.62; 1.24-2.12) and adiponectin in the bottom tertile (2.78; 2.04-3.77). CONCLUSIONS:Overall, metabolically benign overweight/obese women had an intermediate adipokine profile (between at-risk obese and metabolically benign normal-weight women), whereas at-risk normal-weight women had a less favorable profile compared to metabolically benign normal-weight women. As adiponectin was the only adipokine independent of BMI, it may be most likely to have a role in the etiological pathway of these phenotypes.

SUBMITTER: Khan UI

PROVIDER: S-EPMC3883802 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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The adipokine profile of metabolically benign obese and at-risk normal weight postmenopausal women: the Women's Health Initiative Observational Study.

Khan Unab I UI Ogorodnikova Alexandra D AD Xu Linzhi L Wang Dan D Wassertheil-Smoller Sylvia S Ho Gloria Y F GY Sowers Mary Fran R MF Rajpathak Swapnil N SN Allison Matthew A MA Mackey Rachel H RH Vitolins Mara Z MZ Manson Joann E JE Wildman Rachel P RP

Obesity (Silver Spring, Md.) 20131220 3

<h4>Objective</h4>Nearly, a third of obese individuals, termed metabolically benign obese, have a low burden of adiposity-related cardiometabolic abnormalities, whereas a substantial proportion of normal-weight individuals possess risk factors.<h4>Methods</h4>In cross-sectional analyses of 699 normal weight and 1,294 overweight/obese postmenopausal women enrolled in a nested case-control stroke study ancillary to the Women's Health Initiative Observational Study, we compared levels of adiponecti ...[more]

PMID: 24357553

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Project description:ObjectivesTo determine associations between postmenopausal change in body weight and incidence of fracture and associations between voluntary and involuntary weight loss and risk of fracture.DesignPost hoc analysis of data from the Women's Health Initiative Observational Study and Clinical Trials.Setting40 clinical centers in the United States.Participants120,566 postmenopausal women, aged 50-79 at baseline (1993-98), followed through 2013 (mean fracture follow-up duration 11 years from baseline).ExposuresAnnualized percentage change in measured body weight from baseline to year 3, classified as stable (<5% change), weight loss (≥ 5%), or weight gain (≥ 5%). Self assessment of whether weight loss was intentional or unintentional. Cox proportional hazards regression models were adjusted for age, race/ethnicity, baseline body mass index (BMI), smoking, alcohol intake, level of physical activity, energy expenditure, calcium and vitamin D intake, physical function score, oophorectomy, hysterectomy, previous fracture, comorbidity score, and drug use.Main outcomesIncident self reported fractures of the upper limbs, lower limbs, and central body; hip fractures confirmed by medical records.ResultsMean participant age was 63.3. Mean annualized percent weight change was 0.30% (95% confidence interval 0.28 to 0.32). Overall, 79,279 (65.6%) had stable weight; 18,266 (15.2%) lost weight; and 23,021 (19.0%) gained weight. Compared with stable weight, weight loss was associated with a 65% higher incidence rates of fracture in hip (adjusted hazard ratio 1.65, 95% confidence interval 1.49 to 1.82), upper limb (1.09, 1.03 to 1.16), and central body (1.30, 1.20 to 1.39); weight gain was associated with higher incidence rates of fracture in upper limb (1.10, 1.05 to 1.18) and lower limb (1.18, 1.12 to 1.25). Compared with stable weight, unintentional weight loss was associated with a 33% higher incidence rates of hip fracture (1.33, 1.19 to 1.47) and increased incidence rates of vertebral fracture (1.16, 1.06 to 1.26); intentional weight loss was associated with increased incidence rates of lower limb fracture (1.11, 1.05 to 1.17) and decreased incidence of hip fracture (0.85, 0.76 to 0.95).ConclusionsWeight gain, weight loss, and intentional weight loss are associated with increased incidence of fracture, but associations differ by fracture location. Clinicians should be aware of fracture patterns after weight gain and weight loss.

Project description:BACKGROUND. Obesity is associated with insulin resistance and increased intrahepatic triglyceride (IHTG) content, both of which are key risk factors for diabetes and cardiovascular disease. However, a subset of obese people does not develop these metabolic complications. Here, we tested the hypothesis that people defined by IHTG content and insulin sensitivity as "metabolically normal obese" (MNO), but not those defined as "metabolically abnormal obese" (MAO), are protected from the adverse metabolic effects of weight gain. METHODS. Body composition, multiorgan insulin sensitivity, VLDL apolipoprotein B100 (apoB100) kinetics, and global transcriptional profile in adipose tissue were evaluated before and after moderate (~6%) weight gain in MNO (n = 12) and MAO (n = 8) subjects with a mean BMI of 36 ± 4 kg/m2 who were matched for BMI and fat mass. RESULTS. Although the increase in body weight and fat mass was the same in both groups, hepatic, skeletal muscle, and adipose tissue insulin sensitivity deteriorated, and VLDL apoB100 concentrations and secretion rates increased in MAO, but not MNO, subjects. Moreover, biological pathways and genes associated with adipose tissue lipogenesis increased in MNO, but not MAO, subjects. CONCLUSIONS. These data demonstrate that MNO people are resistant, whereas MAO people are predisposed, to the adverse metabolic effects of moderate weight gain and that increased adipose tissue capacity for lipogenesis might help protect MNO people from weight gain-induced metabolic dysfunction. TRIAL REGISTRATION. ClinicalTrials.gov NCT01184170. FUNDING. This work was supported by NIH grants UL1 RR024992 (Clinical Translational Science Award), DK 56341 (Nutrition and Obesity Research Center), DK 37948 and DK 20579 (Diabetes Center Grant), and UL1 TR000450 (KL2 Award); a Central Society for Clinical and Translational Research Early Career Development Award; and by grants from the Longer Life Foundation and the Kilo Foundation.

Project description:Background:After menopause, several androgens continue to be produced primarily by the adrenal glands; these can be converted into estrogens via aromatization or into androgen metabolites. It is unclear if androgens are associated with endometrial cancer risk independently of their being precursors to estrogens or if alternative metabolic pathways influence risk. Methods:We measured prediagnostic serum concentrations of 12 androgens and their metabolites using highly sensitive liquid chromatography-tandem mass spectrometry assays in a nested case-control study of postmenopausal women from the Women's Health Initiative Observational Study (313 endometrial cancer case subjects, 354 matched control subjects). Estrogens were previously assayed. We used conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for endometrial cancer with adjustment for confounders. Results:Compared to the lowest concentrations, the highest levels of adrenal androgens were associated with increased endometrial cancer risk: dehydroepiandrosterone (5th vs 1st quintile: OR = 1.85, 95% CI = 1.06 to 3.25), androstenedione (OR = 2.36, 95% CI = 1.34 to 4.16), and testosterone (OR = 1.91, 95% CI = 1.12 to 3.24). Downstream androgen metabolites were not associated with endometrial cancer. Although increased risks for the parent androgens were still suggested after adjustment for unconjugated estradiol, the associations attenuated, and with the exception of androstenedione, were no longer statistically significant. We also evaluated ratios of estrogens relative to their androgenic precursors; both higher unconjugated estrone:androstenedione and higher unconjugated estradiol:testosterone were associated with increased endometrial cancer risk. Conclusions:We identified increased risks for endometrial cancer with the highest levels of adrenal androgens and high levels of estrogens relative to these androgens. As adrenal androgens can be aromatized to estrogens, this suggests androgens likely influence endometrial carcinogenesis via estrogen metabolism.

Project description:BACKGROUND:Hormonal and reproductive factors contribute to the development of ovarian cancer, but few studies have examined associations between circulating estrogens and estrogen metabolites and ovarian cancer risk. We evaluated whether serum estrogens and estrogen metabolite levels are associated with ovarian cancer risk among postmenopausal women in a nested case-control study in the Women's Health Initiative (WHI) Observational Study (OS). METHODS:We selected all 169 eligible epithelial ovarian cancer cases and 412 matched controls from women enrolled in WHI-OS who were not using menopausal hormones at baseline. Baseline levels of 15 estrogens and estrogen metabolites were measured via liquid chromatography/tandem mass spectrometry. Associations with ovarian cancer risk overall and stratified by histologic subtype (serous/nonserous) were analyzed using logistic regression. The mean time from serum collection to cancer diagnosis was 6.9 years. RESULTS:Overall, we observed modest ovarian cancer risk associations among women with higher levels of estrone [OR (95% confidence interval) quintile (Q)5 vs. Q1: 1.54 (0.82-2.90), Ptrend = 0.05], as well as 2- and 4-methoxyestrone metabolites [2.03 (1.06-3.88), Ptrend = 0.02; 1.86 (0.98-3.56), Ptrend = 0.01, respectively]. Associations of estrogens and estrogen metabolites varied substantially by histologic subtype. Associations with serous tumors were universally null, while estrone [2.65 (1.09-6.45), Ptrend = 0.01, Pheterogeneity = 0.04], unconjugated estradiol [2.72 (1.04-7.14), Ptrend = 0.03, Pheterogeneity = 0.02] and many of the 2-, 4-, and 16-pathway metabolites were positively associated with nonserous tumors. CONCLUSIONS:Our study provides novel molecular data showing an association of the parent estrogens and several estrogen metabolites with nonserous ovarian cancers. IMPACT:These findings further support the heterogeneous etiology of ovarian cancer. Cancer Epidemiol Biomarkers Prev; 25(4); 648-56. ©2016 AACR.

Project description:ObjectiveWith the rise in obesity, there has been a concomitant increase in prescription medications associated with weight gain. The objective of this study is to quantify the magnitude of association between putative weight-promoting medications and 3-year weight change in a diverse cohort of postmenopausal women in the Women's Health Initiative (WHI).MethodsThis is a prospective observational cohort study, considering 40 sites in the WHI and a cohort of seventy six thousand two hundred fifty-two postmenopausal women aged 50-79 years, with weight measured at both baseline and 3 years, in the WHI-Observational Study. Body mass index (BMI) and waist circumference (WC) were measured at baseline and 3 years. An in-clinic medication inventory identified prescribed medications, including antidepressants, beta-blockers, insulin, and/or glucocorticosteroids. Generalized linear models evaluated if intermittent or persistent use of weight-promoting drugs was associated with increased BMI and WC during a 3-year follow up.ResultsWomen with overweight or obesity at baseline were more likely to be taking antidepressants, beta-blockers, and/or insulin. Taking at least one putative weight-promoting medication was associated with a greater increase in BMI (0.37 vs 0.27 kg/m, P = 0.0045) and WC (1.10 cm vs 0.89 cm, P = 0.0077) over the course of 3 years compared to women not on these medications. Both BMI and WC increased with the number of weight-promoting drugs prescribed (P for trend per medication used < 0.00001 for both variables). Those who took either antidepressants or insulin, or a combination of antidepressants and beta-blockers, were most likely to have a significant increase in BMI compared to nonusers.ConclusionsAntidepressants, beta-blockers, and insulin were associated with weight gain in postmenopausal women. This information may help to inform clinical decision-making and efforts to mitigate medication-related weight gain. : Video Summary:http://links.lww.com/MENO/A617.

Dataset Information

The adipokine profile of metabolically benign obese and at-risk normal weight postmenopausal women: the Women's Health Initiative Observational Study.

Publications

The adipokine profile of metabolically benign obese and at-risk normal weight postmenopausal women: the Women's Health Initiative Observational Study.

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