Geum Joon Cho

Postmenopausal status according to years since menopause as an independent risk factor for the metabolic syndrome

Objective: Features of the metabolic syndrome such as abdominal adiposity, insulin resistance, and dyslipidemia develop with the transition from pre- to postmenopausal status in women. We investigated the effects of postmenopausal status on the prevalence of the metabolic syndrome according to years since menopause. Design: We studied 1,002 women, 618 premenopausal and 384 postmenopausal, who participated in annual health examinations at Anam Hospital in Seoul, Korea. Results: Using multivariate logistic regression analysis, we determined that postmenopausal status was an independent risk factor for the metabolic syndrome. Moreover, after controlling for age and body mass index, postmenopausal women had an increased risk of the metabolic syndrome (odds ratio, 2.93; 95% CI, 1.62-5.33) and the abnormalities of its individual components. The risk for the metabolic syndrome increased up to 14 years since menopause, then decreased. For its individual components, postmenopausal women with 5 to 9 years since menopause had the highest risk of high blood pressure; postmenopausal women with less than 5 years since menopause had an increased risk of abdominal obesity and high glucose. With 10 to 14 years since menopause, postmenopausal women had an increased risk of high triglycerides. Conclusions: Postmenopausal status is an independent risk factor for the metabolic syndrome and all of its individual components. The risk for the metabolic syndrome increased up to 14 years since menopause. In addition, postmenopausal status has effects during different periods since menopause for each of these components.

Correlation between estrogens and serum adipocytokines in premenopausal and postmenopausal women.

Objective:The purpose of this study was to investigate the association between serum adipocytokines (adiponectin, resistin, leptin, and tumor necrosis factor &agr; [TNF-&agr;]) and endogenous estrogen (estrone and estradiol) levels in healthy premenopausal and postmenopausal women. Design:This study included 53 healthy premenopausal women, 45 healthy postmenopausal women, and 10 postmenopausal women with the metabolic syndrome who were participating in general health examinations. A secondary analysis was performed on levels of adiponectin, resistin, leptin, TNF-&agr;, estrone (E1), and estradiol (E2). Results:After accounting for body mass index, TNF-&agr; was significantly increased (1.5 ± 0.1 vs 2.0 ± 0.1 pg/mL, P < 0.05) in healthy postmenopausal women as compared with healthy premenopausal women, whereas leptin was decreased (5.6 ± 1.1 vs 4.0 ± 1.1 ng/mL). Estrogen (E1 and E2) was positively correlated with leptin in only healthy premenopausal women, whereas estrogen did not correlate with any adipocytokine in healthy postmenopausal women. In the multiple regression analysis, only leptin significantly contributed to insulin resistance. Combining healthy premenopausal and postmenopausal women, E1 correlated negatively with TNF-&agr; (r = −0.23, P < 0.05) and positively with leptin (r = 0.35, P < 0.01) and did not correlate with resistin. E2 correlated negatively with TNF-&agr; (r = −0.24, P < 0.05) and positively with leptin (r = 0.34, P < 0.01); it did not correlate with adiponectin or resistin. Leptin might stimulate the increase of plasma gonadotropin-releasing hormone levels, which could result in a positive correlation with estrogen in premenopausal women but not in postmenopausal women. Conclusions:Estrogen deficiency resulted in increased TNF-&agr; levels. Serum leptin levels correlated positively with estrogen levels in premenopausal women. However, the increase in obesity in postmenopausal women increased leptin, which increases insulin resistance.

Thyroid stimulating hormone is associated with metabolic syndrome in euthyroid postmenopausal women

OBJECTIVES The aim of this study was to investigate the relationship between thyroid stimulating hormone (TSH) and metabolic syndrome (MetS) in euthyroid postmenopausal women. METHODS We conducted a cross-sectional study of 2205 Korean postmenopausal women. Subjects who were not euthyroid were excluded. Fasting TSH, free thyroxine (FT4), insulin, glucose, and the level of insulin resistance, estimated by the homeostasis model assessment for insulin resistance (HOMA-IR) were measured. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria. RESULTS TSH levels were associated with total cholesterol, LDL-cholesterol, triglycerides and diastolic blood pressure. Using a multiple linear regression analysis, LDL-cholesterol, and triglycerides levels were identified as independently associated with TSH. Multivariate logistic regression analysis determined that TSH levels strongly contributed to MetS. Compared with the lower most quartile (TSH, 0.3-1.44 mIU/L), the adjusted odds ratio for MetS was 1.95 in the upper most quartile (TSH, 2.48-4.00 mIU/L). The prevalence of MetS increased as the TSH quartile showed a gradual increase. CONCLUSION We found a close relationship between TSH and MetS in euthyroid postmenopausal women. Therefore, more attention should be focused on postmenopausal women with high normal TSH levels for the management of cardiovascular disease.

Association of insulin resistance with anti‐Mullerian hormone levels in women without polycystic ovary syndrome (PCOS)

Objective  To explore the relationship of insulin resistance (IR) and adipokines (leptin, adiponectin, RBP4) to anti‐Mullerian hormone (AMH) levels in women without polycystic ovary syndrome (PCOS).

Serum adipocyte fatty acid-binding protein, retinol-binding protein 4, and adiponectin concentrations in relation to the development of the metabolic syndrome in Korean boys: a 3-y prospective cohort study.

BACKGROUND Adipocyte fatty acid-binding protein (A-FABP), retinol-binding protein 4 (RBP4), and adiponectin have been associated with insulin resistance and the metabolic syndrome in adults. OBJECTIVE We evaluated the association of A-FABP, RBP4, and adiponectin with the metabolic syndrome in Korean boys. DESIGN In this prospective cohort study, 159 boys participated in a school-based health examination and were followed up after 3 y. The metabolic syndrome in children was defined by using the pediatric adaptation of the National Cholesterol Education Program criteria. RESULTS Compared with normal-weight participants, overweight children had significantly higher A-FABP (23.6 ± 8.2 compared with 12.8 ± 5.1 μg/L, P < 0.001) and RBP4 (69.3 ± 17.1 compared with 59.7 ± 15.3 μg/mL, P = 0.001) concentrations and significantly lower adiponectin concentrations (11.5 ± 5.4 compared with 18.1 ± 8.4 μg/mL, P < 0.001). Baseline A-FABP concentrations were significantly higher in children who developed the metabolic syndrome than in those who did not, whereas adiponectin concentrations were significantly lower. Baseline RBP4 concentrations were not significantly different between the 2 groups. Multiple logistic regression analysis showed that only A-FABP was an independent predictor of the development of the metabolic syndrome after adjustment for Tanner stage, insulin resistance, body mass index, sleep duration, and physical activity (odds ratio: 17.3; 95% CI: 1.25, 239.76; highest compared with lowest tertile), whereas the significant association between adiponectin and the metabolic syndrome observed by using bivariate analysis reflects, in part, an underlying association with obesity. CONCLUSION A-FABP predicts the development of the metabolic syndrome independently of pubertal status, adiposity, and insulin resistance in Korean boys.

Vitamin D deficiency in gestational diabetes mellitus and the role of the placenta

OBJECTIVE The aim of this study was to evaluate the relationships between maternal vitamin D levels and gestational diabetes mellitus (GDM) and differences in the placental production of vitamin D receptor (VDR), CYP24A, and CYP27B1. STUDY DESIGN Forty normal pregnant women and 20 women with GDM were included in this study. Serum levels of 25-hydroxyvitamin D (25[OH]D) were measured with enzyme-linked immunosorbent assay. The expression and production of VDR, CYP27B1, and CYP24A1 in the placenta were evaluated with real time-polymerase chain reaction and Western blot, respectively. RESULTS We found that 27.5% of normal pregnant women and 85% of women with GDM had vitamin D deficiency, with serum 25(OH)D levels <20 ng/mL. Serum levels of 25(OH)D were lower in women with GDM than normal pregnant women (P < .01). The production of CYP24A1 protein and messenger RNA expression was significantly higher in placental tissue from patients with GDM than in those from normal pregnancies; however, the production of CYP27B1 and VDR protein and messenger RNA expression were not different between 2 the groups. CONCLUSION In this study, vitamin D deficiency was associated with GDM. Given that 25(OH)D is hydroxylated by CYP27B1 to the bioactive 1,25(OH)2D form, and CYP24A1 catabolizes both 25(OH)D and 1,25(OH)2D to the inactive metabolites, respectively, our data indicate that the elevated activity of CYP24A1 in the placenta may play a key role in the development of vitamin D deficiency in GDM.

Cytokine expression in placenta-derived mesenchymal stem cells in patients with pre-eclampsia and normal pregnancies

OBJECTIVES The aim of this study was to investigate the levels of cytokines in placenta-derived mesenchymal stem cells (MSCs) in normal pregnancies and those with pre-eclampsia. MATERIALS AND METHODS C5a, CD40 Ligand, G-CSF, GM-CSF, GROalpha, I-309, sICAM-1, IFN-gamma, IL-1alpha, IL-1beta, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-16, IL-17, IL-17E, IL-23, IL-27, IL-32alpha, IP-10, I-TAC, MCP-1, MIF, MIP-1alpha, MIP-1beta, Serpin E1, RANTES, SDF-1, TNFalpha, and sTREM-1 were measured in mesenchymal stem cells using the human cytokine array panel A. The soluble intracellular adhesion molecule-1 (sICAM-1), stromal-derived factor-1 (SDF-1) and monocyte chemotactic protein-1 (MCP-1) were measured by real-time PCR and confirmed by Western blot analysis. RESULTS MSCs derived from the deciduas of normal pregnancies had significantly elevated levels of sICAM (p=0.000) and SDF-1 (p=0.011), compared to the pregnancies with pre-eclampsia. The level of MCP-1 in the decidua-derived MSCs was not significantly different. No significant difference was observed between normal and pre-eclamptic pregnancies for the amnion-derived MSCs. CONCLUSIONS The decreased levels of sICAM and SDF-1 found in the decidua-derived MSCs from pre-eclamptic pregnancies might be associated with some of the immunological alterations in pre-eclampsia.

Correlations between umbilical and maternal serum resistin levels and neonatal birth weight

Objective. Resistin is a novel hormone secreted by human adipocytes and mononuclear cells. It is expressed in the human placenta, and has been postulated to play a role in the regulation of energy metabolism during pregnancy. However, correlations between umbilical and maternal serum resistin levels and neonatal birth weight remain poorly understood. The purpose of the study was to clarify the correlation between umbilical cord and maternal serum resistin levels and neonatal birth weight. Materials and methods. This study included 37 healthy mothers, neonates. Resistin levels were determined by ELISA, and compared for correlation between umbilical cord and maternal serum resistin levels and neonatal birth weight. Results. The ranges of resistin levels for umbilical and maternal sera were 10.61–40.81 and 1.14–25.54 ng/ml, respectively. Mean umbilical serum resistin level (21.34±1.07 ng/ml) was significantly higher than maternal serum resistin level (10.13±1.12) (p<0.001). Umbilical serum resistin levels were positively correlated with maternal serum resistin levels (r=0.607, p<0.001) and negatively with neonatal birth weight (r= − 0.345, p=0.037). No significant differences in resistin levels were discovered between the female and male neonates. In addition, there were no correlation between the umbilical resistin levels and maternal body mass indices, umbilical leptin levels, or insulin levels. Conclusions. It is suggested that resistin not only affects energy homeostasis by existing in high levels in the fetus, but may play an important role in controlling body weight through effective regulation of adipogenesis by negative feedback.

Calcium intake is inversely associated with metabolic syndrome in postmenopausal women: Korea National Health and Nutrition Survey, 2001 and 2005.

Objective: Calcium intake is known to be associated with the risk of having metabolic syndrome. However, the previous studies did not take into account the fact that intestinal absorption and urinary excretion of calcium are estrogen dependent, and intestinal absorption efficiency and renal conservation of calcium deteriorate after menopause. Therefore, we performed a menopause status-specific analysis of the association between calcium intake and metabolic syndrome. Methods: A total of 9,341 participants (4,118 men, 3,359 premenopausal women, and 1,864 postmenopausal women) from the Korean National Health and Nutrition Examination Survey 2001 and 2005 were included in the study. Results: Calcium and energy intake were significantly higher in men than in women and were lowest in postmenopausal women. On multivariate logistic regression analysis, postmenopausal women with calcium intake in the fourth quartile had a lower risk of having metabolic syndrome (odds ratio, 0.637; 95% CI, 0.452-0.898) compared with women with intake in the first quartile after adjustment for age, body mass index, marital status, education level, alcohol intake, smoking history, exercise, hormone therapy use, and energy intake. However, no association was detected in men and premenopausal women. Conclusions: Calcium intake is inversely associated with the risk of having metabolic syndrome in postmenopausal women. Prospective or longitudinal studies concerning sex and menopause status are necessary to evaluate an association between calcium intake and metabolic syndrome.

High-risk human papillomavirus infection is associated with premature rupture of membranes

BackgroundHuman papillomavirus (HPV) is known to be more prevalent in spontaneous abortions than in elective terminations of pregnancy. More recently, placental infection with HPV was shown to be associated with spontaneous preterm delivery. However, no study has evaluated the prevalence of HPV infection in pregnant Korean females and its association with adverse pregnancy outcomes.MethodsWe conducted a cross-sectional study of 311 females who gave birth at Korea University Medical Center. Our sample included 45 preterm deliveries, 50 cases of premature rupture of the membranes (PROM), 21 preeclampsia cases, and 8 gestational diabetes mellitus (GDM) patients. We used the Hybrid Capture II system to detect high-risk (HR)-HPV infection at six weeks postpartum.ResultsThe prevalence of HR-HPV infection was 14.1%. Women with HR-HPV infection had a higher incidence of PROM than those without HR-HPV. HR-HPV infection was associated with an increased risk of PROM (OR, 2.380; 95% CI, 1.103-5.134). The prevalence of preterm delivery, preeclampsia, or GDM was not different between the two groups.ConclusionsWe observed a high prevalence of HR-HPV infection in pregnant women. Moreover, HR-HPV infection was associated with a risk of PROM at term. Further studies are needed to evaluate mechanisms by which HR-HPV infection induces PROM.