Soon Cheol Hong

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.

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.

Significance of CD44v6 expression in gynecologic malignancies

Aim:  Variants of CD44 have been proposed to be important in cancer invasion and metastasis. The purpose of this study was to evaluate the diagnostic and prognostic value of CD44v6 expression in gynecologic malignancies.

Preventive effects of folic acid supplementation on adverse maternal and fetal outcomes.

Although there is accumulating evidence regarding the additional protective effect of folic acid against adverse pregnancy outcomes other than neural tube defects, these effects have not been elucidated in detail. We evaluated whether folic acid supplementation is associated with favorable maternal and fetal outcomes. This was a secondary analysis of 215 pregnant women who were enrolled in our prior study. With additional data from telephone interviews regarding prenatal folic acid supplementation, existing demographic, maternal and fetal data were statistically analyzed. The concentration of folic acid in maternal blood was significantly higher following folic acid supplementation (24.6 ng/mL vs.11.8 ng/mL). In contrast, homocysteine level in maternal blood decreased with folic acid supplementation (5.5 µmol/mL vs. 6.8 µmol/mL). The rates of both preeclampsia (odds ratio [OR], 0.27; 95% confidence interval [CI], 0.09–0.76) and small for gestational age (SGA; 9.2% vs. 20.0%; OR, 0.42; 95% CI, 0.18–0.99) were lower in the folic acid supplementation group than those in the control group. Other pregnancy outcomes had no association with folic acid supplementation. The findings indicate that folic acid supplementation may help to prevent preeclampsia and SGA. Further studies are warranted to elucidate the favorable effects of folic acid supplementation on pregnancy outcomes.

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.

Homocysteine, folate and pregnancy outcomes

The purpose of this study is to evaluate the relationship between maternal and/or cord blood folate/homocysteine concentrations and adverse pregnancy outcomes. The study population included a random sample of singleton pregnant women in whom we measured total homocysteine and folic acid in maternal or cord blood at deliveries. A total of 227 pregnant women were enrolled. The concentration of folate in maternal blood tended to be significantly lower in pre-term birth than in full-term delivery group (median (95% CI), 14.4 (3.6–73) vs 25 (7.3–105.5) p < 0.01). The total homocysteine in maternal and cord blood was significantly higher in the pre-eclampsia than in the normotensive group (7.9 (1.7–28.2) vs 5.9 (1.8–14.6) μmol/ml, p < 0.05; and 5.8 (2.6–14.4) vs 4.2 (0.7–7.9) ng/ml, p < 0.05, respectively). Lower maternal serum folate concentration is associated with pre-term delivery and higher maternal plasma homocysteine concentration with pre-eclampsia.

Serum levels of YKL-40 and interleukin-18 and their relationship to disease severity in patients with preeclampsia

Preeclampsia is a disease associated with the maternal inflammatory response. YKL-40 and interleukin-18 (IL-18) are inflammatory markers involved in inflammatory states and vascular processes. The aim of this study was to evaluate serum levels of YKL-40 and IL-18 in preeclampsia. Twenty-four patients with preeclampsia and 13 healthy pregnant women were included in this study. Serum levels of YKL-40 and IL-18 were measured using an enzyme-linked immunosorbent assay (ELISA). Serum YKL-40 levels were significantly higher in patients with preeclampsia (median 75.0 ng/mL; range 45.8-125.4 ng/mL) than in normal pregnant women (median 29.3 ng/mL; range 16.2-39.5 ng/mL; p=0.000). Serum IL-18 levels were also significantly higher in patients with preeclampsia (median 159.9 pg/mL; range 125.6-193.5 pg/mL) than in normal pregnant women (median 120.2 pg/mL; range 102.2-157.9 pg/mL; p=0.018). Notably, higher serum YKL-40 levels were observed in patients with more severe proteinuria (>or=3+ by dipstick) than in patients with milder proteinuria (<or=1+ by dipstick; median 121.3 ng/mL, range 63.5-146.7 ng/mL versus median 55.4 ng/mL, range 29.4-116.3 ng/mL; p=0.022). There was, however, no significant difference in serum IL-18 levels between patients with more severe proteinuria and those with milder proteinuria. We conclude that circulating YKL-40 and IL-18 are elevated in patients with preeclampsia, and levels of YKL-40 are related to the severity of the disease.

Secular Trends of Gestational Diabetes Mellitus and Changes in Its Risk Factors

Objective The aim of this study was to evaluate the secular trends of incidence of gestational diabetes mellitus (GDM) and insulin treatment for GDM in a Korean population and to determine the factors that contribute to the trends in the incidence of GDM. Study Design We used data collected by the Health Insurance Review & Assessment Service of Korea and analyzed data from women who had given birth from 2006 to 2010. We evaluated the trends in the incidence of GDM and GDM requiring insulin treatment and the changes in risk factors. Results There were 1,824,913 births during the study period, which included 129,666 cases of GDM, an incidence of 7.11% over this period. The incidence of GDM increased from 3.86% in 2007 to 11.83% in 2010, with a continuous increase after adjustment for age. However, the number of GDM cases that required insulin treatment decreased significantly from 13.87% in 2007 to 5.94% in 2010. The proportion of patients who were at an older age and multiparity, 2 GDM risk factors, increased during the study period. Conclusions In Korea, the incidence of GDM, especially mild GDM, increased dramatically during the period from 2006 to 2010. Further efforts are needed to monitor this trend and to identify associated factors.