Lourdes Basurto

Relationship Between Circulating Adipokines and Insulin Resistance During Pregnancy and Postpartum in Women with Gestational Diabetes

BACKGROUND AND AIMS We undertook this study to assess the relationship between circulating adipokines and insulin resistance during pregnancy and postpartum in women with gestational diabetes mellitus (GDM). METHODS This was a prospective study including 60 women with GDM and 60 subjects with normal gestation who were evaluated at gestational week 30, 6 weeks and 6 months postpartum. Circulating adipokines that were evaluated during the study were leptin, adiponectin, retinol-binding protein-4 (RBP4), and tumor necrosis factor-alpha (TNF-α). RESULTS Women with GDM showed higher insulin resistance measured by HOMA-IR than subjects with normal gestation (2.3 ± 2.3 vs. 1.3 ± 0.95). There was no difference between groups in adipokines; however, in women with a healthy pregnancy, RBP4 was associated with insulin resistance (r = 0.47, p <0.05). At 6 weeks and 6 months postpartum, women with previous GDM exhibited persistent elevated leptin and insulin resistance. RBP4 was associated with insulin resistance only in women with a previous healthy pregnancy (r = 0.51, p <0.05). In addition, progressively impaired glucose tolerance was observed after delivery in women with previous GDM. CONCLUSIONS It was demonstrated that GDM is associated with greater insulin resistance than observed in normal pregnancy; however, adipokines are similar in both groups. RBP4 levels are significantly associated with insulin resistance in healthy women during pregnancy and postpartum. After a pregnancy complicated by GDM, leptin and insulin resistance remain elevated and glucose tolerance worsens.

Adiponectin is associated with low bone mineral density in elderly men

OBJECTIVE Recent evidence suggests that adiponectin may play a role in bone metabolism. Previous studies demonstrated that the adiponectin levels had a negative correlation with bone mineral density (BMD) in women. However, little is known about the relationship between adiponectin and BMD in men. The aim of this study was to determinate the relationship between the adiponectin levels and BMD in elderly men. DESIGN Cross-sectional study including 92 healthy men aged 60-80 years. METHODS Main outcome measures were the adiponectin levels estimated by RIA and BMD at lumbar spine and femoral neck using dual energy X-ray absorptiometry. Results The negative correlation between adiponectin and BMD at the spine was r=-0.209, (P<0.05) and at the femoral neck was r=-0.237, (P<0.001). These correlations disappeared after adjustment for body mass index (BMI). When stratified by BMI, the relationship between BMD and adiponectin remained significant in the subgroup of participants with BMI >27 kg/m(2), but disappeared in men with BMI <or=27 kg/m(2). In multiple regression analysis, adiponectin was a significant determinant of BMD at the spine, not at the femoral neck, in those with BMI >27. CONCLUSION BMD is negatively associated with the adiponectin levels in men older than 60 years and this relationship is greater in those men with BMI >27, which suggests a plausible connection between bone and fat tissue.

Transdermal estradiol in menopausal women depresses interleukin-6 without affecting other markers of immune response

Objective: The aim of this study was to analyze the effect of transdermal estradiol replacement therapy (HRT) on immune function in menopausal women. Study Design: A prospective comparative study was carried out in 30 women, aged 48–55 years, who were divided into two groups; 20 of them received transdermal estradiol 50 µg/day during 3 months and 10 who refused to receive HRT served as controls. Serum interleukins were quantified by specific immunoenzymatic assays; in addition, hormones of somatotropin axis and prolactin (PRL) were quantified by IRMA and RIA. Results: Baseline elevated interleukin (IL)-6 levels decreased significantly (p < 0.001) after transdermal HRT as compared with the nontreated group. Contrarily, IL-2 and IL-10 levels as well as mitogenic induced T-cell proliferation were unchanged under HRT. Insulin-like growth factor-I, growth hormone and PRL levels were unaltered by transdermal HRT. Conclusion: Decrement of IL-6 in parallel with absent effect on some indices of immune activity suggests a beneficial action of transdermal HRT. These findings contrast with those demonstrating an increment of immune response in women taking oral HRT. Thus, the route of administra tion determines the effect of HRT on immune function.

Effect of testosterone therapy on lumbar spine and hip mineral density in elderly men

Objective. The aim of the present study was to analyse the effect of testosterone therapy on bone mineral density in healthy elderly men who had low levels of total testosterone. Design. Randomized, double-blind, placebo-controlled study. Participants. Forty-eight men over 60 years old with decreased testosterone levels (≤320 ng/dL) comprised the study. Twenty-five out of 48 received intramuscular injections of testosterone enanthate every three weeks during 12 months; the remaining 23 participants formed the control group. All participants had measurements of bone mineral density (BMD) in both lumbar spine and hip before and at the end of the study as well as testosterone and 17-β estradiol levels. Results: Testosterone treated group exhibited a significant (p < 0.05) increment (from 1.198 ± 0.153 to 1.240 ± 0.141 g/cm2) in lumbar BMD in parallel with a significant (p < 0.001) increment (from 301 ± 32 to 471 ± 107 ng/dL) in testosterone concentrations, whereas no significant change occurred in femoral neck BMD. Conclusions. Testosterone therapy elicited a positive effect only in lumbar BMD in elderly men with diminished testosterone serum levels.

Hormone replacement therapy increases ACTH/dehydroepiandrosterone sulfate in menopause

OBJECTIVE To demonstrate that hypoestrogenism in menopause is in part responsible for the decrease in circulating dehydroepiandrosterone sulfate (DHEA-S) and ACTH levels. To test this hypothesis, 25 postmenopausal women aged 47-60 years, were given orally conjugated equine estrogen (CEE) to study the effect on circulating DHEA-S, cortisol and ACTH. DESIGN A prospective, non-blinded study was performed. Hormonal levels were analyzed before and after three cycles of CEE 0.625 mg/day for 21 days followed each by chlormadinone acetate for 5 days. RESULTS Low baseline levels of DHEA-S increased significantly after HRT (1.71+/-0.75 to 3.3+/-1.5 micromol/l, (P<0.001). ACTH levels augmented moderately from 3.26+/-1.4 to 4.7+/-1.8 pmol/l (P<0.05) and cortisol from 350.4+/-118 to 450.8+/-144 nmol/l (P<0.01). A positive correlation was obtained between 17 beta-estradiol and ACTH (r=0.48), estradiol and cortisol (r=0.52) as well as estradiol and DHEA-S (r=0.60). In addition, the correlation was highly significant (P<0.001) between ACTH and DHEA-S at the term of HRT. CONCLUSION HRT increased DHEA-S, ACTH and cortisol concentrations, which may suggest that this therapy may exert a stimulatory effect on the pituitary gland when baseline hypoestrogenism is present, but further studies are required to clarify the mechanism underlying this process.

Serum leptin and somatotropin components correlate with neonatal birth weight.

Objective: To determine whether cord sera leptin and components of the somatotropin axis – growth hormone (GH), total (t) and free (f) insulin-like growth factor (IGF), IGF-binding protein-3 (IGFBP-3), and insulin – correlate with birth weight. Design: Cross-sectional study of 22 newborns, 12 with normal birth weight (NBW) and 10 with low birth weight (LBW), in a population of healthy mothers with an apparent normal pregnancy. Methods: Paired mother–neonate blood samples were obtained at vaginal delivery in order to measure leptin and the somatotropin axis components. Results: In all cases maternal blood concentrations of leptin, t and fIGF-I, its carrier protein IGFBP-3, and insulin were higher than in the cord sera of the newborns, regardless of their birth weight. On the contrary, maternal GH levels were lower than in their neonates. LBW neonates had decreased levels of leptin, tIGF-I, and IGFBP-3 as compared with those levels in NBW offspring; however, GH concentrations were higher in LBW neonates. Birth weight showed a significant correlation with cord sera leptin, tIGF-I, IGFBP-3, and GH; nevertheless birth weight was neither interrelated with fIGF-I nor with insulin levels. Conclusion: These data demonstrate that birth weight is significantly correlated with both leptin and some components of the somatotropin axis; on the other hand, no correlation was observed between leptin concentrations and each one of the components of the somatotropin axis. It is suggested that fetal leptin and the somatotropin axis cooperate in intrauterine growth and birth weight.

Women with Gestational Diabetes Develop Glucose Intolerance with High Frequency within One Year Postpartum

Objective: To investigate the incidence of glucose intolerance postpartum in women with gestational diabetes (GDM) and assess body weight, cholesterol and triglyceride concentrations after delivery. Methods: This was a study of an initial cohort of 100 women with GDM who were tested at 6 weeks, 6 months, and 1 year postpartum. Postpartum evaluations were glucose tolerance, weight and cholesterol and triglycerides. Results: Impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) was present in 36.5% of 52 participants who were assessed at 6 weeks postpartum and diabetes in 17.3%; the remaining 48 women failed to return for the 3 evaluations. By 6 months, IFG/IGT was demonstrated in 55.8% and diabetes in 32.7% of the women. At 1 year, 46.2% exhibited IFG/IGT and 48% diabetes. Moreover, the weight was higher in those women who presented IFG/IGT (75.5 ± 15.2 kg, mean ± SD) and diabetes (79.0 ± 16.2 kg) compared with those who had normal glucose tolerance (65.3 ± 14.5 kg; p < 0.05). In addition, triglycerides were higher in mothers with glucose intolerance (181.3 ± 85.9 mg/dl in IFG/IGT and 230.9 ± 90.9 mg/dl in diabetes) than in women with normal glycemia (147.8 ± 11.2 mg/dl; p < 0.05). Conclusion: We demonstrated an increased incidence of women exhibiting glucose intolerance within 1 year postpartum, mainly in those who remained obese.

Effect of Pulsed Estrogen Therapy on Hemostatic Markers in Comparison with Oral Estrogen Regimen in Postmenopausal Women

Background/Aims: Hormone replacement therapy (HRT) is associated with an increased risk of thromboembolism dependent on the type of HRT; therefore, we compared therapy effects of intranasal with oral estrogens on coagulation and fibrinolysis markers in postmenopausal women. Methods: A randomized study in which 29 healthy hysterectomized women received intranasal 17β-estradiol or oral estrogens for 3 months. Results: There were no significant differences in the baseline characteristics between groups. Those women receiving intranasal estradiol showed a mild increment in plasminogen activator inhibitor-1 (PAI-I) (from 6.8 ± 3.5 to 9.6 ± 3.9 U/ml, p < 0.01); however, fibrinogen, factor VII-tissue factor complex (VIIa-rTF), antithrombin III (ATIII), protein C (PC) activity, protein S (PS) activity, plasminogen (PLG), and tissue-type plasminogen activator antigen (t-PA) were unchanged. In contrast, oral unopposed estrogens elevated t-PA (from 4.9 ± 2.9 to 9.6 ± 5.1 ng/ml, p < 0.01) in parallel with a decrement in PAI-I (from 5.2 ± 4.0 to 2.7 ± 1.7 U/ml, p < 0.05) and VIIa-rTF (from 201.2 ± 181.0 to 140.6 ± 108.7 mU/ml, p < 0.05). Fibrinogen, ATIII, PC, PS, and PLG were unchanged. Conclusions: Nasal 17β-estradiol had no effect on the coagulation markers, except a moderate increment in PAI-1. In contrast, oral estrogens elicited a decrement in both VIIa-rTF and PAI-1; however, those changes did not surpass normal limits.

Low-dose conjugated equine estrogens elevate circulating neurotransmitters and improve the psychological well-being of menopausal women

OBJECTIVE To assess the effect of low-dose conjugated equine estrogens (E) on circulating neurotransmitters and the efficacy for the treatment of psychological symptoms. DESIGN Controlled comparative clinical study. SETTING Endocrine Research Unit, Instituto Mexicano del Seguro Social, Mexico. PATIENT(S) Thirty postmenopausal women received conjugated equine E. Ten women acted as a comparison group. INTERVENTION(S) Conjugated equine E, 0.312 mg/day, for 21 days per cycle during six cycles and added chlormadinone acetate, 2 mg/day, for the last 5 days of each cycle. Green scale for climateric women and Blatt-Kupperman Menopausal Index were used for measuring psychological well-being. MAIN OUTCOME MEASURE(S) Serum levels of dopamine (DA), noradrenaline, serotonin, and beta-endorphin were quantified by specific assays at baseline and at the end of treatment. RESULT(S) Low baseline levels of DA, serotonin, and beta-endorphin increased significantly (P<.001) from 181.9 +/- 47.8 pg/mL to 202.9 +/- 32.8 pg/mL (mean +/- SD); from 206.4 +/- 94.2 ng/mL to 279.2 +/- 67.9 ng/mL; from 11.2 +/- 1.8 pmol/L to 13.8 +/- 2.4 pmol/L, respectively, after conjugated equine E. In parallel, augmented baseline noradrenaline levels diminished significantly (P<.05) from 30.2 +/- 4.7 ng/mL to 24.0 +/- 4.7 ng/mL. All neurotransmitter levels had a significant correlation with 17beta-E(2) concentrations at the end of the study. Alleviation of psychological symptoms was observed in all but eight treated women. CONCLUSION(S) Low-dose conjugated equine E associated with periodic administration of chlormadinone acetate elicited favorable changes in neurotransmitters and relieved psychological symptoms.

Gene variants in the FTO gene are associated with adiponectin and TNF-alpha levels in gestational diabetes mellitus

BackgroundObesity may have a role in the development of gestational diabetes mellitus (GDM). Single-nucleotide-polymorphisms (SNPs) of the FTO (fat mass and obesity associated) gene have been associated with obesity. The aim of this study was to investigate SNPs rs8050136, rs9939609, and rs1421085 of the FTO gene in women with GDM and their associations with maternal pre-pregnancy weight and body mass index, gestational weight gain and mediators of insulin resistance in GDM like leptin, adiponectin, ghrelin and tumor necrosis factor-alpha (TNF-alpha), compared with healthy pregnant controls.Methods80 women with GDM and 80 women with normal pregnancy were considered for the present study. Genotyping of selected SNPs in all study subjects was done using the Taq-Man assay and the adipokines and ghrelin were measured by immunoassays. Chi square test, odds ratios (OR) and their respective 95% confidence intervals were used to measure the strength of association between FTO SNPs and GDM.ResultsThere was no association among FTO SNPs and GDM. Interestingly, in GDM group, women carrying the risk alleles of the three SNPs had increased TNF-alpha, and decreased adiponectin levels; these associations remained significant after adjusting for pre-gestational body weight and age. Moreover, the risk allele of rs1421085 was also associated with increased weight gain during pregnancy.ConclusionsThe FTP SNPs rs8050136, rs9939609, and rs1421085 are not a major genetic regulator in the etiology of GDM in the studied ethnic group. However, these SNPs were associated with adiponectin and TNF-alpha concentrations in GDM subjects.