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

BACKGROUND: Obesity 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. METHODS: 80 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. RESULTS: There 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. CONCLUSIONS: The 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.

La lactancia prolongada se relaciona con menores niveles de leptina en pacientes con diabetes mellitus gestacional / Duration of lactation is associated with lower leptin levels in patients with gestational diabetes mellitus

Las mujeres con diabetes mellitus gestacional (DBTG) tienen un riesgo elevado de presentar diabetes tipo 2 en el posparto. La lactancia materna se ha asociado con una disminución del riesgo de diversas enfermedades metabólicas. El objetivo de este estudio fue evaluar el impacto de la duración de la lactancia sobre niveles de leptina en mujeres con DBTG previa, en comparación con mujeres con embarazo normal. Materiales y métodos: Se realizó un análisis secundario a una base de datos de un estudio prospectivo comparativo en el que se evaluaron en el embarazo y el posparto 43 mujeres con DBTG y 43 embarazadas normotensas euglucémicas. Se clasificó a las participantes de acuerdo con el tiempo de lactancia materna en duración breve (menos de 6 semanas) o duración prolongada (más de 6 semanas a menos de 6 meses) y se determinaron sus niveles de leptina. Resultados: Las mujeres con DBTG que tuvieron una lactancia de duración prolongada presentaron una mayor disminución de peso en el posparto y un menor nivel de leptina, en comparación con las de lactancia materna de duración breve. Esta diferencia permaneció estadísticamente significativa después del ajuste por el peso de las participantes. En el grupo de control, las mujeres con lactancia de duración prolongada presentaron menores niveles de triglicéridos, insulina y resistencia a la insulina. Conclusiones: La duración prolongada de la lactancia se asoció con menores niveles de leptina y con mejor perfil metabólico en el período posparto temprano de las mujeres con DBTG previa y con embarazo normal, respectivamente...

RBP4 gene variants are associated with insulin resistance in women with previous gestational diabetes.

OBJECTIVE: This study aimed to examine possible genetic effects of some retinol binding protein-4 (RBP4) single nucleotide polymorphisms (SNPs) on the risk of gestational diabetes mellitus (GDM). In addition, the SNPs were examined for their possible association with insulin resistance at 6 weeks after delivery. METHODS: This was a prospective study of 100 women with GDM and 100 participants with normal gestation who were evaluated at gestational week 30 and 6 weeks postpartum. Three SNPs of RBP4 (rs3758539, rs116736522, and rs34571439) were genotyped using TaqMan assay. The genotype distributions between GDM patients and normal controls were analyzed using logistic regression models. In addition, differences in clinical characteristics among subjects grouped by genotype were assessed using the analysis of covariance test. RESULTS: The frequencies of the rare alleles were not significantly different between GDM patients and controls. However, we identified two variants rs3758539 and rs34571439 associated with insulin levels and insulin resistance in women with previous GDM. CONCLUSION: Noncoding SNPs of the RBP4 gene are not associated with GDM, but two SNPs showed associations with insulin resistance and insulin levels in women with prior GDM. Additional studies with increased sample size will be necessary in other GDM cohorts.

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.

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.

[New trends in gestational diabetes]. / El nuevo enfoque hacia la diabetes gestacional.

It has been considered that gestational diabetes (GD) is onset along a pregnancy and resolves after delivery. It is also believed that GD is a risk factor for the development of diabetes; however it remains controversial the time of pregnancy for looking for and the diagnostic test and protocol to apply. Mother's age and obesity are closely associated with the presence of glucose intolerance; likewise there are an unsatisfactory number of women who return for evaluation after delivery. The purpose of the paper is to discuss this controversial topic and set out a point of view.

Fetal malnutrition affects hypothalamic leptin receptor expression after birth in male mice.

BACKGROUND AND AIMS: Epidemiological associations between an adverse intrauterine environment and the induction of obesity in adult life led to the concept of fetal programming whereby an unfavorable prenatal environment induces adaptations that improve fetal survival or prepare the fetus in expectation of a particular range of postnatal environments. However, these adaptations (predictive adaptive responses) may later prove to be a disadvantage when the pre- and postnatal environments show discrepancies. We investigated the effect of maternal restricted diet on body weight and expression of hypothalamic Ob-Rb of the offspring. METHODS: Balb C mice were mated after pregnancy and were randomly assigned to control (C) and undernutrition group (UN) groups. Control group was allowed food ad libitum and UN group had a 50% restriction of food intake during gestation. In the present study we assessed changes in hypothalamic Ob-Rb mRNA by RT-PCR in offspring from C and UN groups. RESULTS: The offspring of UN at birth showed 17% less body weight compared with C, but at 90 days the UN had a greater body weight than C (p<0.01). The UN group also presented an increase in the expression of Ob-Rb at 90 postnatal days (p<0.01). CONCLUSIONS: The results suggest that maternal caloric restriction programs a greater expression of Ob-Rb in the hypothalamus in offspring, as well as a body weight gain that persists into adulthood. In addition, changes in Ob-Rb expression suggest that Ob-Rb mRNA in the hypothalamus is sensitive to fetal undernutrition.

[Efficacy of strontium ranelate for the mineralization of bone in postmenopausal women]. / Eficacia del ranelato de estroncio para la mineralización ósea en mujeres posmenopáusicas.

INTRODUCTION: Osteoporosis is the most common skeletal disorder and is considered a risk of fracture. Most medication used for the treatment of osteoporosis are antiresorptive; however strontium therapy in postmenopausal women has shown a double effect on resorption and bone formation. OBJECTIVE: To evaluate the effect of strontium on bone mineral density (BMD) and circulating biochemical markers of bone turnover in postmenopausal women who had a decreased BMD. MATERIAL AND METHODS: A prospective study was carried out in 23 postmenopausal women who had decreased BMD, who received daily strontium orally by night during 12 months. Evaluation of BMD at lumbar spine and hip as well as biochemical markers in blood for bone turnover before and during therapy. RESULTS: BMD at the spine (0.755 +/- 0.104 to 0.792 +/- 0.094, p < 0.05) and hip (0.833 +/- 0.096 to 0.856 +/- 0.100, p < 0.05) increased significantly after 12 months of treatment. Bone turnover markers showed a decrement of osteocalcin, by contrast the specific alkaline phosphatase increased after 6 months of therapy; however C-terminal telopeptide of type 1 collagen was not modified. CONCLUSIONS: Strontium ranelate increased significantly BMD at the spine and at the hip in postmenopausal women and simultaneously improved bone turnover estimated by circulating bone markers.

Effect of estrogen therapy on insulin resistance and plasminogen activator inhibitor type 1 concentrations in postmenopausal women.

BACKGROUND/AIMS: An elevated thrombotic risk due to abnormal fibrinolysis might be associated with insulin resistance in postmenopause. The aim of this study was to investigate the association of insulin resistance with a biochemical marker of fibrinolysis as well as the effect of transdermal estrogen treatment (ET) on this association. METHODS: Thirty postmenopausal hysterectomized women received transdermal estradiol during 3 months. 17Beta-estradiol, FSH, LH, plasminogen activator inhibitor type 1 (PAI-1), insulin and glucose were measured in blood samples before and after ET. Insulin resistance was calculated by the use of the homeostasis model assessment for insulin resistance (HOMA-IR). RESULTS: ET induced a significant decrement in both PAI-1 levels and HOMA-IR values. The study also showed that HOMA-IR was a significant predictor for PAI-1 concentrations. CONCLUSION: Short-term ET improved HOMA-IR values in parallel with a decrease in PAI-1 levels.

[Adiponectin concentrations during menstrual cycle]. / Variación de adiponectina en el ciclo menstrual.

BACKGROUND: Adiponectin has a direct relationship with cellular sensibility grade to insulin action. OBJECTIVE: To determine adiponectin concentrations during the three phases of the menstrual cycle in young women, and to study the relationship with 17-beta estradiol and progesterone levels. PATIENT AND METHODS: Longitudinal and prospective study that included 30 normal menstruating women aged between 19 and 36 years; none had received any hormonal therapy prior to this study. Adiponectin, 17-beta estradiol, progesterone, LH and FSH were determined in blood in three phases of one menstrual cycle for each participant. RESULTS: Adiponectin concentrations were lower in the postovulatory phase as compared with the other two phases. Adiponectin levels did not significantly correlate with 17-beta estradiol and progesterone. CONCLUSION: Adiponectin blood levels are variable during the menstrual cycle, but the lower concentrations are observed in the postovulatory period that could be associated with other metabolic processes, such as insulin resistance.

[How the studies of the reproduction process contributed to the appearance of neuroendocrinology]. / Cómo los estudios del proceso de la reproducción contribuyeron a la aparición de la neuroendocrinología.

Geoffrey W. Harris, inspired by Francis H. Marshall, began the experimental studies in order to demonstrate a vascular connection between the hypothalamus and the adenohypophysis, with neuropeptides as messengers. This confirmed his theory that the mechanism consists in that the nerve fibers in the hypothalamus release hormonal substances in the capillaries of the primary plex in the medium eminence, and that these substances are carried by the vessels of the portal circulation to stimulate or inhibit the pars distalis cells of the hypophysis. This theory placed the hypothalamus as the fundamental structure to understand the link between the brain and the hypophysis. Later, it was known the structure of neurohormones, particularly the responsible for producing gonadotrophins. By this way, it was possible to go into the processes involved in reproduction. This was the origin of neuroendocrinology, gestated by investigations made in the reproduction of animals, including man. The purification, sequentiation and synthesis of the hormone that controls the FSH and LH production have allowed to study the physiology and disorders of the neuroendocrine circuit.

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 17beta-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 17beta-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.

[Current criterion for diagnosing polycystic ovary syndrome]. / Criterio actual para el diagnóstico del síndrome del ovario poliquístico.

The current consensus on diagnostic criteria of polycystic ovary syndrome has concluded that it is a syndrome of ovarian dysfunction along with hyperandrogenism and morphology of polycystic ovary. The clinical manifestations may include irregular menses, androgen excess, and obesity, but insulin resistance is also a common feature. There is an increased risk of type 2 diabetes mellitus. Treatment of polycystic ovary includes ovulation induction, amelioration of androgen signs and correction of insulin resistance.

[The metabolic syndrome in postmenopausal women. Clinical implications]. / El síndrome metabólico de la mujer posmenopáusica. Implicaciones clínicas.

Cardiovascular diseases (CVD) remain the major cause of death in postmenopausal women. Before menopause, women are relatively protected from ischemic heart disease and thromboembolism by their circulating estrogens, but this protection is lost after menopause. Following menopause, adverse lipid changes occur and the levels of several coagulation factor increase. One of the major predisposing factors for CVD is the metabolic syndrome, including myriad risk biomarkers: abdominal girth, blood pressure, fasting glucose, triglycerides, lipids. In many ways, the metabolic syndrome is a precursor to the development of abnormalities of insulin action and diabetes. In parallel, there are effects upon blood coagulation and fibrinolysis. Common preventive therapies require rigorous evaluation. Hormone replacement therapy (HRT) has not produced the expected reduction in CVD and the ideal HRT is probably unobtainable. For long-term HRT users, the risk of thromboembolism needs to be weighed against probable benefits. With respect to the effects of HRT, oral estrogen is associated with elevation in C-reactive protein and varied effects on IL-6, but transdermal estradiol has no significant effect on these parameters. Despite the varied effects of HRT on inflammatory biomarkers, there is no definitive evidence that change in these markers results in modification of cardiovascular risk.

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.

[Hormone replacement therapy with transdermal estradiol lowers insulin-cortisol and lipoproteins levels in postmenopausal women]. / La terapia de reemplazo hormonal con estradiol transdérmico disminuye los niveles de insulina-cortisol y lipoproteínas en mujeres posmenopáusicas.

Increased levels of circulating insulin and cortisol, interpreted as part of aging process, have been associated with an increase risk of developing cardiovascular disease and diabetes mellitus. Because estrogens affect insulin balance, hypoestrogenism in menopausal women may lead to elevations in both insulin and cortisol. The purpose of the present study was to determine the effect of transdermal estradiol administration on the insulin-cortisol binomial. A prospective study was carried out in 30 menopausal women aged 48 to 55 yr, receiving transdermal estradiol 50 micrograms/day during three months. Ten healthy menopausal women (49 to 58 yr) were the control group. Serum levels of cortisol, insulin, lipoproteins, and leptin were quantified by specific assays before and after 3 months of transdermal estradiol therapy. Baseline cortisol levels decreased significantly from 143.4 +/- 10.6 ng/mL to 110.2 +/- 6.7 ng/mL (M +/- SE) (p < 0.001) after 3 months of transdermal estradiol. In parallel, augmented baseline insulin levels diminished significantly from 26.1 +/- 2.0 microlitersU/mL to 21.7 +/- 1.2; (M +/- SE) (p < 0.05). Glucose level were unaffected by this therapy, but it was restored to normal the augmented baseline levels of both triglycerides and low-density cholesterol. Total cholesterol and high-density-cholesterol as well as circulating leptin were unchanged. Transdermal estrogen induced-decrease in circulating cortisol, insulin, triglycerides, and low-density cholesterol to normal values may have a beneficial metabolic effect in menopausal women.

Los trastornos tiroideos en la mujer / Thyroid malfunction in womwn

La prevalencia de trastornos tiroideos en la mujer es elevada y existe una marcada preponderancia que se ha relacionado con una mayor susceptibilidad a alteraciones de la autoinmunidad. Los trastornos tiroideos presentan como características su aparición insidiosa y la baja especificidad de sus manifestaciones. Por ello, se recomienda sospechar patología tiroidea en caso de depresión posparto, alteraciones menstruales, síndrome de amenorrea con galactorrea, pubertad precoz o retardada, esterilidad inexplicable o aborto de repetición. La dificultad en el diagnóstico clínico es compensada por la accesibilidad y relativa facilidad del diagnóstico biológico mediante las pruebas de función tiroidea, principalmente la medición de TSH y FT4, por lo que es útil considerar a estas pruebas en el estudio de los trastornos ginecológicos. Un diagnóstico precoz y oportuno resolverá en las mejores condiciones los trastornos ginecológicos originados por el mal funcionamiento de la glándula tiroides.

Eficacia de la acarbosa para controlar el deterioro de la tolerancia a la glucosa durante la gestación / Efficacy of acarbosa ato control deterioration of glucose tolerance during gestation

La diabetes gestacional es una intolerancia a los carbohidratos demostrada durante el curso de un embarazo, pero puede existir una etapa previa de hiperglucemia moderada en el ayuno con cierto grado de intolerancia después de la ingesta de alimentos. La hipótesis del presente trabajo consistió en que un deterioro en la tolerancia a los carbohidratos en embarazadas puede corregirse con la administración de un fármaco que disminuya la absorción de carbohidratos durante las comidas. Para probar esta suposición se estudiaron seis mujeres en quienes se encontró accidentalmente una hiperglucemia moderada en la etapa final del embarazo y se administró acarbosa, inhibidor de la alfa-glucosilasa, antes de cada una de las tres principales comidas y se efectuaron determinaciones mensuales de glucemia y hemoglobina glucosilada hasta el término de la gestación. En todas las pacientes se normalizaron los niveles de glucosa en sangre y no se presentaron trastornos obstétricos ni alteraciones en los recién nacidos. La acarbosa produjo molestias intestinales que fueron toleradas y permitieron continuar en tratamiento hasta el final del embarazo.

Usefulness of insulin-like growth factor binding protein-3 levels to determine acromegaly activity and effectiveness of transsphenoidal pituitary surgery

Background. Several series reported in the literature concerning the results of the treatment of acromegaly have difficult to evaluated because the indicators are inaccurate Methods. We investigated the usefulness of insulin. Like growth factor binding protein-3 (IGFBP) levels to determine disease activity after surgical treatment of acromegaly in 13 patients with confirmed somatotroph adenoma. Results. Before surgery, all 13 non-treated patients had levated serum levels of IGFBP-3 as well as total and free IGF-I. In addition, there was no overlap with the normal controls (p < 0.001). IGFBP-3 levels correlated significantly (0.91, p < 0.001) with GH suppressibility by glucose after surgery. Conclusions. These data confirm that IGFBP-3 is a better indicator of acromegalic activity than either total or free IGF-i. There was a high correlation with GH suppressibility by glucose after surgery; both free and total IGF-I could be considered sensitive markers only for diagnosis of active acromegaly but not for efficacy of surgery