Wagner Silva Dantas

Metabolic Disturbance in PCOS: Clinical and Molecular Effects on Skeletal Muscle Tissue

Polycystic ovary syndrome is a complex hormonal disorder affecting the reproductive and metabolic systems with signs and symptoms related to anovulation, infertility, menstrual irregularity and hirsutism. Skeletal muscle plays a vital role in the peripheral glucose uptake. Since PCOS is associated with defects in the activation and pancreatic dysfunction of β-cell insulin, it is important to understand the molecular mechanisms of insulin resistance in PCOS. Studies of muscle tissue in patients with PCOS reveal defects in insulin signaling. Muscle biopsies performed during euglycemic hyperinsulinemic clamp showed a significant reduction in glucose uptake, and insulin-mediated IRS-2 increased significantly in skeletal muscle. It is recognized that the etiology of insulin resistance in PCOS is likely to be as complicated as in type 2 diabetes and it has an important role in metabolic and reproductive phenotypes of this syndrome. Thus, further evidence regarding the effect of nonpharmacological approaches (e.g., physical exercise) in skeletal muscle of women with PCOS is required for a better therapeutic approach in the management of various metabolic and reproductive problems caused by this syndrome.

Can creatine supplementation form carcinogenic heterocyclic amines in humans

There is a long‐standing concern that creatine supplementation could be associated with cancer, possibly by facilitating the formation of carcinogenic heterocyclic amines (HCAs). This study provides compelling evidence that both low and high doses of creatine supplementation, given either acutely or chronically, does not cause a significant increase in HCA formation. HCAs detection was unrelated to creatine supplementation. Diet was likely to be the main factor responsible for HCAs formation after either placebo (n = 6) or creatine supplementation (n = 3). These results directly challenge the recently suggested biological plausibility for the association between creatine use and risk of testicular germ cell cancer.

Obesity, but not polycystic ovary syndrome, affects circulating markers of low-grade inflammation in young women without major cardiovascular risk factors

OBJECTIVEThe aim of this study was to evaluate the influence of polycystic ovary syndrome (PCOS) and obesity on circulating markers of low-grade inflammation—tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6) and high sensitive C-reactive protein (hsCRP)—in young women without major cardiovascular (CV) risk factors (diabetes, dyslipidemia and arterial hypertension).DESIGNTwenty-five young women with PCOS and 23 eumenorrheic women without major CV risk factors and matched for body mass index (BMI) were studied. They were subdivided according to BMI and PCOS status and comparisons were made between the PCOS and Control groups, regardless of BMI, and between the Obese and Lean groups, regardless of the presence of PCOS.RESULTSLevels of TNF-α, IL-6 and hsCRP were similar between the PCOS group and the Control group (2.1 vs 1.9 pg/ml, p=0.397, 3.8 vs 5.7 pg/ml, p=0.805 and 0.9 vs 0.5 ng/ml, p=0.361, respectively). Levels of TNF-α were similar between the obese group and the lean group (2.1 vs 1.9 pg/ml, p=0.444). Levels of IL-6 and hsCRP were higher in the obese group than in the lean group (8.7 vs 2.0, p <0.001 and 1.4 vs 0.2 ng/ml, p <0.001, respectively).CONCLUSIONObesity, but not polycystic ovary syndrome, affects circulating markers of low-grade inflammation in young women without major CV risk factors.

GLUT4 translocation is not impaired after acute exercise in skeletal muscle of women with obesity and polycystic ovary syndrome

The aim of this study was to examine the effects of acute exercise on insulin signaling in skeletal muscle of women with polycystic ovary syndrome (PCOS) and controls (CTRL).

Performance Enhancement Drugs and Sports Supplements for Resistance Training

In general, nutritional sports ergogenics are designed to enhance energy production and/or improve body composition, promoting muscle growth and decreasing body fat. Many nutritional supplements and pharmacological substances have been used during resistance training without knowledge of the effects on human metabolism caused by their chronic administration. Before the utilization or prescription of any ergogenic aid, it is important to consider some questions about that substance: Is it effective? Is it safe? Is it legal and ethical? In this chapter we discuss the most widely utilized drugs and supplements among individuals engaged in resistance training—testosterone, creatine, beta-hydroxy beta-methylbutyrate (HMB) and caffeine—focusing on their effects on strength and body composition, the safety of their utilization, and their mechanisms of action.

Discriminating between virilizing ovary tumors and ovary hyperthecosis in postmenopausal women: clinical data, hormonal profiles and image studies

BACKGROUND The presence of virilizing signs associated with high serum androgen levels in postmenopausal women is rare. Virilizing ovarian tumors (VOTs) and ovarian stromal hyperthecosis (OH) are the most common etiologies in virilized postmenopausal women. The differential diagnosis between these two conditions is often difficult. OBJECTIVE To evaluate the contribution of clinical features, hormonal profiles and radiological studies to the differential diagnosis of VOT and OH. DESIGN A retrospective study. SETTING A tertiary center. MAIN OUTCOME MEASURES Clinical data, hormonal status (T, E2, LH and FSH), pelvic images (transvaginal sonography and MRI) and anatomopathology were reviewed. PATIENTS Thirty-four postmenopausal women with a diagnosis of VOT (13 women) and OH (21 women) were evaluated retrospectively. RESULTS Clinical signs of hyperandrogenism were more prevalent in the VOT group than the OH group. Although the VOT group showed higher T and E2 levels and lower gonadotropin levels than the OH group, a great overlap occurred among the hormone levels. A pelvic MRI provided an accurate differentiation of these two conditions. CONCLUSION In this group of patients, the main features contributing to the differential diagnosis of VOT and OH were serum levels of testosterone and gonadotropins and the presence of an ovarian nodule identified on the MRI. Although the association of clinical, hormonal and radiological features contributes to the differential diagnosis of these two conditions, histopathological analysis remains the gold standard for the diagnosis of ovarian hyperandrogenism in postmenopausal women.

Acute exercise elicits differential expression of insulin resistance genes in the skeletal muscle of patients with polycystic ovary syndrome.

This study aimed to explore the role of acute exercise on skeletal muscle gene expression related to insulin resistance in patients with polycystic ovary syndrome (PCOS) and controls.

Increased Insulin Resistance and Glucagon Levels in Mild/Inactive Systemic Lupus Erythematosus Patients Despite Normal Glucose Tolerance

To assess insulin sensitivity in patients with systemic lupus erythematosus (SLE) in response to a meal tolerance test (MTT).

Reversal of Improved Endothelial Function After Bariatric Surgery Is Mitigated by Exercise Training

Flow-mediated dilation (FMD) is a marker of endothelial function and a strong independent predictor of cardiovascular events, constituting a valid prognostic tool beyond traditional cardiovascular risk factors [(1)][1]. Bariatric surgery elicits short-term improvements in FMD [(2)][2], but

Exercise Increases Insulin Sensitivity and Skeletal Muscle AMPK Expression in Systemic Lupus Erythematosus: A Randomized Controlled Trial

Systemic lupus erythematosus (SLE) patients may show increased insulin resistance (IR) when compared with their healthy peers. Exercise training has been shown to improve insulin sensitivity in other insulin-resistant populations, but it has never been tested in SLE. Therefore, the aim of the present study was to assess the efficacy of a moderate-intensity exercise training program on insulin sensitivity and potential underlying mechanisms in SLE patients with mild/inactive disease. A 12-week, randomized controlled trial was conducted. Nineteen SLE patients were randomly assigned into two groups: trained (SLE-TR, n = 9) and non-trained (SLE-NT, n = 10). Before and after 12 weeks of the exercise training program, patients underwent a meal test (MT), from which surrogates of insulin sensitivity and beta-cell function were determined. Muscle biopsies were performed after the MT for the assessment of total and membrane GLUT4 and proteins related to insulin signaling [Akt and AMP-activated protein kinase (AMPK)]. SLE-TR showed, when compared with SLE-NT, significant decreases in fasting insulin [−39 vs. +14%, p = 0.009, effect size (ES) = −1.0] and in the insulin response to MT (−23 vs. +21%, p = 0.007, ES = −1.1), homeostasis model assessment IR (−30 vs. +15%, p = 0.005, ES = −1.1), a tendency toward decreased proinsulin response to MT (−19 vs. +6%, p = 0.07, ES = −0.9) and increased glucagon response to MT (+3 vs. −3%, p = 0.09, ES = 0.6), and significant increases in the Matsuda index (+66 vs. −31%, p = 0.004, ES = 0.9) and fasting glucagon (+4 vs. −8%, p = 0.03, ES = 0.7). No significant differences between SLT-TR and SLT-NT were observed in fasting glucose, glucose response to MT, and insulinogenic index (all p > 0.05). SLE-TR showed a significant increase in AMPK Thr 172 phosphorylation when compared to SLE-NT (+73 vs. −12%, p = 0.014, ES = 1.3), whereas no significant differences between groups were observed in Akt Ser 473 phosphorylation, total and membrane GLUT4 expression, and GLUT4 translocation (all p > 0.05). In conclusion, a 12-week moderate-intensity aerobic exercise training program improved insulin sensitivity in SLE patients with mild/inactive disease. This effect appears to be partially mediated by the increased insulin-stimulated skeletal muscle AMPK phosphorylation. Clinical Trial Registration www.ClinicalTrials.gov, identifier NCT01515163.