Effect of dietary myo-inositol supplementation on the insulin resistance and the prevention of gestational diabetes mellitus: study protocol for a randomized controlled trial.

BACKGROUND: Gestational diabetes mellitus (GDM) is defined as impaired glucose tolerance with onset or first recognition during pregnancy, which is characterized by an increased insulin resistance. Gestational diabetes mellitus is associated with pregnancy-related maternal and fetal morbidity (both antenatal and perinatal). Myo-inositol has been suggested to improve insulin resistance in women with polycystic ovary syndrome. The aim of this study is to examine the impact of myo-inositol supplementation during pregnancy on the incidence of gestational diabetes mellitus. METHODS: We will conduct a single-center, open-label, randomized controlled trial. A total of 160 healthy pregnant women with singleton pregnancy at 11-13+6 weeks of gestation will be randomly allocated in two groups: intervention group (N = 80) and control group (N = 80). The intervention group will receive myo-inositol and folic acid (4000 mg myo-inositol and 400 mcg folic acid daily) from 11 to 13+6 weeks of gestation until 26-28 weeks of gestation, while the control group will receive folic acid alone (400 mcg folic acid daily) for the same period of time as intervention group. The primary outcome will be gestational diabetes incidence rate at 26-28 weeks of gestation, according to the results of a 75 g oral glucose tolerance test held at 26-28 weeks of gestation. The secondary outcomes will include fasting blood glucose levels, glycated hemoglobin levels, insulin resistance level (evaluated by homeostasis model assessment of insulin resistance and Matsuda Index), and incidence rate of diet-treated gestational diabetes and diabetes requiring insulin therapy at 26-28 weeks of gestation. DISCUSSION: This trial will provide evidence for the effectiveness of myo-inositol supplementation during pregnancy in reducing the incidence of gestational diabetes mellitus. TRIAL REGISTRATION: ISRCTN registry: ISRCTN16142533 . Registered on 9 March 2017.

Comparative efficacy and safety of oral antihypertensive agents in pregnant women with chronic hypertension: a network metaanalysis.

OBJECTIVE DATA: Chronic hypertension is associated with adverse perinatal outcomes, although the optimal treatment is unclear. The aim of this network metaanalysis was to simultaneously compare the efficacy and safety of antihypertensive agents in pregnant women with chronic hypertension. STUDY: Medline, Scopus, CENTRAL, Web of Science, Clinicaltrials.gov, and Google Scholar databases were searched systematically from inception to December 15, 2019. Both randomized controlled trials and cohort studies were held eligible if they reported the effects of antihypertensive agents on perinatal outcomes among women with chronic hypertension. STUDY APPRAISAL AND SYNTHESIS METHODS: The primary outcomes were preeclampsia and small-for-gestational-age risk. A frequentist network metaanalytic random-effects model was fitted. The main analysis was based on randomized controlled trials. The credibility of evidence was assessed by taking into account within-study bias, across-studies bias, indirectness, imprecision, heterogeneity, and incoherence. RESULTS: Twenty-two studies (14 randomized controlled trials and 8 cohorts) were included, comprising 4464 women. Pooling of randomized controlled trials indicated that no agent significantly affected the incidence of preeclampsia. Atenolol was associated with significantly higher risk of small-for-gestational age compared with placebo (odds ratio, 26.00; 95% confidence interval, 2.61-259.29) and is ranked as the worst treatment (P-score=.98). The incidence of severe hypertension was significantly lower when nifedipine (odds ratio, 0.27; 95% confidence interval, 0.14-0.55), methyldopa (odds ratio, 0.31; 95% confidence interval, 0.17-0.56), ketanserin (odds ratio, 0.29; 95% confidence interval, 0.09-0.90), and pindolol (odds ratio, 0.17; 95% confidence interval, 0.05-0.55) were administered compared with no drug intake. The highest probability scores were calculated for furosemide (P-score=.86), amlodipine (P-score=.82), and placebo (P-score=.82). The use of nifedipine and methyldopa were associated with significantly lower placental abruption rates (odds ratio, 0.29 [95% confidence interval, 0.15-0.58] and 0.23 [95% confidence interval, 0.11-0.46], respectively). No significant differences were estimated for cesarean delivery, perinatal death, preterm birth, and gestational age at delivery. CONCLUSION: Atenolol was associated with a significantly increased risk for small-for-gestational-age infants. The incidence of severe hypertension was significantly lower when nifedipine and methyldopa were administered, although preeclampsia risk was similar among antihypertensive agents. Future large-scale trials should provide guidance about the choice of antihypertensive treatment and the goal blood pressure during pregnancy.

The influence of thyroid disorders on bone density and biochemical markers of bone metabolism.

Background Thyroid dysfunction, predominantly hyperthyroidism, has been previously linked to impaired bone mass density (BMD) and increased risk of fractures. On the other hand, data in the field of hypothyroidism (HT) are missing. The purpose of the present study was to investigate the impact of thyroid disorders on bone density serum and urine calcium (Ca) and phosphate (P) as well as serum osteocalcin and alkaline phosphatase and urine hydroxyproline in a series of post-menopausal women. Materials and methods The study was conducted in the Reproductive Endocrinology Outpatient Clinic of our hospital. A consecutive series of post-menopausal women was included, after excluding patients under hormone treatment (including levothyroxine supplementation) and those who received raloxifene, tamoxifen or tibolone during the study period as well as those who received treatment during the previous 12 months were excluded from the present study. Results Overall, 188 women were included in the present study. Among them, 143 women had normal thyroid function, 32 women had hyperthyroidism and 13 women had HT. Correlation of thyroid function indices with osteoporosis indices revealed statistically significant correlations between thyroxine (T4) and free triiodothyronine (T3) with T-, Z-scores and BMD. Logistic regression analysis concerning the impact of HT and hyperthyroidism on T-score, Z-score and bone mass density revealed that both pathological entities negatively affect bone health (p < 0.05). Conclusion The findings of our study suggest that not only hyperthyroidism, but also HT negatively affects BMD. Future studies should investigate this association and corroborate our findings.

The effect of Vitamin D supplementation on hormonal and glycaemic profile of patients with PCOS: A meta-analysis of randomised trials.

BACKGROUND: Vitamin D deficiency is frequently manifested in women with polycystic ovarian syndrome (PCOS). To date, supplementation of deficient patients has not been correlated with the hormonal and metabolic status of these patients. PURPOSE: We aimed to investigate the impact of vitamin D supplementation on the hormonal and metabolic profile of PCOS women. MATERIALS AND METHODS: We searched Medline, Scopus, ClinicalTrials.gov and Cochrane Central Register databases for published randomised controlled trials. The meta-analysis was performed with the RevMan 5.3.5 software. RESULTS: Nine studies were included in the present meta-analysis which investigated the impact of vitamin D supplementation in 647 patients. According to our meta-analysis neither serum testosterone (MD 0.04 ng/mL, 95% CI -0.09 to 0.17) nor serum LH (MD -0.48 IU/mL, 95% CI -1.97 to 1.00) were significantly affected by vitamin D supplementation in any of the subgroup comparisons. On the contrary, serum DHEAS was significantly affected by vitamin D (MD -32.24 µg/dL, 95% CI -32.24 to -14.01) an effect which was mainly affected by the vitamin D vs placebo comparison. Vitamin D supplementation did not have an impact on fasting glucose (MD 0.42 mg/dL, 95% CI -2.75 to 3.60) or fasting insulin (MD 1.27 µU/mL, 95% CI -1.42 to 3.97) levels. HOMA-IR was, however, increased among patients that received placebo compared to vitamin D (MD 0.52, 95% CI 0.39-0.65). CONCLUSION: There is no evidence to support that vitamin D supplementation significantly benefits PCOS patients. However, given the relatively small number of enrolled patients further studies are needed to elucidate this field.

Restoration of the pubourethral ligament with platelet rich plasma for the treatment of stress urinary incontinence.

Stress urinary incontinence (SUI) is a major health problem, which affects nearly 20% of adult women and has a detrimental impact on their daily activities and quality of life. Several surgical techniques have been proposed for the treatment of SUI including the Burch colposuspension, retropubic mid-urethral slings (TVT), trans-obturator tapes (TOT), trans-obturator tapes inside out (TVT-O), bladder neck injections and the insertion of an artificial urethral sphincter. All of these treatments aim to either restore the urethral support, which is naturally preserved by the pubourethral ligament (PUL) or to increase the urethral resistance at rest. Most surgical techniques are associated with a variety of intraoperative and postoperative complications. Platelet rich plasma (PRP) is extremely rich in growth factors and cytokines, which regulate tissue reconstruction and has been studied extensively among trauma patients and trauma experimental models. To date, however, there is no evidence to support or oppose its use in women who suffer from SUI due to PUL damage. PRP is an easily produced and relatively inexpensive biologic material. It is produced directly from the patient's blood and is, thus, superior to synthetic materials in terms of potential adverse effects such as from foreign body reaction. In the present article we summarize the existing evidence in the field, which supports the conduct of animal experimental and clinical studies to elucidate the potential role of PRP in treating SUI.

An explanation of the pathophysiology of adverse neurodevelopmental outcomes in iron deficiency.

Iron deficiency (ID) is a major public health problem worldwide among children aged 0-12 months. Several factors seem to contribute to the iron-deficient state in infancy, including insufficient antenatal and neonatal iron supplementation, exclusive breastfeeding, and early umbilical cord clamping after birth. The most concerning complications of ID, except for anemia, are related to altered long-term neurodevelopment. Clinical studies have shown a negative impact of ID anemia on fetal and neonatal behavior including impairments of motor maturity, autonomic response, memory/learning, and mood. ID-induced defects during infancy seem to persist later in life, even after ID treatment. The underlying mechanisms involve dysfunctional myelination, neurotransmission alterations, and altered synaptogenesis and/or dendritogenesis. The purpose of the present review is to summarize these mechanisms and to provide recommendations for future clinical research in the field.

Impact of N-acetylcysteine and sesame oil on lipid metabolism and hypothalamic-pituitary-adrenal axis homeostasis in middle-aged hypercholesterolemic mice.

Hyperlipidemia and stress are important factors affecting cardiovascular health in middle-aged individuals. We investigated the effects of N-acetylcysteine (NAC) and sesame oil on the lipidemic status, liver architecture and the hypothalamic-pituitary-adrenal (HPA) axis of middle-aged mice fed a cholesterol-enriched diet. We randomized 36 middle-aged C57bl/6 mice into 6 groups: a control group, a cholesterol/cholic acid diet group, a cholesterol/cholic acid diet group with NAC supplementation, a cholesterol/cholic acid diet enriched with 10% sesame oil and two groups receiving a control diet enriched with NAC or sesame oil. NAC administration prevented the onset of the disturbed lipid profile, exhibiting decreased lipid peroxidation and alkaline phosphatase (ALP) levels, restored nitric oxide bioavailability and reduced hepatic damage, compared to non-supplemented groups. High-cholesterol feeding resulted in increased hypothalamic glucocorticoid receptors (GR) levels, while NAC supplementation prevented this effect. NAC supplementation presented significant antioxidant capacity by means of preventing serum lipid status alterations, hepatic damage, and HPA axis disturbance due to high-cholesterol feeding in middle-aged mice. These findings suggest a beneficial preventive action of plant-derived antioxidants, such as NAC, on lipid metabolism and on the HPA axis.