Incretin Hormone Secretion in Women with Polycystic Ovary Syndrome: Roles of Obesity, Insulin Sensitivity and Treatment with Metformin and GLP-1s.

BACKGROUND: The purpose of this narrative review is to describe the mechanisms that are responsible for the development of infertility and PCOS, with a focus on the role of obesity, insulin sensitivity and treatment with metformin and GLP-1s. METHODS: The relevant publications were identified after systematic queries of the following sources: PubMed, Google Scholar, Web of Science, and publishers' databases, complemented by a cross-check of the reference lists. We used a combination of the search terms "polycystic ovary syndrome", "obesity" and "insulin resistance" with "metformin", "exenatide", "liraglutide", "semaglutide", "orlistat" and terms relevant to the topic of each paragraph (e.g., "pathophysiology", "metabolism", "infertility", "treatment"). RESULTS: All articles describing the mechanisms responsible for the development of infertility and PCOS, with a focus on the role of obesity, insulin sensitivity and treatment with metformin and GLP-1s, were considered for this review. CONCLUSIONS: The existing research on GLP-1 receptor agonists (GLP-1RAs) has not conclusively established a specific therapeutic use for these drugs. Additionally, the efficacy of the newer generation of GLP-1RAs, particularly in terms of dosage and duration of exposure, warrants more extensive research. Understanding the optimal dosing and treatment duration could significantly enhance the therapeutic use of GLP-1RAs in managing PCOS and its associated conditions.

Associations of Diet with Cardiometabolic and Inflammatory Profiles in Pregnant Women at Risk for Metabolic Complications.

Dietary intakes play an important role in the development of metabolic complications during pregnancy. While reported observational studies reveal an inverse association of healthy diets with weight gain, gestational diabetes, and hypertensive complications during pregnancy, there is a paucity of studies conducted among women of specific ethnicities vulnerable to higher risks of pregnancy complications. This is a secondary cross sectional analysis using baseline data from a previously reported clinical trial. We aim to identify associations of maternal habitual dietary intakes with cardiometabolic risks and inflammatory profiles in primarily African American (AA) and Hispanic women in the first half of pregnancy. Fifty-two women met the study criteria and anthropometric, clinical, and dietary data were obtained at baseline. Linear regression analysis was used to determine associations after covariate adjustments. Among the maternal dietary nutrient intakes, total fats were positively associated with maternal body weight, BMI, and serum CRP (ß ± SE: 0.25 ± 0.13, 0.28 ± 0.18, and 0.29 ± 0.14, respectively, all p < 0.05), and saturated fats were positively associated with glycated hemoglobin (0.32 ± 0.12). Dietary fiber intake showed a consistent inverse association with body weight (-0.26 ± 0.13), BMI (-0.19 ± 0.15), glycated hemoglobin (-0.22 ± 0.16), as well as serum CRP (-0.19 ± 0.14). Among the maternal food group intakes, dairy intake was inversely associated with systolic blood pressure (-0.18 ± 0.15) and serum IL-6 (-0.22 ± 0.17), and vegetable intake showed an inverse association with serum CRP (-0.17 ± 0.12) all in adjusted analyses (all p < 0.05). Thus, maternal diet modifications, especially decreasing fats and increasing fiber and dairy may help address obesity and inflammation leading to pregnancy complications in AA and Hispanic women.

Dietary Blueberry and Soluble Fiber Improve Serum Antioxidant and Adipokine Biomarkers and Lipid Peroxidation in Pregnant Women with Obesity and at Risk for Gestational Diabetes.

Pregnancies affected by obesity are at high risk for developing metabolic complications with oxidative stress and adipocyte dysfunction contributing to the underlying pathologies. Few studies have examined the role of dietary interventions, especially those involving antioxidants including polyphenolic flavonoids found in fruits and vegetables on these pathologies in high-risk pregnant women. We conducted an 18 gestation-week randomized controlled trial to examine the effects of a dietary intervention comprising of whole blueberries and soluble fiber vs. control (standard prenatal care) on biomarkers of oxidative stress/antioxidant status and adipocyte and hormonal functions in pregnant women with obesity (n = 34). Serum samples were collected at baseline (<20 gestation weeks) and at the end of the study period (32-26 gestation weeks). Study findings showed maternal serum glutathione and antioxidant capacity to be significantly increased, and malondialdehyde to be decreased in the dietary intervention vs. control group (all p < 0.05). Among the adipokine biomarkers, serum plasminogen activator inhibitor-1 and visfatin, as biomarkers of adipocyte dysfunction and insulin resistance, were also decreased following dietary intervention (all p < 0.05). These findings support the need for supplementing maternal diets with berries and fiber to improve oxidative stress and risks of metabolic complications during pregnancy.

Dietary Blueberry and Soluble Fiber Supplementation Reduces Risk of Gestational Diabetes in Women with Obesity in a Randomized Controlled Trial.

BACKGROUND: Gestational diabetes mellitus (GDM) is a growing public health concern and maternal obesity and poor dietary intakes could be implicated. Dietary polyphenols and fiber mitigate the risk of diabetes and its complications, but little is known about their efficacy in preventing GDM. OBJECTIVES: We examined the effects of whole blueberry and soluble fiber supplementation on primary outcomes of cardiometabolic profiles in women at high risk of developing GDM. METHODS: Women (n = 34; mean ± SD age: 27 ± 5 y; BMI: 35.5 ± 4.0 kg/m2; previous history of GDM ∼56%; Hispanic ∼79%) were recruited in early pregnancy (<20 weeks of gestation) and randomly assigned to 1 of the following 2 groups for 18 wk: intervention (280 g whole blueberries and 12 g soluble fiber per day) and standard prenatal care (control). Both groups received nutrition education and maintained 24-h food recalls throughout the study. Data on anthropometrics, blood pressure, and blood samples for biochemical analyses were collected at baseline (<20 weeks), midpoint (24-28 weeks), and end (32-36 weeks) of gestation. Diagnosis of GDM was based on a 2-step glucose challenge test (GCT). Data were analyzed using a mixed-model ANOVA. RESULTS: Maternal weight gain was significantly lower in the dietary intervention than in the control group at the end of the trial (mean ± SD: 6.8 ± 3.2 kg compared with 12.0 ± 4.1 kg, P = 0.001). C-reactive protein was also lower in the intervention than in the control group (baseline: 6.1 ± 4.0 compared with 6.8 ± 7.2 mg/L; midpoint: 6.1 ± 3.7 compared with 7.5 ± 7.3 mg/L; end: 5.5 ± 2.2 compared with 9.5 ± 6.6 mg/L, respectively, P = 0.002). Blood glucose based on GCT was lower in the intervention than in the control (100 ± 33 mg/dL compared with 131 ± 40 mg/dL, P < 0.05). Conventional lipids (total, LDL, and HDL cholesterol and triglycerides) did not differ between groups over time. No differences were noted in infant birth weight. CONCLUSIONS: Whole blueberry and soluble fiber supplementation may prevent excess gestational weight gain and improve glycemic control and inflammation in women with obesity.This trial was registered at clinicaltrials.gov as NCT03467503.

Associations of Dietary Bioactive Compounds with Maternal Adiposity and Inflammation in Gestational Diabetes: An Update on Observational and Clinical Studies.

Gestational diabetes mellitus (GDM) is a common complication of pregnancy that adversely affects maternal and offspring health. Maternal obesity, oxidative stress, and inflammation have been implicated in GDM. In non-pregnant adults, intakes of dietary bioactive compounds inversely associate with insulin resistance and inflammation. However, associations of dietary bioactive compounds with biomarkers of adiposity, antioxidant vitamin and mineral status, oxidative stress, and inflammation in GDM have not been fully elucidated. We addressed this gap by conducting a semi-quantitative review of observational studies and randomized controlled trials published between 2010 and 2020 and retrieved from Google Scholar, Medline, and PubMed. Our analysis revealed that women with GDM are more likely to consume a pro-inflammatory diet before pregnancy and tend to consume fewer antioxidant vitamins and minerals during pregnancy than healthy pregnant women. Women with GDM also have lower blood levels of vitamins A, C, and D and certain adipokines. Several dietary bioactive compounds were noted to improve antioxidant status and biomarkers of inflammation. The Dietary Approaches to Stop Hypertension (DASH) diet and soybean oligosaccharides increased antioxidant enzyme levels. Supplementing n-3 fatty acids, probiotics, synbiotics, and trace elements increased antioxidant enzymes and reduced hs-CRP and MDA. Improvements in inflammation by vitamin D may be contingent upon co-supplementation with other dietary bioactive compounds.

Antenatal interventions based upon fetal surveillance of the daily opioid-exposed fetus: a descriptive analysis.

Objective: Daily opioid dependence for maternal pain management, methadone maintenance, or buprenorphine/naloxone therapy is an increasing trend in modern obstetrics. Opioids may produce depressive effects on fetal neurobehavioral status and thus on fetal heart rate patterns. Our primary objective was to describe the current methods utilized in antenatal monitoring of the daily opioid exposed fetus; and to describe interventions based upon monitoring which precipitated a recommendation for delivery. Our ultimate goal was to determine an optimal, evidence-based recommendation for fetal assessment of the daily opioid exposed pregnancy.Study design: A retrospective review of patients undergoing antenatal assessment from January 2016 through April 2017 at two maternal-fetal medicine testing centers identified singleton, fetuses without a known major genetic abnormality with daily opioid exposure. Nonstress tests, amniotic fluid indexes, biophysical profiles, umbilical artery Doppler measurements, and serial biometry were analyzed. Test characteristics and frequency of interventions for abnormal monitoring were quantified.Results: Criteria for daily opioid exposure was identified in 27 patients (77.8% on methadone (n = 21), 14.8% on prescription opioid for chronic pain (n = 4), and 7.4% on buprenorphine/naloxone (n = 2)). Mean maternal age was 30.3 years ±5.5 (range 21-42 years). Parity zero was 6/27 (22.2%). Identified race was 52% Caucasian, 26% African American, 19% Hispanic, and 4% Pacific Islander. There were 112 growth scans, 102 biophysical profiles, 10 isolated nonstress tests, and 81 umbilical artery Doppler studies reviewed. Delivery precipitated by abnormal testing occurred in 6/27 patients (22.2%). Gestational ages of delivery were all between 36 and 38 weeks. Indications for delivery were isolated oligohydramnios 2/6 (one at 37 weeks, one at 38 weeks), oligohydramnios with associated intrauterine growth restriction 2/6 (both at 36 weeks), isolated nonreactive nonstress test 1/6 (occurring at 38 weeks), and low biophysical profile score 1/6 (occurring at 36 weeks). The average nonstress test baseline was 131 (±11) beats per minute (range of 120-150), with no episodes of significant fetal bradycardia or tachycardia. Overall, 94.6% (106/112) of the nonstress tests were reactive, all nonstress tests had variability, 96.4% (108/112) had moderate variability, and 99.1% (111/112) had no decelerations. Time to nonstress test reactivity was <20 min in 93% (104/112), with a mean time to first acceleration of 5.3 (±7.7) min (range of 1-44). Umbilical artery Doppler measurements had an elevated systolic to diastolic ratio >95% for gestational age in 9/83 cases, with no measurements demonstrating absent or reversed end diastolic flow. Umbilical artery Doppler studies did not initiate changes in management.Conclusion: In our population, antepartum assessment with a biophysical profile at no later than 36-week gestation identified all fetuses with testing abnormalities necessitating delivery in the daily opioid exposed fetus (6/27, 22.2%). Oligohydramnios was the most frequent indication for delivery. Serial growth ultrasounds by 32 weeks were necessary to identify the 11.1% of growth restricted, opioid exposed fetuses. A depressive effect of daily opioids on nonstress test reactivity or variability was not evident in our cohort. Future studies should attempt to define optimal monitoring based upon category of opioid dependence, type and dose of opioid consumed, and timing of opioid administration.

Cornual abscess rupture: A rare etiology of acute abdomen.

Ruptured cornual abscess or pyometra can resemble other more common causes of acute abdomen, including appendicitis, diverticulitis, tubo-ovarian abscess, and perforated viscus. Despite its rarity, the diagnosis of ruptured pyometra should always be considered in females presenting with acute abdominal pain, particularly in the setting of a retained intrauterine device.