Giancarlo Paradisi

Polycystic Ovary Syndrome Is Associated With Endothelial Dysfunction

Background —We recently reported endothelial dysfunction as a novel cardiovascular risk factor associated with insulin resistance/obesity. Here, we tested whether hyperandrogenic insulin-resistant women with polycystic ovary syndrome (PCOS) who are at increased risk of macrovascular disease display impaired endothelium-dependent vasodilation and whether endothelial function in PCOS is associated with particular metabolic and/or hormonal characteristics. Methods and Results —We studied leg blood flow (LBF) responses to graded intrafemoral artery infusions of the endothelium-dependent vasodilator methacholine chloride (MCh) and to euglycemic hyperinsulinemia in 12 obese women with PCOS and in 13 healthy age- and weight-matched control subjects (OBW). LBF increments in response to MCh were 50% lower in the PCOS group than in the OBW group (P <0.01). Euglycemic hyperinsulinemia increased LBF above baseline by 30% in the PCOS and 60% in OBW group (P <0.05 between groups). Across all subjects, the maximal LBF response to MCh exhibited a strong inverse correlation with free testosterone levels (r =−0.52, P <0.007). This relationship was stronger than with any other parameter, including insulin sensitivity. Conclusions —PCOS is characterized by (1) endothelial dysfunction and (2) resistance to the vasodilating action of insulin. This endothelial dysfunction appears to be associated with both elevated androgen levels and insulin resistance. Given the central vasoprotective role of endothelium, these findings could explain, at least in part, the increased risk for macrovascular disease in women with PCOS.

Type II Diabetes Abrogates Sex Differences in Endothelial Function in Premenopausal Women

BACKGROUND Obesity is a more potent cardiovascular risk factor (CVRF) in men than in women. Because traditional CVRFs cannot fully account for this sex difference, we tested the hypothesis that compared with men, women exhibit more robust endothelial function independent of obesity and that this sex difference is abrogated by diabetes. METHODS AND RESULTS We studied leg blood flow (LBF) responses to graded intrafemoral artery infusions of the endothelium-dependent vasodilator methacholine chloride (Mch) and the endothelium-independent vasodilator sodium nitroprusside (SNP) in groups of lean, obese (OB), and type II diabetic (DM) premenopausal women and age- and body mass index-matched men. LBF response to intrafemoral administration of L-NMMA, an inhibitor of nitric oxide synthase, was also assessed in normal men and women. Maximum LBF increments in response to Mch were 347+/-57% versus 231+/-22% in lean women versus men (P<0.05) and 203+/-25% versus 111+/-17% in OB women versus men (P<0.01), respectively. In DM, maximum LBF increments in response to Mch were 104+/-24% and 138+/-33% in women and men, respectively, (P=NS). LBF decrements in response to L-NMMA were 34.9+/-4.1% and 17.1+/-4.2% in women and men, respectively (P<0.01). The response to SNP was not different between sexes and groups. CONCLUSIONS Premenopausal nondiabetic women exhibit more robust endothelium-dependent vasodilation owing to higher rates of nitric oxide release than men. Given the protective vascular action of nitric oxide, this difference may partially explain the lower incidence of macrovascular disease in women. In premenopausal women, DM causes impairment of endothelial function beyond that observed with obesity alone and leads to endothelial dysfunction similar to that observed in DM men. These findings may help explain the similar rates of coronary artery disease and mortality in diabetic men and women.

Vaginal microbial flora and outcome of pregnancy

BackgroundThe vaginal microflora of a healthy asymptomatic woman consists of a wide variety of anaerobic and aerobic bacterial genera and species dominated by the facultative, microaerophilic, anaerobic genus Lactobacillus. The activity of Lactobacillus is essential to protect women from genital infections and to maintain the natural healthy balance of the vaginal flora. Increasing evidence associates abnormalities in vaginal flora during pregnancy with preterm labor and delivery with potential neonatal sequelae due to prematurity and poor perinatal outcome. Although this phenomenon is relatively common, even in populations of women at low risk for adverse events, the pathogenetic mechanism that leads to complications in pregnancy is still poorly understood.ObjectiveThis review summarizes the current knowledge and uncertainties in defining alterations of vaginal flora in non-pregnant adult women and during pregnancy, and, in particular, investigates the issue of bacterial vaginosis and aerobic vaginitis. This could help specialists to identify women amenable to treatment during pregnancy leading to the possibility to reduce the preterm birth rate, preterm premature rupture of membranes, chorioamnionitis, neonatal, puerperal and maternal–fetal infectious diseases.ConclusionsVaginal ecosystem study with the detection of pathogens is a key instrument in the prevention of preterm delivery, pPROM, chorioamnionitis, neonatal, puerperal and maternal-fetal infections.

Effect of maternal carbohydrate metabolism on fetal growth.

Objective To determine the effect of maternal carbohydrate metabolism and anthropometric characteristics on fetal growth. Methods Eight pregnant women in the third trimester with unexplained fetal growth restriction (FGR) and 11 women with normal pregnancies in the third trimester were evaluated for maternal carbohydrate metabolism, using oral glucose tolerance tests and hyperinsulinemic-euglycemic clamps. These data and maternal anthropometric characteristics subsequently were related to relative birth weight, defined as observed birth weight × 100/50th percentile birth weight. Results The women with FGR pregnancies were more insulin sensitive than were controls (21.6 ± 66 4.4 versus 16.7 ± 4.8 mmol/kg × min, P < .05) and showed reduced insulin and glucose areas under the curve (96,293 ± 25,870 versus 145,291 ± 49,356 pmol/L, P < .03; 1057.0 ± 184.7 versus 1210.1 ± 85.9 mmol/L, P < .05, respectively). No differences were seen in fasting plasma glucose, insulin and human placental lactogen samples, age, height, pregravid weight, weight gain, and parity. In all patients, maternal insulin sensitivity and weight gain correlated well with relative birth weight (r = −.65, P < .002; r = .68, P < .001, respectively). When the same analysis was computed separately in the groups, insulin sensitivity exhibited a strong negative correlation with relative birth weight in the FGR group but not in controls (r = −.84, P < .007; r = −.54, P = .08, respectively). Conversely, in control women the best correlation between relative birth weight and the other variables studied was seen with maternal weight gain (r = .82, P < .002). Conclusion Women with unexplained FGR have a differ-ent glucose metabolic pattern than do normals. We speculate that increased insulin sensitivity leads to a reduction in metabolic substrates for fetal growth.

Longitudinal changes of adiponectin, carbohydrate and lipid metabolism in pregnant women at high risk for gestational diabetes

To evaluate, in pregnant women at high risk for gestational diabetes (GDM), the longitudinal changes of adiponectin, carbohydrate and lipid metabolism, and to assess their independent value as risk factors for the development of GDM. Fifty women at beginning of pregnancy were studied. Adiponectin, insulin sensitivity (homeostasis model assessment, HOMA) and lipid panel were measured at 1st, 2nd and 3rd trimesters of pregnancy. Twelve patients developed GDM. In both groups, GDM and normal glucose tolerance (NGT), adiponectin decreased from 1st to 2nd and 3rd trimesters by about 5 and 20% (GDM, p < 0.05), and of about 17 and 25% in NGT (p < 0.05), respectively. Values observed in NGT were similar to those of GDM (F = 9.401; p = 0.238). The Cox regression model identified as the strongest independent risk factor for GDM HOMA over 1.24 (RR = 14.12) at 1st trimester, fasting glycaemia over 87 mg/dl (RR = 42.68) triglycerides over 158 mg/dl (RR = 5.87) and body mass index (BMI) over 27 kg/m2 (RR = 4.38) at 2nd trimester. Adiponectin in high-risk women is characterised by a constant reduction throughout gestation, irrespective of the development of GDM. HOMA, fasting glycaemia, triglycerides and BMI, but not adiponectin are independent predictors of GDM.

Role of amylin in insulin secretion and action in humans: antagonist studies across the spectrum of insulin sensitivity.

Amylin is a peptide co‐secreted with insulin by pancreatic β‐cells. A role for amylin in the pathogenesis of type 2 diabetes mellitus (DM2) has been suggested by in vitro and in vivo studies indicating an effect of amylin to cause insulin resistance and/or inhibit insulin secretion.

Emergency cerclage in the presence of protruding membranes: is pregnancy outcome predictable?

Background. The aim of this retrospective study is to verify whether some maternal features are related to pregnancy outcome in cases of emergency mid‐trimester cerclage when membranes are protruding through the dilated cervix.

Carbohydrate metabolism in gestational diabetes: effect of chronic hypertension

OBJECTIVE To evaluate whether the coexistence of chronic hypertension and gestational diabetes mellitus (GDM) is characterized by a greater impairment of carbohydrate metabolism than GDM alone. METHODS Carbohydrate metabolism of eight women with chronic hypertensive GDM and 15 normotensive women with GDM was evaluated in the third trimester using the oral glucose tolerance test (GTT) and hyperinsulinemic-euglycemic clamp technique. Controls were ten normotensive, glucose-tolerant, pregnant women in the third trimester. RESULTS Insulin sensitivity of women with chronic hypertension and GDM was approximately twofold lower than those with GDM only (1.54+/-0.35 versus 4.15+/-0.31, P < .001) and approximately fivefold lower than controls (1.54+/-0.35 versus 7.65+/-0.66, P < .001). Women with chronic hypertension and concomitant GDM had higher insulin levels in response to GTT than controls (P < .001 repeated measures analysis of variance). In all subjects, mean arterial pressure (MAP) had a strong negative correlation with maternal insulin sensitivity (r = -0.62, P < .001). Significant correlation was also found between percent of body fat and insulin sensitivity (r = -0.53, P < .002). Those regressions were still significant when adjusted for percent of body fat and MAP. CONCLUSION Gravidas with chronic hypertension and GDM are more insulin resistant than those with GDM alone. Blood pressure, in a population of pregnant women with normal and abnormal carbohydrate metabolism, is a stronger predictor of insulin resistance than adiposity.

Pregnancy outcome in women with cardiac valve prosthesis

Twenty-one pregnancies in 16 women who conceived after cardiac valve replacement were reviewed. Oral anticoagulants were discontinued before conception or as soon as possible for subcutaneous heparin treatment (8000-14,000 IU every 8-12 h) and resumed in the second trimester until the last period of pregnancy when oral anticoagulants were replaced again by heparin. No therapeutic abortion was performed. The spontaneous abortion rate was found to be 14.3% (3/21). Preterm delivery (< or = 37 weeks) and low birth weight babies (< 2500 g) were 29.4% (5/17) and 35.3% (6/17), respectively, significantly more frequent than those of the control group (P < 0.02 and P < 0.0005). No significant statistical difference was found when the rate of spontaneous abortion [14.3% (3/21)] and the rate of fetal growth retardation [11.8% (2/17)] were compared with the control group. The majority of thromboembolic events (6/7) occurred during heparin regimen in three mothers; one of them subsequently died. No coumarin embryopathy was observed and the physical and mental development in the 16 surviving children was good. This study confirms: (1) the increased rate of preterm delivery and infants weighing < 2500 g; (2) the increased risk of maternal thrombosis related to heparin use; and (3) the good follow-up in the surviving children.

Spontaneous Heterotopic Pregnancy, Simultaneous Ovarian, and Intrauterine: A Case Report

Spontaneous heterotopic pregnancy is a rare clinical condition in which intrauterine and extrauterine pregnancies occur at the same time. The occurrence of an ovarian heterotopic pregnancy is a singular event as it comprises only 2.3% of all heterotopic pregnancies, extremely rare among women who conceive naturally. A case of a 28-year old patient was treated for spontaneously conceived heterotopic pregnancy. The patient was admitted to our center with lower abdominal pain and amenorrhoea. A transvaginal ultrasound scan showed an ovarian and an intrauterine heterotopic pregnancy. This was managed laparoscopically. Considering spontaneous pregnancies, every physician treating women of reproductive age should be aware of the possibility of heterotopic pregnancy. It can occur in the absence of any predisposing risk factors; only with an early diagnosis and treatment the intrauterine pregnancies will reach viability with a great chance of a favorable obstetric outcome.