Angelo Santamaria

The effect of myoinositol supplementation on insulin resistance in patients with gestational diabetes

Diabet. Med. 28, 972–975 (2011)

Myo-inositol Supplementation for Prevention of Gestational Diabetes in Obese Pregnant Women: A Randomized Controlled Trial.

OBJECTIVE: To evaluate whether myo-inositol supplementation, an insulin sensitizer, reduces the rate of gestational diabetes mellitus (GDM) and lowers insulin resistance in obese pregnant women. METHODS: In an open-label, randomized trial, myo-inositol (2 g plus 200 micrograms folic acid twice a day) or placebo (200 micrograms folic acid twice a day) was administered from the first trimester to delivery in pregnant obese women (prepregnancy body mass index 30 or greater. We calculated that 101 women in each arm would be required to demonstrate a 65% GDM reduction in the myo-inositol group with a statistical power of 80% (&agr;=0.05). The primary outcomes were the incidence of GDM and the change in insulin resistance from enrollment until the diagnostic oral glucose tolerance test. RESULTS: From January 2011 to April 2014, 220 pregnant women at 12–13 weeks of gestation were randomized at two Italian university hospitals, 110 to myo-inositol and 110 to placebo. Most characteristics were similar between groups. The GDM rate was significantly reduced in the myo-inositol group compared with the control group, 14.0% compared with 33.6%, respectively (P=.001; odds ratio 0.34, 95% confidence interval 0.17–0.68). Furthermore, women treated with myo-inositol showed a significantly greater reduction in the homeostasis model assessment of insulin resistance compared with the control group, −1.0±3.1 compared with 0.1±1.8 (P=.048). CONCLUSION: Myo-inositol supplementation, started in the first trimester, in obese pregnant women seems to reduce the incidence in GDM through a reduction of insulin resistance. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01047982.

One-year effects of myo-inositol supplementation in postmenopausal women with metabolic syndrome.

ABSTRACT Objective To evaluate the 12-month effect of myo-inositol treatment on some biochemical parameters of women affected by metabolic syndrome. Methods Eighty outpatient postmenopausal women, affected by metabolic syndrome, were enrolled in a 12-month study. All women were treated with a low-energy diet, and then they were randomly assigned to myo-inositol 2 g b.i.d. (n = 40) or placebo (n = 40). All the women were evaluated for serum glucose, insulin, HOMA-IR (Homeostasis Model Assessment-Insulin Resistance), triglycerides, total and high density lipoprotein cholesterol, body mass index (BMI), waist circumference and blood pressure at baseline and after 12 months of treatment. Results With the exception of BMI and waist circumference, after 12 months of treatment, all the parameters studied showed a significant improvement in the myo-inositol group compared to the control group. At the end of the study, in the myo-inositol group, the number of women without metabolic syndrome was eight (20%) whereas, in the control group, only one woman no longer had the metabolic syndrome after 12 months of diet. Conclusions Myo-inositol might be considered one of the insulin-sensitizing substances in the treatment of metabolic syndrome.

Myo-inositol may prevent gestational diabetes onset in overweight women: a randomized, controlled trial

Abstract Objective: To evaluate whether myo-inositol supplementation may reduce gestational diabetes mellitus (GDM) rate in overweight women. Methods: In an open-label, randomized trial, myo-inositol (2 g plus 200 μg folic acid twice a day) or placebo (200 μg folic acid twice a day) was administered from the first trimester to delivery in pregnant overweight non-obese women (pre-pregnancy body mass index ≥ 25 and < 30 kg/m2). The primary outcome was the incidence of GDM. Results: From January 2012 to December 2014, 220 pregnant women were randomized at two Italian University hospitals, 110 to myo-inositol and 110 to placebo. The incidence of GDM was significantly lower in the myo-inositol group compared to the placebo group (11.6% versus 27.4%, respectively, p = 0.004). Myo-inositol treatment was associated with a 67% risk reduction of developing GDM (OR 0.33; 95% CI 0.15–0.70). Conclusions: Myo-inositol supplementation, administered since early pregnancy, reduces GDM incidence in overweight non-obese women.

Effects of a New Flavonoid and Myo-Inositol Supplement on Some Biomarkers of Cardiovascular Risk in Postmenopausal Women: A Randomized Trial

Background and Aim. Cardiovascular risk is increased in women with menopause and metabolic syndrome. Aim of this study was to test the effect of a new supplement formula, combining cocoa polyphenols, myo-inositol, and soy isoflavones, on some biomarkers of cardiovascular risk in postmenopausal women with metabolic syndrome. Methods and Results. A total of 60 women were enrolled and randomly assigned (n = 30 per group) to receive the supplement (NRT: 30 mg of cocoa polyphenols, 80 mg of soy isoflavones, and 2 gr of myo-inositol), or placebo for 6 months. The study protocol included three visits (baseline, 6, and 12 months) for the evaluation of glucose, triglycerides, and HDL-cholesterol (HDL-C), adiponectin, visfatin, resistin, and bone-specific alkaline phosphatase (bone-ALP). At 6 months, a significant difference between NRT and placebo was found for glucose (96 ± 7 versus 108 ± 10 mg/dL), triglycerides (145 ± 14 versus 165 ± 18 mg/dL), visfatin (2.8 ± 0.8 versus 3.7 ± 1.1 ng/mL), resistin (27 ± 7 versus 32 ± 8 µg/L), and b-ALP (19 ± 7 versus 15 ± 5 µg/mL). No difference in HDL-C concentrations nor in adiponectin levels between groups was reported at 6 months. Conclusions. The supplement used in this study improves most of the biomarkers linked to metabolic syndrome. This Trial is registered with NCT01400724.

Italian risk factor-based screening for gestational diabetes

Abstract There is a debate about whether universal or risk factors-based screening is most appropriate for gestational diabetes diagnosis. The aim of our retrospective study was to compare in our population the universal screening test recommended by the International Association of Diabetes in Pregnancy Study Group (IADPSG) panel and the American Diabetes Association (ADA) versus the selective screening proposed by the United Kingdom National Institute for Health and Clinical Excellence guidelines (NICE) but modified by the Italian National Institute of Health. From May 2010 to October 2011 all consecutive pregnant women were screened for gestational diabetes according to the IADPSG’s panel criteria, while all the risk factors for each patient were registered. Of the 1015 pregnant women included in the study, 113 (11%) were diagnosed with gestational diabetes and 26 (23%) of them would not have been identified by the selective screening proposed by the Italian National Institute of Health. However, all the risk factors considered by the selective screening revealed a good predictive role except for maternal age ≥35 years (OR: 0.98). In the group without the risk factors considered, it was reported the predictive role for gestational diabetes of prepregnancy BMI and nulliparity. The selective risk factors-based screening proposed by the Italian National Institute of Health has detected 77% of gestational diabetes cases in our population, sparing the oral glucose tolerance test for more than 40% of pregnant women at the same time. More information on the clinical impact of this choice could be obtained by a strict analysis of treatment, perinatal outcome and follow-up of an adequate sample size of “missed” gestational diabetes.

Cadmium delays puberty onset and testis growth in adolescents

Cadmium (Cd) has been shown to impair pubertal development in experimental animals. However, no data are available for male adolescents with increased urinary cadmium levels.

Prenatally identified Pallister–Killian syndrome: Ultrasound pattern and diagnostic considerations

Introduction Pallister – Killian syndrome (PKS; OMIM #601803) is a sporadic rare chromosomal disorder (1: 25,000) (Pallister et al. 1977; Srinivasan and Wright 2014). Th is syndrome may comprise webbed neck, low-set ears, lower jaw tooth bud, left simian crease, shield chest, streaks of hypo (hyper)pigmentation or focal aplasia cutis, diaphragmatic hernia, hypoplastic lungs, agenesis of pericardium, Meckel ’ s diverticulum, severe mental retardation, hypotonia, seizures, heart defects and other systemic abnormalities (Mourali et al. 2010). Th e facial dysmorphism is characterised by coarse and fl at facies, macroglossia, prognathia and everted lower lip, which is a pattern similar to that observed in Fryns syndrome (Rodr í guez et al. 1994). PKS is caused by mosaicism for isochromosome 12p. Th is mosaicism is usually limited to skin fi broblasts, which have 47 chromosomes with an extra small metacentric chromosome, while lymphocytes display a normal karyotype (Ozl ü et al. 2014). Here we report a case of prenatally diagnosed PKS. Th is case report is in accordance with the Helsinki Declaration, COPE guidelines (http://publicationethics.org/), Uniform Requirements for Manuscripts Submitted to Biomedical Journals, the CARE guideline available through the EQUATOR network (http:// www.equator-network.org/), and approved by an independent Institutional Review Board or IRB.

Perinatal outcome in a Caucasian population with gestational diabetes and preexisting diabetes first diagnosed in pregnancy

AIM Our objective was to compare, in a Caucasian population, the perinatal outcomes of pregnancies complicated by pregestational diabetes diagnosed in the first-trimester of pregnancy with those of pregnancies complicated by gestational diabetes. METHODS A retrospective evaluation of maternal and neonatal outcomes was performed for all consecutive pregnancies complicated by gestational or pregestational diabetes that happened between 2005 and 2011. Pregestational diabetes was diagnosed for the first time in pregnancy if the first-trimester fasting glycaemia was ≥126 mg/dL. Gestational diabetes was diagnosed according to Carpenter-Coustan criteria until May 2010, and then according to the International Association of Diabetes and Pregnancy Study Groups (IADPSG) panel criteria modified by the American Diabetes Association. A specific diet, self-monitoring of blood glucose and, if required, insulin treatment were prescribed. RESULTS Overall, 411 pregnant women were considered eligible for the study (379 with gestational diabetes and 32 with pregestational diabetes). Women with pregestational vs. gestational diabetes were diagnosed earlier in pregnancy (11.6±1.0 weeks vs. 25.9±1.7 weeks; P=0.0001), had a higher mean first-trimester fasting glycaemic level (129.5±3.6 mg/dL vs. 81.6±10.5mg/dL; P=0.0001), more often had a family history of diabetes (46.9% vs. 25.9%; P=0.02) and more often needed insulin treatment (78.1% vs. 14.0%; P=0.0001). Furthermore, a higher rate of fetal malformations in women with pregestational diabetes was detected (9.4% vs. 1.6%, P=0.02). No other differences in neonatal outcomes were identified. CONCLUSION In a Caucasian population, the prevalence of fetal malformations and insulin requirements with pregestational diabetes first diagnosed in pregnancy were significantly higher compared with women with gestational diabetes. In any case, glucose impairment in pregnancy needs to be diagnosed in a timely fashion and appropriately treated to improve both maternal and fetal outcomes.

ADAM 12 and PAPP-A at 14-17 weeks' gestation as biomarkers of pre-eclampsia

Pre-eclampsia (PE) is a pregnancy complication that affects 2–5% of all pregnancies and represents a major cause of maternal and fetal death (Walker, 2000). Currently, prevention may be performed only for cases at risk; however, this syndrome frequently occurs in women without known risk factors, in whom no treatment other than delivery may be offered. In this way, for patients at low risk for this syndrome, an early prediction would be of great importance. Recently, a growing number of biochemical markers have been tested for predicting PE (Carty et al., 2008), but at the moment, there are no sufficient data to justify their employment in clinical use. However, the biomarkers included in the second trimester quadruple test for the screening of Down syndrome showed a detection rate (DR) over 40% in predicting PE, at a 6.5% false-positive rate (Wald et al., 2006). We studied two other potential markers of PE: a disintegrin and metalloprotease (ADAM) 12 and pregnancy-associated plasma protein A (PAPP-A). Both are produced by the placenta and exert a proteolytic activity against different types of insulin-like growth factor-binding protein (IGFBP): PAPP-A on IGFBP-4 (Lawrence et al., 1999) and ADAM 12 on IGFBP-3 and IGFBP-5 (Loechel et al., 2000), with the aim of releasing insulin-like growth factor (IGF), which is thought to play an important role in fetal growth. ADAM 12 serum evaluated at the time of first trimester screening for Down syndrome (10–14 weeks’ gestation) gave contrasting results with regard to PE, including those which were found to be significantly decreased compared to the control cases (Laigaard et al., 2005), and others which failed to highlight any difference (Poon et al., 2008), whereas serum PAPP-A has been shown to be a predictive first trimester marker for PE (Poon et al., 2009). In our study, we considered the period from 14 to 17 weeks’ gestation. From the beginning of 2008 to June 2009 we considered the first 40 women affected by PE who delivered in our hospital and from whom we already had stored blood samples at the time of the second trimester Down syndrome screening (14–17 weeks’ gestation).