Antonino Di Benedetto

Serum ionized magnesium levels in relation to metabolic syndrome in type 2 diabetic patients.

Objective: To evaluate circulating serum ionized magnesium (i-Mg) concentrations in patients with type 2 diabetes mellitus, and to investigate its relationship with the components of the metabolic syndrome. Design: cross-sectional study. Setting: Outpatients’ service for diabetic patients at the University Hospital of Messina, Italy. Subjects: 290 patients with type 2 diabetes mellitus. Measures of Outcome: Serum i-Mg was measured by ion selective electrode. Age, gender, body mass index (BMI), waist circumference, blood pressure, fasting glucose, HbA1c, HDL cholesterol, triglycerides, and urinary albumin excretion rate (UAER) were considered in the analyses. Patients with hypomagnesemia, defined as serum i-Mg <0.46 mmol/l, were compared with those having normal serum i-Mg levels, and variables proven to be associated with low i-Mg levels in the univariate analysis were entered in a multivariable logistic regression model to obtain a deconfounded estimate of the association between metabolic parameters and hypomagnesemia. Results: In univariate analysis, serum i-Mg levels were significantly reduced in patients with low HDL cholesterol, high triglycerides values, high waist circumference, high blood pressure, microalbuminuria and clinical proteinuria. Hypomagnesemia was highly prevalent in our study population (N = 143, 49.3%). After adjusting for potential confounders, plasma triglycerides (OR = 4.71; 95% CI = 2.56–8.67), waist circumference (OR = 2.21; 95% CI = 1.21–4.04), microalbuminuria (OR = 2.43; 95% CI = 1.16–5.08) and clinical proteinuria (OR = 2.04; 95% CI = 1.02–5.68) were independently associated with hypomagnesemia. Conclusions: Hypomagnesemia is highly prevalent in diabetic outpatients. High plasma triglycerides, waist circumference and albuminuria are independent correlates of hypomagnesemia.

myo-Inositol Supplementation and Onset of Gestational Diabetes Mellitus in Pregnant Women With a Family History of Type 2 Diabetes: A prospective, randomized, placebo-controlled study

OBJECTIVE To check the hypothesis that myo-inositol supplementation may reduce gestational diabetes mellitus (GDM) onset in pregnant women with a family history of type 2 diabetes. RESEARCH DESIGN AND METHODS A 2-year, prospective, randomized, open-label, placebo-controlled study was carried out in pregnant outpatients with a parent with type 2 diabetes who were treated from the end of the first trimester with 2 g myo-inositol plus 200 µg folic acid twice a day (n = 110) and in the placebo group (n = 110), who were only treated with 200 µg folic acid twice a day. The main outcome measure was the incidence of GDM in both groups. Secondary outcome measures were as follows: the incidence of fetal macrosomia (>4,000 g), gestational hypertension, preterm delivery, caesarean section, shoulder dystocia, neonatal hypoglycemia, and neonatal distress respiratory syndrome. GDM diagnosis was performed according to the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) recommendations. RESULTS Incidence of GDM was significantly reduced in the myo-inositol group compared with the placebo group: 6 vs. 15.3%, respectively (P = 0.04). In the myo-inositol group, a reduction of GDM risk occurrence was highlighted (odds ratio 0.35). A statistically significant reduction of fetal macrosomia in the myo-inositol group was also highlighted together with a significant reduction in mean fetal weight at delivery. In the other secondary outcome measures, there were no differences between groups. CONCLUSIONS myo-Inositol supplementation in pregnant women with a family history of type 2 diabetes may reduce GDM incidence and the delivery of macrosomia fetuses.

Genistein in the Metabolic Syndrome: Results of a Randomized Clinical Trial

CONTEXT This study was performed to evaluate the effects of genistein on metabolic and cardiovascular risk factors in Caucasian postmenopausal subjects with metabolic syndrome (MetS). OBJECTIVE Our objective was to assess the effects of genistein on surrogate endpoints associated with diabetes and cardiovascular disease. DESIGN AND SETTING This was a randomized, double-blind, placebo-controlled trial at 3 university medical centers in Italy. PATIENTS Patients included 120 postmenopausal women with MetS according to modified Third Report of the National Cholesterol Education Program (NCEP), Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) criteria. INTERVENTION After a 4-week stabilization period, postmenopausal women with MetS were randomly assigned to receive placebo (n = 60) or 54 mg genistein daily (n = 60) for 1 year. MAIN OUTCOME MEASURES The primary outcome was homeostasis model assessment for insulin resistance (HOMA-IR) at 1 year. Secondary outcomes were fasting glucose, fasting insulin, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, visfatin, adiponectin, and homocysteine levels. Data on adverse events were also recorded. RESULTS At 1 year in genistein recipients, fasting glucose, fasting insulin, and HOMA-IR (mean from 4.5 to 2.7; P < .001) decreased and were unchanged in placebo recipients. Genistein statistically increased HDL-C (mean from 46.4 to 56.8 mg/dL) and adiponectin and decreased total cholesterol, LDL-C (mean from 108.8 to 78.7 mg/dL), triglycerides, visfatin, and homocysteine (mean from 14.3 to 11.7 μmol/L) blood levels. Systolic and diastolic blood pressure was also reduced in genistein recipients. Genistein recipients neither experienced more side adverse effects than placebo nor discontinued the study. CONCLUSION One year of treatment with genistein improves surrogate endpoints associated with risk for diabetes and cardiovascular disease in postmenopausal women with MetS.

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.

Gender differences in sclerostin and clinical characteristics in type 1 diabetes mellitus

BACKGROUND Sclerostin is an osteocyte-derived inhibitor of the Wnt/β-catenin signaling pathway, which acts as a negative regulator of bone formation. Published data on sclerostin levels in type 1 diabetes mellitus (T1DM) are few. OBJECTIVE To evaluate gender differences in sclerostin serum levels and the association among sclerostin, bone mass, bone metabolism, and the main clinical characteristics of subjects with T1DM. DESIGN AND METHODS A total of 69 patients with T1DM (mean age, 33.7±8.1; 49% males) were enrolled in this cross-sectional study in a clinical research center. Bone mineral density was measured by phalangeal quantitative ultrasound (QUS); bone turnover markers (urinary pyridinoline, deoxypyridinoline (D-PYR), and urine hydroxyproline (OH-PRO) to evaluate bone resorption; serum bone alkaline phosphatase and BGP to evaluate bone formation) and sclerostin were assessed. RESULTS D-PYR and sclerostin were significantly higher in women when compared with men (P=0.04). A disease duration >15 years was associated with higher sclerostin levels (P=0.03). Bone turnover markers and QUS parameters were not correlated with sclerostin. A significant negative correlation was observed among QUS parameters, BMI, and OH-PRO. Sclerostin serum levels were correlated with homocysteine (r=-0.34, P=0.005) and vitamin B12 (r=-0.31, P=0.02). Generalized linear model showed that macroangiopathy was the only predictor of sclerostin serum levels (β=-11.8, 95% CI from -21.9 to -1.7; P=0.02). CONCLUSIONS Our data demonstrate that women with T1DM exhibit higher sclerostin levels than men and that circulating sclerostin is not associated with bone turnover markers and phalangeal QUS measurements. Macroangiopathy was associated with sclerostin levels.

Genistein and endothelial function in postmenopausal women with metabolic syndrome.

Previous data have suggested that genistein could exert beneficial effects on endothelial function and on predictors of cardiovascular risk in healthy postmenopausal women. In a randomized clinical trial, we studied the effects of genistein on endothelial function in postmenopausal women with metabolic syndrome (MS).

Age and Metabolic Control Influence Lens Opacity in Type I, Insulin-Dependent Diabetic Patients

Cataract is a frequent ocular complication in diabetic patients, but few data are available concerning early modifications occurring in the lens of these patients and their relationship with metabolic control and other clinical parameters. We measured lens opacity in 73 type I, insulin-dependent diabetic patients aging 50 years or less and without clinical evidence of cataract, and in 46 healthy volunteers of similar age. We used a quick, simple, and reliable instrument, the Lensmeter 701, which is based on a back-light scattering quantification system and is able to quantify lens transparency along the nuclear axis. Mean lens opacity was significantly (p = 0.0001) higher in diabetic patients than in the control group, and multiple regression analysis showed that it correlated with age (p = 0.0001) and HbA1c levels (p = 0.009). Moreover in the younger group of patients (age < or =20 years) the only observed correlation was that with Hba1c (p = 0.03), whereas in the older ones (age 21-30 and >30 years) lens opacity correlated with age (p = 0.02 and p = 0.01). These data indicate that early opacifications of the lens occur in type I, insulin-dependent diabetic patients and are influenced by the degree of the metabolic control in the younger ones, whereas the well-known role of aging on lens transparency became prevalent in the older patients. Only longitudinal studies, however, can demonstrate whether these alterations represent any early stage of cataractagenesis and the role of good metabolic control in preventing this ocular complication.

Midtrimester Amniotic Fluid Leptin and Insulin Levels and Subsequent Gestational Diabetes

Aims: To evaluate midtrimester amniotic fluid leptin levels in pregnancies subsequently complicated by gestational diabetes. Methods: We studied 32 pregnant women with gestational diabetes and a control group of 43 normal pregnancies with an adequate gestational age fetus. All underwent a midtrimester amniocentesis: leptin and insulin were measured in the amniotic fluid. Data were compared with the Mann-Whitney U-test. Results: Median leptin concentrations in the amniotic fluid of the gestational diabetes mellitus patients were significantly higher than in the control group (15.1 vs. 7.9 ng/ml) (p = 0.001); amniotic insulin concentrations were also higher in the gestational diabetes mellitus than in the control group (0.67 vs. 0.38 µU/ml) (p = 0.02). Furthermore, amniotic fluid leptin levels were directly correlated with amniotic insulin concentrations; instead, there was no correlation with maternal BMI and birth weight. Conclusion: Our data suggest that in pregnancies subsequently complicated by gestational diabetes, amniotic fluid leptin and insulin levels are higher in the early fetal period.

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.

Improvement of selective screening strategy for gestational diabetes through a more accurate definition of high-risk groups

OBJECTIVE This study aimed to assess the predictive value of risk factors (RFs) for gestational diabetes mellitus (GDM) established by selective screening (SS) and to identify subgroups of women at a higher risk of developing GDM. DESIGN A retrospective, single-center study design was employed. METHODS Data of 1015 women screened for GDM at 24-28 weeks of gestation and diagnosed according to the International Association of Diabetes and Pregnancy Study Groups criteria were evaluated. Information on RFs established by SS was also collected and their association with GDM was determined. To identify distinct and homogeneous subgroups of patients at a higher risk, the RECursive Partitioning and AMalgamation (RECPAM) method was used. RESULTS Overall, 113 (11.1%) women were diagnosed as having GDM. The application of the SS criteria would result in the execution of an oral glucose tolerance test (OGTT) in 58.3% of women and 26 (23.0%) cases of GDM would not be detected due to the absence of any RF. The RECPAM analysis identified high-risk subgroups characterized by fasting plasma glucose values >5.1 mmol/l (odds ratio (OR)=26.5; 95% CI 14.3-49.0) and pre-pregnancy BMI (OR=7.0; 95% CI 3.9-12.8 for overweight women). In a final logistic model including RECPAM classes, previous macrosomia (OR=3.6; 95% CI 1.1-11.6), and family history of diabetes (OR=1.8; 95% CI 1.1-2.8), but not maternal age, were also found to be associated with an increased risk of developing GDM. A screening approach based on the RECPAM model would reduce by over 50% (23.0 vs 10.6%) the number of undiagnosed GDM cases when compared with the current SS approach, at the expense of 50 additional OGTTs required. CONCLUSIONS A screening approach based on our RECPAM model results in a significant reduction in the number of undetected GDM cases compared with the current SS procedure.