Giacoma Di Vieste

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.

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).

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.

The Effectiveness of Myo-Inositol and D-Chiro Inositol Treatment in Type 2 Diabetes

Inositol has been used as a supplement in treating several pathologies such as PCOS, metabolic syndrome, and gestational diabetes. Both myo-inositol and its isomer d-chiro-inositol showed insulin mimetic effects in conditions of insulin resistance. Type 2 diabetes (T2DM) is a condition typically caused by insulin resistance. There is a lack of evidence of inositol use in T2DM. We evaluated the effectiveness and safety of myo-inositol and d-chiro-inositol treatment in T2DM. This was a pilot study involving a consecutive sample of patients with T2DM with suboptimal glycemic control (HbA1c 7.0–10.0%) already treated with glucose-lowering agents. Patients (23.1% males, mean age of 60.8 ± 11.7 years) took for three months a combination of myo-inositol (550 mg) and d-chiro-inositol (13.8 mg) orally twice a day as add-on supplement to their glucose-lowering drugs. Possible occurrence of side effects was investigated. After three months of treatment fasting blood glucose (192.6 ± 60.2 versus 160.9 ± 36.4; p = 0.02) and HbA1c levels (8.6 ± 0.9 versus 7.7 ± 0.9; p = 0.02) significantly decreased compared to baseline. There was no significant difference in blood pressure, lipid profile, and BMI levels. None of the participants reported side effects. In conclusion, a supplementation with a combination of myo- and d-chiro-inositol is an effective and safe strategy for improving glycemic control in T2DM.

Genistein Supplementation and Cardiac Function in Postmenopausal Women with Metabolic Syndrome: Results from a Pilot Strain-Echo Study

Genistein, a soy-derived isoflavone, may improve cardiovascular risk profile in postmenopausal women with metabolic syndrome (MetS), but few literature data on its cardiac effects in humans are available. The aim of this sub-study of a randomized double-blind case-control study was to analyze the effect on cardiac function of one-year genistein dietary supplementation in 22 post-menopausal patients with MetS. Participants received 54 mg/day of genistein (n = 11) or placebo (n = 11) in combination with a Mediterranean-style diet and regular exercise. Left ventricular (LV) systolic function was assessed as the primary endpoint, according to conventional and strain-echocardiography measurements. Also, left atrial (LA) morphofunctional indices were investigated at baseline and at the final visit. Results were expressed as median with interquartile range (IQ). A significant improvement of LV ejection fraction (20.3 (IQ 12.5) vs. −1.67 (IQ 24.8); p = 0.040)), and LA area fractional change (11.1 (IQ 22.6) vs. 2.8 (9.5); p = 0.034)) were observed in genistein patients compared to the controls, following 12 months of treatment. In addition, body surface area indexed LA systolic volume and peak LA longitudinal strain significantly changed from basal to the end of the study in genistein-treated patients. One-year supplementation with 54 mg/day of pure genistein improved both LV ejection fraction and LA remodeling and function in postmenopausal women with MetS.

Comment on Farren et al. The Prevention of Gestational Diabetes Mellitus With Antenatal Oral Inositol Supplementation: A Randomized Controlled Trial. Diabetes Care 2017;40:759–763

We read with interest the study by Farren et al. (1) investigating the effect of a combination of myo -inositol and D -chiro-inositol on preventing gestational diabetes mellitus (GDM) in women with a family history of diabetes. The authors reported a not statistically different incidence of GDM in the intervention group compared with control subjects. However, it seems that important factors were not considered for the complete interpretation of results. First, the selection of the study population was not limited to women with only a family history of diabetes as a risk factor for GDM. Women with other well-known risk factors (i.e., obesity, previous GDM) were also included. The presence/absence of previous macrosomia was not specified. With regard …