Effectiveness, Safety, and Acceptance of an Interim Orthosis in Patients with Diabetes in the Immediate Postoperative Chopart Surgery.

Chopart amputation is the consequence of severe diabetes-related foot complications. A new interim orthosis allowing the patient a greater degree of mobility after Chopart surgery than currently used systems is now available. The aim of this study was to evaluate the effectiveness of the new orthosis compared with traditional treatment. Safety and level of patient acceptance of the device were also investigated. We performed a retrospective case-control observational study involving people with diabetes who underwent Chopart amputation between January 2016 and January 2018. The sample of subjects treated with the innovative orthosis was compared with consecutive patients, who were treated with traditional management. The main study outcomes include major amputation occurrence, ulcer recurrence, healing time, and patient acceptance of the orthosis. Patient satisfaction was evaluated using the Italian validated version of the Orthotic Prosthetic User's Survey (OPUS) questionnaire. Overall, 27 subjects were enrolled using the new device (mean age 68.7 ± 8.4 years, 70.4% males, mean diabetes duration 22.7 ± 15 years). Clinical baseline characteristics were comparable between the cases and the controls. There was no difference between the groups in the healed wound rate (81.5% vs 80.0% for cases and the control group, respectively, P = .53). The ulcer recurrence rate was higher in the control group compared with subjects using the new orthosis (62.5% vs 24.0%, respectively, P = .04). The use of the innovative orthosis was associated with an 81% lower probability to have ulcer recurrence (odds ratio 0.19, 95% confidence interval 0.04-1.04). No between groups difference was detected for a major amputation rate. The wound healing time was faster for cases compared with controls (160.4 ± 114.1 vs 256.5 ± 112.9 days, P = .05). No adverse events related to the use of the new orthosis were recorded. Patient acceptance of the new orthosis was high. This orthosis can be recommended as an efficient, safe, and well-accepted device after Chopart amputation.

Diagnosing Gestational Diabetes with a Probably Too Simplified Diagnostic Procedure Compared to International Criteria: The Indian Case Study.

Diagnostic procedures for the diagnosis of gestational diabetes mellitus (GDM) are not uniformly defined worldwide. We retrospectively applied two diagnostic procedures (i.e., the IADPSG and the Indian) to the same pregnant women in order to compare the clinical characteristics and the prevalence of risk factors for GDM. Overall, 1015 pregnant women were evaluated. GDM was diagnosed in 113 cases (11.1%) by the IADPSG criteria and in 105 cases (10.3%) by the Indian criteria. The women diagnosed with GDM according to the IADPSG criteria had higher pre-gestational BMIs, higher previous macrosomia rates, higher first trimester fasting blood glucose levels, higher fasting and 1 h glucose levels after glucose load at OGTT, and lower 2 h glucose levels at OGTT compared with the women with GDM diagnosed according to the Indian criteria. Only 49.6% of the women who were diagnosed by the IADPSG criteria were also diagnosed with GDM by the Indian diagnostic criteria. For 47.8% of the women who were diagnosed by the IADPSG criteria, a diagnosis of GDM was missed by applying the Indian diagnostic criteria. Interestingly, 49 women were diagnosed with GDM by the Indian criteria but were normal according to the IADPSG criteria. Different diagnostic criteria could lead to different GDM detection rates with different practical approaches.

The Effectiveness of Superbolus on Postprandial Blood Glucose Management of Pregnant Women With Type 1 Diabetes.

AIM: Pregnancies of women with pregestational diabetes are at risk of after-meal glucose peaks and late after-meal hypoglycemia, particularly at breakfast. We aimed to explore the effectiveness of a specific feature of insulin pump therapy called superbolus in preventing these glucose swings. METHODS: In this retrospective observational study, we analyzed continuous glucose monitoring data of patients with type 1 diabetes in pregnancy who were advised to use superbolus to manage their breakfast. Some of the postprandial basal insulin delivery was partially reduced and delivered instead as additional insulin bolus on top of a normal bolus. Outcomes of interest were one hour after breakfast glucose levels, the time in glucose range for after breakfast period, the number of late hypoglycemic episodes. RESULTS: Overall, 21 consecutive pregnant women with type 1 diabetes (mean age 34.3 ± 5.5 years, mean pregestational body mass index 23.7 ± 4.7 kg/m2, HbA1c levels during pregnancy 6.1 ± 0.6%) were studied. Superbolus reduced after breakfast glucose peaks (one hour after breakfast glucose levels 130 ± 17 mg/dL vs 123 ± 10 mg/dL before and after superbolus use, respectively, P = .01), improved the time in glucose range for after breakfast period (70.4% vs 50.8%, P = .001), and reduced the number of late hypoglycemic episodes (3 [1-5] vs 1 [0-2], P< .0001). CONCLUSION: Superbolus was effective in avoiding after-meal glucose peaks, increased postprandial glucose time in target, without late hypoglycemia occurrence. It represents a valid option for the treatment of pregnant women with type 1 diabetes using insulin pump.

The Analytical Reliability of the Oral Glucose Tolerance Test for the Diagnosis of Gestational Diabetes: An Observational, Retrospective Study in a Caucasian Population.

The Oral Glucose Tolerance Test (OGTT) is currently the gold standard reference test for the diagnosis of gestational diabetes mellitus (GDM). Several critical issues related to analytical variables have challenged its reproducibility and accuracy. This study aimed to assess the analytical reliability of the OGTT for the diagnosis of GDM. A total of 1015 pregnant women underwent a 2 h 75 g OGTT between 24 and 28 weeks of gestation. As recommended by National Academy of Clinical Biochemistry, we considered the total maximum allowable error for glucose plasma measurement as <6.9%. Assuming the possibility of analytical errors within this range for each OGTT glucose plasma value, different scenarios of GDM occurrence were estimated. GDM prevalence with standard criteria was 12.2%, and no hypothetical scenarios have shown a comparable GDM prevalence. Considering all the three OGTT values estimated at the lowest or the highest allowed value according to total maximum allowable error, GDM prevalence significantly varied (4.5% and 25.3%, respectively). Our results indicate that the OGTT is not completely accurate for GDM diagnosis.

Efficacy and Safety of Bioactive Glass S53P4 as a Treatment for Diabetic Foot Osteomyelitis.

Osteomyelitis represents a challenging condition in the diabetic foot with an associated high risk of major amputation. S53P4 Bioactive Glass (BG) has bacterial inhibiting properties on the market and indicated to be used in osteomyelitis. The objective of the study was to test the efficacy and safety of BG in treating diabetic foot osteomyelitis. This was an observational, retrospective, single-centre study involving subjects with diabetes affected by osteomyelitis of the foot who underwent surgical debridement from 01/2016 to 10/2018. Overall, 44 diabetic patients (14 [31.8%] female, aged 68.0 ± 10.2 years, diabetes duration 26.8 ± 11.9 years) were studied: 22 (50%) treated with surgical debridement and a local application of BG; 22 (50%) treated by means of surgical debridement. The primary outcome was the osteomyelitis resolution. Revascularization was performed before surgical procedure in 31 (70.5%) of patients. Systemic antibiotics were used in both groups. The osteomyelitis resolution rate was significantly higher in subjects treated with BG than in subjects treated with traditional procedure (18 [90%] vs 13 [61.9%], respectively p = .03). The odds of BG to reach osteomyelitis resolution was 5.54 times greater than for traditional treatment (odds ratio 5.54, 95% confidence interval 1.10-30.5). The use of BG was associated with an 81% lower probability to need additional antibiotic therapy compared to subjects treated with traditional procedure (odds ratio 0.19, 95% confidence interval 0.04-0.87). The debridement of osteomyelitis followed by application of BG could be an effective and safe option in the treatment of osteomyelitis of the diabetic foot.

From Prediabetes to Type 2 Diabetes Mellitus in Women with Polycystic Ovary Syndrome: Lifestyle and Pharmacological Management.

AIMS: Despite the very clear association between polycystic ovary syndrome (PCOS) and dysglycemia, few studies have explored the continuum of glycemic alterations leading from minor glucose abnormalities to overt diabetes. The purpose of this review is to trace the natural history of glycemic alteration in women with PCOS. METHODS: We performed a literature review without time limit until August 2019. Inclusion criteria were studies addressing the association between impaired glucose tolerance or impaired fasting glucose or type 2 diabetes (T2D) and PCOS with at least an English abstract. The exclusion criteria were no PCOS or impaired glucose tolerance or impaired fasting glucose or T2D as outcome. The outcomes of interest were the onset of impaired glucose tolerance, impaired fasting glucose, T2D, and the progression from impaired glucose tolerance or impaired fasting glucose to T2D. RESULTS: Healthy diet and physical activity are the first-line therapy for PCOS. Treatment with metformin was associated with significant lower 2-hour postload glucose levels and with reduction in fasting glucose when compared to placebo. Thiazolidinediones were more effective in reducing fasting glucose levels compared to placebo. Metformin and pioglitazone treatments showed similar effects on fasting glucose levels. The sodium-glucose cotransporter-2 inhibitor empagliflozin did not show differences in metabolic parameters when compared to metformin. The combination therapy with metformin plus the glucagon-like peptide-1 receptor agonist liraglutide was associated with significant improvements in basal and postload glucose levels compared with only liraglutide. Likewise, a combination therapy with the dipeptidyl peptidase-4 inhibitor saxagliptin and metformin demonstrated superiority versus metformin in fasting glucose and oral glucose tolerance test normalization. Myo-inositol supplementation was associated with lower insulin levels, glucose levels, and insulin resistance when compared with placebo, metformin, or estrogen treatments. CONCLUSIONS: The use of insulin-sensitizing agents, such as metformin and inositols, along with lifestyle interventions may improve the metabolic profile in PCOS women.

Effect of inositol stereoisomers at different dosages in gestational diabetes: an open-label, parallel, randomized controlled trial.

AIMS: Gestational diabetes mellitus (GDM) is the most common metabolic disorder of pregnancy. The aim of the study is to compare the effect of different dosages of inositol stereoisomers supplementation on insulin resistance levels and several maternal-fetal outcomes in GDM women. METHODS: Participants were randomly allocated to receive daily: 400 mcg folic acid (control treatment), 4000 mg myo-inositol plus 400 mcg folic acid (MI treatment), 500 mg D-chiro-inositol plus 400 mcg folic acid (DCI treatment) or 1100/27.6 mg myo/D-chiro-inositol plus 400 mcg folic acid (MI plus DCI treatment). The homeostasis model assessment of insulin resistance (HOMA-IR) was measured at the diagnosis of GDM and after 8 weeks of treatment. Secondary outcomes, obstetric outcomes and any maternal or fetal complication at delivery were also collected. RESULTS: Eighty GDM women were assigned to one of the four arms of study (20 per arm). A significant delta decrease in HOMA-IR index was found in subjects of MI group without insulin therapy compared to control group (p < 0.001). A lower variation in average weight gain (at delivery vs pre-pregnancy and OGTT period) was detected in MI group vs control group (p = 0.001 and p = 0.019, respectively). Moreover, women exposed to MI and MI plus DCI required a significantly lower necessity of an intensified insulin treatment. Women of the control group had newborns with higher birth weight compared with women treated with inositol (p = 0.032). CONCLUSIONS: Our study provides interesting but preliminary results about the potential role of inositol stereoisomers supplementation in the treatment of GDM on insulin resistance levels and several maternal-fetal outcomes. Further studies are required to examine the optimal and effective dosages of different inositol supplements. CLINICAL TRIAL REG. NO.: NCT02097069, ClinicalTrial.gov.

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.

[Depression, anxiety and anger in patients with type 1 diabetes mellitus.] / Depressione, ansia e rabbia in soggetti affetti da diabete mellito di tipo 1.

INTRODUCTION: The aim of this study is to evaluate the influence of negative emotions such as depression, anxiety and anger on clinical expression of type 1 diabetes, also assessing possible gender differences. MATERIALS AND METHODS: 75 subjects with type 1 diabetes mellitus afferent to Diabetology Unit of the University Hospital in Messina underwent the following psychodiagnostic tests: Hamilton Rating Scale For Depression (HDRS), State-Trait Anxiety Inventory form Y (STAI-Y), State-Trait Anger Expression Inventory-2 (STAXI-2). Continuous data were expressed as mean ± standard deviation, and the comparison between groups was performed using T Student test; the data not continuous were expressed as a percentage and the differences between groups were evaluated using Chi-square test. We considered the results for values of p<0.05. RESULTS: The mean age of 75 subjects (49.3% males) was 41.0±11.4 years, age of disease onset was 21.1 ± 11.8 years and mean duration of disease was 19.9±11.9 years; 30.7% of subjects were treated with CSII (Subcutaneus Insulin Infusion). Mild levels of depression (HDRS= 10.71±7.9) and anxiety (STAI-Y= 52.37±6.11) were found, whereas STAXI-2 subscales scores were within the normal range. Statistical analysis did not show significant gender differences. DISCUSSION: Our results, according to data from literature, confirm the association between negative emotions, particularly anxiety, and diabetes. No gender differences were found. CONCLUSIONS: Our results suggest the importance of investigating the association between diabetes and negative emotional states and the psychological and psychopathological dimensions which may have a potential role in the therapeutic management of diabetes.

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.

Preventing Adolescents' Diabesity: Design, Development, and First Evaluation of "Gustavo in Gnam's Planet".

OBJECTIVE: The goal of this study was to design, develop, and evaluate a game for health, "Gustavo in Gnam's Planet" ("Gustavo"), aimed to improve knowledge on healthy foods and to increase consumption of healthy foods. SUBJECTS AND METHODS: Eighty-three high school students were enrolled in the study. The game was designed and developed by a multidisciplinary team. Behavioral change theories were adopted to guide the design of the health messages. Participants were assessed about food frequency, healthy food knowledge, and the game's interest. RESULTS: Forty-seven subjects (mean age, 14.9±1.0 years; 72.3 percent males) completed the study. At posttest, participants showed significant higher scores (i.e., increased knowledge) in the questionnaire on knowledge of healthy foods (70.0±9.2 versus 71.3±10.0 for pretest and posttest, respectively; P<0.05). Improvements in healthy eating habits were also detected: higher frequency of consumption during a week of white meat (1 [1-2] versus 2 [1-2]; P=0.01), eggs (1 [1-1] versus 1 [1-2]; P=0.01], and legumes (1 [0-1] versus 1 [1-2]; P=0.03) and lower frequency of consumption of sugar-containing packaged snacks (1 [0-1] versus 0 [0-1]; P=0.009). Most of the participants found the game easy to use and clear in its content. Half of the participants found the game interesting. CONCLUSIONS: Our study shows that "Gustavo" is a promising tool for health education, in schools or in other environments. Limitations of the study and future directions are discussed.

Serum thyroid hormone autoantibodies in type 1 diabetes mellitus.

CONTEXT: Autoimmune thyroid diseases (AITDs) can be associated with type 1 diabetes (DM1). The prevalence of serum antibodies against thyroid hormones (THAb) in subjects with autoimmune diseases other than DM1 is increasing. No data are available for DM1. OBJECTIVE: The objectives were evaluate the rate of associated AITD; the rate of positiveness for serum THAb; the panel of THAb based on thyroid hormone interaction and on Ig class; and the association of AITD alone, THAb alone, or AITD plus THAb with diabetes-related complications. DESIGN: This was an observational, prospective study with 6-year (2005-2011) follow-up. SETTING: The setting was an outpatient diabetes clinic. PATIENTS: Fifty-two consecutive subjects (53.8% males; mean age, 37.4 ± 7.4 y; diabetes duration, 19.9 ± 8.2 y) with DM1. All participants completed the study. MAIN OUTCOME MEASURES: Main outcome measures were AITD rate; THAb positivity according to hormone interaction and Ig class; association of AITD and THAb with diabetes-related complications. RESULTS: AITD rate increased from baseline (34.6%) to follow-up (38.5%). Subjects with DM1 had a high prevalence of THAb (92.3%). The presence of AITD at baseline was associated with subsequent development of macroangiopathy (0 vs 33% at baseline and follow-up, respectively; P = .029). Some THAb patterns, the majority having T3 binding in common, were associated with the progression and development of diabetes-related complications. CONCLUSIONS: THAb synthesis in DM1 might be driven by increased glycosylation of thyroglobulin. Anti T3-THAb may cause a relative "tissue hypothyroidism" by sequestering thyroid hormone, this at least partially contributing to worsening diabetes-related vascular complications. In a clinical setting THAb positivity could identify subjects more likely to develop diabetes complications.

The long-term effects of stillbirth on women with and without gestational diabetes: a population-based cohort study.

AIMS/HYPOTHESIS: The aim of this study was to estimate the incidence of type 2 diabetes (primary objective) and hospitalisation for cardiovascular events (secondary objective) in women with previous gestational diabetes mellitus (GDM) and in those with normal glucose tolerance (NGT) in pregnancy, and to evaluate the role of stillbirth in differentiating the risks. METHODS: This was a population-based cohort study using administrative data and involving 12 local health authorities. Women with GDM (n = 3,851) during the index period from 2002 to 2010 were propensity matched with women with NGT (n = 11,553). Information was collected on type 2 diabetes development and hospitalisation for cardiovascular events. RESULTS: During a median follow-up of 5.4 years, the incidence rate per 1,000 person-years of type 2 diabetes was 2.1 (95% CI 1.8, 2.5) in women without GDM and 54.0 (95% CI 50.2, 58.0) among women with GDM and pregnancy at term (incidence rate ratio [IRR] 26.9; 95% CI 22.1, 32.7 compared with NGT and pregnancy at term). A history of stillbirth increased the risk of type 2 diabetes development by about twofold, irrespective of GDM status. No significant interaction between stillbirth and GDM on type 2 diabetes risk was found. GDM was associated with a significantly higher risk of cardiovascular events compared with NGT (IRR 2.4; 95% CI 1.5, 3.8). CONCLUSIONS/INTERPRETATION: Pregnancy complicated by GDM and ending in stillbirth represents an important contributory factor in determining type 2 diabetes development. Women with GDM are at a high risk of future cardiovascular events. Women with pregnancy complicated by GDM and stillbirth deserve careful follow-up.

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

BACKGROUND: Sclerostin is an osteocyte-derived inhibitor of the Wnt/ß-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 (ß=-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.

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.

Genistein and endothelial function in postmenopausal women with metabolic syndrome.

BACKGROUND: 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). METHODS: Twenty postmenopausal women with MS, according to modified NCEP-ATP III criteria were randomly assigned to receive placebo or genistein (54 mg/day) for 6 months, along with a Mediterranean-style diet. Postmenopausal women without MS (n = 15), served as controls. The primary goal was the assessment of endothelial function by flow-mediated vasodilation (FMD) of brachial artery; moreover, time-to-peak dilation in the FMD response has been evaluated. Secondary outcomes were fasting glucose, fasting insulin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, visfatin, adiponectin and homocysteine blood levels. Data on adverse events were also recorded. RESULTS: After 6 months of treatment, FMD at 50s and peak FMD significantly increased in genistein recipients compared with placebo. Moreover, genistein significantly decreased the blood levels of total cholesterol, triglycerides, homocysteine and visfatin compared with placebo, while blood adiponectin levels were increased. Genistein recipients neither experienced more side-adverse effects than placebo nor discontinued the study. CONCLUSIONS: Six months of treatment with genistein effectively improves brachial artery flow-mediated vasodilation in postmenopausal women with metabolic syndrome.

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.