Soy protein improves cardiovascular risk in subclinical hypothyroidism : a randomized double-blinded crossover study

© 2017 Endocrine Society. Background: Soy protein with isoflavones appears to have an adverse effect on thyroid function, but it is not known whether it is the protein or isoflavone component that is deleterious. The effect of isoflavone-free soy on thyroid function was determined in patients with subclinical hypothyroidism, with a secondary aim of assessing its effect on cardiovascular risk indices. Methods: This was a randomized, double-blind, crossover study involving 80 patients with subclinical (compensated) hypothyroidism. Patients were randomly assigned to either isolated soy (isoflavone-free) protein (SP) or casein protein (CP) supplementation for 8 weeks, washed out for 8 weeks, and then crossed over for a further 8-week period. Results: Thyroid function was unaffected by either a SP or CP. There were significant decreases in fasting glucose (4.760.6 vs 5.561.4, P < 0.01), insulin resistance (3.3±3.0 vs 3.8±3.4, P = 0.05), total cholesterol (4.4 ± 0.9 vs 5.3 ± 1.2, P < 0.01), triglycerides (0.9 ± 0.5 vs 1.7 ± 0.9, P < 0.1), and highly sensitive C-reactive protein (hsCRP; 0.8 ± 0.7 vs 2.6 ± 2.8, P < 0.01) in the SP group compared with the CP group. Blood pressure, low-density lipoprotein, and high-density lipoprotein remained unchanged in both groups. Conclusion: SP alone had no effect on thyroid function in patients with subclinical hypothyroidism and resulted in a significant reduction in fasting glucose, insulin resistance, total cholesterol, triglycerides, and hsCRP compared with CP

Effect of soy in men with type 2 diabetes mellitus and subclinical hypogonadism: a randomised controlled study

Context: Isoflavones found in soy products have a chemical structure similar to estrogen, leading to concerns of an adverse estrogenic effect in men, particularly in those with type 2 diabetes mellitus (T2DM) who have low testosterone levels due to hypogonadism. Objective: The primary outcome was change in total testosterone levels. The secondary outcomes were the changes in glycaemia and cardiovascular risk markers. Design: Randomised double blind parallel study. Setting: Secondary care setting in UK. Participants: 200 men with T2DM with a total testosterone level≤12nmol/L Intervention: 15g soy protein with 66mg of isoflavones (SPI) or 15g soy protein alone without isoflavones (SP) daily as snack bars for three months. Results: There was no change in either total testosterone or in absolute free testosterone levels with either SPI or SP. There was an increase in TSH and reduction in fT4 (p&lt;0.01) after SPI supplementation. Glycaemic control improved with a significant reduction in HbA1c (-4.19(7.29)mmol/mol,p&lt;0.01) and HOMA-IR after SPI. Cardiovascular risk improved with a reduction in triglycerides, CRP and diastolic BP (p&lt;0.05) with SPI versus SP supplementation. There was 6% improvement in 10-year coronary heart disease risk after three months of SPI supplementation. Endothelial function improved with both SPI and SP supplementation (p&lt;0.01) with an increased reactive hyperemia index that was greater for the SPI group (p&lt;0.05). Conclusions: Testosterone levels were unchanged and there was a significant improvement in glycaemia and cardiovascular risk markers with SPI compared to SP alone over three months. There was significant increase in TSH and a reduction in fT4

Effect of Glucose Variability on the Long-Term Risk of Microvascular Complications in Type 1 Diabetes

OBJECTIVE This study analyzed data from the Epidemiology of Diabetes Interventions and Complications (EDIC) study to see whether longer-term follow-up of Diabetes Control and Complications Trial (DCCT) patients reveals a role for glycemic instability in the development of microvascular complications.RESEARCH DESIGN AND METHODS The mean area under the curve glucose and the within-day glucose variability (SD and mean amplitude of glycemic excursions [MAGE]) during the DCCT were assessed to see whether they contributed to the risk of retinopathy and nephropathy by year 4 of the EDIC.RESULTS Logistic regression analysis showed that mean glucose during the DCCT and mean A1C during EDIC were independently predictive of retinopathy (each P 0.25 using SD or MAGE).CONCLUSIONS Glucose variability in the DCCT did not predict the development of retinopathy or nephropathy by EDIC year 4.Analysis of the Diabetes Control and Complications Trial (DCCT) dataset has shown that glucose variability did not appear to be a further factor in the development or progression of either retinopathy or nephropathy (1,2). More recently, variability in A1C, a longer-term marker of glycemic control, during the DCCT has been found to add to the risk already indicated by the mean A1C value (3).This current study has examined data from the first 4 years of the DCCT extension study, the Epidemiology of Diabetes Interventions and Complications (EDIC) study. The EDIC has already shown the long-term beneficial effects of intensive treatment on microvascular complications (4–6). Our goal was to establish whether the follow-up study also unearths a longer-term relationship between glucose variability during the DCCT and subsequent retinopathy and nephropathy

The effect of soy phytoestrogen supplementation on thyroid status and cardiovascular risk markers in patients with subclinical hypothyroidism: A randomized, double-blind, crossover study

Context: There is concern whether soy phytoestrogens may affect thyroid function. If true, soy phytoestrogens may be expected to have a greater impact in subjects with subclinical hypothyroidism. Objective: The primary aim was to determine the effect of soy phytoestrogen supplementation on thyroid function, with a secondary aim of assessing the effects on cardiovascular risk indices in patients with subclinical hypothyroidism. Design and Setting: We conducted a randomized, double-blind, crossover study in a tertiary care setting. Participants: Sixty patients with subclinical hypothyroidism participated in the study. Intervention: Patients were randomly assigned to either low-dose phytoestrogen (30 g soy protein with 2 mg phytoestrogens, representative of a Western diet) or high-dose phytoestrogen (30 g soy protein with 16 mg phytoestrogens, representative of a vegetarian diet) supplementation for 8 wk, then crossed over after an 8-wk washout period. Main Outcome Measures: The primary outcome was progression to overt hypothyroidism, with secondary outcome measures of blood pressure, insulin resistance, lipids, and highly sensitive C-reactive protein (hsCRP). Results: Six female patients in the study progressed into overt hypothyroidism with a standardized rate ratio of 3.6 (95% confidence interval, 1.9, 6.2) after 16-mg phytoestrogen supplementation. Both systolic and diastolic blood pressure decreased with 16 mg phytoestrogens, whereas systolic pressure alone decreased with 2 mg phytoestrogens. Insulin resistance (homeostasis model assessment of insulin resistance, 3.5 ± 0.09 vs. 2.6 ± 0.08; P < 0.02) and hsCRP (4.9 ± 0.04 vs. 3.9 ± 0.03; P < 0.01) decreased with 16 mg phytoestrogens. Lipid profile remained unchanged. Conclusion: There is a 3-fold increased risk of developing overt hypothyroidism with dietary supplementation of 16 mg soy phytoestrogens with subclinical hypothyroidism. However, 16-mg soy phytoestrogen supplementation significantly reduces the insulin resistance, hsCRP, and blood pressure in these patients. Copyright © 2011 by The Endocrine Society

Development of a composite model derived from cardiopulmonary exercise tests to predict mortality risk in patients with mild-to-moderate heart failure

Objective: Cardiopulmonary exercise testing (CPET) is used to predict outcome in patients with mild-to-moderate heart failure (HF). Single CPET-derived variables are often used, but we wanted to see if a composite score achieved better predictive power. Methods: Retrospective analysis of patient records at the Department of Cardiology, Castle Hill Hospital, Kingston-upon-Hull. 387 patients [median (25th-75th percentile)] [age 65 (56-72) years; 79% males; LVEF 34 (31-37) %] were included. Patients underwent a symptomlimited, maximal CPET on a treadmill. During a median follow up of 8.6 ± 2.1 years in survivors, 107 patients died. Survival models were built and validated using a hybrid approach between the bootstrap and Cox regression. Nine CPET-derived variables were included. Z-score defined each variable's predictive strength. Model coefficients were converted to a risk score. Results: Four CPET-related variables were independent predictors of all-cause mortality in the survival model: the presence of exertional oscillatory ventilation (EOV), increasing slope of the relation between ventilation and carbon dioxide production (VE/VCO2 slope), decreasing oxygen uptake efficiency slope (OUES), and an increase in the lowest ventilatory equivalent for carbon dioxide (VEqCO2 nadir). Individual predictors of mortality ranged from 0.60 to 0.71 using Harrell’s C-statistic, but the optimal combination of EOV + VE/VCO2 slope + OUES + VEqCO2 nadir reached 0.75. The Hull CPET risk score had a significantly higher area under the curve (0.78) when compared to the Heart Failure Survival Score (AUC=0.70;

Effect of increased inspired oxygen on exercise performance in patients with heart failure and normal ejection fraction

Introduction: We investigated whether increased concentrations of inspired oxygen (FiO2) affects exercise tolerance in patients with heart failure and normal ejection fraction (HeFNEF). Methods: 46 patients (mean age 75 years (63% male) and median NTproBNP 1432 (interquartile range: 543–2378 ng/l)) with HeFNEF (defined as signs or symptoms of heart failure requiring treatment with diuretics, with a left ventricular ejection fraction of >45% by echocardiography and amino terminal pro brain natriuretic peptide (NTproBNP) >220 ng/l) completed three maximal incremental exercise tests with different FiO2 (21%, 28% and 40%) in random order. FiO2 was controlled by investigator but blinded to patients. The primary outcome was exercise time (ET). Results: Increasing FiO2 significantly increased exercise time (522 ± 180 seconds for 21% to 543 ± 176 seconds, and 542 ± 177 seconds, for 28% and 40%, respectively, P = 0.04) with no difference in peak workload (57 ± 25 W, 58 ± 25 W and 57 ± 25 W, for 21%, 28% and 40%, respectively, P = 0.50). There was an increase in oxygen saturation but no change in peak heart rate with increasing FiO2. Compared to patients with LVEF ≥50%, patients with LVEF between 45 and 49% had a significantly greater exercise time and peak workload. There was a correlation between the difference in exercise time between FiO2 21% and 40% and age; but not with BMI, haemoglobin, creatinine or NTproBNP. Conclusion: Increasing FiO2 during exertion leads to a small increase in exercise time in patients with HeFNEF

Pseudotumor cerebri syndrome in childhood : incidence, clinical profile and risk factors in a national prospective population-based cohort study

Aim To investigate the epidemiology, clinical profile and risk factors of pseudotumor cerebri syndrome (PTCS) in children aged 1-16 years. Methods A national prospective population-based cohort study over 25 months. Newly diagnosed PTCS cases notified via British Paediatric Surveillance Unit (BPSU) were ascertained using classical diagnostic criteria and categorised according to 2013 revised diagnostic criteria. We derived national age, sex and weight-specific annual incidence rates and assessed effects of sex and weight category. Results We identified 185 PTCS cases of which 166 also fulfilled revised diagnostic criteria. The national annual incidence (95% CI) of childhood PTCS aged 1-16 years was 0.71 (0.57- 0.87) per 100,000 population increasing with age and weight to 4.18 and 10.7 per 100,000 in obese 12-15 year old boys and girls respectively. Incidence rates under 7 years were similar in both sexes. From 7 years onwards, the incidence in girls was double that in boys, but only in overweight (including obese) children. In 12-15 year old children, an estimated 82% of the incidence of PTCS was attributable to obesity. Two subgroups of PTCS were apparent: 168 (91%) cases aged from 7 years frequently presented on medication and with headache, and were predominantly female and obese. The remaining 17 (9%) cases under 7 years often lacked these risk factors and commonly presented with new onset squint. Conclusions This uniquely largest population-based study of childhood PTCS will inform the design of future intervention studies. It suggests that weight reduction is central to the prevention of PTCS

The effect of high dose isoflavone supplementation on serum reverse T3 in euthyroid men with Type 2 Diabetes and post-menopausal women

Background: The health benefits of soy are widely reported but there are queries on the effect of soy isoflavones on thyroid function and the underlying mechanism of action.Materials and Methods: We examined the effect of soy isoflavones on reverse tri-iodothyronine (or 3,3′,5′-tri-iodothyronine; rT3) in two studies comprising 400 patients: 200 men (study 1; 3 months) and 200 post-menopausal women (study 2; 6 months) who were randomized to consume 15 g soy protein with 66 mg of isoflavones (SPI) daily, or 15 g soy protein alone without isoflavones (SP) daily.Results: SPI supplementation increased rT3 serum concentration in both men 0.41 (0.12) vs. 0.45 (0.14) nmol/L and women 0.33 (0.12) vs. 0.37 (0.09) nmol/L at 3 months compared to SP that was not seen at 6 months. Thyroid stimulating hormone (TSH) serum concentrations increased while free thyroxine (fT4) concentrations decreased with 3 months of SPI compared to SP supplementation for both men and women. rT3 correlated with TSH in both studies (p = 0.03) but not with either fT3 or fT4. fT3 levels did not differ between the SPI and SP preparations.Conclusion: Soy isoflavones transiently increased rT3 levels within 3 months though reverted to baseline at 6 months. The mechanism for this would be either rT3 degrading deiodinase 1 and/or deiodinase 2 activities are transiently inhibited at 3 months, or inhibition of deiodinase 3, which generates rT3 from T4 is induced at 6 months. These changes were mirrored in the TSH concentrations, suggesting that short-term high dose isoflavone transiently impairs thyroid function in the first 3 months and may impact on general health during this period

The effects of empagliflozin vs metformin on endothelial microparticles in overweight/obese women with polycystic ovary syndrome

Context: Endothelial microparticles (EMPs) are novel, surrogate biomarkers of endothelial function and have been shown to be elevated in women with polycystic ovary syndrome (PCOS). It remains poorly understood how pharmacological options for managing PCOS affect EMP levels. Objective: To characterise and compare the effects of empagliflozin vs metformin on the circulating levels of EMPs in overweight/obese women with PCOS. Methods: This was a randomised, comparative, 12-week single-centre trial conducted at the Academic Diabetes, Endocrinology and Metabolism Research Centre, Hull, UK. This analysis includes data from 39 overweight/obese women with PCOS who completed the study and were randomised to empagliflozin (15 mg/day) (n = 19) or metformin (1500 mg/day) (n = 20). Blood samples were collected at baseline and 12 weeks after treatment and analysed for specific surface proteins (ICAM-1, VCAM-1, PECAM-1, E-selectin and endoglin) expressed by circulating EMPs using flow cytometry. Results: In the empagliflozin group, ICAM-1 (P = 0.006), E-selectin (P = 0.016) and VCAM-1 (P = 0.001) EMPs increased significantly following 12 weeks of treatment, but no changes were seen in PECAM-1 (P = 0.93) or endoglin (P = 0.13) EMPs. In the metformin group, VCAM-1 EMPs (P < 0.001) increased significantly after 12 weeks of treatment, whereas all other EMPs remained unchanged. When data were expressed as percentage change from baseline in each group, no significant differences were seen between groups for any biomarker (P-values from 0.22 to 0.80). Conclusions: Short-term administration of empagliflozin and metformin in overweight/ obese women with PCOS appear to increase EMPs expressed by endothelial cells during their activation

Soy isoflavones improve cardiovascular disease risk markers in women during 1 the early menopause 2 1

BackgroundHormone replacement therapy may be beneficial for cardiovascular disease risk (CVR) in post-menopausal women. Soy isoflavones may act as selective estrogen receptor modulators. The aim of this study was to evaluate whether soy isoflavones had an effect on CVR markers.MethodsThe expected 10-year risk of cardiovascular disease and mortality were calculated as a secondary endpoint from a double blind randomised parallel study involving 200 women (mean age 55 years, Caucasian, Hull, UK, 2012) in the early menopause who were randomised to 15 g soy protein with 66 mg isoflavone (SPI) or 15 g soy protein alone (depleted of all isoflavones; SP) given as a snack bar between meals daily for 6 months. Age, diabetes, smoking, blood pressure and lipid profiles were used to calculate CVR using the Framingham CVR engine.ResultsSPI treatment resulted in a significant reduction in the metabolic parameters and systolic blood pressure compared to SP (p < 0.01). There were no changes in fasting lipid profile and diastolic blood pressure with either treatment. At 6 months, changes in these parameters with SPI treatment were reflected in a calculated 27% (p < 0.01) reduction in 10 year coronary heart disease risk, a 37% (p < 0.01) reduction in myocardial infarction risk, a 24% (p < 0.04) reduction in cardiovascular disease and 42% (p < 0.02) reduction in cardiovascular disease death risk.ConclusionsSupplementation with soy protein with isoflavones for 6 months significantly improved CVR markers and calculated CVR at 6 months during early menopause compared to soy protein without isoflavones