Salivary testosterone measurement in women with and without polycystic ovary syndrome

Clinical and/or biochemical hyperandrogenism is one of the diagnostic criteria for PCOS. An evaluation of the role of salivary testosterone (salT) and androstenedione (salA) for the diagnosis of PCOS was undertaken in a cross sectional study involving 65 women without PCOS and 110 women with PCOS fulfilling all 3 diagnostic Rotterdam criteria. Serum and salivary androgen measurements were determined by LC-MS/MS. salT and salA were significantly elevated in PCOS compared to controls (P<001). No androgen marker was more predictive than another using ROC curves, but multiple logistic regression suggested salT was more predictive than free androgen index (FAI)(p<0.01). The combination of salT or FAI identified 100% of PCOS women. PCOS women with both biochemical and clinical hyperandrogenism as opposed to clinical hyperandrogenism alone showed a metabolic phenotype (p<0.05) and insulin resistance(p<0.001). PCOS patients with an isolated elevated FAI showed increased insulin resistance compared to those with an isolated salT(P<0.05). salT appeared to be at least as predictive as FAI for the diagnosis of the classical PCOS phenotype, and the combination of salT or FAI identified 100% of PCOS patients. This suggests that salT measurement by LC-MS/MS holds the promise of complementing existing laboratory tests as a means of assessing hyperandrogenemia

The effect of atorvastatin on pancreatic beta cell requirement in women with polycystic ovary syndrome

Background There is an increased risk of developing T2DM in women with polycystic ovary syndrome (PCOS) and there is evidence that statins improve metabolic parameters in these patients. However, there is some data to show that statins increase the risk of incipient diabetes. Material and Methods We have previously shown that 12-weeks of atorvastatin improves insulin resistance when measured using HOMA-IR. This post hoc-analysis was designed to look at the effect of atorvastatin on pancreatic β cell function using HOMA-β in the same study. In this randomised, double blind placebo controlled study, 40 medication naïve patients with PCOS were randomized to either atorvastatin 20 mg daily or placebo for 3 months. A 3-month extension study for both groups of patients was undertaken with metformin 1500 mg daily after completing initial 3 months of atorvastatin or placebo. Results There was a significant reduction in HOMA-β (240±3.2vs.177±2.3; pvalue<0.01) after 12 weeks of atorvastatin treatment which was maintained by metformin in the subsequent 12 weeks. There were no changes in HOMA-β after the placebo or after subsequent metformin treatment. There was no linear correlation between reduction in HOMA-β with improvement of free androgen index (FAI) (r2=0.02;p=0.72), testosterone (r2=0.13;p=0.49), SHBG (r2=0.22;p=0.48), hsCRP (r2=0.19;p=0.64), triglycerides (r2=0.09;p=0.12), total cholesterol (r2=0.11;p=0.32) or LDL-C (r2=0.19;p=0.38). Conclusion Treatment with atorvastatin for 12 weeks in women with PCOS significantly reduced HOMA-β. This could be potentially due to fall in βcell requirement with improvement of insulin resistance rather than a reduction of βcell function

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

Endocannabinoid receptor blockade increases vascular endothelial growth factor and inflammatory markers in obese women with polycystic ovary syndrome

© 2016 John Wiley & Sons Ltd Context: Animal studies suggest that cannabinoid receptor-1 (CB-1) blockade reduces inflammation and neovascularization by decreasing vascular endothelial growth factor (VEGF) levels associated with a reduction in inflammatory markers, thereby potentially reducing cardiovascular risk. Objective: To determine the impact of CB1 antagonism by rimonabant on VEGF and inflammatory markers in obese PCOS women. Design: Randomized, open-labelled parallel study. Setting: Endocrinology outpatient clinic in a referral centre. Subjects: Twenty patients with PCOS (PCOS) and biochemical hyperandrogenaemia with a body mass index of ≥30 kg/m 2 were recruited. Patients were randomized to 1·5 g daily of metformin or 20 mg daily of rimonabant. Main outcome measures: Post hoc review to detect VEGF and pro-inflammatory cytokines TNF-α, IL-1β, IL-1ra, IL-2, IL6, IL-8, IL-10 and MCP-1 before and after 12 weeks of treatment. Results: After 12 weeks of rimonabant treatment, there was a significant increase in VEGF (99·2 ± 17·6 vs 116·2 ± 15·8 pg/ml, P < 0·01) and IL-8 (7·4 ± 11·0 vs 18·1 ± 13·2 pg/ml, P < 0·05) but not after metformin (VEGF P = 0·7; IL-8 P = 0·9). There was no significant difference in the pro-inflammatory cytokines TNF-α, IL-1β, IL-1ra, IL-2, IL6, IL-8, IL-10 and MCP-1 following either treatment. Conclusion: This study suggests that rimonabant CB-I blockade paradoxically raised VEGF and the cytokine IL-8 in obese women with PCOS that may have offset the potential benefit associated with weight loss

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

The Metabolic Assessment of Patients With Diabetes Mellitus

This thesis critically evaluates two developments which have both brought about major advances in the assessment of glycaemic control in diabetic patients. First is the measurement of glycated proteins in the form of glycated haemoglobin and serum fructosamine and the second is the use of portable test strips and meters for the self-monitoring of blood glucose. Both methods of assessment have gained widespread acceptance but there remains a number of clinical and methodological problems associated with their use. This thesis reviews the literature relating to the use of these tests and describes a number of studies demonstrating new benefits and difficulties which exist. The majority of clinicians now use glycated haemoglobin measurement as their principal objective indicator of glycaemic control in diabetic patients. We have performed several detailed studies elucidating clinically relevant aspects of glycated haemoglobin measurement which can affect the assessment of glycaemia in these patients. The setting of target values for glycated haemoglobin measurement is severely hindered by the lack of standardisation in methodology. In an attempt to account for this, European guidelines define categories of glycaemic control as an HbA1 or HbA1c concentration so many standard deviations from a particular method's non-diabetic population mean. Using these guidelines, we found that HbA1 could classify the same diabetic patients differently to HbA1c, even when using the same instrument and reference range individuals. This new finding led, in part, to a change in the European guidelines for glycated haemoglobin targets. Many commonly used glycated haemoglobin methods include both glycated and non-glycated fetal haemoglobin (HbF) in their result. This means patients with elevated HbF concentrations (>0.5%) can have spuriously high glycated haemoglobin values. We presented the first evidence that insulin treated adult patients had a significantly greater prevalence of elevated HbF concentrations than either non-insulin treated or non-diabetic controls, thereby compounding the problem in this group of patients. In addition, we found that HbF increased the apparent imprecision of these assays. Discrepancies exist when comparing glycated haemoglobin and serum fructosamine as indicators of glycaemic control. We found that in newly diagnosed Type II diabetes, fructosamine only showed a correlation with HbA1 after glucose control had stabilised and not during the period of changing glycaemia. However, because changes in fructosamine preceded those of HbA1, the ratio of fructosamine/ HbA1 was able to predict the change in HbA1 in the forthcoming month. Thus, parallel measurement of fructosamine with HbA1 provided additional information on the future trend of a HbA1concentration. A further reason for disparity between fructosamine and glycated haemoglobin was established when investigating the effects of ageing on glycation in non-diabetic subjects. Mean HbA1 values rose with increasing subject age while fructosamine and fasting plasma glucose values did not. Consequently, when Type II diabetic patient samples were classified according to European HbA1 guidelines, significantly fewer patients were in good control and more in poor control when a young reference population was used compared to an age matched one. Thus, age related reference intervals may be required for glycated haemoglobin measurement. Using test strips and meters to measure blood glucose has become widespread amongst diabetic patients in the community and in the monitoring of acutely ill hospital patients. We have documented studies which describe the effect on glucose measurement of variations in several physiological parameters. We also describe how new technology is improving glucose meter measurement. In vitro variations of sample haematocrit have been shown to be a source of error in several glucose meter systems. Red cell count and mean cell volume are intimately related to haematocrit, so it makes it impossible to distinguish if the test strip error is due to haematocrit variations per se or to changes in the number of red cells. We found that in groups of individuals with different mean cell volumes, meter error was still related to the haematocrit of the sample rather than its red cell count. Having established this, 10 patients undergoing cardiopulmonary bypass (whose haematocrits routinely fall to 20% intraoperatively) were investigated to determine the effect of in vivo variations in haematocrit. Changes in test strip glucose accuracy were found to be consistent with those shown previously in vitro. While the use of whole blood to measure glucose is convenient, it is not possible, unlike plasma or serum, to tell if a sample is in any way haemolysed. We showed that extreme sample haemolysis can affect several glucose meter systems, while even modest degrees of red cell lysis were found to give clinically inaccurate results when using the Accutrend instrument. (Abstract shortened by ProQuest.)

Endocannabinoid receptor blockade increases hepatocyte growth factor and reduces insulin levels in obese women with polycystic ovary syndrome

There is evidence from animal and in-vitro studies that activation of the endocannabinoid system (EC) through cannabinoid receptor 1 (CB-1) is associated with liver injury, inflammation and hepatocellular carcinoma.1 Data suggests endogenous cannabinoids (EC) are related to fatty liver metabolism with a role in non-alcoholic fatty liver disease (NAFLD) through modulating lipid metabolism that may be ameliorated by CB1 receptor antagonism with rimonabant.2 This is of particular importance as NAFLD is the most common cause of chronic liver disease with liver dysfunction leading liver cirrhosis. The diagnosis of NAFLD can only be confirmed by a liver biopsy, as liver enzymes such as alanine aminotransferase (ALT) used, as a serum marker may not be elevated

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

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 effects of soy protein and cocoa with or without isoflavones on glycemic control in type 2 diabetes. A double-blind, randomized, placebo-controlled study

Objective: Soy and cocoa have been suggested to be beneficial for diabetes. The aim of this study was to identify the effects of soy protein, isoflavones, and cocoa on glycemic control parameters.Research design and methods: The study was a parallel, double-blind, placebo-controlled study where patients with diet or metformin controlled type 2 diabetes were randomized to, casein soy protein with or without isoflavones (SPI, SP), and with or without cocoa (SPIC, SPC) arms for an 8 week period. Glycemic control and cardiovascular risk factors were assessed prior to and after the completion of the dietary intervention. Sixty participants completed the study.Results: Soy protein improved HbA1c compared to casein (p < 0.05). The addition of isoflavones improved indices of insulin resistance and LDL [delta QUICKIE (SPI: −0.12 ± 0.04 vs. SP: 0.03 ± 0.06, p = 0.03); delta LDL (−0.27 ± 0.41 vs. 0.22 ± 0.43, p = 0.02); percentage change in HOMA (31.02 ± 54.75 vs. −14.42 ± 27.07, p = 0.02); percentage change in QUICKIE (−3.89 ± 7.07 vs. 6.11 ± 10.54, p = 0.01)]. However, the addition of cocoa provided no benefit with or without isoflavones.Summary: Soy protein had intrinsic activity on glycemic control compared to casein. Isoflavones improved both insulin resistance and LDL, but cocoa did not have added benefit on these indices