Glucose Homeostasis Markers Research Articles

The effect of fenofibrate on cardiometabolic risk factors in bromocriptine-treated women with mixed dyslipidemia: A pilot study.

Elevated prolactin levels are associated with metabolic and hormonal complications. No previous study has investigated the effect of any fibrate on plasma levels of lipids and other cardiometabolic risk factors in patients receiving dopamine agonist therapy. The study included 36 premenopausal women with mixed dyslipidemia and slightly increased prolactin levels, 17 of whom had already been treated with bromocriptine (5.0-7.5mg daily). The included patients received micronized fenofibrate (200mg daily) for 6 months. Plasma lipids, glucose homeostasis markers, as well as plasma levels of prolactin, uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine and fibrinogen were determined before and after 12 weeks of fenofibrate therapy. Insulin sensitivity was more expressed while baseline plasma levels of hsCRP and fibrinogen were lower in patients treated with bromocriptine than in women not receiving dopamine agonist therapy. Although fenofibrate improved plasma lipids and insulin sensitivity, as well as reduced plasma levels of the investigated cardiometabolic risk factors in both groups of patients, its action on HDL cholesterol, triglycerides, insulin sensitivity, hsCRP and fibrinogen was stronger in subjects receiving bromocriptine. Moreover, only in bromocriptine-naïve patients, fenofibrate increased plasma homocysteine. Our study shows that the effect of fenofibrate on plasma lipids and circulating levels of cardiometabolic risk factors may be potentiated by bromocriptine treatment. They also suggest that hyperprolactinemic women with mixed dyslipidemia and early glucose metabolism abnormalities may receive the greatest benefits from concomitant treatment with a fibrate and bromocriptine.

Higher Serum 25-Hydroxyvitamin D and Lower Plasma Glucose Are Associated with Larger Gray Matter Volume but Not with White Matter or Total Brain Volume in Dutch Community-Dwelling Older Adults ,

Background: Previous studies have shown beneficial associations between 25-hydroxyvitamin D [25(OH)D] status and cognitive performance, but results are inconclusive. Studies on 25(OH)D status and brain volumetric measures may provide more insight in the potential role of vitamin D in cognitive performance.Objectives: The aims of this study were to cross-sectionally investigate the association between vitamin D status and brain tissue volumes in 217 Dutch community-dwelling older adults aged ≥65 y and to examine whether surrogate markers of glucose homeostasis act as modifiers in these associations.Methods: Serum 25(OH)D, plasma glucose, and plasma insulin were analyzed, serving as exposure measures. Estimates of total brain volume, gray matter volume, and white matter volume were obtained using MRI, serving as outcome measures. Associations of serum 25(OH)D, plasma glucose, and plasma insulin concentrations with brain tissue volumes were evaluated using multiple linear regression analyses. Potential effect modification by glucose homeostasis in the association between 25(OH)D and brain volumetric measures was examined by stratification and testing for interaction.Results: After full adjustment, higher serum 25(OH)D concentrations and lower plasma glucose concentrations were associated with larger gray matter volume, [β ± SE: 0.20 ± 0.08 mL (P = 0.02) and −3.26 ± 1.59 mL (P = 0.04), respectively]. There were no associations between serum 25(OH)D and plasma insulin concentrations with total brain volume and white matter volume. Furthermore, there was no evidence for a mediation or modification effect of plasma glucose on the associations between serum 25(OH)D and brain tissue volumes.Conclusion: Higher serum 25(OH)D and lower plasma glucose are associated with larger gray matter volume, but not white matter or total brain volume, in a population of Dutch adults aged ≥65 y. This trial was registered at clinicaltrials.gov as NCT00696514.

The effect of testosterone on cardiovascular risk factors in men with type 2 diabetes and late-onset hypogonadism treated with metformin or glimepiride.

Men with type 2 diabetes are often characterized by abnormal plasma testosterone levels. This study was aimed at investigating whether testosterone treatment has an impact on cardiovascular risk factors in patients with type 2 diabetes and late-onset hypogonadism (LOH), chronically treated with hypoglycemic agents. This study included 51 men with type 2 diabetes, 26 of whom had already been treated with metformin and 25 with glimepiride for at least 6 months. On the basis of patient preference, 15 men receiving metformin and 12 receiving glimepiride were treated with intramuscular testosterone enanthate (100mg weekly) for 12 weeks. Plasma lipids, glucose homeostasis markers, as well as plasma levels of androgens, uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine and fibrinogen were determined before and at the end of the study. With the exception of insulin sensitivity, plasma hsCRP and homocysteine, there were no differences between patients treated with metformin and glimepiride. Testosterone enanthate administered to both groups of patients increased plasma testosterone, reduced plasma hsCRP and improved insulin sensitivity. Testosterone-metformin combination therapy reduced also circulating levels of uric acid, homocysteine and fibrinogen. These effects, stronger in patients treated with metformin than glimepiride, correlated with the impact of testosterone on insulin sensitivity. Our results suggest that testosterone may bring more clinical benefits to metformin- than sulfonylurea-treated men with diabetes and LOH.

The loss-of-function PCSK9 p.R46L genetic variant does not alter glucose homeostasis.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a critical regulator of cholesterol homeostasis. PCSK9 inhibitors are being actively developed to lower LDL-cholesterol levels. However, there are conflicting data regarding the consequences of Pcsk9 deficiency on glucose homeostasis in mouse models. Here, we analysed in humans the association between the PCSK9 p.R46L loss-of-function (LOF) variant and (1) glucose homeostasis variables; (2) type 2 diabetes status; and (3) the risk of 9 year incident type 2 diabetes in a prospective study. PCSK9 p.R46L was genotyped in 4630 French participants from the Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) prospective study and in 1342 French participants with type 2 diabetes. The association between p.R46L and metabolic traits or type 2 diabetes risk was assessed through linear or logistic regression models adjusted for age, sex and BMI. The association between p.R46L and incident type 2 diabetes was assessed using a Cox regression model adjusted for sex, age and BMI at baseline. Significant associations (p < 10(-6)) were found between p.R46L and lower total cholesterol (-0.394 mmol/l), LDL-cholesterol (-0.393 mmol/l) and apolipoprotein B concentrations (-0.099 g/l). However, no significant association was observed between p.R46L and markers of glucose homeostasis (including fasting glucose, fasting insulin, HbA1c, HOMA-B, HOMA-IR) or type 2 diabetes risk. Furthermore, no significant association between p.R46L variant and risk of incident type 2 diabetes was observed in DESIR. The PCSK9 p.R46L LOF variant was not associated with impaired glucose homeostasis in humans. These data are reassuring regarding the safety of PCSK9 inhibitors.

Bisphenol-A plasma levels are related to inflammatory markers, visceral obesity and insulin-resistance: a cross-sectional study on adult male population

BackgroundThe current increase of obesity and metabolic syndrome (MS) focuses attention on bisphenol-A (BPA), “obesogen” endocrine disruptor, main plastic component. Aim was to verify the role of BPA in metabolic alterations, insulin resistance, low grade inflammation and visceral obesity.MethodsA cross-sectional study was performed in 76 out of 139 environmentally exposed adult males, unselected Caucasian subjects, enrolled by routine health survey at the “Federico II” University of Naples outpatient facilities. BPA plasma levels (ELISA), metabolic risk factors, homeostasis model assessment of insulin resistance index, plasma monocyte chemoattractant protein 1, interleukin-6 (IL-6) and tumor necrosis factor-alpha were performed. Clinical and biochemical parameters have been compared with BPA and pro-inflammatory cytokines levels.ResultsIn total 24 subjects out of 76 (32%) presented with waist circumference (WC) >102 cm, 36 (47%) had impaired fasting glucose and 24 (32%) subjects had insulin resistance [11 out 52 (21%) with WC ≤102 cm and 13 out of 24 with WC >102 cm (54%), χ2 6.825, p = 0.009]. BPA and pro-inflammatory cytokine levels were significantly higher in subjects with visceral adiposity (WC > 102 cm). BPA correlated with WC, triglycerides, glucose homeostasis and inflammatory markers. At the multivariate analysis WC and IL-6 remained the main predictors of BPA.ConclusionsDetectable BPA plasma levels have been found also in our population. The strictly association between BPA and WC, components of MS, and inflammatory markers, further supports the BPA role in visceral obesity-related low grade chronic inflammation.

Toxicological assessments of rats exposed prenatally to inhaled vapors of gasoline and gasoline–ethanol blends

The primary alternative to petroleum-based fuels is ethanol, which may be blended with gasoline in the United States at concentrations up to 15% for most automobiles. Efforts to increase the amount of ethanol in gasoline have prompted concerns about the potential toxicity of inhaled ethanol vapors from these fuels. The well-known sensitivity of the developing nervous and immune systems to ingested ethanol and the lack of information about the neurodevelopmental toxicity of ethanol-blended fuels prompted the present work. Pregnant Long–Evans rats were exposed for 6.5h/day on days 9–20 of gestation to clean air or vapors of gasoline containing no ethanol (E0) or gasoline blended with 15% ethanol (E15) or 85% ethanol (E85) at nominal concentrations of 3000, 6000, or 9000ppm. Estimated maternal peak blood ethanol concentrations were less than 5mg/dL for all exposures. No overt toxicity in the dams was observed, although pregnant dams exposed to 9000ppm of E0 or E85 gained more weight per gram of food consumed during the 12days of exposure than did controls. Fuel vapors did not affect litter size or weight, or postnatal weight gain in the offspring. Tests of motor activity and a functional observational battery (FOB) administered to the offspring between post-natal day (PND) 27–29 and PND 56–63 revealed an increase in vertical activity counts in the 3000- and 9000-ppm groups in the E85 experiment on PND 63 and a few small changes in sensorimotor responses in the FOB that were not monotonically related to exposure concentration in any experiment. Neither cell-mediated nor humoral immunity were affected in a concentration-related manner by exposure to any of the vapors in 6-week-old male or female offspring. Systematic concentration-related differences in systolic blood pressure were not observed in rats tested at 3 and 6months of age in any experiment. No systematic differences were observed in serum glucose or glycated hemoglobin A1c (a marker of long-term glucose homeostasis). These observations suggest a LOEL of 3000ppm of E85 for vertical activity, LOELs of 9000ppm of E0 and E85 for maternal food consumption, and NOELs of 9000ppm for the other endpoints reported here. The ethanol content of the vapors did not consistently alter the pattern of behavioral, immunological, or physiological responses to the fuel vapors. The concentrations of the vapors used here exceed by 4–6 orders of magnitude typical exposure levels encountered by the public.

The effect of metformin on the hypothalamic-pituitary-thyroid axis in patients with type 2 diabetes and subclinical hyperthyroidism.

In hypothyroid patients, metformin was found to reduce serum levels of TSH. No previous study investigated metformin action on hypothalamic-pituitary-thyroid axis in patients with hyperthyroidism. The aim of our study was to assess the effect of metformin treatment on thyroid function tests in patients with untreated subclinical hyperthyroidism. We studied 15 patients with low but detectable TSH levels (0.1-0.4 mIU/L) (group 1), 12 patients with suppressed TSH levels (less than 0.1 mIU/L) (group 2) and 15 euthyroid patients with a history of hyperthyroidism, who because of coexisting 2 diabetes were treated with metformin (2.55-3 g daily). Glucose homeostasis markers, as well as serum levels of TSH and total and free thyroxine and triiodothyronine levels were assessed at baseline and after 3 and 6 months of therapy. As expected, metformin reduced plasma glucose, insulin resistance and glycated hemoglobin. However, with the exception of an insignificant decrease in TSH levels after 3-month therapy in group 2, metformin therapy did not affect thyroid function tests. Our results indicate that metformin has a negligible effect on hypothalamic-pituitary-thyroid axis activity in type 2 diabetic patients with subclinical hyperthyroidism.

Different Effects of Atorvastatin on Metabolic and Cardiovascular Risk Factors in Hypercholesterolemic Women with Normal Thyroid Function and Subclinical Hypothyroidism

The presence of hypothyroidism seems to be associated with increased cardiovascular risk. No previous study compared circulating levels of plasma lipids and other cardiovascular risk factors in statin-treated patients with different thyroid function states. We studied 15 women with untreated subclinical hypothyroidism (group A), 16 women with treated hypothyroidism (group B) and 17 women with normal thyroid function (group C) who, because of coexistent hypercholesterolemia, were treated with atorvastatin. Plasma lipids, glucose homeostasis markers and plasma levels of cardiovascular risk factors were assessed before and after 12 weeks of therapy. 46 patients completed the study. Baseline lipid levels were similar in all groups of patients. Plasma levels of high-sensitivity C-reactive protein (hsCRP), homocysteine and fibrinogen were higher in group A than in groups B and C. Although the effect on total and LDL cholesterol was observed in all treatment groups, it was less pronounced in patients with untreated hypothyroidism. Similarly, the effect of atorvastatin on hsCRP, homocysteine, fibrinogen and uric acid was stronger in groups B and C than in group A. Our results suggest that the effect of atorvastatin on plasma lipids and circulating levels of other cardiovascular risk factors partially depends on thyroid function.

Different effects of fenofibrate on metabolic and cardiovascular risk factors in mixed dyslipidemic women with normal thyroid function and subclinical hypothyroidism.

Subclinical hypothyroidism is suggested to increase cardiovascular risk. No previous study compared the effect of any fibrate on plasma levels of lipids and other cardiovascular risk factors in patients with different thyroid function status. The study included three age-, weight- and lipid-matched groups of women with mixed dyslipidemia in different thyroid function status: patients with untreated subclinical hypothyroidism (group 1, n = 18), women with treated hypothyroidism (group 2, n = 15), and subjects without thyroid disorders (group 3, n = 19). Plasma lipids, glucose homeostasis markers, as well as plasma levels of uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine, and fibrinogen were determined before and after 12 weeks of fenofibrate therapy. Despite similar plasma lipid levels, mixed dyslipidemic patients with untreated hypothyroidism had decreased insulin sensitivity, as well as higher circulating levels of uric acid, hsCRP, homocysteine, and fibrinogen in comparison with the other groups. The effect of fenofibrate on plasma lipids and, with the exception of homocysteine, on circulating levels of all investigated risk factors was stronger in patients from groups 2 and 3 than in patients from group 1. The obtained results indicate that the effect of fenofibrate on plasma lipids and circulating levels of cardiovascular risk factors is partially related to thyroid function. They also suggest that to improve the strength of fibrate action in dyslipidemic patients with subclinical hypothyroidism, they should be administered together with L-thyroxine.

Effects of hepatic protein tyrosine phosphatase 1B and methionine restriction on hepatic and whole-body glucose and lipid metabolism in mice

AimsMethionine restriction (MR) and hepatic protein tyrosine phosphatase 1B (PTP1B) knockdown both improve hepatic insulin sensitivity by targeting different proteins within the insulin signaling pathway, as well as diminishing hepatic triglyceride content through decreasing hepatic lipogenesis. We hypothesized that a combined approach of hepatic PTP1B inhibition and methionine restriction could lead to a synergistic effect on improvements in glucose homeostasis and lipid metabolism. MethodsMale and female hepatic PTP1B knockout (Alb-Ptp1b-/-) and control wild-type (Ptp1bfl/fl) mice were maintained on control diet (0.86% methionine) or MR diet (0.172% methionine) for 8weeks. Body weight and food intake were recorded and physiological tests for whole-body glucose homeostasis were performed. Serum and tissues were analyzed biochemically. ResultsMR decreased body weight and increased food intake in Ptp1bfl/fl mice as expected, without changing PTP1B protein expression levels or activity. In females, MR treatment alone improved glucose tolerance in Ptp1bfl/fl mice, which was further amplified with hepatic PTP1B deficiency. However, other markers of glucose homeostasis were similar between MR-fed groups. In males, MR improved glucose homeostasis in both, Alb-Ptp1b-/- and wild-type Ptp1bfl/fl mice to a similar extent. Hepatic PTP1B inhibition in combination with MR could not further enhance insulin-stimulated hepatic protein kinase B/Akt phosphorylation compared to MR treatment alone and therefore led to no further increase in hepatic insulin signaling. The combined treatment did not further improve lipid metabolism relative to MR diet alone. ConclusionsMethionine restriction improves glucose and lipid homeostasis; however, adding hepatic PTP1B inhibition to MR is unlikely to yield any additional protective effects.

The effect of atorvastatin and atorvastatin-ezetimibe combination therapy on androgen production in hyperandrogenic women with elevated cholesterol levels.

Statins decreased serum androgen levels in hyperandrogenemic women with polycystic ovary syndrome. No previous study has investigated whether this effect is dose-dependent and observed in patients simultaneously treated with other hypolipidemic agents. The study included 23 premenopausal women with elevated total testosterone levels coexisting with hypercholesterolemia, unsuccessfully treated for at least 6 months with atorvastatin (20 mg daily). These patients were then treated with either an increased dose of atorvastatin (40 mg daily, n=11) or atorvastatin (20 mg daily) plus ezetimibe (10 mg daily) (n=12). Plasma lipids, glucose homeostasis markers and serum levels of androgens, sex hormone-binding globulin and gonadotropins were assessed at baseline and after 3 months of treatment. Although both treatments decreased plasma levels of total and LDL-cholesterol levels, only high-dose atorvastatin reduced serum levels of total testosterone, free testosterone and androstendione. The effect of high-dose atorvastatin on serum androgen levels did not differ between insulin-resistant and insulin-sensitive subjects. The obtained results suggest that atorvastatin reduces serum androgen levels in a dose-dependent manner and that its administration in a higher dose is associated with a more pronounced effect on serum androgens than combination therapy with low-dose atorvastatin and ezetimibe.

The effect of ezetimibe-statin combination on steroid hormone production in men with coronary artery disease and low cholesterol levels

BackgroundAggressive statin treatment was found to slightly reduce testosterone production. The aim of this study was to compare the effects of ezetimibe-statin combination and high-dose statin therapy on testicular and adrenal cortex function in men with LDL cholesterol levels below 70mg/dL. MethodsThe study included 26 adult men with coronary artery disease. Twelve of these patients did not tolerate high-dose statin therapy and were treated with lower doses of a statin plus ezetimibe. Fourteen patients tolerating high-dose simvastatin or rosuvastatin treatment continued high-dose statin therapy throughout the study period. Plasma lipids, glucose homeostasis markers and plasma levels of testosterone, cortisol, dehydroepiandrosterone sulphate, sex hormone-binding globulin, gonadotropins and ACTH, as well as urine free cortisol were assessed at baseline and after 16 weeks of treatment. ResultsReplacing high-dose statin therapy with ezetimibe/statin combination therapy reduced plasma levels of LH by 32% (p=0.043), as well as increased plasma levels of testosterone by 20% (p=0.038). Ezetimibe/statin combination did not induce any significant changes in plasma levels or urine excretion of the remaining hormones. At the end of the study, plasma LH levels were higher, while plasma testosterone levels were lower in patients receiving the combination therapy than in those treated only with high-dose statin. ConclusionsOur results indicate that ezetimibe combined with moderate statin dose exerts a less pronounced effect on testicular function in comparison with high-dose statin therapy.

Biological correlates of blood pressure variability in elderly at high risk of cardiovascular disease.

Visit-to-visit variability in blood pressure is an independent predictor of cardiovascular disease. This study investigates biological correlates of intra-individual variability in blood pressure in older persons. Nested observational study within the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) among 3,794 male and female participants (range 70-82 years) with a history of, or risk factors for cardiovascular disease. Individual visit-to-visit variability in systolic and diastolic blood pressure and pulse pressure (expressed as 1 SD in mm Hg) was assessed using nine measurements over 2 years. Correlates of higher visit-to-visit variability were examined at baseline, including markers of inflammation, endothelial function, renal function and glucose homeostasis. Over the first 2 years, the mean intra-individual variability (1 SD) was 14.4mm Hg for systolic blood pressure, 7.7mm Hg for diastolic blood pressure, and 12.6mm Hg for pulse pressure. After multivariate adjustment a higher level of interleukin-6 at baseline was consistently associated with higher intra-individual variability of blood pressure, including systolic, diastolic, and pulse pressure. Markers of endothelial function (Von Willebrand factor, tissue plasminogen activator), renal function (glomerular filtration rate) and glucose homeostasis (blood glucose, homeostatic model assessment index) were not or to a minor extent associated with blood pressure variability. In an elderly population at risk of cardiovascular disease, inflammation (as evidenced by higher levels of interleukin-6) is associated with higher intra-individual variability in systolic, diastolic, and pulse pressure.

The effect of ezetimibe on androgen production in hypercholesterolemic women with polycystic ovary syndrome.

Statin therapy was found to reduce circulating androgen levels in patients with polycystic ovary syndrome (PCOS). No similar data are available for ezetimibe. The study included 14 women with PCOS and hypercholesterolemia, intolerant to statins or having contraindications to this treatment, who were treated with ezetimibe (10mg daily). They were compared with 14 matched women with both of these disorders receiving simvastatin (40mg daily). Plasma lipids, glucose homeostasis markers, and serum levels of androgens, sex hormone-binding globulin, and gonadotropins were assessed at baseline and after 3months of treatment. Both simvastatin and ezetimibe decreased plasma levels of total and LDL cholesterol. Ezetimibe, but not simvastatin, slightly reduced insulin resistance. Simvastatin decreased serum levels of total testosterone (-23%, P<0.001), free testosterone (-32%, P<0.001), androstendione (-20%, P<0.01), and dehydroepiandrosterone sulfate (-17%, P<0.05), as well as tended to reduce the luteinizing hormone/follicle-stimulating hormone ratio (-23%, P=0.095). Ezetimibe only insignificantly reduced serum levels of free testosterone (-14%, P=0.098). There were no differences in the effects of simvastatin on circulating hormone levels between insulin-resistant and insulin-sensitive subjects. In turn, the effect of ezetimibe on free testosterone levels was stronger in insulin-resistant patients. Although ezetimibe and simvastatin are equipotent in lowering lipid levels in hypercholesterolemic patients with coexisting PCOS, simvastatin exhibits a more pronounced effect on circulating androgen levels in this group of patients.

Vitamin D insufficiency and insulin resistance in obese adolescents.

Obese adolescents represent a particularly vulnerable group for vitamin D deficiency which appears to have negative consequences on insulin resistance and glucose homeostasis. Poor vitamin D status is also associated with future risk of type 2 diabetes and metabolic syndrome in the obese. The biological mechanisms by which vitamin D influences glycemic control in obesity are not well understood, but are thought to involve enhancement of peripheral/hepatic uptake of glucose, attenuation of inflammation and/or regulation of insulin synthesis/secretion by pancreatic β cells. Related to the latter, recent data suggest that the active form of vitamin, 1,25-dihydroxyvitamin D, does not impact insulin release in healthy pancreatic islets; instead they require an environmental stressor such as inflammation or vitamin D deficiency to see an effect. To date, a number of observational studies exploring the relationship between the vitamin D status of obese adolescents and markers of glucose homeostasis have been published. Most, although not all, show significant associations between circulating 25-hydroxyvitamn D concentrations and insulin sensitivity/resistance indices. In interpreting the collective findings of these reports, significant considerations surface including the effects of pubertal status, vitamin D status, influence of parathyroid hormone status and the presence of nonalcoholic fatty liver disease. The few published clinical trials using vitamin D supplementation to improve insulin resistance and impaired glucose tolerance in obese adolescents have yielded beneficial effects. However, there is a need for more randomized controlled trials. Future investigations should involve larger sample sizes of obese adolescents with documented vitamin D deficiency, and careful selection of the dose, dosing regimen and achievement of target 25-hydroxyvitamn D serum concentrations. These trials should also include clamp-derived measures of in vivo sensitivity and β-cell function to more fully characterize the effects of vitamin D replenishment on insulin resistance.

The effect of metformin on androgen production in diabetic women with non-classic congenital adrenal hyperplasia.

Non-classic congenital adrenal hyperplasia (NC-CAH), one of the most common genetic disorders, is often associated with the clinical features of hyperandrogenism. This study included 19 women with recently diagnosed and previously untreated type 2 diabetes, 8 of whom suffered from NC-CAH, treated with metformin (2.55-3.0 g daily). Glucose homeostasis markers, plasma lipids, as well as plasma levels of 17-hydroxyprogesterone, androgens and gonadotropins were assessed at baseline and after 6 months of therapy. In both groups of patients, metformin reduced fasting plasma glucose, insulin resistance, triglycerides and glycated hemoglobin. Moreover, in patients with NC-CAH, but not in women with normal adrenal function, metformin decreased plasma levels of 17-hydroxyprogesterone, total and free testosterone, androstenedione and dehydroepiandrosterone sulphate. The obtained results suggest that metformin partially normalizes androgen production in symptomatic patients with NC-CAH.

A Fraxinus excelsior L. seeds/fruits extract benefits glucose homeostasis and adiposity related markers in elderly overweight/obese subjects: A longitudinal, randomized, crossover, double-blind, placebo-controlled nutritional intervention study

PurposeThe aim of this study was to investigate the potential benefits of an extract obtained from seeds/fruits of an Oleaceae (Fraxinus excelsior L.) on glucose homeostasis and associated metabolic markers in non-diabetic overweight/obese subjects. Materials and methodsThis study was performed in 22 participants (50–80 years-old; BMI 31.0kg/m2). The design was a longitudinal, randomized, crossover, double-blind, placebo-controlled 7-week nutritional intervention. The participants received daily 3 capsules each containing either 333mg of an extract from Fraxinus excelsior L. seeds (Glucevia®) or placebo capsules (control) in a random order for 3 weeks with 1 week of washout between treatments. Moreover, they followed a balanced covert energy-restricted diet (−15% energy). All variables were measured at the beginning and at the end of each period. ResultsCompared to baseline, the administration of 1g of Glucevia® for 3 weeks resulted in significantly lower incremental glucose area under the curve (−28.2%; p<0.01), and significantly lower 2h blood glucose values (−14%; p<0.01) following an oral glucose tolerance test. No significant changes were found in the control group (−7.9% AUC, −1.6% 2h blood glucose). Furthermore, significant differences were found between responses in the control and Glucevia® groups with respect to serum fructosamine and plasma glucagon levels (p<0.01 and p<0.05, respectively). Interestingly, administration of Glucevia® significantly increased the adiponectin:leptin ratio (p<0.05) and decreased fat mass (p<0.01) compared to control (p<0.05). ConclusionThe administration of an extract from Fraxinus excelsior L. seeds/fruits in combination with a moderate hypocaloric diet may be beneficial in metabolic disturbances linked to impaired glucose tolerance, obesity, insulin resistance and inflammatory status, specifically in older adults.

The effect of ezetimibe on adipose tissue hormones in patients with isolated hypercholesterolemia

BackgroundExtra-lipid effects of ezetimibe, a new lipid-lowering agent, are so far poorly understood. MethodsTwenty-two patients with elevated total and LDL cholesterol levels, statin-intolerant or having contraindications to statin therapy, were treated with ezetimibe (10mg daily) for 90 days. Plasma levels of lipids, apolipoproteins, glucose homeostasis markers, leptin, adiponectin, visfatin, tumor necrosis factor-α (TNF-α), free fatty acids (FFA) and high sensitivity C-reactive protein (hsCRP) were examined at the beginning of the study and after 30 and 90 days of treatment. ResultsCompared with the control age-, sex-, and weight-matched healthy subjects, isolated hypercholesterolemic patients exhibited higher plasma levels of leptin, visfatin and TNF-α and lower plasma levels of adiponectin. Their baseline FFA and hsCRP levels were also increased. Ezetimibe decreased circulating levels of total cholesterol, LDL cholesterol and apolipoprotein B-100. The drug significantly reduced plasma levels of visfatin and only tended to reduce plasma levels of leptin, TNF-α, visfatin, FFA and CRP. The effect of ezetimibe on these markers was lipid-independent but stronger in insulin-sensitive than in insulin-resistant patients. ConclusionsThe obtained results indicate that the presence of isolated hypercholesterolemia is associated with abnormal hormonal function of the adipose tissue. They also show that ezetimibe induces relatively small changes in adipose tissue hormonal function and systemic inflammation in patients with elevated cholesterol levels.

The Effect of Simvastatin–Ezetimibe Combination Therapy on Adipose Tissue Hormones and Systemic Inflammation in Patients with Isolated Hypercholesterolemia

Pleiotropic effects of ezetimibe have only been investigated in a few studies. The aim of this article was to compare the effects of simvastatin and the combined treatment with simvastatin and ezetimibe on low-grade systemic inflammation and plasma levels of selected adipokines in patients with isolated hypercholesterolemia. The study included 69 patients with elevated cholesterol levels, who were allocated to one of the three groups treated for 12weeks, respectively, with simvastatin (40mg daily), simvastatin (40mg daily) plus ezetimibe (10mg daily), or placebo. Plasma levels of lipids, apolipoproteins, glucose homeostasis markers, leptin, adiponectin, visfatin, tumor necrosis factor-α (TNF-α), free fatty acids (FFA), and high-sensitive C-reactive protein (hsCRP) were determined on the allocation day and after 12weeks of therapy. Apart from improving lipid profile, simvastatin administered alone or in combination with ezetimibe, decreased plasma levels of hsCRP, FFA, leptin, visfatin, and TNF-α, as well as increased plasma levels of adiponectin. The combination therapy was superior to simvastatin in influencing plasma lipids/lipoproteins, hsCRP, FFA, and the investigated adipokines. The effect of the combination therapy, but not of simvastatin, on systemic inflammation and plasma adipokines was stronger in insulin-resistant than in insulin-sensitive subjects. The obtained results suggest that insulin-resistant patients with hypercholesterolemia and high cardiovascular risk may benefit the most from the combined treatment with simvastatin and ezetimibe.

Dietary intake of fried and processed foods in the USA is inversely associated with obesity but positively associated with glucose intolerance

Purpose– Foods rich in polyunsaturated fatty acids are vulnerable to oxidation during processing and storage. The intake of oxidized lipids (OLs) and their subsequent relation with chronic disease risk are unknown in the US population. The paper aims to discuss these issues.Design/methodology/approach– The association between OL intake and markers of adiposity and glucose homeostasis was determined based on data collected from two cycles of National Health and Nutrition Examination Surveys with a survey sample of 9,982 subjects between the ages of two to 85 years. Means or geometric means of markers of adiposity, glucose and lipid parameters were compared between the “low” and “high” consumers of OL using thet-test. Associations between OL intake and markers of adiposity, glucose and lipid parameters were determined by multivariate regression analysis.Findings– Mean markers of adiposity were all significantly lower in subjects in the “high” OL group as compared to the “low” OL group. Fasting glucose concentrations were positively associated with OL intake unlike markers of adiposity which were negatively associated with OL intake.Practical implications– Higher intake of OLs is associated with lower BMI and adiposity. However, the direct association between OL intake and fasting glucose levels suggests that lower markers of adiposity do not suggest a decreased risk of glucose intolerance.Originality/value– This is the first study to estimate the consumption of OLs in the US population and its link to adiposity and glucose tolerance.