We investigated thyroid hormone levels in menopausal BrC patients, and verified the action of triiodothyronine (T3) on genes regulated by estrogen (E2) and by T3 itself in BrC tissues. We selected 15 postmenopausal BrC patients and a control group of 18 postmenopausal women without BrC. We measured serum thyroid peroxidase antibody, TSH, free thyroxine, and estradiol, before and after surgery, and used immunohistochemistry to examine E2 and progesterone receptors. BrC primary tissue cultures received the following treatments: ethanol, T3, T3+tamoxifen (TAM), TAM, E2, or E2+TAM. Genes regulated by E2 (TGFA, TGFB1, PGR) and by T3 (TNFRSF9, BMP‐6, THRA) in vitro were evaluated in each patient. Three BrC patients presented with clinical hyperthyroidism. Thyroxine levels of BrC patients were statistically higher than controls (1.78±0.20 vs. 0.95±0.16 ng/dl). TGFA and TGFB1 were upregulated and downregulated, respectively, after E2 and T3 treatment. T3 treatment increased PGR expression, however TAM did not block T3 action on PGR expression. TAM, alone or associated with T3, modulated gene expression of TNFRSF9, BMP‐6 and THRA, similar to T3 treatment, showing that TAM can interfere with gene expression modulated by T3. Our results reinforce that the thyroid hormone status of BrC patients can influence E2‐controlled processes, even after TAM intervention and/or in the absence of circulating E2 postmenopause.
The factor V Leiden (FVL) mutation is the most frequent genetic cause of venous thrombosis in Caucasians. However, protective effects have been suggested to balance the disadvantages. We have recently observed protective effects of FVL mutation on experimental diabetic nephropathy in mice as well as an association with reduced albuminuria in two human cohorts of diabetic patients. In the present study we aimed to reevaluate these findings in an independent, larger cohort of 1905 Caucasians at risk of developing type 2 diabetes and extend possible associations to earlier disease stages of nephropathy. Carriers of FVL mutation had a significantly lower urine albumin excretion (P = 0.03) and tended to have lower plasma creatinine concentrations (P = 0.07). The difference in plasma creatinine concentrations was significant after adjustment for the influencing factors: age, gender, and lean body mass (P = 0.048). These observations at a very early "disease" stage are an important extension of previous findings and suggest that modification of glomerular dysfunction by FVL mutation is relevant during very early stages of diabetic nephropathy. This makes the underlying mechanism an interesting therapeutic target and raises the question whether FVL mutation may also exert protective effects in other glomerulopathies.
Metabolic syndrome is defined as a group of coexisting metabolic risk factors, such as central obesity, lipid disorders, carbohydrate disorders, and arterial hypertension. According to the 2005 IDF criteria, subsequently revised in 2009, abdominal obesity is identified as the waist circumference of ≥80 cm in women and ≥94 cm in men. It is responsible for the development of insulin resistance. The aim of our study was to demonstrate a correlation between waist circumference (WC) and body mass index (BMI) in patients with metabolic syndrome in relation with hypertension, lipid disorders, and carbohydrate disorders. A cross-sectional two-site study was conducted in the Kuyavian-Pomeranian Voivodeship for 24 months. The study group consisted of 839 patients with diagnosed metabolic syndrome: 345 men (41.1%) and 494 women (58.9%) aged 32–80. In the study group, WC was found to be significantly correlated with BMI ( R = 0.78, P < 0.01). The presence of overweight in men (BMI 25, 84 kg/m 2 ) and even normal body weight in women (BMI 21,62 kg/m 2 ) corresponds to an increased volume of visceral tissue in the abdomen. Introduction of primary prophylaxis in those people to limit the development of diabetes mellitus type 2 and cardiovascular diseases should be considered.
Background. Insulin resistance has been associated with dyslipidemia and cardiovascular disease. Even though homeostasis model assessment of insulin resistance (HOMA-IR) is a well-known insulin resistance predictor, estimation of serum lipoprotein ratios has been recently suggested as a surrogate marker for insulin resistance. Here, we evaluated the relationship between lipoprotein ratios and insulin resistance in normoglycemic nondiabetic south Indians with acute coronary syndrome. Methods. 100 normoglycemic nondiabetic ACS patients and 140 controls were enrolled in the study. Levels of fasting glucose, fasting insulin, and lipid profile [total cholesterol (TC), triglycerides (TG), and high density lipoprotein cholesterol (HDL-C)], lipoprotein(a) [Lp(a)] levels were measured and lipoprotein ratios were computed. HOMA-IR was used to calculate the insulin resistance. Receiver operating characteristic curves (ROC) analysis was used to compare the power of these lipoprotein ratios to predict insulin resistance. Results. Lipoprotein ratios were significantly higher in normoglycemic nondiabetic ACS patients, as compared to healthy controls, and were significantly correlated with HOMA-IR by Spearman's rank correlation analysis. ROC curve showed that Lp(a)/HDL-C and TG/HDL-C ratios were the best surrogate predictors of insulin resistance in normoglycemic nondiabetic ACS. Conclusion. This study demonstrates that serum lipoprotein ratios significantly correlate with insulin resistance in normoglycemic nondiabetic ACS. Lp(a)/HDL-C and TG/HDL-C ratios could be used as surrogate markers of insulin resistance in atherosclerosis-prone south Indians with normoglycemic nondiabetic ACS.
The antihyperglycaemic activity of Tetracarpidium conophorum nut (walnut) was investigated in albino rats. A total of 20 albino rats were used for the study. The rats were divided into five groups (A–E) of four rats each. Diabetes were induced in the rats except four which served as the positive control group A. Groups B (negative control), C, D, and E contain diabetic rats each with blood sugar level ≥17.00 mmol/L. Groups A and B were fed on 85.2 g of top feed grower over the test period. Test groups C, D, and E were fed on 21.3 g, 42.6 g, and 85.2 g of walnuts, respectively, and their fasting blood sugar (FBS) levels were checked on daily basis. Fasting blood glucose levels of the test groups were significantly lower than negative control P < 0.05, for 3rd, 7th, and 10th days of the test. There were also significant increase in the body weight and hemoglobin concentration and a decreased urine output of the test group compared with the controls. These results indicate that Tetracarpidium conophorum nut (walnut) has an antihyperglycemic effect in diabetic rats.
Background. Exercise training intervention is underused in the management of type 2 diabetes mellitus in East Africa. Methods. 41 physically-active males with type 2 diabetes mellitus living in Mozambique were recruited and randomly assigned to 12 weeks of supervised exercise of low intensity exercise (LEX), vigorous intensity exercise (VEX), or to a control group (CON). Since there were no differences for any outcome variables between the exercise groups, VEX and LEX were combined into one exercise group (EX). Results. Age and baseline body weight were similar between EX and CON. Plasma glucose at 120 min following glucose load (Glu 120) was significantly reduced in the EX group after training (Glu 120 : 17.3 mmol/L to 15.0 mmol/L, P < 0.05), whereas Glu 120 remained unchanged in the CON (Glu 120 : 16.6 mmol/L to 18.7 mmol/L). After controlling for baseline blood pressure (BP), posttraining systolic BP and diastolic BP were lower in the EX group than in the CON group (EX: 129/77 mm Hg, CON: 152/83 mm Hg, P < 0.05). Conclusion. Adding exercise to already active African men with type 2 diabetes improved glucose control and BP levels without concomitant changes in weight.
Objective. The effect of a proprietary formulation of trans-resveratrol (t-RSV) on manifestations of diabetic foot syndrome (DFS) was studied in type 2 diabetic patients with newly diagnosed diabetic foot ulcers. Method. Placebo-controlled, examiner-blinded, parallel-group randomized controlled pilot clinical trial (ACTRN Clinical Trial Registry number 12610000629033) involving 24 patients with DFS (15 males and 9 females, average age of 56.4 ± 9.1 years) divided into the placebo and RSV-treatment groups was performed. 50 mg of t-RSV or placebo capsules was given to each patient twice a day over a 60-day time period. Results. Reduction in the parameters reflecting diabetic ulcer size was more profound in the RSV group as compared to placebo. RSV-treated patients also had a marginally improved performance in the foot pressure test. A statistically significant decline in the plasma fibrinogen level, but not CRP, was also found in the RSV-treated patients. Some improvement in the plasma lipid profile and fasting glucose levels were not related to RSV-treatment, since they have been seen on both the RSV and placebo groups, revealing the effectiveness of medical supervision and education in the newly diagnosed patients with DFS. Conclusion. t-RSV supplementation promotes reduction of the foot ulcer size and reduces plasma fibrinogen level in type 2 diabetic patients.
Objective. Zinc-α2-glycoprotein (ZAG) has recently been proposed as a new adipokine involved in body weight regulation. The purpose of this study is to investigate serum levels of ZAG in patients with hypertension and its association with related characteristics. Methods. 32 hypertension patients and 42 normal controls were recruited and the relationship between serum ZAG, total and high molecular weight (HMW) adiponectin, and tumor necrosis factor-α (TNFα) determined by enzyme-linked immunosorbent assay (ELISA) and metabolic-related parameters was investigated. Results. Serum ZAG concentrations were significantly lowered in patients with hypertension compared with healthy controls (61.4 ± 32 versus 78.3 ± 42 μg/mL, P < 0.05). The further statistical analysis demonstrated that serum ZAG levels were negatively correlated with waist-to-hip ratio (WHR) (r = −0.241, P < 0.05) and alanine aminotransferase (ALT) (r = −0.243, P < 0.05). Additionally, serum HMW adiponectin significantly decreased, while TNFα greatly increased in hypertension patients as compared with healthy controls (2.32 ± 0.41 versus 5.24 ± 1.02 μg/mL, 3.30 ± 1.56 versus 2.34 ± 0.99 pg/mL, P < 0.05). Conclusions. Serum ZAG levels are significantly lowered in hypertension patients and negatively correlated with obesity-related item WHR, suggesting ZAG is a factor associated with hypertension.
Aim. The purpose of this study was to investigate the effects of pioglitazone on oxidative stress and the expressions of p22(phox) and p47(phox), subunits of NADPH oxidase, in mesangial cells (MCs). Method. Rat mesangial cells were cultured and randomly divided into normal glucose (NG) group, high glucose (HG) group, and pioglitazone group. After 48 h exposure, the supernatants and cells were collected. The expressions of p22(phox) and p47(phox) in MCs were detected by RT-PCR and western blot. The levels of intracellular ROS were determined by flow cytometry. Coloimetry method was used to detect malondialdehyde (MDA) concentrations and superoxide dismutase (SOD) activities. Results. Compared with the NG group, the expression levels of p22(phox), p47(phox) and ROS significantly increased, the activity of SOD decreased in HG group, while the concentration of MDA greatly increased (P < 0.01). Pioglitazone significantly suppressed HG-induced p22(phox) and p47(phox) expressions and oxidative stress. The protein and gene expressions of p22(phox) and p47(phox) were markedly reduced after pioglitazone treatment, so did the ROS generation. The activities of SOD in MCs increased, while the concentrations of MDA in the supernatant decreased greatly by pioglitazone. Conclusions. Pioglitazone can inhibit HG-induced oxidative stress in MCs through suppressing p22(phox) and p47(phox) expressions.
Aim. To assess the plasma leptin responses after exercise stress testing in patients with metabolic syndrome (MS). Material and Methods. We investigated 67 patients with MS, with mean age of 55 ± 7 years. They underwent exercise stress testing on cycloergometer. The lot was divided into three groups: group 1-10 patients with a true positive test, group 2-18 patients with a true negative test, and group 3-39 patients with a false negative test. Leptin levels were measured using the ELISA method. Results. Leptin levels decreased after effort in patients with MS (9.42 ± 11.08 ng/mL before and 8.18 ± 11.5 ng/mL after the exercise stress test, P = 0.0005, r = 0.874). In groups 1 (8.98 ± 9.09 at rest versus 5.98 ± 8.73 ng/mL after the exercise test, P = 0.002) and 3 (8.6 ± 10.53 at rest versus 6.91 ± 9.07 ng/mL, P = 0.0005), lower leptin levels were recorded immediately after exercise testing. Leptin levels were not significantly lower in group 2 before effort (9.49 ± 11.36 ng/ml) and after (9.46 ± 13.81 ng/mL). We found no correlation between leptinemia and exercise stress testing parameters, regardless of group. Conclusion. Our research showed that short-term exercise lowers leptin levels in coronary patients, without a relationship between its parameters and leptin values.
Vitamin D and its analogues are widely used as treatments by clinical nephrologists, especially when treating chronic kidney disease (CKD) patients with secondary hyperparathyroidism. As CKD progresses, the ability to compensate for elevations in parathyroid hormone (PTH) and fibroblast growth factor-23 and for decreases in 1,25(OH) 2 D 3 becomes inadequate, which results in hyperphosphatemia, abnormal bone disorders, and extra-skeletal calcification. In addition to its calciotropic effect on the regulation of calcium, phosphate, and parathyroid hormone, vitamin D has many other noncalciotropic effects, including controlling cell differentiation/proliferation and having immunomodulatory effects. There are several immune dysregulations that can be noted when renal function declines. Physicians need to know well both the classical and nonclassical functions of vitamin D. This review is an analysis from the nephrologist's viewpoint and focuses on the relationship between the vitamin D and the immune system, together with vitamin's clinical use to treat kidney diseases.
We aimed to observe the association between degree of obesity and metabolic syndrome and plasma thyrotropin levels in obese, euthyroid Turkish patients. 947 obese and overweight patients who admitted to our outpatient clinic were assessed retrospectively. 150 healthy euthyroid cases were also recruited as the control group. Cases with metabolic syndrome were determined. Patients were divided into various subgroups as overweight, obese, morbid obese, men, and women. No statistical significance was determined when all the patients' and subgroups' plasma thyrotropin levels were compared to normal weight control group. No association was shown between the presence of metabolic syndrome and plasma thyrotropin levels for both all patients and subgroups. Also there was not any association between each component of metabolic syndrome and plasma thyrotropin levels. In conclusion, we did not found any significant association between plasma thyrotropin levels and obesity and metabolic syndrome in our euthyroid subjects.
The impact of neonatal androgen receptor (AR) stimulation/blockage, due to testosterone propionate (TP)/AR antagonist treatment, on individual anthropometry and neuroendocrine-metabolic function was evaluated in the juvenile female rat. Pups (age 5 days) were s.c. injected with TP (1.25 mg), flutamide (F; 1.75 mg), and TP + F or vehicle (control, CT) and studied on day 30 of age. Body weight (BW), parametrial adipose tissue (PMAT) mass, food intake, adipoinsular axis, and steroidogenic functions were examined. Opposite to TP-rats, F-treated rats developed hypophagia, grew slowly (BW and PMAT), and displayed heightened peripheral insulin sensitivity. These F effects were abrogated in TP + F animals. Accordingly, TP rats displayed hyperleptinemia, an effect fully prevented by F cotreatment. Finally, androgen-treated animals bore an irreversible ovarian dysfunction (reduced circulating levels of 17HOP4 and ovary 17HOP4 content and P450c17 mRNA abundance). These data indicate that early stimulation of AR enhanced energy store, blockage of AR activity resulted in some beneficial metabolic effects, and neonatally androgenized rats developed a severe ovarian dysfunction. Our study highlights the important role of AR in the early organizational programming of metabolic and neuroendocrine functions.
Background. Serum lipids including total cholesterol (TC), triglycerides (TG), and low density lipoprotein cholesterol (LDL-C) are increased in pregnancy. Serum proprotein convertase subtilisin kexin 9 (PCSK9) is a significant player in lipoprotein metabolism. Circulating PCSK9 downregulates the LDL receptor on the surface of the liver, inhibiting clearance of LDL-C. Therefore, our study assessed serum PCSK9 concentrations at parturition (Maternal) compared to a nonpregnant (Control) cohort, as well as between mother and newborn (Maternal and Newborn). Methods. Blood was collected from women at parturition and from umbilical cords. Serum lipids and PCSK9 were measured and data were analysed for significance by Mann-Whitney U test at P < 0.05 and presented as median levels. Spearman's correlations were made at a 95% confidence interval. Results. Serum PCSK9 was significantly higher in Maternal versus Control cohorts (493.1 versus 289.7 ng/mL; P < 0.001, resp.), while the Newborn cohort was significantly lower than Maternal (278.2 versus 493.1 ng/mL; P < 0.0001, resp.). PCSK9 was significantly correlated with TC and HDL-C in Maternal and with TC, LDL-C, and HDL-C in Newborn cohorts. Conclusions. Our study provides the first quantitative report on PCSK9 in pregnancy (at parturition) and in umbilical cord blood. Further research will determine how these changes may affect lipoprotein levels during this physiological state.
Type 1 diabetes is a metabolic disease caused by autoimmunity towards β -cells. Different strategies have been developed to restore β -cell function and to reestablish immune tolerance to prevent and cure the disease. Currently, there is no effective treatment strategy to restore endogenous insulin secretion in patients with type 1 diabetes. This study aims to restore insulin secretion in diabetic mice with experimental antigen-specific immunotherapy alone or in combination with rapamycin, a compound well known for its immunomodulatory effect. Nonobese diabetic (NOD) mice develop spontaneous type 1 diabetes after 12 weeks of age. Autologous tolerogenic dendritic cells-consisting in dendritic cells pulsed with islet apoptotic cells-were administered to diabetic NOD mice alone or in combination with rapamycin. The ability of this therapy to revert type 1 diabetes was determined by assessing the insulitis score and by measuring both blood glucose levels and C-peptide concentration. Our findings indicate that tolerogenic dendritic cells alone or in combination with rapamycin do not ameliorate diabetes in NOD mice. These results suggest that alternative strategies may be considered for the cure of type 1 diabetes.
Recent Italian guidelines exclude women <35 years old, without risk factors for gestational diabetes mellitus (GDM), from screening for GDM. To determine the effectiveness of these measures with respect to the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria, we evaluated 2,448 pregnant women retrospectively enrolled in Calabria, southern Italy. GDM was diagnosed following the IADPSG 2010 criteria. Among 538 women <35 years old, without risk factors, who would have not been tested according to the Italian guidelines, we diagnosed GDM in 171 (31.8%) pregnants (7.0% of total pregnants). Diagnosis was made at baseline (55.6%), 1 hour (39.8%), or 2 hours (4.7%) during OGTT. Despite of appropriate treatment, GDM represented a risk factor for cesarean section, polyhydramnios, increased birth weight, admission to neonatal intensive care units, and large for gestational age. These outcomes were similar to those observed in GDM women at high risk for GDM. In conclusion, Italian recommendations failed to identify 7.0% of women with GDM, when compared to IADPSG criteria. The risk for adverse hyperglycaemic-related outcomes is similar in low-risk and high-risk pregnants with GDM. To limit costs of GDM screening, our data suggest to restrict OGTT to two steps (baseline and 1 hour).
Objectives. Assess the prevalence of thyroid nodules and predictors of malignant origin in patients with autoimmune thyroid diseases. Patients and Methods. Retrospective study including 275 patients, 198 with Graves' disease and 77 with Hashimoto's thyroiditis. Clinical and demographical data, ultrasonographical nodule characteristics, total thyroid volume and histological characteristics were recorded. Results. Graves' disease: the prevalence of thyroid nodules and thyroid carcinoma were 27.78% and 5.05%, respectively. Older age (OR = 1.054; 95% CI = 1.029-1.080) and larger thyroid volumes (OR = 1.013; 95% CI = 1.003-1.022) increased the chance of nodules. Younger age (OR = 1.073; 95% CI = 1.020-1.128) and larger thyroid volume (OR = 1.018; 95% CI = 1.005-1.030) predicted thyroid carcinoma. Hashimoto's thyroiditis: the prevalence of thyroid nodules and carcinomas were 50.7% and 7.8%, respectively. Nodules were predicted by thyroid volume (OR = 1.030; 95% CI = 1.001-1.062). We found higher number of nodules in patients with thyroid carcinoma than in those with benign nodules (3 versus 2; P = 0.03). Patients with Hashimoto's thyroiditis presented nodules more frequently than patients with Graves' disease (50.65% versus 27.28%; P < 0.001), while the prevalence of carcinoma was similar (P = 0.751). Conclusions. Larger goiter was associated with carcinoma in Graves' disease and Hashimoto's thyroiditis. Younger patients presented higher risk of papillary thyroid carcinoma in Graves' disease. The prevalence of carcinoma was similar in both conditions.
Purpose of Review. Studies have been published in the field of autoimmune thyroid diseases since January 2005. The review is organized into areas of etiology, autoimmune features, autoantibodies, mechanism of thyroid cell injury, B-cell responses, and T-cell responses. Also it reviews the diagnosis and the relationship between autoimmune thyroid disease, neoplasm, and kidney disorders. Recent Findings. Autoimmune thyroid diseases have been reported in people living in different parts of the world including North America, Europe, Baalkans, Asia, Middle East, South America, and Africa though the reported figures do not fully reflect the number of people infected per year. Cases are unrecognized due to inaccurate diagnosis and hence are treated as other diseases. However, the most recent studies have shown that the human autoimmune thyroid diseases (AITDs) affect up to 5% of the general population and are seen mostly in women between 30 and 50 years. Summary. Autoimmune thyroid disease is the result of a complex interaction between genetic and environmental factors. Overall, this review has expanded our understanding of the mechanism involved in pathogenesis of AITD and the relationship between autoimmune thyroid disease, neoplasm, and kidney disease. It has opened new lines of investigations that will ultimately result in a better clinical practice.
Recent clinical studies have spurred rigorous debate about the benefits of hormone therapy (HT) for postmenopausal women. Controversy first emerged based on a sharp increase in the risk of cardiovascular disease in participants of the Women's Health Initiative (WHI) studies, suggesting that decades of empirical research in animal models was not necessarily applicable to humans. However, a reexamination of the data from the WHI studies suggests that the timing of HT might be a critical factor and that advanced age and/or length of estrogen deprivation might alter the body's ability to respond to estrogens. Dichotomous estrogenic effects are mediated primarily by the actions of two high-affinity estrogen receptors alpha and beta (ER α & ER β ). The expression of the ERs can be overlapping or distinct, dependent upon brain region, sex, age, and exposure to hormone, and, during the time of menopause, there may be changes in receptor expression profiles, post-translational modifications, and protein:protein interactions that could lead to a completely different environment for E2 to exert its effects. In this review, factors affecting estrogen-signaling processes will be discussed with particular attention paid to the expression and transcriptional actions of ER β in brain regions that regulate cognition and affect.
Diabetic nephropathy (DN) is a major cause of end-stage kidney disease, and therefore early diagnosis and intervention may help reverse renal damage. One hundred and sixty-eight patients with T2DM and 56 healthy volunteers (control group) were enrolled at Shandong University Qilu Hospital between April 2010 and October 2012. All subjects underwent blood sampling for sera homocysteine (Hcy) and cystatin C (Cys C) assays and a urine microalbumin test. The patients were divided into three groups according to the urine microalbumin excretion rate (UMAER): the simple DM group (SDM group, n = 51), the early-stage DN group (EDN group, n = 60), and the clinical DN and renal failure group (CDN group, n = 57). Correlation analysis was performed to examine the association between sera Hcy and Cys C levels with UMAER. Our findings showed that sera Hcy level, Cys C level, and UMAER increased significantly in the SDM group (P < 0.05, P < 0.01), the EDN group (P < 0.01), and the CDN group (P < 0.01) as compared with the control group. These three biochemical markers also increased significantly with DN progression (P < 0.01). Correlation analysis showed that sera Hcy and Cys C levels were positively correlated with UMAER (r = 0.702, P < 0.01; r = 0.873, P < 0.01). In conclusion, our results showed that sera Hcy and Cys C levels increased consistently with the development and progression of DN as indicated by UMAER. Sera Hcy and Cys C are sensitive biomarkers for the detection of early-stage DN and monitoring its progression.
