Vitamin D receptor and estrogen receptor gene polymorphisms in men with type 2 diabetes: Effects on Bone Metabolism.

Purpose: There is an increased fracture risk in type 2 diabetes mellitus [DM] patients independent of bone mineral density [BMD], both in men and women. Estrogen receptor [ER]-alpha and vitamin D receptor [VDR] gene polymorphisms may predispose patients to increased osteoporosis and fracture risk. This study aims to analyze the relationship of the ER-alpha gene and VDR gene polymorphisms with indicators of bone turnover and BMD in male type 2 diabetic patients. Methods: Type 2 diabetic men diagnosed with diabetes for at least one year and healthy controls were included in this cross-sectional study. BMD was measured by dual X ray absorptiometry. Gene polymorphisms were evaluated with polymerase chain reaction-restriction length polymorphism. Serum iPTH, calcium, beta-CrossLaps (cTx), osteocalcin, and free testosterone levels were also evaluated. Results: Participants were 141 type 2 diabetic men [55 ± 8 years] and 100 healthy controls [53 ± 7 years]. BMD measurements were not statistically different between the groups. While iPTH [p < 0.05] and serum calcium levels [p = 0.03] were higher in men with type 2 DM; beta-CrossLaps [p = 0.0001], osteocalcin [p = 0.005], and free testosterone [p = 0.04] were lower than controls. The differences in terms of the frequencies of VDR Apa, Taq, Bsm, Fok and ER-alpha polymorphisms were not statistically significant between the groups. No relationship was observed between polymorphisms and BMD in both groups. Conclusions: VDR and ER-alpha gene polymorphisms seem to have no effect on BMD and bone turnover in men with DM.

The pituitary-gonadal-thyroid and lactotroph axes in critically ill patients.

INTRODUCTION: The normal circadian rhythm of hormones in critical patients becomes chaotic causing some hormones to increase and others to decrease abnormally. The goal of this study is to evaluate hormonal changes in severely ill patients and to investigate the relationship between hormonal changes and mortality and morbidity. MATERIAL AND METHODS: We enrolled 20 patients (10 F/10 M). Blood samples were collected on day 0, day 5, and day 10. If a patient was discharged before these defined days, a sample was drawn on that day. Twenty healthy controls were included. RESULTS: Female patients had lower LH, FSH, and fT3 and higher PRL and cortisol levels than controls on admission to the intensive care unit (ICU) (pLH = 0.021, pFSH:0.001, pfT3 = 0.021, pPRL = 0.042, pCortisol <0.001, respectively). Men had significantly low testosterone and fT3, and high PRL and cortisol levels on ICU admission (pT = 0.01, pfT3 = 0.043, pPRL = 0.005, pCortisol < 0.001, respectively). The lowest levels of gonadotropins in both genders and testosterone in men were measured on day 5. Cortisol levels decreased in the patients discharged from the ICU (p = 0.01). FSH levels increased in recovered women (pFSH = 0.043). The mortality rate was 30%. There were correlations between admission TSH and NIMV duration (p = 0.006), fT3 and APACHE II (p = 0.001), and PRL and mortality (p = 0.044). Positive correlations between E2 and APACHE II (p = 0.003) in females, and PRL and APACHE II (p = 0.022) in males were also displayed. CONCLUSIONS: Critically ill patients develop significant changes in neuroendocrine axes. Alterations in hormones correlate with the disease severity and mortality. (Endokrynol Pol 2016; 67 (3): 305-312).

Effects of restoration of the euthyroid state on epicardial adipose tissue and carotid intima media thickness in subclinical hypothyroid patients.

Epicardial adipose tissue (EAT) thickness is a novel cardiovascular risk indicator, whereas carotid intima media thickness (CIMT) is a known marker of subclinical atherosclerosis. The aim of this study was to measure EAT thickness and CIMT in subclinical hypothyroid (SCH) patients and to determine the effect of restoration of the euthyroid state on these variables. The study included 43 patients with SCH (mean age: 35.2±10.7 years; F-M ratio: 42:1) and 30 healthy controls (mean age: 34.5±8.2 years; F-M ratio: 25:5). EAT thickness and CIMT were measured via conventional echocardiography and ultrasonography. Among the patients, 23 were followed up with L-thyroxine replacement until restoration of the euthyroid state and re-evaluated 6 months after baseline. Basal EAT thickness was higher in the SCH patients than in the controls (3.2±0.7 vs. 2.3±0.3 mm-p<0.0001), whereas CIMT was similar in both groups (0.50±0.09 vs. 0.48±0.04 mm). EAT thickness was correlated with CIMT in the patient group (r=0.39, p=0.01), but this correlation was not evident based on multivariate analysis when corrected for age and body mass index (r2=0.47 and p=0.0001 for the model). In the follow-up patient subgroup, both EAT thickness and CIMT decreased significantly following L-thyroxine treatment, when normal TSH levels were attained (3.4±0.7 vs. 2.3±0.5 mm-p=0.007 and 0.51±0.09 vs. 0.46±0.07 mm-p=0.01, respectively). EAT thickness was greater in the SCH patients than in controls, whereas CIMT was similar in both groups. Restoration of the euthyroid state with L-thyroxine treatment was associated with significant decreases in EAT thickness and CIMT in the group of patients that received L-thyroxine treatment and, as such, might reduce the cardiovascular risk associated with SCH.

The effect of physicians' awareness on influenza and pneumococcal vaccination rates and correlates of vaccination in patients with diabetes in Turkey: an epidemiological Study "diaVAX".

We aimed to examine the effect of increased physician awareness on the rate and determinants of influenza and pneumococcal vaccinations in diabetic patients. Diabetic patients (n = 5682, mean [SD] age: 57.3 [11.6] years, 57% female) were enrolled by 44 physicians between Sept 2010 and Jan 2011. The physicians were initially questioned regarding vaccination practices, and then, they attended a training program. During the last five years, the physicians recommended influenza and pneumococcal vaccinations to 87.9% and 83.4% of the patients, respectively; however; only 27% of the patients received the influenza and 9.8% received the pneumococcal vaccines. One year after the training, the vaccination rates increased to 63.3% and 40.7%, respectively. The logistic regression models revealed that variables which increased the likelihood of having been vaccinated against influenza were: longer duration of diabetes, presence of hyperlipidemia and more use of concomitant medications whereas more use of anti-hyperglycemic medications was associated with increased odds of vaccination. On the other hand, older age, longer duration of diabetes and presence of a cardiovascular disease were variables which decreased the likelihood of having been vaccinated against pneumococcal disease during the past five years. However, during the study period, variables which decreased the odds of having been vaccinated included: older age and anti-hyperglycemic medications for influenza, and presence of hyperlipidemia and a family history of hypertension for pneumococcal disease. While variables which increased the likelihood of vaccination in the same period were: increased number of co-morbidities for influenza, and family history of diabetes for pneumococcal disease. We conclude that increased awareness of physicians may help improve vaccination rates against influenza and pneumococcal disease. However, diabetic patients with more severe health conditions are less likely to having been vaccinated. More structural/systematic vaccination programs are needed to increase the vaccination rates in patients with diabetes.

Impaired diastolic function and elevated Nt-proBNP levels in type 1 diabetic patients without overt cardiovascular disease.

Diabetic cardiomyopathy is an important complication of type 1 diabetes mellitus. Diastolic heart failure is an early manifestation of diabetic cardiac disease. Nt-proBNP is a valuable marker of ventricular dysfunction. The aim of this study was to determine Nt-proBNP concentrations in type 1 diabetic patients and determine their relationship with ventricular diastolic dysfunction (DD) and carotid artery intima media thickness (CIMT) measurements. Sixty-seven type 1 diabetic patients (30.2 ± 8.0 years; W/M: 24/43) without known cardiovascular disease and 48 healthy controls (30.5 ± 6.4 years; W/M: 19/29) were recruited. Nt-proBNP levels were measured. Conventional and tissue Doppler echocardiography were used to evaluate left ventricular diastolic function and CIMT. Nt-proBNP in diabetic patients was significantly higher than in controls (38 ± 34.8 vs. 15.1 ± 12.7 pg/ml) (P = 0.004). Ea level was higher (12.3 ± 3 vs. 10.3 ± 4 cm/s, P = 0.003) and E/Ea ratio was lower in patients (6.6 ± 2.5 vs. 9.7 ± 5.9, P = 0.001) compared with controls. Ratio of DD was higher in patients than controls (11.1 vs. 2.1%, P = 0.01). CIMT measurements in diabetic patients were higher than controls (0.54 ± 0.11 vs. 0.48 ± 0.05 mm, P = 0.02). Logistic regression revealed age and HbA1c to be independently associated with the presence of DD. Nt-proBNP levels are elevated in type 1 diabetic patients without overt cardiovascular disease and the presence of DD is increased in diabetic patients in comparison with controls. Nt-proBNP levels do not seem to be related to the presence of DD and subclinical atherosclerosis in this group of patients.

Serum adipokine levels in type 1 diabetic patients: association with carotid intima media thickness.

BACKGROUND: Adipokines are markers of insulin resistance and play a role in the atherosclerotic process. The association of adipokines with the macrovascular complications of type 1 diabetes mellitus (DM) needs to be determined. The aim of this study was to measure serum adiponectin, leptin, and resistin levels in type 1 DM patients and investigate their relationship with carotid intima media thickness (CIMT), a clinical marker of atherosclerosis. METHODS: Seventy-five type 1 DM patients and 115 sex and age-matched healthy controls were included in the study. Serum adiponectin, leptin, and resistin levels were measured by the enzyme-linked immunosorbent assay (ELISA method). CIMT was assessed by Doppler ultrasonography. RESULTS: Adiponectin levels in diabetics were higher (25.8±14.8 µg/mL vs. 5.5±7.3 µg/mL; P<0.0001) and leptin levels were lower than controls (9.4±6.2 ng/mL vs. 12.8±8.6 ng/mL; P=0.01). Resistin levels were also higher in the diabetic group compared to controls (2.1±1.4 ng/mL vs. 1.6±0.8 ng/mL; P=0.04). Adiponectin was correlated negatively with CIMT (r=-0.24, P=0.03), age (r=-0.30, P=0.02), BMI (r=-0.33, P=0.02), waist-to-hip ratio (WHR) (r=-0.38, P=0.01) and positively with creatinine (r=0.44, P=0.004). Leptin levels were correlated with total cholesterol (r=0.53, P=0.01) and high-density lipoprotein (HDL) (r=0.67, P=0.001). Resistin was correlated with CIMT (r=0.24, P=0.03) and systolic blood pressure (r=0.48, P=0.009). Multivariate analysis revealed resistin and creatinine to be independent predictors of CIMT among adiponectin, leptin, resistin, WHR, glycosylated hemoglobin (HbA1c), and creatinine. CONCLUSIONS: Increased adiponectin correlates negatively and resistin positively with CIMT in type 1 diabetic patients, but adjusting for other known predictors reveals only resistin to be associated with subclinical atherosclerosis in this group of patients.

Bulky gastrinoma of the common bile duct: unusual localization of extrapancreatic gastrinoma--case report.

Zollinger-Ellison syndrome is characterized by elevated levels of serum gastrin associated with increased gastric acid secretion, gastrointestinal ulcerations and diarrhea. Most gastrinomas (75%) occur sporadically and are located within the gastrinoma triangle. Extraduodenal, extrapancreatic and extranodal gastrinomas have been shown in 5.6% of the patients with Zollinger-Ellison syndrome who underwent surgery. We report a 44-year-old female who had been complaining of nausea and diarrhea for 12 years. Abdominal computed tomography and magnetic resonance imaging detected a homogeneous, regular-shaped 6 x 7 cm solid mass, located between the liver, right kidney and inferior vena cava. Somatostatin receptor positive scanning led us to investigate a neuroendocrine tumor. Serum gastrin level was found very high and the patient underwent surgery. Local excision of the tumor was performed, and an 8x6x5 cm, well-capsulated, solitary mass, originating from the common bile duct was removed. The unique feature of our case is the unusual localization, and although the tumor was very large in size, only capsule invasion was observed with no evidence of distant metastasis.

Vitamin D receptor gene BsmI, FokI, ApaI, TaqI polymorphisms and bone mineral density in a group of Turkish type 1 diabetic patients.

Previous studies have suggested an influence of vitamin D receptor alleles on bone metabolism and on susceptibility to type 1 diabetes mellitus in different ethnic populations. We aimed to investigate the distribution of vitamin D receptor (VDR) alleles in relation to biochemical bone turnover parameters and bone densitometry measurements in a group of Turkish type 1 diabetic patients. One hundred and seventeen patients (M/F 57/60, 27.6 ± 7.3 y duration of diabetes 8.1 ± 6.3 y) and 134 healthy controls (M/F 61/73, 26.2 ± 5.3 y) were included in the study. Bone mineral density (BMD) was evaluated by dual-energy X-ray absorptiometry (DEXA). The vitamin D receptor gene (VDR) polymorphisms FokI, Bsm1, Apa1, and Taq1 were examined using a PCR-based restriction analysis. Serum levels of calcium, phosphor osteocalcin, intact parathyroid hormone, and C telopeptide were measured. Vitamin D receptor Bsm1 Fok1, Apa1, and Taq1 genotype distributions were not different between patient with diabetes and control groups. BMD was 0.77 ± 0.2 g/cm(2) vs. 0.97 ± 0.2 g/cm(2) (P = 0.0001) for the femur, 1.0 ± 0.1 g/cm(2) vs. 1.13 ± 0.1 g/cm(2) (P = 0.001) for type 1 diabetic patients and controls. Bone turnover markers were significantly lower in type 1 diabetic group. BMD measurements and bone metabolic markers were not different between the genotypes in either the patient with diabetes or the controls. The VDR gene polymorphisms, Bsm1, Fok 1, Apa1, and Taq1 showed no influence on bone metabolism in our group of type 1 diabetic patients.

Epicardial adipose tissue thickness in type 1 diabetic patients.

Insulin resistance is getting important in the course of type 1 diabetes mellitus. Visceral fat depot is associated with insulin resistance and assessment of epicardial fat thickness is a way of measuring visceral fat. The aim of the study was to measure epicardial adipose tissue (EAT) thickness and to determine its relationship with waist-hip-ratio (WHR) and estimated glucose disposal rate (eGDR) in adult type 1 diabetic patients. Thirty-six type 1 diabetic patients (aged 31±8 years; Female/Male: 22/14) and 43 age, gender and BMI matched healthy controls were included. Fasting blood glucose (FBG), hemoglobin A1c, and lipid profiles were measured. Waist-hip-ratio (WHR) was calculated. Daily insulin dose/kg of patients were recorded and eGDR of all subjects was calculated. Epicardial adipose tissue (EAT) thickness was evaluated by echocardiography. EAT thickness of the type 1 diabetic patients was significantly higher than controls (3.30±1.06 vs. 2.30±0.34 mm, P<0.0001). EAT thickness was correlated with age (P=0.05; r=0.35), WHR (P=0.003; r=0.67), daily insulin dose/kg (r=0.45, P=0.005), and eGDR (r=-0.55, P=0.0004). Multivariate analysis revealed WHR and eGDR to be related to EAT among age, WHR, daily insulin dose/kg, eGDR, FBG, and hemoglobin A1c (r2 of the model=0.64). Epicardial adipose tissue thickness is increased in type 1 diabetic patients compared to controls and is related to WHR and eGDR in this group of patients. This measurement may point to the presence of insulin resistance in type 1 diabetic patients.

Shared sporadic and somatic thyrotropin receptor mutations display more active in vitro activities than familial thyrotropin receptor mutations.

BACKGROUND: Germline thyrotropin receptor (TSHR) mutations are associated with sporadic congenital nonautoimmune hyperthyroidism and familial nonautoimmune hyperthyroidism. Somatic TSHR mutations are associated with toxic thyroid nodules (TTNs). The objective of the study was to define a relation of the clinical appearance and the in vitro activity (IVA) of the TSHR mutations described by several authors for these thyroid disorders. METHODS: We analyzed the IVAs published as linear regression analysis (LRA) of the constitutive activity as a function of the TSHR expression and the basal cyclic adenosine monophosphate (cAMP) values to determine differences between exclusively somatic, exclusively familial, and shared sporadic and somatic TSHR-mutations. Further, we investigated correlations of the LRAs/basal cAMP values with clinical activity characteristics (CACs) of TTNs, such as largest diameter of the TTN and the age of the patient at thyroid surgery. RESULTS: Shared sporadic and somatic mutations showed higher median LRA (14.5) and higher median basal cAMP values (fivefold) than exclusively familial mutations (6.1, p = 0.0002; 2.9-fold, p < 0.0001, respectively). Moreover, mutations shared between sporadic congenital nonautoimmune hyperthyroidism and toxic thyroid nodules (TTNs) showed higher median LRA/basal cAMP values (p < 0.0001) than exclusively somatic mutations in TTNs (5.1; 3.89-fold, respectively). Exclusively somatic mutations and exclusively familial mutations showed no significant difference in their median LRA values (p = 0.786) but a significant difference for basal cAMP values (p = 0.0006). The two examined CACs showed no correlation with the IVA characterized by LRA/basal cAMP values or with the presence or absence of a TSHR-mutation. CONCLUSIONS: This systematic analysis of published constitutively activating TSHR-mutations, their CACs, and their IVA provides evidence for higher IVA of shared sporadic and somatic TSHR mutations as compared with familial TSHR mutations. CACs of somatic TSHR mutations in TTNs did not have a clear association with the IVA as characterized by LRA or basal cAMP values.

Diet-supported aerobic exercise reduces blood endothelin-1 and nitric oxide levels in individuals with impaired glucose tolerance.

BACKGROUND: Impaired glucose tolerance (IGT) forms an intermediate stage in the natural history of diabetes mellitus. Insulin-resistant states might be associated with dysfunction of the vascular endothelium. OBJECTIVES: To determine the effects of chronic exercise and a low-calorie diet on plasma nitric oxide (NO) and endothelin-1 (ET-1) levels in patients with IGT and to elucidate the relationship between the oxidant stress markers and NO/ET-1 levels of blood before and after exercise. METHODS: Patients with IGT (n = 14) participated in a regular exercise program and exercised for 40 minutes each day, 3 days a week for 12 weeks. Physiological, anthropometric, and biochemical measurements were performed before, during the 6th week, and at the end of the program. RESULTS: There was a significant reduction in body mass index, body fat content, systolic and diastolic blood pressures, as well as NO and ET-1 concentrations after 12 weeks of exercise and diet program. Exercise training significantly elevated subjects' maximum oxygen consumption, whereas the resting metabolic rates of the patients did not change. The formation of thiobarbituric acid reactive substances were significantly reduced, whereas sulfhydryl groups were significantly increased on the 6th week (P < .05) and at the end of program (P < .01). CONCLUSION: Our results demonstrate that exercise, along with low-calorie diet, induced reductions in the plasma of both ET-1 and NO. Beneficial effects were observed on anthropometric measurements and plasma oxidant stress markers, indicating weight loss associated with exercise training and calorie restriction may effectively improve endothelial dysfunction in patients with IGT.

Anti-Saccaromyces Cerevisiae antibodies (ASCA) are elevated in autoimmune thyroid disease ASCA in autoimmune thyroid disease.

Environmental factors have been implicated in the development of autoimmune thyroid disease (AITD). Anti-Saccaromyces Cerevisiae Antibodies (ASCA) were shown to be elevated in several autoimmune diseases. The aim of the study was to determine ASCA levels and their relationship with thyroid autoantibodies in patients with AITD. One-hundred and twelve patients with AITD (age 41.1±12.8 years; F/M:96/16) and 103 healthy controls (38.5±10.3 years; F/M:82/21) were included. Twenty-four patients had Graves disease (GD), and 88 had Hashimoto's thyroiditis (HT). ASCA IgA and IgG, TSH, free T4, anti-thyroglobulin, and anti-thyroid peroxidase antibody concentrations were determined. ASCA IgA positivity in patients with GD (16.6%) was similar to patients with HT (13.6%) and was higher than controls (5.8%). No significant difference was present between the frequencies of IgG positivity among GD (12.5%), HT (7.9%), and control groups (5.8%). The mean levels of ASCA IgA and IgG were comparable within the groups. No correlation of ASCA and anti-thyroglobulin and anti-thyroid peroxidase levels was observed. Increased IgA ASCA positivity is observed in patients with GD, suggesting a role of environmental stimuli in its pathogenesis. The role of ASCA in the etiology of AITD needs to be further examined.

Alterations of NIS expression in functioning thyroid nodules.

OBJECTIVES: This study aimed to analyze both the level and the cell site of the sodium-iodide symporter (NIS) protein expression in autonomously functioning thyroid nodules (AFTNs) and extranodular thyroid tissues. In addition, this study sought to compare the clinical results of patients with the levels of human NIS (hNIS) protein expression. PATIENTS AND METHODS: The histological slides consisted of 36 AFTNs and 31 extranodular thyroid tissues from 28 patients (5 males, 23 females; mean age 54.5±11.0 years; range 37 to 72 years) who underwent surgery for toxic multinodular goitre. The expression of NIS protein was investigated by immunohistochemistry in paraffin-embedded tissue sections using anti-hNIS monoclonal antibody by the labeled streptavidin-biotin method. RESULTS: The percentage of hNIS positive follicular cells was significantly higher in the AFTNs (13.33±12.09) than in the extranodular thyroid tissues (1.35±3.03). Staining for hNIS was mostly confined to the cell membrane in the AFTNs (88.9%) and in the extranodular thyroid tissues (54.5%). The clinical parameters and nodule volume did not establish any correlation with hNIS immunoreactivity. CONCLUSION: Our data indicate that functioning nodules express higher amounts of NIS protein than the extranodular thyroid tissue, but the level of hNIS immunoreactivity was lower than had been reported in the previous literature. This result may be due to interindividual variability between different populations, and iodine status. Furthermore, the localization of the NIS protein might not give an indication of its functional status.

The endocrinologic changes in critically ill chronic obstructive pulmonary disease patients.

BACKGROUND: Alterations in the neuroendocrine system occur during critical illness. Chronic obstructive pulmonary disease (COPD) itself causes hormonal changes. The aim of this study was to determine neu roendocrine hormones of COPD patients with acute respiratory failure and to investigate the relationship between hormonal changes, mortality, and morbidity. METHODS: We enrolled 21 patients (13 F/8 M) with COPD exacerbation requiring artificial airway support. Blood samples were collected on admission to the ICU, and on the day of hospital discharge. Eighteen healthy people were included as controls. RESULTS: Female patients had lower luteinizing hormone (LH), follicle stimulating hormone (FSH), and free triiodothyronine (fT3), and higher prolactin (PRL) levels than controls on admission to the ICU (FSH: 70.3 vs. 29.3 mlU/mL; LH: 26.6 vs. 6.8 mlU/mL; fT3: 2.9 vs. 2.0 pg/mL; PRL: 12.4 vs. 21.3 ng/mL). Male patients had low testosterone and TSH and high PRL but only changes in TSH and PRL reached statistical significance (testosterone: 3.5 vs. 1.5 ng/mL, TSH: 1.1 vs. 0.5 ulU/mL, PRL: 9.7 vs. 14.2 ng/mL). Female patients had lower fT3 than males (fT3(female): 2.7 vs. fT3(male): 2.0 pg/mL). On follow-up, significantly elevated FSH and fT3 and decreased estradiol concentrations were documented among recovered women (FSH: 28.4 vs. 46.6 mlU/mL, fT3(,): 2.0 vs. 2.6 pg/mL, E(2): 27.7 vs. 19.0 pg/mL). Patients had high C-reactive protein levels and acute physiologic and chronic health evaluation II scores. Mortality rate was 9.5% and a negative correlation between E(2) and duration of noninvasive mechanical ventilation and length of hospital stay was found in male patients. CONCLUSION: Men and women with acute respiratory failure in the presence of COPD develop significant changes in the neuroendocrine axis. Hormonal suppression vanishes with disease improvement.

Epicardial fat tissue thickness correlates with endothelial dysfunction and other cardiovascular risk factors in patients with metabolic syndrome.

BACKGROUND: Epicardial adipose tissue has shown to be related to cardiovascular risk. The aim of this study is to investigate the relationship between epicardial adiposity and endothelial function in metabolic syndrome. METHODS: Fifty patients with metabolic syndrome were recruited. Anthropometric measurements, fasting blood glucose, insulin, lipid profile, high-sensitivity C-reactive protein (hsCRP), fibrinogen, apolipoprotein A (Apo A), Apo B1, and lipoprotein (a) [Lp(a)] were determined. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Epicardial fat thickness was measured via two-dimensional M-mode echocardiography. Endothelial function was assessed as flow-mediated dilatation at the brachial artery. RESULTS: Epicardial fat tissue thickness was shown to be correlated negatively with FMD and positively with age, diastolic blood pressure, hsCRP, fibrinogen, HOMA-IR, and lipid parameters. Multiple regression analysis showed epicardial fat tissue thickness to be an independent factor influencing the endothelial function. CONCLUSIONS: Epicardial fat tissue may be a useful parameter in the assessment of patients with metabolic syndrome.

Circulating endothelial cells are elevated in patients with type 1 diabetes mellitus.

OBJECTIVE: Circulating endothelial cells (CECs) have emerged as vascular damage markers and are increased in type 2 diabetic patients. Since type 1 diabetes is associated with vascular damage, we hypothesized high CEC numbers in this patient population. METHODS: Thirty-nine patients with type 1 diabetes and 39 controls were included. CECs were isolated using anti-CD146-coated Dynabeads, stained with Ulex lectin-1, and counted by fluorescence microscopy. Endothelial function was measured as flow-mediated dilation (FMD). Thiobarbituric acid reactive substances (TBARS), total glutathione levels (GSH), and paraoxonase (PON) activity levels were measured as oxidative stress markers. RESULTS: Patients with type 1 diabetes mellitus had higher number of CECs (7.46+/-5.37 vs 2.13+/-1.13 cells/ml, P<0.001), lower FMD (7.87+/-2.19 vs 12.06+/-2.34%, P<0.001), higher TBARS (4.94+/-1.20 vs 3.07+/-0.75 nmol/MDA, P<0.001), lower GSH (206.12+/-98.06 vs 353.61+/-68.45 microM, P<0.001), and lower PON activity levels (89.10+/-17.82 vs 127.65+/-29.01 U/l, P<0.001) as compared to controls. There was positive correlation between CEC numbers and HbAlc levels (r=0.49, P=0.002). CECs and fasting glucose levels were not correlated. There was no correlation between the number of CECs and FMD. Furthermore, there were no correlations between the number of CECs and TBARS, GSH and PON activity levels. Multiple regression analysis showed that HbAlc levels (r(2)=0.40, P<0.009) were associated with CEC numbers. CONCLUSION: CECs are elevated in patients with type 1 diabetes mellitus reflecting endothelial damage. This increase is dependent on long-term glucose control.

Short-term oral magnesium supplementation suppresses bone turnover in postmenopausal osteoporotic women.

Magnesium has been shown to increase bone mineral density when used in the treatment of osteoporosis, yet its mechanism of action is obscure. In this study, the effects of daily oral magnesium supplementation on biochemical markers of bone turnover were investigated. Twenty postmenopausal women have been divided into two groups. Ten patients were given magnesium citrate (1,830 mg/day) orally for 30 days. Ten postmenopausal women of matching age, menopause duration, and BMI were recruited as the control group and followed without any medication. Fasting blood and first-void urine samples were collected on days 0, 1, 5, 10, 20, and 30, respectively. Total magnesium, calcium, phosphorus, iPTH and osteocalcin were determined in blood samples. Deoxypyridinoline levels adjusted for creatinine were measured in urine samples. Thirty consecutive days of oral magnesium supplementation caused significantly decrease in serum iPTH levels in the Mg-supplemented group (p < 0.05). Serum osteocalcin levels were significantly increased (p < 0.001) and urinary deoxypyridinoline levels were decreased (p < 0.001) in the Mg-supplemented group. This study has demonstrated that oral magnesium supplementation in postmenopausal osteoporotic women suppresses bone turnover.

Effect of vitamin D deficiency and replacement on endothelial function in asymptomatic subjects.

CONTEXT: Vitamin D receptors are present in many tissues. Hypovitaminosis D is considered to be a risk factor for atherosclerosis. OBJECTIVE: This study explores the effects of vitamin D replacement on insulin sensitivity, endothelial function, inflammation, oxidative stress, and leptin in vitamin D-deficient subjects. DESIGN, SETTING, AND PATIENTS: Twenty-three asymptomatic vitamin D-deficient subjects with 25-hydroxyvitamin D [25(OH)D] levels below 25 nmol/liter were compared with a control group that had a mean 25(OH)D level of 75 nmol/liter. The vitamin D-deficient group received 300,000 IU im monthly for 3 months. The following parameters were evaluated before and after treatment: vitamin D metabolites, leptin, endothelial function by brachial artery flow mediated dilatation (FMD), insulin sensitivity index based on oral glucose tolerance test, and lipid peroxidation as measures of thiobarbituric acid reactive substances (TBARS). RESULTS: FMD measurements were significantly lower in 25(OH)D-deficient subjects than controls (P = 0.001) and improved after replacement therapy (P = 0.002). Posttreatment values of TBARS were significantly lower than pretreatment levels (P < 0.001). A positive correlation between FMD and 25(OH)D (r = 0.45; P = 0.001) and a negative correlation between FMD and TBARS (r = -0.28; P < 0.05) were observed. There was a significant increase in leptin levels after therapy, and the leptin levels were positively correlated with 25(OH)D levels (r = 0.45; P < 0.05). CONCLUSIONS: This study shows that 25(OH)D deficiency is associated with endothelial dysfunction and increased lipid peroxidation. Replacement of vitamin D has favorable effects on endothelial function. Vitamin D deficiency can be seen as an independent risk factor of atherosclerosis. Hypovitaminosis D-associated endothelial dysfunction may predispose to higher rates of cardiovascular disease in the winter.

Diurnal blood pressure abnormalities are related to endothelial dysfunction in patients with non-complicated type 1 diabetes.

Patients with diabetes have an increased cardiovascular morbidity and mortality despite interventions to prevent these outcomes. Abnormalities in diurnal blood pressure patterns are also associated with excess cardiovascular mortality. The aim of this study was to determine the effects of diurnal blood pressure patterns on endothelial function and oxidative stress in patients with uncomplicated type 1 diabetes mellitus. Thirty-two normotensive and normoalbuminuric type 1 diabetic patients (21 dipper and 11 nondipper) and 37 healthy (27 dipper and 10 nondipper) volunteers underwent 24-h ambulatory blood pressure monitoring. Their endothelial functions were evaluated using flow mediated dilatation (FMD) and by measuring nitric oxide and thiobarbituric acid reactive substances (TBARS). Dippers were defined as subjects who exhibited an average reduction in both systolic and diastolic blood pressure of greater than 10% between day and night periods. Nondipper type 1 diabetic patients and controls had nighttime systolic and diastolic blood pressure values that were significantly higher than those of dipper diabetic patients (p<0.05) and dipper controls (p<0.01). Values of FMD for nondipper diabetic patients (5.12+/-2.2%) were significantly lower than those in dipper diabetic patients (10.19+/-2.5%, p<0.01), nondipper (10.08+/-2.9%, p<0.001) and dipper controls (11.76+/-3.8%, p<0.001). Additionally, levels of TBARS in the dipper diabetic group and dipper controls were significantly lower than those in the nondipper diabetic group (p<0.05). In conclusion, only type 1 diabetic patients with a nondipping pattern of blood pressure exhibited changes that may lead to endothelial dysfunction and atherosclerosis. (Hypertens Res 2008; 31: 2065-2073).