Effect of Hospital Admission on Glycemic Control 1 Year After Discharge

ObjectiveTo assess the effect of hospital admission on glycemic control in patients with diabetes up to 1 year after discharge.MethodsWe retrospectively studied 826 adults with diabetes admitted to a tertiary care medical center and with available hemoglobin A_1c (A1C) values for 6 months before admission and 1 year after discharge. We compared them with 826 nonhospitalized adults with diabetes matched for age, sex, race, comorbidity, and baseline A1C level. We determined the change in A1C value relative to hospitalization and baseline A1C level by using multivariate random effects models for repeated measures. Logistic regression analysis was performed to determine predictors of achieving recommended A1C levels at 1 year.ResultsPatients with baseline A1C levels ≥ 9% had an adjusted rate of change in A1C value of − 0.10% per month (95% confidence interval [CI], − 0.18 to − 0.022; P = .012) during the course of 1 year, without significant differences between hospitalized and nonhospitalized patients in the mean rate of change. Hospitalized patients, however, were less likely to achieve an A1C goal of ≤ 7% at 1 year (odds ratio, 0.68; 95% CI, 0.55 to 0.86; P < .001) or an A1C of < 8% at 1 year (odds ratio, 0.62; 95% CI, 0.48 to 0.81; P < .001) in comparison with the nonhospitalized patients.ConclusionDespite an overall trend toward improved glycemia over time, hospitalized patients with uncontrolled diabetes were less likely to achieve glycemic targets at 1 year in comparison with matched nonhospitalized patients. These results suggest a missed opportunity to improve long-term glycemic control in hospitalized patients with diabetes. (Endocr Pract. 2012;18:456-463)     

Evolución clínica a 5 años desde el inicio de la insulinoterapia en pacientes con diabetes tipo 2 en España: resultados del estudio EDIN

ObjectivesThe primary study objective was to assess the proportion of patients with type 2 diabetes and an HbA_1c value ≤ 6.5% from the start of insulin therapy to five years later in the outpatient setting in Spain.Material and methodsThis was an observational, multicenter, naturalistic study with retrospective collection of clinical data. Investigators were endocrinologists or internal medicine specialists from all over Spain. During standard clinical care, patients started insulin therapy, which was continued for at least 5 years.ResultsThe clinical records of 405 patients were reviewed. The final analysis set included records from 346 patients. At baseline (start of insulin therapy), 51.2% of patients were female; mean (SD) age was 64.6 (9.0) years; body mass index, 29.8 (4-5) kg/m²; time since diagnosis, 8.8 (6.8) years; HbA_1c, 9.4% (1.5); fasting glucose, 223.7 (55.9) mg/dL; and mean 2-hour postprandial glucose, 293.6 (71.0) mg/dL. When insulin therapy was started, < 1.0% of patients had an HbA_1c value ≤ 6.5%. At 5 years, 10.3% of patients achieved the HbA_1c goal of ≤ 6.5% (mean, 7.72%). All glucose parameters (HbA_1c, fasting glucose, and 2-hour postprandial glucose) improved at 5 years as compared to values at the start of insulin therapy.ConclusionsGlucose parameters improved over time in patients with type 2 diabetes in this naturalistic study. However, blood glucose control exceeded the internationally recommended target values. These results therefore suggest that there is still some margin for improvement in outpatient care in Spain.     

Initial Combination Therapy with Metformin and Colesevelam for Achievement of Glycemic and Lipid Goals Min Early Type 2 Diabetes

ObjectiveTo evaluate the efficacy and safety of initial combination therapy with metformin plus colesevelam in patients with early type 2 diabetes.MethodsIn this 16-week, randomized, double-blind, placebo-controlled study, adults with type 2 diabetes (hemoglobin A1c [A1C] values of 6.5% to 10.0%) and hypercholesterolemia (low-density lipoprotein cholesterol [LDL-C] levels ≥ 100 mg/dL) were randomly assigned (1:1) to colesevelam (3.75 g/d) or placebo in combination with open-label metformin (850 mg/d; uptitrated at week 2 to 1, 700 mg/d). The primary efficacy evaluation was change in A1C from baseline to study end (week 16 with last observation carried forward).ResultsIn total, 286 patients were randomized: metformin/colesevelam (n = 145) or metformin/placebo (n = 141). Mean A1C was reduced by 1.1% with metformin/ colesevelam (from 7.8% at baseline to 6.6% at study end) and by 0.8% with metformin/placebo (from 7.5% to 6.7%), resulting in a treatment difference of -0.3% at study end (P = .0035). In addition, metformin/colesevelam significantly reduced LDL-C (-16.3%), total cholesterol (-6.1%), non-high-density lipoprotein cholesterol (-8.3%), apolipoprotein B (-8.0%), and high-sensitivity C-reactive protein (-17%) and increased apolipoprotein A-I (+ 4.4%) and triglycerides (+ 18.6%) versus metformin/placebo (P < .01 for all). The proportions of patients who achieved recommended goals with metformin/colesevelam versus metformin/placebo, respectively, were as follows: A1C < 7.0% (67% versus 56% [P = .0092]), LDL-C < 100 mg/dL (48% versus 18% [P < .0001]), and composite A1C < 7.0% + LDL-C < 100 mg/dL (40% versus 12% [P < .0001]). Safety and tolerability were similar between the treatment groups.ConclusionMetformin plus colesevelam may be a valid option for initial therapy to achieve glycemic and lipid goals safely in early type 2 diabetes. (Endocr Pract. 2010;16:629-640)     

Is the Measurement of Accessory Pathway Refractory Period Reproducible?

IntroductionShort accessory pathway (AP) effective refractory period (ERP) is one of the risk factors in Wolff-Parkinson-White syndrome (WPW). The purpose of study was to evaluate the reproducibility of APERP measurement during a same electrophysiological study (EPS).MethodsEPS consisted of 2 APERP measurements performed prospectively in 77 patients for a WPW in control state (CS) at a cycle length of 400 ms (n = 76) and after isoproterenol (n = 56).ResultsIn CS, 18 patients (24 %) had the same APERP at both measurements; 41 (54.6 %) had differences from 10 to 40 ms, 17 (22.4 %) had differences > 40 ms. Among 45 patients with initial APERP > 240 ms, 7 had an APERP ≤ 240 ms at 2nd study. Among 31 patients with initial APERP ≤ 240 ms, 5 had an APERP > 240 ms at 2nd study. Pearson’s productmoment correlation was 0.75. After isoproterenol, 5 patients (9 %) had the same APERPs; 37 (66 %) had differences from 10 to 40 ms and 14 had differences > 40 ms. Among 38 patients with initial APERP > 200 ms, 12 had an AP ERP ≤ 200 ms at 2nd study. Among 18 patients with initial APERP ≤ 200 ms, 10 had still APERP ≤ 200 ms at 2nd study. Pearson’s productmoment correlation was 0.54.ConclusionsThere are important variations of APERPs during EPS mainly after isoproterenol infusion. Therefore the values of APERPs should be interpreted cautiously.     

Clinical Outcomes Using Long-Term Combination Therapy with Insulin Glargine and Exenatide in Patients with Type 2 Diabetes Mellitus

ObjectiveTo examine the long-term effects of combination insulin glargine/exenatide treatment on glycemic control.MethodsWe conducted a 24-month retrospective US chart review of patients with inadequately controlled type 2 diabetes (T2DM) and hemoglobin A_1c (A1C) levels > 7.0% for whom glargine and exenatide were coprescribed in differing order (glargine added after exenatide [exenatide/glargine]; exenatide added after glargine [glargine/exenatide]). Treatment order groups were combined to form a pooled treatment group. Changes from baseline in A1C, patients with A1C ≤ 7.0%, body weight, glargine/exenatide daily dose, oral antidiabetic drug (OAD) use, and hypoglycemia were evaluated.ResultsTreatment groups were similar at baseline; however, patients in the glargine/exenatide group (n = 121) (vs exenatide/glargine group [n = 44]) had longer disease duration (11.8 vs 8.0 years) and took fewer OADs (1.7 vs 2.3). Overall, baseline A1C was 8.8 ± 1.3% and weight was 109.5 ± 25.3 kg. Significant A1C reductions emerged at month 6 and persisted throughout 24 months (vs baseline) in both treatment groups (pooled: –0.7 ± 1.6; P < .001), and 33.0% of patients achieved an A1C level ≤ 7.0%. After 24 months of exenatide/glargine, body weight remained unchanged (0.7 ± 8.3 kg; P = .640). With glargine/exenatide, body weight decreased (–2.5 ± 6.7 kg; P = .001). At month 24, daily glargine dose was 0.40 ± 0.23 units/kg for the exenatide/glargine group and 0.47 ± 0.30 units/kg for the glargine/exenatide group. Hypoglycemia frequency was similar in both treatment groups.ConclusionsRegardless of treatment order, long-term combined therapy with glargine and exenatide for up to 24 months in patients with inadequately controlled T2DM suggests reduction of A1C without significant weight gain or increased hypoglycemia risk. (Endocr Pract. 2012;18:17-25)     

Adapting to the new consensus guidelines for managing hyperglycemia during critical illness: the updated Yale insulin infusion protocol

ObjectiveTo report our preliminary experience with the revised, more conservative Yale insulin infusion protocol (IIP) that targets blood glucose concentrations of 120 to 160 mg/dL.MethodsWe prospectively tracked clinical responses to the new IIP in our medical intensive care unit (ICU) by recording data on the first 115 consecutive insulin infusions that were initiated. All blood glucose values; insulin doses; nutritional support including intravenous dextrose infusions; caloric values for enteral and parenteral nutrition; and use of vasopressors, corticosteroids, and hemodialysis or continuous venovenous hemodialysis were collected from the hospital record.ResultsThe IIP was used 115 times in 90 patients (mean age, 62 [± 14 years]; 51% male; 35% ethnic minorities; 66.1% with history of diabetes). The mean admission Acute Physiology and Chronic Health Evaluation II score was 24.4 (± 7.5). The median duration of insulin infusion was 59 hours. The mean baseline blood glucose concentration was 306.1 (± 89.8) mg/dL, with the blood glucose target achieved after a median of 7 hours. Once the target was reached, the mean IIP blood glucose concentration was 155.9 (± 22.9) mg/dL (median, 150 mg/dL). The median insulin infusion rate required to reach and maintain the target range was 3.5 units/h. Hypoglycemia was rare, with 0.3% of blood glucose values recorded being less than 70 mg/dL and only 0.02% being less than 40 mg/dL. In all cases, hypoglycemia was rapidly corrected using intravenous dextrose with no evident untoward outcomes.ConclusionsThe updated Yale IIP provides effective and safe targeted blood glucose control in critically ill patients, in compliance with recent national guidelines. It can be easily implemented by hospitals now using the original Yale IIP. (Endocr Pract. 2012;18:363-370)     

Clinical Use of Liraglutide in Type 2 Diabetes and its Effects on Cardiovascular Risk Factors

ObjectiveTo assess whether liraglutide, a glucagonlike peptide-1 receptor agonist, has cardioprotective properties in addition to its glycemic effects.MethodsWe performed a retrospective analysis of medical records of 110 obese patients with type 2 diabetes mellitus treated with liraglutide for at least 6 months between March 2010 and April 2011 at our tertiary care referral center. The variables analyzed were body mass index, hemoglobin A_1c (A1C), systolic blood pressure (SBP), plasma C-reactive protein (CRP) concentrations, and serum lipids.ResultsIn our overall study cohort, we noted a reduction in mean weight from 120 ± 5 kg to 115 ± 3 kg and a decrease in mean A1C from 7.8% ± 0.6% to 7.2% ± 0.2%. The mean triglyceride concentration decreased from 173 ± 19 mg/dL to 151 ± 15 mg/dL, the mean SBP was reduced from 132 ± 6 mm Hg to 125 ± 4 mm Hg, and the mean CRP concentration declined from 4.7 ± 0.8 mg/L to 3.2 ± 0.4 mg/L after treatment with liraglutide for a minimal duration of 6 months and a mean duration of 7.5 months (for all the foregoing changes, P < .05).These variables decreased whether these patients were previously treated with orally administered hypoglycemic agents alone or in combination with insulin or exenatide.ConclusionOur findings in a clinical practice show that liraglutide is a potent antidiabetes drug, whether given in combination with orally administered agents or insulin or as a substitution for exenatide. It lowers body weight, A1C levels, SBP, and CRP and triglyceride concentrations. (Endocr Pract. 2012;18:140-145)     

Exogenous intravascular nitric oxide enhances ventricular function after hemodilution with plasma expander

AimsThis study evaluated the hypothesis that exogenous nitric oxide (NO) supplementation during acute hemodilution with plasma expander (PE) provides beneficial effects on cardiac function.Main methodsAcute hemodilution in golden Syrian hamsters was induced by a 40% of blood volume exchange with dextran 70 kDa. Intravascular NO supplementation after hemodilution was accomplished with a NO donor, diethylenetriamine NONOate (DETA NONOate). The test group was treated with DETA NONOate, while the control group received only vehicle. Left ventricular cardiac function was studied using pressure–volume measurements obtained with a miniaturized conductance catheter.Key findingsCardiac output increased to 122 ± 5% and 107 ± 1% of the baseline in the group treated with NO donor and the vehicle group, respectively. Stroke work per stroke volume (SW/SV) after hemodilution reduced to 90% of the baseline and the NO donor significantly reduced SW/SV compared to the vehicle. The minimum rate of pressure change (dP/dt_min) was significantly lower in animals treated with the NO donor compared to vehicle treated animals. Systemic vascular resistance (SVR) decreased to 62 ± 5% of the baseline in the NO donor group whereas the vehicle group SVR decreased to 83 ± 5% of the baseline. Using intravital microscopy analysis of microvessel in the dorsal skinfold window chamber, we established that the NO donor group induced significant vasodilation compared to the vehicle group.SignificanceNO supplementation in an acute hemodilution with PE has beneficial effects on cardiac performance. However, the NO supplementation effects with a NO donor are dose-independent and short-lasting.     

Validez predictiva del cuestionario VIDA considerando pérdida funcional,institucionalización o muerte en pacientes pluripatológicos

IntroductionThe VIDA Spanish questionnaire assesses instrumental activities of daily living (IADL) in elderly people, and has shown to have adequate content, construct validity, and reliability.The objective was to analyse its predictive validity in patients with multiple morbidities aged ≥ 65 years without severe/total dependence in basic activities (BADL, Barthel index ≥ 60 points), by measuring any changes in this severe/total level of dependence, institutionalisation, or death at 8 and 18 months of follow-up.MethodsA prospective study of a diagnostic test was conducted on 197 patients (8 months) and 185 (18 months) included in the multiple morbidities program according to stratification by Adjusted Clinical Groups (ACG) or by fulfilling the Ollero criteria. Patients that were institutionalised, at the end of life, or on dialysis, or with a baseline Barthel index ≥ 60 points were excluded. The VIDA questionnaire was applied at baseline. The other baseline variables included age, gender, Charlson index, number of drugs, and Lawton-Brody index.The outcome event was changing the Barthel index to < 60, or institutionalisation, or death, in each follow-up period.ResultsThe median age was 81 years (IQR 74.5-85), and 45.2% were women.At 8 months, the best cut-off point for VIDA was ≤ 31 points (Sensitivity [S] 81.5%, [95% CI; 61.2-93.0]; Specificity (Sp) 58.2% [95% CI; 50.4-65.7], PPV 23.7%; NPV 95.2%), ≤ 30 in women, ≤ 34 in men. And at 18 months, ≤ 29 points (S 61.4 [95% CI; 47.6-73.7]; Sp 76.6 [95% CI; 68.1-83.4]; PPV 53.9; NPV 81.7).ConclusionsOverall cut-off points are provided as well as those for gender, predicting severe/total BADL decline, or institutionalization or death in patients with multiple morbidities. It seems to detect short-term events better and rules them out in the long term.     

Role of proinflammatory markers and NT-proBNP in patients with an implantable cardioverter-defibrillator and an electrical storm

BackgroundSeveral studies have attempted to identify risk factors for the development of an electrical storm (ES), which is defined as ⩾3 separate ventricular tachyarrhythmic (VT/VF) events, but in the majority of studies no triggers have been found. However, little is known about the role of inflammation and NT-proBNP in patients with ES. The aim of this study was therefore to assess the relationship of Interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP) and NT-proBNP serum concentrations in ICD-patients with or without single spontaneous ventricular tachyarrhythmic events (VT/VF) and in ES.MethodsMarkers were determined in 51 patients without ICD-intervention, in 15 ICD-patients with single VT/VF-episodes during 9-months follow-up and in 20 ICD-patients with ES (blood sampling performed within 60 min after fulfilling ES criteria). VT/VF-episodes were analysed by stored ICD-electrograms.ResultsAll patients had idiopathic dilated cardiomyopathy (n = 23) or coronary artery disease (n = 63). Patients with ES revealed significantly higher mean serum concentrations of all markers (IL-6 15.19 ± 10.34 pg/mL, hs-CRP 20.12 ± 14.4 mg/L, NT-proBNP 4799 ± 4596 pg/mL) compared to baseline values of patients with single VT/VF-events during follow-up (IL-6 8.37 ± 5.8 pg/mL (p = 0.03), hs-CRP 4.7 ± 5.3 mg/dL (p < 0.001), NT-proBNP 1913 ± 2665 pg/mL (p = 0.04)) and compared to baseline values of ICD-patients without device intervention (IL-6 4.62 ± 3.66 pg/mL (p < 0.001), hs-CRP 4.1 ± 3.4 mg/L (p < 0.001), NT-proBNP 1461 ± 2281 pg/mL (p < 0.001)). In 9/20 patients presenting with ES (45%) baseline values were available. All markers were significantly higher during ES compared to event-free determination (IL-6 14.54 ± 10.43 vs. 7.03 ± 2.83 pg/mL (p = 0.04), hs-CRP 19.07 ± 16.07 vs. 6.5 ± 3.9 mg/L (p = 0.02), NT-proBNP 4218 ± 2561 vs. 2099 ± 1279 pg/mL (p = 0.03)).ConclusionsElectrical storm is associated with significantly elevated IL-6, hs-CRP and NT-proBNP serum concentrations in ICD-patients with structural heart disease. Thus, ES may be triggered by proinflammatory activity. Combined intraindividual elevation of determined markers might help to identify patients at risk of impending electrical storm.     

Serum interleukin-6 concentration reflects the extent of asymptomatic left ventricular dysfunction and predicts progression to heart failure in patients with stable coronary artery disease

BackgroundLeft ventricular ejection fraction (LVEF) remains one of the strongest predictors of long-term prognosis in patients with stable coronary artery disease (CAD). Asymptomatic left ventricular systolic dysfunction (LVSD) often precedes clinically overt heart failure (HF) and is an area of extensive research nowadays. We studied the association between serum IL-6 concentrations and the extent of LV dysfunction in patients with asymptomatic LVSD. We aimed to investigate the diagnostic value of serum IL-6 concentrations in predicting the risk of progression to HF. Seventy-one patients entered the study and were divided into three groups based on LVEF: group 1 – patients with LVEF <30% (N = 7), group 2 – patients with LVEF 30–50% (N = 37) and group 3 – patients with LVEF >50% (N = 27).ResultsDemographics were similar in all three groups. IL-6 concentration was the highest in group 1 (median 8.6 pg/mL) and the lowest in group 3 (median 2.6 pg/mL), whereas IL-6 concentration in group 2 was intermediate (median 3.7 pg/mL) (P = 0.002). We found a significant, inverse correlation between IL-6 concentration and ejection fraction. During 18-month follow-up clinically overt HF developed in 71.4% of patients in group 1 and in 37.5% of patients in group 2. None of the patients in group 3 manifested HF symptoms (P < 0.001). ROC analysis revealed high diagnostic value of serum IL-6 and LVEF in predicting progression to HF. We also found a strong, inverse correlation between IL-6 and the time of progression to HF.ConclusionsThere is a strong correlation between IL-6 and the extent of asymptomatic LVSD in patients with documented CAD. Elevated IL-6 concentrations preceded progression to clinically overt HF. Moreover, the higher the IL-6 concentration the earlier the manifestation of HF symptoms.     

An outpatient-based clinical program for diabetes prevention: an update

ObjectiveTo update outcomes of the Diet-ExerciseActivity-Lifestyle (DEAL) program, a clinic-based diabetes prevention intervention.MethodsChanges in weight, fasting blood glucose, and 2-hour glucose after a 75-g oral glucose tolerance test were evaluated in patients who enrolled in the DEAL program between January 2007 and August 2009.ResultsThe 221 qualified participants had a mean age of 62 years, weight of 87.4 kg, body mass index of 31.2 kg/m², fasting glucose level of 109 mg/dL, and 2-hour glucose value of 138 mg/dL. Among the program participants, 67% were women and 88% were white; 56% had isolated impaired fasting glucose, 5% had impaired glucose tolerance only, and 39% had both. The 6-month follow-up medical appointment was kept by 72% of program participants, but only 56% attended the 12-month visit. By 6 months after baseline, 59% had significantly lower fasting glucose concentrations, 59% had improvement in 2-hour glucose levels, and 61% had weight loss. Nearly 40%, however, were nonresponders and had increased fasting glucose, 2-hour glucose, and weight by 6 months. By the 12-month visit, significant declines in fasting glucose (P < .001), 2-hour glucose (P < .001), and weight (P = .008) occurred in comparison with baseline values; however, no significant changes occurred in these measures between the 6and 12-month visits (P > .30 for all).ConclusionMost DEAL participants showed improvement in glucose levels and weight, but some patients exhibited worsening glucose intolerance. Factors underlying nonresponse need to be identified. Ongoing experience and analysis should help revise the DEAL program so that outcomes for all participating patients will improve. (Endocr Pract. 2012;18:200-208)     

Concomitant Oral Antihyperglycemic Agent Use and Associated Treatment Outcomes After Initiation of Insulin Therapy

ObjectiveTo compare outcomes in patients with type 2 diabetes initiating insulin lispro mix 75/25 (75% insulin lispro protamine suspension and 25% lispro) or insulin glargine therapy, stratified by baseline oral antihyperglycemic agent (OHA) use.MethodsWe performed a post hoc analysis of 6-month data from the DURABLE clinical trial, which enrolled patients with hemoglobin A_1c (A1C) levels > 7.0% treated with 2 or more OHAs (metformin, sulfonylurea, and thiazolidinedione), and randomly assigned them to treatment with twice-daily insulin lispro 75/25 or oncedaily glargine.ResultsIn both insulin treatment groups, metformin/ thiazolidinedione-treated patients had significantly greater improvement in A1C levels (-2.19% to -2.36%), lower end point A1C values, and lower rates of occurrence of hypoglycemia in comparison with metformin/sulfonylurea-treated patients (all P < .05). Patients treated with sulfonylurea/thiazolidinedione or metformin/sulfonylurea/thiazolidinedione did not differ significantly from metformin/sulfonylurea-treated patients in A1C change (-1.56% to -1.84%) or rates of occurrence of hypoglycemia.ConclusionIn these post hoc analyses, patients with type 2 diabetes initiating premixed or basal insulin therapy and treated concomitantly with the OHA combination of metformin/thiazolidinedione at baseline demonstrated significantly greater A1C improvement with less hypoglycemia in comparison with patients treated with metformin/ sulfonylurea. (Endocr Pract. 2011;17:563-567)     

Polymorphisms of endothelial nitric oxide synthase gene in systolic heart failure: an haplotype analysis

BackgroundEndothelial nitric oxide synthase (eNOS) gene polymorphisms have been associated with the pathogenesis of cardiovascular diseases, but few studies have evaluated the role of eNOS haplotypes on the risk and prognosis of heart failure (HF). This prospective study was designed to analyze the impact of three eNOS polymorphisms (T-786C, VNTR4a/b and Glu298Asp) and their haplotypes on the susceptibility and clinical outcomes in HF outpatients with systolic dysfunction.Methods and resultsWe conducted a case-control and a cohort study in which 316 HF patients and 360 healthy controls were recruited from a tertiary care university hospital. DNA was extracted from peripheral blood and eNOS polymorphisms were detected by PCR or PCR-RFLP. Patients were predominantly men, had a mean left ventricular ejection fraction of 31% and were followed-up for a median of 41 months; there were 96 deaths, including 58 HF-related deaths. Genotype distribution of the eNOS T-786C, VNTR 4a/b and Glu298Asp was similar between HF patients and controls. Haplotype frequencies differed between HF patients and controls only in African–Brazilians (p = 0.043). African–Brazilian patients that carried the haplotype -786C/4b/Asp298 had a better prognosis than patients that carried other haplotypes (log rank p value = 0.016 for all-cause mortality). In a Cox proportional hazard model adjusted for clinical variables of risk, the -786C/4b/Asp298 haplotype remained as an independent genetic predictor of survival (adjusted HR = 0.11; 95% CI = 0.01–0.83; p = 0.03).ConclusionsThe -786C/4b/Asp298 eNOS haplotype had a significant impact on HF susceptibility and prognosis, particularly in African–Brazilian patients.     

Effect of dietary selenite on development and intestinal absorption in offspring rats

AimThe present study aims to compare selenium (Se) status in offspring rats born to selenium-deficient and selenium supplemented dams and to analyse Se's influence on intestinal parameters and the intestinal absorption of selenomethionine (Se-Met).Main methodsMale and female Wistar rats (150–200 g) were randomised in: control (C) (0.1 ppm Se), Se-deficient (SD) (0.01 ppm Se) and Se-supplemented (SS) (0.5 ppm Se) groups; and were mated to obtain their offspring. Se levels in serum, urine and faeces in offspring and in mothers' milk were measured by graphite-furnace atomic absorption spectrometry. Duodenal transport studies in offspring were performed using an in vivo perfusion of different Se-Met concentrations (2, 5, 10, 25, 75 and 150 μM).Key findingA Se-deficient diet provoked a decrease in the offspring's body weight and intestinal parameters, while the supplemented diet increased these values. Serum Se levels were similar between Se-deficient and control offspring because the urinary excretion of Se was smaller to compensate for Se homeostasis. Intestinal Se-Met absorption obeys the Michaellis–Menten equation with lower apparent constant (K_m) and maximal velocity (V_max) in the SD group. However, the C and SS groups presented similar K_m and different V_max. The V_max showed greater values in the following order of rank: SS > C > SD groups.SignificanceSelenium intake deficiencies in offspring lead to the development of compensatory mechanisms in order to normalise serum selenium levels. These mechanisms, however, do not permit normal body development; nor do they regulate intestinal parameters and Se-Met transport.     

Propofol decreases the axonal excitability in rat primary sensory afferents

AimsThe aim of this present study was to investigate the changes of peripheral sensory nerve excitability produced by propofol.Main methodsIn a recently described in vitro model of rodent saphenous nerve we used the technique of threshold tracking (QTRAC®) to measure changes of axonal nerve excitability of Aβ-fibres caused by propofol. Concentrations of 10 μMol, 100 μMol and 1000 μMol were tested. Latency, peak response, strength-duration time constant (τSD) and recovery cycle of the sensory neuronal action potential (SNAP) were recorded.Key findingsOur results have shown that propofol decreases nerve excitability of rat primary sensory afferents in vitro. Latency increased with increasing concentrations (0 μMol: 0.96 ± 0.07 ms; 1000 μMol 1.10 ± 0.06 ms, P < 0.01). Also, propofol prolonged the relative refractory period (0 μMol: 1.79 ± 1.13 ms; 100 μMol: 2.53 ± 1.38 ms, P < 0.01), and reduced superexcitability (0 μMol: ? 14.0 ± 4.0%; 100 μMol: ? 9.5 ± 5.5%) and subexcitability (0 μMol: 7.5 ± 1.2%; 1000 μMol: 3.6 ± 1.2) significantly during the recovery cycle (P < 0.01).SignificanceOur results have shown that propofol decreases nerve excitability of primary sensory afferents. The technique of threshold tracking revealed that axonal voltage-gated ion channels are significantly affected by propofol and therefore might be at least partially responsible for earlier described analgesic effects.     

Effect of Metformin Therapy on Vitamin D and Vitamin B12 Levels in Patients with Type 2 Diabetes Mellitus

ObjectiveTo determine the effect of metformin on 25-hydroxyvitamin D [25(OH)D] and vitamin B₁₂ levels in patients with type 2 diabetes mellitus.MethodsWe performed a retrospective review of medical records of patients treated between 2003 and 2009 at Loyola University Medical Center, Maywood, Illinois, in both ambulatory primary care and endocrinology clinics. The study cohort consisted of 706 patients with type 2 diabetes mellitus who were 20 to 93 years old (mean age, 63 ± 13) and had a mean body mass index of 33.1 kg/m². Of these patients, 42% were treated with metformin, and 34% had been diagnosed with osteoporosis or osteopenia.ResultsPatients taking metformin had statistically significant lower vitamin B₁₂ levels than those not receiving metformin (P < .0001; 95% confidence interval [CI] = − 220 to − 84 pg/mL). No statistically significant difference was found between users and nonusers of metformin in regard to 25(OH)D levels when adjusted for variables (P = .297; 95% CI for mean difference = − 0.7 to 2.2 ng/mL). Metformin use did not adversely affect successful treatment of vitamin D deficiency in this patient population as a whole, nor did it affect the subgroup with osteoporosis (P = .956). The patients with osteoporosis had statistically significant lower baseline 25(OH)D levels in comparison with those without osteoporosis, when adjustments were made for all variables (P = .003; 95% CI = 0.7 to 3.5 ng/ mL).ConclusionThis study confirms the higher prevalence of vitamin B₁₂ deficiency in metformin-treated patients with type 2 diabetes than in those not treated with metformin. This study also suggests that vitamin D deficiency is not a clinical concern among metformin-treated patients with type 2 diabetes and that metformin does not negatively affect treatment of vitamin D deficiency in these patients. (Endocr Pract. 2012;18:179–184)     

Plasma renin and aldosterone levels in obese and non-obese women with polycystic ovary syndrome

ObjetiveTo assess plasma renin and aldosterone levels in obese and non-obese women with polycystic ovary syndrome (PCOS).MethodsObese women (body mass index [BMI] > 30 kg/m2; group A, n = 34) and non-obese women (BMI < 25 kg/m2; group B, n = 13) with PCOS were selected. The control group (group C, n =47) consisted of age-matched women with regular menses and normal ultrasonographic ovaries. Luteinizing hormone, follicle-stimulating hormone, androstenedione, testosterone, sex hormone-binding globulin, serum glucose, insulin, renin, plasma renin activity, and aldosterone levels were measured.ResultsObese and non-obese women with PCOS had higher luteinizing hormone, follicle-stimulating hormone, androstenedione, testosterone, and insulin levels as compared to women in the control group (p < 0.05). Women with PCOS had significantly higher renin levels (group A: 50.2 ± 4.9 picoU/mL, group B: 39.9 ± 2.7 picoU/mL, and group C: 24.6 ± 2.6 picoU/mL), plasma renin activity (group A: 3.7 ± 0.3 ng/mL/h, group B: 3.6 ± 0.3 ng/mL/h, and group C: 2.2 ± 0.4 ng/mL/h), and aldosterone levels (group A: 31.2 ± 3.3 ng/dL, group B: 29.3 ± 2.9 ng/dL, and group C: 22.2 ± 3.9 ng/dL) as compared with controls.ConclusionSignificant differences exist in plasma renin and aldosterone levels between obese and non-obese women as compared with polycystic ovary syndrome and normal controls.     

Development and validation of a procedure to isolate viable bone marrow cells from the vertebrae of cadaveric organ donors for composite organ grafting

Background aimsDonor-derived vertebral bone marrow (BM) has been proposed to promote chimerism in solid organ transplantation with cadaveric organs. Reports of successful weaning from immunosuppression in patients receiving directed donor transplants in combination with donor BM or blood cells and novel peri-transplant immunosuppression has renewed interest in implementing similar protocols with cadaveric organs.MethodsWe performed six pre-clinical full-scale separations to adapt vertebral BM preparations to a good manufacturing practice (GMP) environment. Vertebral bodies L4–T8 were transported to a class 10 000 clean room, cleaned of soft tissue, divided and crushed in a prototype bone grinder. Bone fragments were irrigated with medium containing saline, albumin, DNAse and gentamicin, and strained through stainless steel sieves. Additional cells were eluted after two rounds of agitation using a prototype BM tumbler.ResultsThe majority of recovered cells (70.9 ± 14.1%, mean ± SD) were eluted directly from the crushed bone, whereas 22.3% and 5.9% were eluted after the first and second rounds of tumbling, respectively. Cells were pooled and filtered (500, 200 μm) using a BM collection kit. Larger lumbar vertebrae yielded about 1.6 times the cells of thoracic vertebrae. The average product yielded 5.2 ± 1.2 × 10¹⁰ total cells, 6.2 ± 2.2 × 10⁸ of which were CD45⁺ CD34⁺. Viability was 96.6 ± 1.9% and 99.1 ± 0.8%, respectively. Multicolor flow cytometry revealed distinct populations of CD34⁺ CD90⁺ CD117^dim hematopoietic stem cells (15.5 ± 7.5% of the CD34 ⁺ cells) and CD45^? CD73⁺ CD105⁺ mesenchymal stromal cells (0.04 ± 0.04% of the total cells).ConclusionsThis procedure can be used to prepare clinical-grade cells suitable for use in human allotransplantation in a GMP environment.     

Effect of transcatheter renal arterial embolization combined with cryoablation on regulatory CD4+CD25+ T lymphocytes in the peripheral blood of patients with advanced renal carcinoma

ObjectiveTo analyze the effect of Argon-Helium cryosurgery (AHCS) combined with transcatheter renal arterial embolization (TRAE) on the differentiation of regulatory CD4⁺ CD25⁺ T cell (Treg) and its implication in patients with renal carcinoma.MethodsSeventy seven patients are included in the study, and divided into two groups: TRAE group (n = 45, receiving TRAE only) and TRAE + cryoablation group (n = 32, receiving cryoablation 2–3 weeks after TRAE). The percentage of Treg cells and T lymphocyte subsets (CD4⁺T, CD8⁺T, and CD4⁺T/CD8⁺T) in the peripheral blood is measured by flow cytometry previous to the therapy and 3 months after therapy. Meanwhile, the extent of tumor necrosis is measured by MRI or CT 1 month after therapy.ResultsThe percentages of Treg cells of patients in TRAE + cryoablation group decrease from (6.65 ± 1.22)% to (3.93 ± 1.16)%, (t = 42.768, P < 0.01), and the percentages of CD4⁺T and CD4⁺T/CD8⁺T increase significantly (P < 0.01). However, the results of patients in TRAE group show that the percentages of Treg, CD4⁺T, CD8⁺T and CD4⁺T/CD8⁺T increase slightly although the differences had no statistical significance (P > 0.05). The tumor necrosis rate of TRAE + cryoablation group is 57.5%, significantly higher than those of TRAE group, which shows 31.6% (t = 6.784, P < 0.01). The median survival duration of the TRAE + cryoablation group is 20 months, significantly longer than that of the TRAE group (χ² = 7.368, P < 0.01). The decreasing extent of Treg cells is correlated with tumor necrosis rates (r = 0.90, P < 0.01) and life time (r = 0.67, P < 0.01).ConclusionThe therapy of TRAE combined with cryoablation contributes to reduce the percentage of Treg cells and improve the immune situation of patients with renal cell carcinoma, which consequently increase tumor necrosis rate and prolong the patients‘ survival duration.