24-hour Serum Research Articles

Abstract 016: Effect of Dietary Carbohydrate (Amount and Type) on Risk Factors for Cardiovascular Disease and Diabetes: The OmniCarb Trial

Background: Foods that have similar carbohydrate content can differ in the amount they raise blood glucose. The effects of this property, called the glycemic index (GI), on risk factors for cardiovascular disease and diabetes, are not well understood, especially in the context of a healthful dietary pattern that itself improves risk factors. Aims: To study the effects of the amount of dietary carbohydrate (40% vs 58% energy) and GI (40% vs 65% on the glucose scale) on insulin sensitivity (determined by glucose and insulin levels during a 2 hour oral glucose tolerance test), systolic blood pressure (SBP), and fasting lipids (LDL-C, HDL-C, and TG) in non-diabetic, overweight adults with SBP 120 - 159 mmHg. Methods: We randomized 163 adults, mean age 53 y, in a 4 period crossover feeding study. The 4 diets, each studied for 5 weeks, were (1) higher-carbohydrate, higher-GI; (2) higher-carbohydrate, lower-GI; (3) lower-carbohydrate, higher-GI; and (4) lower-carbohydrate, lower-GI. All diets were based on a healthful DASH-type dietary pattern. At the end of each feeding period in a subsample of participants (N=51-57) we obtained hourly blood samples for glucose, insulin, and TG over 12 hours while participants ate the day’s meals in the research facility. Results: The four study diets did not significantly differentially affect insulin sensitivity, LDL-C, or SBP. The lower-carbohydrate or lower-GI diets increased HDL-C by about 4% (with between diet P-values <0.016) and lowered TG by 20% (P<0.031, compared to the higher-carbohydrate, higher-GI diet. Most of these effects were accounted for by lower amount of carbohydrate rather than lower GI. Similarly, the lower carbohydrate or lower GI diets lowered 12-hour blood glucose by an average of 20% (P<0.031) compared to the higher carbohydrate, higher GI diet. The lower-carbohydrate, lower-GI diet reduced 12-hour serum insulin levels the most by 17% (P=0.032). Compared to levels measured when the participants were eating their own diets, all study diets lowered SBP by an average of 9 mm (7%) and LDL-C by 13 mg/dL (9%). Conclusions: In the context of healthful dietary patterns, varying the amount of carbohydrate or its GI in non-diabetic overweight adults does not affect fasting insulin sensitivity, SBP or LDL-C over 5 weeks. HDL-C and triglycerides improved on the lower carbohydrate diets but were not affected by GI. However, postprandial glycemia is reduced either by lowering GI or amount of carbohydrate, and hyperinsulinemia is reduced by the combination of low GI and low carbohydrate. We speculate that consistent associations in populations of reduced CVD event rates with lower intakes of carbohydrate and GI, if causal, result more from reduced postprandial glycemia and hyperinsulinemia than from lower BP and improved lipid risk factors.

2-Hour postload serum glucose levels and maternal blood pressure as independent predictors of birth weight in "appropriate for gestational age" neonates in healthy nondiabetic pregnancies.

Introduction. Increased neonatal birth weight (NBW), often associated with diabetic pregnancies, is a recognized indicator of childhood obesity and future metabolic risk. Predictors of NBW in healthy non-diabetic pregnancies are not yet established. Here, we investigated the association of maternal parameters of healthy non-diabetic mothers with NBW of their “appropriate-for-gestational age” neonates. Methods. The study involved 36 healthy mother/infant pairs. Examined parameters included NBW, maternal age, first and last trimester (BMI), weight gain, fasting serum lipids and glucose, 2-hour postload glucose levels and blood pressure. Results. Postload-glucose levels were significantly higher in mothers of heavier neonates. ANOVA results indicated that 15% increase in postload-glucose levels corresponded to more than 0.5 Kg increase in NBW in the third tertile. NBW correlated positively with postload glucose levels, and negatively with systolic blood pressure. Regression analysis showed that the main predictors of NBW were postload-glucose levels (B = 0.455, P = 0.003), followed by systolic blood pressure (B = −0.447, P = 0.004), together predicting 31.7% NBW variation. Conclusion. This study highlights that increased maternal postload sugar levels and blood pressure, within the normal range, highly predicts NBW of healthy mothers. These findings may provide focus for early dietary intervention measures to avoid future risks to the mother and baby.

Influence of Renal and Hepatic Impairment on the Pharmacokinetic and Pharmacodynamic Properties and Tolerability of Fluticasone Furoate and Vilanterol in Combination

BackgroundRenal and hepatic disease may lead to alterations in drug absorption, distribution, and elimination, and, therefore, the potential effect of renal and hepatic impairment should be investigated in drugs under development. ObjectiveTo assess the effects of renal and hepatic impairment on the pharmacokinetic and pharmacodynamic properties and tolerability of fluticasone furoate/vilanterol (FF/VI) administered in combination. MethodsTwo open-label, parallel-group studies were conducted. Eligible study participants included adults with severe renal impairment (CrCl <30 mL/min) and those with mild, moderate, or severe hepatic impairment (by Child-Pugh classification). Patients were matched with healthy subjects. Participants received 7 days of inhaled FF/VI 200/25 or 100/12.5 μg (severe hepatic impairment only) once daily in the morning. Lack of effect was defined as an upper 90% confidence limit of the Cmax and AUC geometric mean impaired:healthy ratios (GMRs) of <2. ResultsStudy participants included patients with severe renal impairment (n = 9) or with mild (n = 9), moderate (n = 9), or severe (n = 8) hepatic impairment, together with matched healthy subjects (n = 9 per study). Lack of effect of severe renal impairment was demonstrated with FF (GMRs [90% CI]: Cmax, 0.96 [0.57–1.61]; AUC0–24, 0.91 [0.60–1.38]) and VI (Cmax, 0.70 [0.49–1.00]; AUC0–24, 1.56 [1.27–1.92]). Day-7 dose-normalized FF AUC0–24 was greater in the groups with mild, moderate, and severe hepatic impairment than in healthy subjects (GMRs [90% CI]: 1.34 [0.82–2.20], 1.83 [1.11–2.99], and 1.75 [1.05–2.91], respectively); lack of effect was not demonstrated. There was no effect of hepatic impairment on dose-normalized VI Cmax or AUC0–24. Apart from reduced serum cortisol weighted mean (0–24 hour) in patients with moderate hepatic impairment (34% reduction [90% CI, 11%–51%] compared with healthy subjects), there was no evidence of a difference in heart rate, serum potassium, or 24-hour serum cortisol between patients with severe renal impairment of any hepatic impairment and healthy subjects. No safety concerns were identified in any of the groups with impairment or their matched healthy controls. ConclusionsSevere renal impairment had no apparent clinically relevant effects on the pharmacokinetic or pharmacodynamic properties or tolerability of FF/VI. Hepatic impairment had no apparent effect on VI systemic exposure but increased FF exposure. Fluticasone furoate was associated with reduced serum cortisol in patients with moderate hepatic impairment. These data suggest that caution should be exercised when prescribing FF/VI in patients with moderate or severe hepatic impairment due to a risk for unwanted systemic corticosteroid effects associated with increased FF systemic exposure. Clinicaltrials.gov identifiers: NCT01266941 and NCT01266980.

Once-daily treatment with beclomethasone dipropionate nasal aerosol does not affect hypothalamic-pituitary-adrenal axis function

BackgroundIntranasal corticosteroids are effective in controlling allergic rhinitis (AR) symptoms; however, chronic administration of corticosteroids may suppress hypothalamic-pituitary-adrenal (HPA)-axis function. ObjectiveTo evaluate the effects of 6 weeks of treatment with beclomethasone dipropionate (BDP) hydrofluoroalkane nasal aerosol on HPA-axis function in subjects with perennial AR (PAR). MethodsIn this randomized, double-blind, placebo- and active-controlled study, subjects aged 12 to 45 years were randomized to receive BDP nasal aerosol 320 μg/day (n = 50), placebo (n = 46), or placebo/prednisone (prednisone 10 mg/day for the last 7 days of the treatment period [n = 11]). The primary end point was change from baseline in 24-hour serum cortisol (SC) weighted mean (expressed as geometric mean ratio [GMR]) in the BDP and placebo group after 6 weeks of treatment. ResultsGeometric SC-weighted mean values were similar in the BDP and placebo groups at baseline (9.04 and 8.45 μg/dL, respectively) and after 6 weeks (8.18 and 8.01 μg/dL, respectively). After 6 weeks of treatment, BDP was noninferior to placebo with respect to the ratio from baseline in SC-weighted mean (GMR: 0.96 [95% CI: 0.87, 1.06]). In contrast, 7 days of prednisone treatment substantially reduced geometric SC-weighted mean values from baseline (approximate 3-fold reduction [from 7.33 to 2.31 μg/dL]) compared with placebo. BDP nasal aerosol was well tolerated, and the safety profile was similar to that of placebo. ConclusionTreatment with BDP nasal aerosol, 320 μg once daily, was not associated with HPA-axis suppression in adolescent and adult subjects with PAR. Trial RegistrationClinicaltrials.gov Identifier: NCT01133626.

Effect of Once-Daily Fluticasone Furoate/Vilanterol on 24-Hour Pulmonary Function in Patients With Chronic Obstructive Pulmonary Disease: A Randomized, Three-Way, Incomplete Block, Crossover Study

BackgroundAvailable inhaled corticosteroid/long-acting β2-agonist combinations for chronic obstructive pulmonary disease (COPD) require twice-daily administration. The combination of fluticasone furoate (FF) and vilanterol (VI) FF/VI is being developed in a novel dry powder inhaler for the treatment of COPD and asthma with the potential for once-daily dosing. Results from Phase II studies have shown clinically and statistically significant improvements over placebo in trough (24-hour postdose) forced expiratory volume in 1 second (FEV1) after once-daily dosing with FF or VI (VI concurrently with an inhaled corticosteroid) in asthma and VI in COPD. ObjectivesThis Phase III, multicenter, randomized, double-blind, placebo-controlled study was designed based on guidance from drug regulators with the goal of evaluating the 24-hour spirometric effect of once-daily FF/VI in patients with COPD. MethodsPatients (aged ≥40 years) who completed a 2-week placebo run-in period were randomized to 1 of 18 three-course sequences of placebo and 2 of 3 dose combinations of FF/VI (50/25 μg, 100/25 μg, and 200/25 μg), dosed once daily in the morning. Each 28-day treatment period was separated by a 2-week, single-blind, placebo washout period. The primary end point was time-adjusted (weighted mean) 0 to 24-hour FEV1 (AUC) at the end of each 28-day treatment period (period days 28–29). Safety profile assessments included incidence of adverse events (AEs) (defined according to the Medical Dictionary for Regulatory Activities), 12-lead ECG outputs, vital signs (pulse rate, diastolic and systolic blood pressure) and clinical laboratory assessments (including fasting serum glucose and potassium) and 24-hour serum cortisol. The pharmacokinetics of FF and VI were assessed at the end of each 28-day treatment period with FF/VI. ResultsEighty-seven patients were screened; 54 completed run-in and were randomized to double-blind treatment. The mean patient age was 57.9 years, and 46% were male. The majority of patients were current smokers (83%) and were receiving short-acting β2-agonists within the 3 months before screening (63%). All 3 strengths of once-daily FF/VI demonstrated significantly higher 0 to 24-hour (period days 28–29) change from period baseline weighted mean FEV1 than placebo: adjusted mean improvements from placebo in FEV1 for FF/VI were 220 to 236 mL (all, P < 0.001). Improvements versus placebo in change from period baseline serial FEV1 measures were observed at each time-point and with each strength of FF/VI over the 0 to 25-hour period (period days 28–29), indicating sustained bronchodilation. The overall incidence of on-treatment AEs was low (10%–12% with FF/VI; 4% with placebo); 2 serious AEs were reported during washout periods (1 AE after FF/VI 50/25 μg and 1 AE after placebo) but neither was considered treatment related. No serious AEs were reported during the treatment periods or during the follow-up period. No clinically or statistically significant differences from placebo were reported for serum glucose or potassium. No significant effects on vital signs, ECG, or 24-hour serial serum cortisol were reported. The extent of systemic exposure to FF and VI at steady state was low for all strengths of FF/VI. ConclusionsFF/VI inhaled once daily in the morning for 28 days produced significant improvements in pulmonary function with a prolonged (>24 hours') duration of action in this population of patients with COPD. The combination was well tolerated. ClinicalTrials.gov identifier: NCT01072149.

The Application of Serum Cystatin C in Estimating the Renal Function in Women With Preeclampsia

Serum cystatin C (Cys-C) is known to reflect the glomerular filtration rate (GFR) more precisely in native kidney diseases and renal dysfunctions secondary to other diseases. This study investigated the serum Cys-C in estimating the renal function in preeclamptic women. A total of 96 patients with normal pregnancy (controls) and 48 cases of severe preeclampsia were recruited in this study. We measured the 24-hour creatinine clearance (CrCl), serum creatinine, Cys-C, uric acid (UA), and beta trace protein (BTP) concentrations on all the pregnant women in the second trimester and third trimester and in the postpartum of the patients with severe preeclampsia. Multiple comparisons and correlation analysis were used to analyze the indexes estimating the GFR. In the normal pregnancies, the concentrations of serum creatinine, UA, and BTP were significantly higher in the third trimester compared to the second trimester, however with no significant differences in the serum Cys-C levels. Comparison between the second and third trimester in patients with severe preeclampsia indicated that significant difference existed in the serum Cys-C, with higher concentration in third trimester. Correlation analyses demonstrated that significant negative correlations could be detected between Cys-C and 24-hour CrCl in the second trimester and third trimester of all the 144 pregnant women and in the postpartum of the patients with severe preeclampsia, and better correlations in normal participants than in participants with preeclampsia. Serum Cys-C seems to reflect the GFR precisely in women with severe preeclampsia and can be a good marker to monitor the renal function from antepartum to postpartum.

Effects of Sleep Restriction on Glucose Control and Insulin Secretion During Diet‐Induced Weight Loss

Insufficient sleep is associated with changes in glucose tolerance, insulin secretion, and insulin action. Despite widespread use of weight-loss diets for metabolic risk reduction, the effects of insufficient sleep on glucose regulation in overweight dieters are not known. To examine the consequences of recurrent sleep restriction on 24-hour blood glucose control during diet-induced weight loss, 10 overweight and obese adults (3F/7M; mean [SD] age 41 [5] y; BMI 27.4 [2.0] kg/m2) completed two 14-day treatments with hypocaloric diet and 8.5 or 5.5-h nighttime sleep opportunity in random order 7 [3] months apart. Oral and intravenous glucose tolerance test (IVGTT) data, fasting lipids and free-fatty acids (FFA), and 24-hour blood glucose, insulin, C-peptide, and counter-regulatory hormone measurements were collected after each treatment. Participants had comparable weight loss (1.0 [0.3] BMI units) during each treatment. Bedtime restriction reduced sleep by 131 [30] min/day. Recurrent sleep curtailment decreased 24-hour serum insulin concentrations (i.e. enhanced 24-hour insulin economy) without changes in oral glucose tolerance and 24-hour glucose control. This was accompanied by a decline in fasting blood glucose, increased fasting FFA which suppressed normally following glucose ingestion, and lower total and LDL cholesterol concentrations. Sleep-loss-related changes in counter-regulatory hormone secretion during the IVGTT limited the utility of the test in this study. In conclusion, sleep restriction enhanced 24-hour insulin economy without compromising glucose homeostasis in overweight individuals placed on a balanced hypocaloric diet. The changes in fasting blood glucose, insulin, lipid and FFA concentrations in sleep-restricted dieters resembled the pattern of human metabolic adaptation to reduced carbohydrate availability.

Pharmacokinetics of Modified Slow‐Release Oral Testosterone Over 9 Days in Normal Men With Experimental Hypogonadism

Oral administration of testosterone has potential use for the treatment of hypogonadism. We have recently demonstrated that a novel formulation of oral testosterone transiently normalized serum testosterone in a single-dose pharmacokinetic study. In this report, we present the steady-state pharmacokinetics of this formulation. Twelve healthy young men were rendered hypogonadal with the gonadotropin-releasing hormone antagonist acyline (300 μg/kg subcutaneously) and administered 300 mg of oral testosterone 3 times daily for 9 days. Serum testosterone, dihydrotestosterone (DHT), estradiol, and sex hormone-binding globulin (SHBG) were measured before and 1, 2, 4, 5, 6, 8, 10, 11, 12, 14, 16, and 24 hours on the first and ninth day of dosing. Before testosterone administration, all men had serum testosterone under 75 ng/dL. Over day 1, the 24-hour average (geometric mean [%CV]) serum total testosterone was 378 (45) ng/dL. This decreased to 315 (41) ng/dL after 9 days of continuous treatment (P = .1 compared with day 1). The 24-hour average serum SHBG was 27 (46) nmol/L on day 1 and was significantly reduced to 19 (47) nmol/L by day 9 (P < .01). As a result, the calculated free testosterone values were similar between day 1 and day 9: 8.7 (43) and 8.3 (37) ng/dL, respectively. DHT was in the reference range and estradiol was slightly below on day 9. Oral testosterone (300 mg) dosed 3 times daily normalized serum testosterone in men with experimentally induced hypogonadism after 9 days of dosing and significantly suppressed SHBG. This formulation of oral testosterone may have efficacy for the treatment of testosterone deficiency.

Abstract 5486: Reliability of biomarkers of inflammation from repeated measures in healthy individuals

Abstract Biomarkers of low-grade systemic inflammation are used to study the associations of inflammation with chronic diseases, including cancers. However, little is known about the reliability (i.e., intraindividual variability) of most of these measures. Fasting (12-hour) serum samples, which were collected at the end of ≥3 week washout periods in a 4-diet crossover feeding trial, were used to measure the inflammatory markers hsCRP, IL-6, TNF-α, IL-8 and sTNFRI and II. Participants included 32 men and 31 women (5 men and 2 women were missing from analyses of IL-8, TNF-α, and sTNFR I and II), aged 20-40, who were free of factors known to influence inflammation, e.g., chronic disease, medication use, heavy alcohol use, smoking and obesity (body mass index &amp;gt;30 kg/m2). Intraclass correlations (ICC) were estimated using random effects analysis of variance, across all 4 time points (∼5 weeks apart). For TNF-α and sTNFRI &amp; II, the ICCs were very high (ICC= 0.92, 95% CI: 0.89 - 0.96; 0.92, 95% CI: 0.88 - 0.95; and 0.90, 95% CI: 0.85 - 0.94, respectively). The ICCs for IL-8 and hsCRP were 0.73 (95% CI: 0.63-0.83 and 0.68 (95% CI: 0.58-0.78), respectively. The ICC for IL-6 was considerably lower, (ICC = 0.48, 95% CI: 0.36-0.62). With the exception of IL-6, reliability of all inflammatory markers in our panel over 4 time points was high, suggesting that a single measure accurately captures the variability within an individual and is a good measure for use in epidemiologic studies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5486. doi:1538-7445.AM2012-5486

Abstract P070: The Relationship Between Weight and Fruit and Vegetable Consumption, Assessed by Serum Carotenoids and Self-Report: Results from the PREMIER Trial

Background: Increased intake of fruits and vegetables (F/V) may protect against adiposity, but effects on weight have been inconsistent. Our objective was to examine the relationship between fruit and vegetable intake and weight, using direct and indirect measures of dietary intake: self-reported 24-hour recall and serum carotenoid levels. Methods: Participants from the PREMIER lifestyle intervention trial were included in this analysis (n=554). Dietary measures included 24-hour dietary recalls and serum carotenoid levels, from a fasting blood sample. The outcome was weight in pounds. Nested linear mixed models were used to examine the association between F/V and weight. Results: Mean F/V increased from 4.6 (SD 2.4) to 5.6 (SD 3.2) (p=&lt;.01), mean serum carotenoids increased from 53.2 (SD 31.9) to 68.1 (SD 42.5) (p=&lt;.01). At 18 months, participants in the lowest quintile of fruit and vegetable change reported an average intake of 4.42.8 servings of fruits and vegetables, and those in the highest quintile of change reported an average intake of 7.73.2 servings. In a multivariate model adjusting for age, race, gender, intervention, energy, study site, and time, lower body weight was associated with higher F/V intake measured by dietary recall (−0.63 lbs, 95% CI −0.83 to −0.42, per 1 serving increase in F/V) and serum carotenoids (−0.13 lbs, 95% CI −0.15 to −0.11, per 1 ug/dl increase in carotenoids). Results were somewhat attenuated but consistent after additional adjustments for working heart rate, exercise, calories from sugar-sweetened beverages, marital and employment status, and alcohol use . Conclusions: Greater fruit and vegetable consumption was associated with decreased body weight. Results were consistent for both objective and self-reported measures of fruit and vegetable intake.

Moderate glucose control results in less negative nitrogen balances in medical intensive care unit patients: a randomized, controlled study

IntroductionHyperglycemia and protein loss are common in critically ill patients. Insulin can be used to lower blood glucose and inhibit proteolysis. The impact of moderate insulin therapy on protein metabolism in critically ill patients has not been evaluated. We compared urinary nitrogen excretion, nitrogen balance, serum albumin concentrations, prealbumin concentrations, and clinical outcomes between patients receiving moderate insulin therapy (MIT) and conventional insulin therapy (CIT) in a medical ICU.MethodsPatients were randomly divided into groups and treated with MIT (glucose target 120 to 140 mg/dl) or CIT (glucose target 180 to 200 mg/dl). Calories and protein intake were recorded each day. On days 3, 7 and 14, the 24-hour urinary nitrogen excretion, nitrogen balance, and serum albumin and prealbumin concentrations were measured. Clinical outcomes data were collected.ResultsA total of 112 medical ICU patients were included, with 55 patients randomized to the MIT group and 57 patients randomized to the CIT group. Patients treated with MIT showed a trend towards increased nitrogen balance (P = 0.070), significantly lower urinary nitrogen excretion (P = 0.027), and higher serum albumin (P = 0.047) and prealbumin (P = 0.001) concentrations than patients treated with CIT. The differences between the two groups were most significant on day 3, when all factors showed significant differences (P < 0.05).ConclusionsModerate glucose control results in less negative nitrogen balances in medical ICU patients. Differences are more significant in the early stages compared with the late stages of critical illness.Trial registrationClinicalTrial.Gov NCT 01227148

Diagnosing Growth Hormone Deficiency in Adults

Adult growth hormone (GH) deficiency is a recognised syndrome associated with adverse phenotypic, metabolic, and quality-of-life features which improve in many patients when GH is substituted. The appropriate selection of patients at risk of growth hormone deficiency (GHD) is the crucial first step in arriving at a correct diagnosis. Although multiple diagnostic modalities are available including a 24-hour serum GH profile, stimulated GH levels, and insulin-like growth factor-1 (IGF-1) levels, the use of dynamic tests for GH reserves is required in most cases. This paper discusses the utility and drawbacks of the various testing modalities with reference to international guidelines. Regardless of the test chosen, clinical pitfalls including age and obesity must be taken into account. In addition, there is considerable analytical variation in the biochemical measurements of GH and IGF-1 which must be considered before making a diagnosis of GHD in adulthood.

Accuracy of a Novel Non-Invasive technology based EZSCAN system for the diagnosis of diabetes mellitus in Chinese

BackgroundA new simple technique based on iontophoresis technology (EZSCAN, Impeto Medical, Paris, France) has recently been developed for the screening of diabetes. In the present study, we investigated the accuracy of this system for the diagnosis of diabetes mellitus in Chinese.MethodsWe performed the EZSCAN test in diabetic and non-diabetic subjects. EZSCAN measures electrochemical conductance (EC) at forehead, hands and feet, and derives a diabetes index with a value ranging from 0 to 100. Diabetes mellitus was defined as a plasma glucose concentration of at least 7 mmol/l at fasting or 11.1 mmol/l at 2 hours after glucose load, or as the use of antidiabetic drugs.ResultsThe 195 study participants (51% men, mean age 52 years) included 75 diabetic patients (use of antidiabetic drugs 81%) and 120 non-diabetic subjects. EC (micro Siemens, μSi) was significantly (P < 0.001) lower in diabetic patients at the hands (44 vs. 61) and feet (51 vs. 69) locations, but not at the forehead (15 vs. 17, P = 0.39). When a diabetes index of 40 (suggested by the manufacturer) was used as the threshold, the sensitivity and specificity for the diagnosis of diabetes mellitus was 85% and 64%, respectively. In 80 patients who underwent an oral glucose tolerance test, EC at hands and feet and the diabetes index were significantly (P < 0.001) associated with both 2-hour post-load plasma glucose and serum glycosylated haemoglobin.ConclusionsEZSCAN might be useful in screening diabetes mellitus with reasonable sensitivity and specificity.

Safety and efficacy of Rituximab in refractory pediatric systemic lupus erythematosus nephritis: a single-center experience of Northern Greece

Lupus nephritis (LN) is the major determinant of outcome in pediatric systemic lupus erythematosus (pSLE), and its treatment remains a challenge. The aim of this study was to report the experience of our center in treating with rituximab (RTX) SLE patients with severe LN. Four pSLE patients with biopsy-proven LN, who are refractory to conventional immunosuppressive treatment, received four doses of 375-500 mg/m(2) RTX, 2-3 weeks apart. All patients were concurrently receiving corticosteroids (CSs) and mycophenolate mofetil. Patients' clinical and laboratory findings were recorded at RTX initiation, after each infusion and at 3.4 ± 2.1 month intervals thereafter. pSLE activity was assessed using the European Consensus Lupus Activity Measurement (ECLAM), while LN activity using 24-hour urine protein excretion and serum cystatin C. Patients were followed up for 6-21 months (median: 16 months). Full Β-cell depletion was noticed 2-4 weeks after RTX initiation and lasted 4-7 months. All patients achieved complete LN remission 3.5 months (range: 2-4) after RTX initiation, which was retained in 3 patients through the follow-up period. One patient relapsed 15 months after RTX initiation and received one additional RTX dose. ECLAM scores and CSs doses were markedly reduced in all patients, while complement levels were increased. No side effects or infections were observed. In conclusion, RTX is an alternative, safe and efficient treatment for refractory LN.

Prevalence and Metabolic Abnormalities of Vitamin D–inadequate Patients Presenting With Urolithiasis to a Tertiary Stone Clinic

To assess the prevalence and metabolic abnormalities of patients with inadequate vitamin D (VD) presenting with urolithiasis to a tertiary stone clinic in North America. A retrospective review of consecutive patients presenting from August 2009 to January 2010 was performed. Demographic and clinical data were collected together with metabolic stone workup, including 2 24-hour urine collections and serum 25-hydroxy VD [25(OH)D]. VD inadequacy (VDI) included VD deficiency and VD insufficiency defined as 25-(OH) VD levels <20 ng/mL and 21-29 ng/mL, respectively. Of 101 patients, 81 (80.2%) were found to have VDI: 34 (33.7%) were deficient and 47 (46.5%) had insufficient VD. Mean age was 50.4 ± 15.8 years and the mean body mass index was 28.7 ± 5.8 kg/m(2). Forty-two percent were smokers, 51% were recurrent stone formers, and 54% had positive family history of urolithiasis. Hyperparathyroidism was detected in 25.9% of patients, of which 91% of them were secondary to VDI. Hypocalcemia and hyperuricemia were found in 36% and 11% of patients, respectively. Of 81 VDI patients, 69 (85.2%) had complete 24-hour urine collections, of which 92.7% had at least one abnormality. However, only 40% of patients with normal VD had metabolic abnormalities (P <.0001). The most prevalent pattern of urinary abnormalities in VDI patients were suboptimal volume (45%), hypocitaturia (24%), hypocalciuria (33%), hypercalciuria (20%), hyperuricosuria (16%), cystinuria (5%), and hyperoxaluria (7.2%). In this preliminary study, patients presenting with urolithiasis were found to have a high prevalence of inadequate VD associated with abnormalities on metabolic stone work-up.

Angiotensin II induces nephrin dephosphorylation and podocyte injury: Role of caveolin-1

Nephrin, an important structural and signal molecule of podocyte slit-diaphragm (SD), has been suggested to contribute to the angiotensin II (Ang II)-induced podocyte injury. Caveolin-1 has been demonstrated to play a crucial role in signaling transduction. In the present study, we evaluated the role of caveolin-1 in Ang II-induced nephrin phosphorylation in podocytes. Wistar rats-receiving either Ang II (400ng/kg/min) or normal saline (via subcutaneous osmotic mini-pumps, control) were administered either vehicle or telmisartan (3mg/kg/min) for 14 or 28days. Blood pressure, 24-hour urinary albumin and serum biochemical profile were measured at the end of the experimental period. Renal histomorphology was evaluated through light and electron microscopy. In vitro, cultured murine podocytes were exposed to Ang II (10−6M) pretreated with or without losartan (10−5M) for variable time periods. Nephrin and caveolin-1 expression and their phosphorylation were analyzed by Western-blotting and immunofluorescence. Caveolar membrane fractions were isolated by sucrose density gradient centrifugation, and then the distribution and interactions between Ang II type 1 receptor (AT1), nephrin, C-terminal Src kinase (Csk) and caveolin-1 were evaluated using Western-blotting and co-immunoprecipitation. Podocyte apoptosis was evaluated by cell nucleus staining with Hoechst-33342.Ang II-receiving rats displayed diminished phosphorylation of nephrin but enhanced glomerular/podocyte injury and proteinuria when compared to control rats. Under control conditions, podocyte displayed expression of caveolin-1 in abundance but only a low level of phospho moiety. Nonetheless, Ang II stimulated caveolin-1 phosphorylation without any change in total protein expression. Nephrin and caveolin-1 were co-localized in caveolae fractions. AT1 receptors and Csk were moved to caveolae fractions and had an interaction with caveolin-1 after the stimulation with Ang II. Transfection of caveolin-1 plasmid (pEGFPC3-cav-1) significantly increased Ang II-induced nephrin dephosphorylation and podocyte apoptosis. Furthermore, knockdown of caveolin-1 expression (using siRNA) inhibited nephrin dephosphorylation and prevented Ang II-induced podocyte apoptosis. These findings indicate that Ang II induces nephrin dephosphorylation and podocyte injury through a caveolin-1-dependent mechanism.

Predictors of Impaired Glucose Regulation in Patients with Non-Alcoholic Fatty Liver Disease

Introduction. Many patients with non-alcoholic fatty liver disease (NAFLD) have impaired glucose regulation or type 2 diabetes mellitus (DM). We investigated characteristics of NAFLD patients associated with hyperglycemia. Methods. During a 2-hour oral glucose tolerance test (OGTT), serum glucose and insulin were measured in 152 NAFLD patients. Results. 48.7% of NAFLD patients had hyperglycemia. Age (odds ratio (OR) = 1.08, 95% confidence interval (CI): 1.03–1.13), body mass index (BMI) (OR = 1.12, 95% CI: 1.01–1.25), and lower high-density lipoprotein cholesterol (HDL-C) (OR = 0.95, 95% CI: 0.92–0.98) proved to be independent predictors of hyperglycemia. After OGTT, 30 min insulin was lower in hyperglycemic patients (74.2 ± 49.7 versus 94.5 ± 53.9 μIU/mL, P = 0.02), while 90 min insulin (170.1 ± 84.6 versus 122.9 ± 97.7 μU/mL, P = 0.01) and 120 min insulin (164.0 ± 101.2 versus 85.3 ± 61.9 μIU/mL, P < 0.01) were higher. Conclusions. NAFLD patients with higher BMI, lower HDL-C, or older age were more likely to have impaired glucose metabolism. An OGTT could be of value for early diagnosis of DM among this population.

Safety and efficacy of rituximab in refractory pediatric Systemic Lupus Erythematosus nephritis: a single-center experience of northern Greece

Lupus nephritis (LN) is the major determinant of outcome in pediatric systemic lupus erythematosus (pSLE), and its treatment remains a challenge. The aim of this study was to report the experience of our center in treating with rituximab (RTX) SLE patients with severe LN. Four pSLE patients with biopsy-proven LN, who are refractory to conventional immunosuppressive treatment, received four doses of 375-500 mg/m(2) RTX, 2-3 weeks apart. All patients were concurrently receiving corticosteroids (CSs) and mycophenolate mofetil. Patients' clinical and laboratory findings were recorded at RTX initiation, after each infusion and at 3.4 ± 2.1 month intervals thereafter. pSLE activity was assessed using the European Consensus Lupus Activity Measurement (ECLAM), while LN activity using 24-hour urine protein excretion and serum cystatin C. Patients were followed up for 6-21 months (median: 16 months). Full Β-cell depletion was noticed 2-4 weeks after RTX initiation and lasted 4-7 months. All patients achieved complete LN remission 3.5 months (range: 2-4) after RTX initiation, which was retained in 3 patients through the follow-up period. One patient relapsed 15 months after RTX initiation and received one additional RTX dose. ECLAM scores and CSs doses were markedly reduced in all patients, while complement levels were increased. No side effects or infections were observed. In conclusion, RTX is an alternative, safe and efficient treatment for refractory LN.

Correlation of Occupational Stress Index with 24-hour Urine Cortisol and Serum DHEA Sulfate among City Bus Drivers: A Cross-sectional Study

ObjectivesThe questionnaire of occupational stress index (OSI) has been popular in the workplace, and it has been tailored for bus drivers in Taiwan. Nevertheless, its outcomes for participants are based on self-evaluations, thus validation by their physiological stress biomarker is warranted and this is the main goal of this study.MethodsA cross-sectional study of sixty-three city bus drivers and fifty-four supporting staffs for comparison was conducted. Questionnaire surveys, 24-hour urine cortisol testing, and blood draws for dehydroepiandrosterone-sulfate (DHEA-S) testing were performed. The measured concentrations of these biological measures were logarithmically transformed before the statistical analysis where various scores of stressor factors, moderators, and stress effects of each OSI domain were analyzed by applying multiple linear regression models.ResultsFor drivers, the elevated 24-hour urine cortisol level was associated with a worker's relationship with their supervisor and any life change events in the most recent 3 months. The DHEA-S level was higher in drivers of younger age as well as drivers with more concerns relating to their salary and bonuses. Non-drivers showed no association between any stressor or satisfaction and urine cortisol and blood DHEA-S levels.ConclusionMeasurements of biomarkers may offer additional stress evaluations with OSI questionnaires for bus drivers. Increased DHEA-S and cortisol levels may result from stressors like income security. Prevention efforts towards occupational stress and life events and health promotional efforts for aged driver were important anti-stress remedies.

Pregnancy Reduces the Accuracy of the Estimated Glomerular Filtration Rate Based on Cockroft-Gault and MDRD Formulas

This study aims to determine the effect of pregnancy on the accuracy of 3 commonly used methods to estimate glomerular filtration rate ([GFR] creatinine clearance, the Cockroft-Gault, and modification of diet in renal disease [MDRD] formulas) using the inulin clearance as a reference. Longitudinal study design. University hospital. A total of 44 parous nonsmoking Caucasian women. They had a history of uneventful pregnancy (n = 9), preeclampsia (n = 27), and intrauterine fetal demise (n = 8). Measurements were performed both in pre-pregnancy and early pregnancy (8 weeks of gestation) and included inulin infusion, blood pressure, and 24-hour urinary and serum creatinine. Agreement between methods to estimate GFR was assessed by the Bland and Altman method. GFR estimated by inulin and creatinine clearances and the Cockroft-Gault and MDRD formulas. During early pregnancy, the GFR measured by inulin increased 32% compared with the pre-pregnant value (from 115 ± 18 to 150 ± 23 mL/min·1.73 m(-2)), whilst the GFR measured by the indirect methods only increased 20%. The observed bias and limits of agreements are larger in early pregnancy relative to the pre-pregnant state for all 3 methods. The renal hyperfiltration during pregnancy decreases further the accuracy of the creatinine clearance and the Cockroft-Gault and MDRD formulas to estimate GFR.