24-h Area Under The Curve Research Articles

Genetic predisposition and high exposure to colistin in the early treatment period as independent risk factors for colistin-induced nephrotoxicity.

Colistin is known to cause nephrotoxicity due to its extensive reabsorption and accumulation in renal tubules. Invitro studies have identified the functional role of colistin transporters such as OCTN2, PEPT2, megalin, and P-glycoprotein. However, the role of these transporter gene variants in colistin-induced nephrotoxicity has not been studied. Utilizing targeted next-generation sequencing, we screened for genetic polymorphisms covering the colistin transporters (SLC15A1, SLC15A2, SLC22A5, LRP2, and ABCB1) in 42 critically ill patients who received colistimethate sodium. The genetic variants rs2257212 ((NM_021082.4):c.1048C>G) and rs13397109 ((NM_004525.3):C.7626C > T) were identified as being associated with an increased incidence of acute kidney injury (AKI) on Day 7. Colistin area under the curve (AUC) was predicted using a previously published pharmacokinetic model of colistin. Using logistic regression analysis, the predicted 24-h AUC of colistin was identified as an important contributor for increased odds of AKI on Day 7. Among 42 patients, 4 (9.5%) were identified as having high predisposition to colistin-induced AKI based on the presence of predisposing genetic variants. Determination of the presence of the abovementioned genetic variants and early therapeutic drug monitoring may reduce or prevent colistin-induced nephrotoxicity and facilitate dose optimization of colistimethate sodium.

Comparison between costotransverse foramen block and thoracic paravertebral block for VATS pulmonary resection: A randomized noninferiority trial

Study objectiveThe present study assessed whether costotransverse foramen block (CTFB) is noninferior to thoracic paravertebral block (TPVB) for postoperative analgesia in video-assisted thoracoscopic surgery (VATS) pulmonary resection. DesignSingle-center, double-blinded, randomized, non-inferiority trial. SettingOperating room and intensive care unit or ward in a tertiary hospital. PatientsPatients aged 20 to 80 years with American Society of Anesthesiology physical status 1 to 3 scheduled for elective VATS pulmonary resection. InterventionsSixty patients were randomly allocated 1:1 to receive CTFB or TPVB using 15 mL aliquots of 0.5% ropivacaine at the T4–5 and T6–7 intercostal levels immediately after the induction of general anesthesia. MeasurementsThe primary outcome was the area under the curve (AUC) of numeric rating scale (NRS, 0 to 10) during 24 h postoperatively (noninferiority limit was 24; NRS 1 per hour). The secondary outcomes included postoperative opioid consumption, rescue analgesic use, postoperative nausea and vomiting, pulmonary function, dermatomal spread of the blockade, and quality of recovery. Main resultsForty-seven patients were included for final analysis. The difference between the mean 24-h AUCs of NRS in the CTFB (34.25 ± 16.30, n = 24) and TPVB (39.52 ± 17.13, n = 23) groups was −5.27 (95% confidence interval [CI], −15.09 to 4.55), with the upper limit of 95% CI being far below the predefined noninferiority margin of 24. There was no significant difference in the dermatomal spread of the blockades between the groups, as both reached the upper and lower most levels of T3 and T7 (median). Additionally, there were no significant differences in other secondary outcomes between the two groups. ConclusionsThe analgesic effect of CTFB was noninferior to that of TPVB during 24 h postoperatively in VATS pulmonary resection. Moreover, CTFB may offer potential safety benefits by keeping the tip of the needle far from the pleura and vascular structure.

Time-restricted eating improves measures of daily glycaemic control in people with type 2 diabetes

AimsExamine the effect of 5 d/wk, 9-h time-restricted eating (TRE) protocol on 24-h glycaemic control in adults with type 2 diabetes (T2D). MethodsNineteen adults with T2D (10 F/9 M; 50 ± 9 y, HbA1c 7.6% (60 mmol/mol), BMI ∼34 kg/m2) completed a pre-post non-randomised trial comprising of a 2-wk Habitual monitoring period followed by 9-h (10:00–19:00 h) TRE for 4-wk. Glycaemic control was assessed via continuous glucose monitoring (CGM; for mean 24-h glucose concentrations, 24-h total area under the curve (AUC) and glucose variability metrics), with dietary records and physical activity monitoring. Changes in CGM measures, dietary intake and physical activity were assessed with linear mixed-effects models. ResultsTRE did not alter dietary energy intake, macronutrient composition or physical activity, but reduced the daily eating window (−2 h 35 min, P < 0.001). Compared to the Habitual period, 24-h glucose concentrations (mean, SD) and AUC decreased in the 4-wk TRE period (mean: -0.7 ± 1.2 mmol/L, P = 0.02; SD: -0.2 ± 0.3 mmol/L, P = 0.01; 24-h AUC: -0.9 ± 1.4 mmol/L⋅h−1 P = 0.01). During TRE, participants spent 10% more time in range (3.9–10.0 mmol/L; P = 0.02) and 10% less time above range (>10.0 mmol/L; P = 0.02). ConclusionsAdhering 5 d/wk. to 9-h TRE improved glycaemic control in adults with T2D, independent of changes in physical activity or dietary intake.Clinical Trial Registration: Australia New Zealand Clinical Trial Registry, ACTRN12618000938202.

Analgesic benefits of the quadratus lumborum block in total hip arthroplasty: a systematic review and meta‐analysis

The quadratus lumborum block (QLB) is reported to reduce pain and improve function following total hip arthroplasty; however, randomised controlled trials evaluating the benefits of adding this block to general or spinal anaesthesia in this population are conflicting. We performed a systematic review seeking randomised controlled trials investigating QLB benefits for total hip arthroplasty, stratifying comparisons regarding the addition of QLB to either general or spinal anaesthesia. The primary outcome was 24-h area under the curve (AUC) pain score. Pain scores were interpreted in the context of a population-specific minimal clinically important difference of 1.86 cm on a 10-cm visual analogue scale, or an AUC pain score of 5.58 cm.h. Secondary outcomes included analgesic consumption, functional recovery and opioid-related side-effects. In all, 18 trials (1318 patients) were included. Adding QLB to general or spinal anaesthesia improved 24-h AUC rest pain scores by a mean difference (95%CI) of -3.56 cm.h (-6.70 to -0.42; p = 0.034) and - 4.19 cm.h (-7.20 to -1.18; p = 0.014), respectively. These improvements failed to reach the pre-determined minimal clinically important difference, as did the reduction in analgesic consumption. Quadratus lumborum block improved functional recovery for general, but not spinal, anaesthesia. Opioid-related side-effects were reduced with QLB regardless of anaesthetic modality. Low-to-moderate quality evidence suggests that the extent to which adding QLB to either general or spinal anaesthesia reduces postoperative pain and opioid consumption after total hip arthroplasty is statistically significant but may be clinically unimportant for most patients. However, adding QLB to general anaesthesia might enhance functional recovery. Taken together, our findings do not support the routine use of QLB as part of multimodal analgesic regimens for total hip arthroplasty.

Effects of Consuming Sugar-Sweetened Beverages for 2 Weeks on 24-h Circulating Leptin Profiles, Ad Libitum Food Intake and Body Weight in Young Adults.

Sugar-sweetened beverage (sugar-SB) consumption is associated with body weight gain. We investigated whether the changes of (Δ) circulating leptin contribute to weight gain and ad libitum food intake in young adults consuming sugar-SB for two weeks. In a parallel, double-blinded, intervention study, participants (n = 131; BMI 18–35 kg/m2; 18–40 years) consumed three beverages/day containing aspartame or 25% energy requirement as glucose, fructose, high fructose corn syrup (HFCS) or sucrose (n = 23–28/group). Body weight, ad libitum food intake and 24-h leptin area under the curve (AUC) were assessed at Week 0 and at the end of Week 2. The Δbody weight was not different among groups (p = 0.092), but the increases in subjects consuming HFCS- (p = 0.0008) and glucose-SB (p = 0.018) were significant compared with Week 0. Subjects consuming sucrose- (+14%, p < 0.0015), fructose- (+9%, p = 0.015) and HFCS-SB (+8%, p = 0.017) increased energy intake during the ad libitum food intake trial compared with subjects consuming aspartame-SB (−4%, p = 0.0037, effect of SB). Fructose-SB decreased (−14 ng/mL × 24 h, p = 0.0006) and sucrose-SB increased (+25 ng/mL × 24 h, p = 0.025 vs. Week 0; p = 0.0008 vs. fructose-SB) 24-h leptin AUC. The Δad libitum food intake and Δbody weight were not influenced by circulating leptin in young adults consuming sugar-SB for 2 weeks. Studies are needed to determine the mechanisms mediating increased energy intake in subjects consuming sugar-SB.

Is neutrophil gelatinase-associated lipocalin a good diagnostic marker for renal injury in asphyxiated preterm infants?

Background:The objective of this study is to evaluate the value of neutrophil gelatinase-associated lipocalin (NGAL) for becoming a good endogenous marker of renal function in asphyxial preterm babies.Materials and Methods:This is a two-center retrospective study. Between October 2016 and October 2017, 71 asphyxial preterm infants were included in asphyxia group. Seventy babies were randomly included in control group. Samples were tested at 24, 48, and 96 h after birth. Quantitative data were compared by independent sample t-test or repeated measures ANOVA. For qualitative data, Pearson's Chi-squared test was performed. Draw ROC and compare the area under the curve (AUC), 95% confidence interval for AUC, specificity (Spe), sensitivity (Sen), and Youden index (Sen+Spe-1) at 24-h, 48-h, and 96-h time points.Results:(1) There are no significant differences concerning on baseline data. However, blood gas, Apgar score, and resuscitation showed a significant difference (P < 0.05). (2) In 24-h samples, only uNGAL and estimated glomerular filtration rate (eGFR) showed differences between the two groups (P < 0.05). In 48-h samples, significant differences could be found in uKIM-1, uNGAL, blood urea nitrogen, and eGFR (P < 0.05). In 96-h samples, almost all indicators have significant differences except urine output and eGFR (P < 0.05). (3) All biomarkers showed statistical difference in the three time points (P < 0.05), but only uNGAL showed a downward trend after the increase of expression. (4) uNGAL has better Sen and Spe than other indicators (24-h AUC 0.870, Youden index 0.606; 48-h AUC 0.879, Youden index 0.692; and 96-h AUC 0.806, Youden index 0.606).Conclusion:uNGAL has a better distinguishability in asphyxial neonates compared with other indicators. Certainly, a larger sample, prospective study is still needed.

Effects of remote ischemic preconditioning in patients with concentric myocardial hypertrophy: A randomized, controlled trial with molecular insights

BackgroundEfficacy of remote ischemic preconditioning (RIPC) for cardioprotection in cardiac surgery is controversial. We aimed to evaluate the clinical and molecular effects of RIPC on the concentrically hypertrophied myocardium. MethodsSeventy-two aortic stenosis patients receiving aortic valve replacement (AVR) under sevoflurane anesthesia were randomly allocated to RIPC (3cycles of 5-min inflation [300mmHg] and deflation on the left arm) or control (deflated cuff placement) group. The primary endpoints were 24-h area under the curve (AUC) for serum creatine kinase (CK)-MB and troponin (Tn)-T levels. The secondary endpoints were myocardial activation of cell signaling pathways, including reperfusion injury salvage kinases (RISK), signal transducer and activator of transcription (STAT), nitric oxide synthase (NOS), and apoptosis related molecules, obtained from right atrial tissue before and after cardiopulmonary bypass (CPB). ResultsThere were no intergroup differences in 24-h AUCs of CK-MB and Tn-T. Phosphorylations of RISK pathway molecules were not enhanced by RIPC before and after CPB. Phosphorylation of STAT5 was significantly lower in the RIPC group before and after CPB. Phosphorylations of STAT3 and endothelial NOS were not enhanced by RIPC before and after CPB. Expression level of cleaved caspases-3/caspase-3 was significantly higher in the RIPC group before CPB. ConclusionsRIPC did not provide clinical benefits or activate protective signaling in patients with concentric left ventricular hypertrophy undergoing AVR.

Pilot Study of a Bayesian Approach To Estimate Vancomycin Exposure in Obese Patients with Limited Pharmacokinetic Sampling.

This study evaluated the predictive performance of a Bayesian PK estimation method (ADAPT V) to estimate the 24-h vancomycin area under the curve (AUC) with limited pharmacokinetic (PK) sampling in adult obese patients receiving vancomycin for suspected or confirmed Gram-positive infections. This was an Albany Medical Center Institutional Review Board-approved prospective evaluation of 12 patients. Patients had a median (95% confidence interval) age of 61 years (39 to 71 years), a median creatinine clearance of 86 ml/min (75 to 120 ml/min), and a median body mass index of 45 kg/m2 (40 to 52 kg/m2). For each patient, five PK concentrations were measured, and four different vancomycin population PK models were used as Bayesian priors to estimate the vancomycin AUC (AUCFULL). Using each PK model as a prior, data-depleted PK subsets were used to estimate the 24-h AUC (i.e., peak and trough data [AUCPT], midpoint and trough data [AUCMT], and trough-only data [AUCT]). The 24-h AUC derived from the full data set (AUCFULL) was compared to the AUC derived from data-depleted subsets (AUCPT, AUCMT, and AUCT) for each model. For the four sets of analyses, AUCFULL estimates ranged from 437 to 489 mg·h/liter. The AUCPT provided the best approximation of the AUCFULL; AUCMT and AUCT tended to overestimate AUCFULL Further prospective studies are needed to evaluate the impact of AUC monitoring in clinical practice, but the findings from this study suggest that the vancomycin AUC can be estimated with good precision and accuracy with limited PK sampling using Bayesian PK estimation software.

Effects of non-nutritive (artificial vs natural) sweeteners on 24-h glucose profiles.

Replacing nutritive sweetener with non-nutritive sweeteners (NNS) has the potential to improve glycaemic control. The objective of this study was to investigate the effects of consuming artificial NNS (that is, aspartame), natural NNS (that is, monk fruit and stevia), and sucrose-sweetened beverages on 24-h glucose profiles. Ten healthy males took part in this randomised, crossover study with the following four treatments: aspartame-, monk fruit-, stevia-, and sucrose- (65 g) sweetened beverages. Participants were asked to consume the test beverage as a preload mid-morning. Medtronic iPro2 continuous glucose monitoring system was used to measure mean 24-h glucose, incremental area under the curve (iAUC) and total area under the curve (AUC) for glucose, and 24-h glycaemic variability. Overall no significant differences were found in mean 24-h glucose, iAUC and total AUC for glucose, and 24-h glycaemic variability between the four test beverages. Twenty-four-hour glucose profiles did not differ between beverages sweetened with non-nutritive (artificial vs natural) and nutritive sweeteners. The simple exchange of a single serving of sucrose-sweetened beverage with NNS over a day appears to have minimal effect on 24-h glucose profiles in healthy males.

Cross-Over Study Comparing Postprandial Glycemic Increase After Addition of a Fixed-Dose Mitiglinide/Voglibose Combination or a Dipeptidyl Peptidase-4 Inhibitor to Basal Insulin Therapy in Patients with Type 2 Diabetes Mellitus.

BackgroundAlthough the efficacy of combination therapy consisting of basal insulin and oral hypoglycemic agents (OHAs) has been shown, which OHAs are the most efficient remains unclear.Material/MethodsFive patients with type 2 diabetes were enrolled and treated with insulin degludec and metformin as a basal therapy. The patients were randomized in a cross-over fashion to receive a combination of mitiglinide (10 mg) and voglibose (0.2 mg) (M+V) 3 times daily or linagliptin (5 mg) (L) once daily for 8 weeks. After 8 weeks, 2 kinds of meal tolerance tests were performed as breakfast on 2 consecutive days. The first breakfast contained 460 kcal (carbohydrates, 49.1%; protein, 15.7%; fat, 35.2%), while the second contained 462 kcal (carbohydrates, 37.2%; protein, 19.6%; fat, 43.2%). Self-monitoring blood glucose levels were measured at 0, 30, 60, and 120 min after the meal tests, and the increase in the postprandial area under the curve (AUC)0–120 min was determined. The HbA1c, glycated albumin, and 1,5-anhydroglucitol (AG) levels were measured, and continuous glucose monitoring was performed.ResultsThe increase in the postprandial AUC0–120 min was significantly smaller in the M+V group than in the L group after both meals. The 24-h average, 24-h standard deviations, 24-h AUC, and mean amplitude of glycemic excursion (MAGE) were similar for both groups and after both meals. The change in 1,5-AG was higher in the M+V group than in the L group.ConclusionsThe combination of M+V with basal therapy improved postprandial glucose excursion more effectively than L in T2DM patients.

Association between CK-MB Area Under the Curve and Tranexamic Acid Utilization in Patients Undergoing Coronary Artery Bypass Surgery.

Myonecrosis after coronary artery bypass graft (CABG) surgery is associated with excess mortality. Tranexamic acid (TA), an anti-fibrinolytic agent, has been shown to reduce peri-operative blood loss without increasing the risk of myocardial infarction (MI); however, no large study has examined the association between TA treatment and post-CABG myonecrosis. In the MC-1 to Eliminate Necrosis and Damage in Coronary Artery Bypass Graft Surgery II trial, inverse probability weighting of the propensity to receive TA was used to test for differences among the 656 patients receiving and 770 patients not receiving TA. The primary outcome was creatine kinase MB (CK-MB) area under the curve (AUC) through 24h. The secondary outcome was 30-day cardiovascular death or MI. Patients who received TA were more frequently female, had a previous MI, heart failure, low molecular weight heparin therapy, on-pump CABG, valvular surgery, and saphenous vein or radial grafts. The median 24-h CK-MB AUC was higher in TA-treated patients [301.9 (IQR 196.7-495.6) vs 253.5 (153.4-432.5) ng h/mL, p < 0.001]. No differences in the 30-day incidence of cardiovascular death or MI were observed (8.7 vs 8.3%, adjusted OR 0.99; 95% CI 0.67-1.45, p = 0.948). In patients undergoing CABG, TA use was associated with a higher risk of myonecrosis; however, no differences were observed in death or MI. Future larger studies should be directed at examining the pathophysiology of TA myonecrosis, and its association with subsequent clinical outcomes.

Estimating systemic exposure to levonorgestrel from an oral contraceptive

ObjectiveThe gold standard for measuring oral contraceptive (OC) pharmacokinetics is the 24-h steady-state area under the curve (AUC). We conducted this study to assess whether limited sampling at steady state or measurements following use of one or two OCs could provide an adequate proxy in epidemiological studies for the progestin 24-h steady-state AUC of a particular OC. Study designWe conducted a 13-sample, 24-h pharmacokinetic study on both day 1 and day 21 of the first cycle of a monophasic OC containing 30-mcg ethinyl estradiol and 150-mcg levonorgestrel (LNG) in 17 normal-weight healthy White women and a single-dose 9-sample study of the same OC after a 1-month washout. We compared the 13-sample steady-state results with several steady-state and single-dose results calculated using parsimonious sampling schemes. ResultsThe 13-sample steady-state 24-h LNG AUC was highly correlated with the steady-state 24-h trough value [r=0.95; 95% confidence interval (0.85, 0.98)] and with the steady-state 6-, 8-, 12- and 16-h values (0.92≤r≤0.95). The trough values after one or two doses were moderately correlated with the steady-state 24-h AUC value [r=0.70; 95% CI (0.27, 0.90) and 0.77; 95% CI (0.40, 0.92), respectively]. ConclusionsSingle time-point concentrations at steady state and after administration of one or two OCs gave highly to moderately correlated estimates of steady-state LNG AUC. Using such measures could facilitate prospective pharmaco-epidemiologic studies of the OC and its side effects. ImplicationsA single time-point LNG concentration at steady state is an excellent proxy for complete and resource-intensive steady-state AUC measurement. The trough level after two single doses is a fair proxy for steady-state AUC. These results provide practical tools to facilitate large studies to investigate the relationship between systemic LNG exposure and side effects in a real-life setting.

Increased glycemic variability and decrease of the postprandial glucose contribution to HbA1c in obese subjects across the glycemic continuum from normal glycemia to first time diagnosed diabetes

ObjectiveThe contribution of postprandial glycemia (PPG) to hyperglycemia has been shown to decrease as HbA1c increased in type 2 diabetic patients. This study aimed at examining, in a series of overweight/obese patients without known glycemic disorder, the contribution of PPG to a “relative” hyperglycemia (glucose values ≥5.5mmol/L) and the presence of glycemic variability according to HbA1c levels. MethodsSeventy overweight/obese inpatients (body mass index 35.2±6.8kg/m2) without known glycemic disorder were included. Participants were classified according to an oral glucose tolerance test (according to the American Diabetes Association criteria) as patients with normoglycemia (n=33), with intermediate hyperglycemia (n=24) or diabetes (n=13). They were separated into HbA1c quartiles (Q1 to Q4). A 24hour continuous glucose monitoring was used under a 1800kcal diet and minimal physical activity. We assessed PPG contribution (3hour period after each meal) to the “relative” 24hour hyperglycemia (glucose values ≥5.5mmol/L); the remaining time was considered as the fasting/post-absorptive period. ResultsHbA1c range was from 5.1% to 7.4% (32 to 57mmol/mmol). From the lowest to the highest HbA1c quartile, the area under the curve (AUC) for the “relative” hyperglycemia presented a 17-fold increase for the fasting/post-absorptive (p<0.001) period and a 7-fold increase postprandially (p<0.001). The percent of PPG contribution to the “relative” hyperglycemia was calculated with the following formula [100×(postprandial 3hour AUC−3h AUC for a constant 5.5mmol/L glycemia)/(total 24h AUC−24h AUC for constant 5.5mmol/L glycemia)] and decreased from Q1 to Q4 of HbA1c (81.2%, 66%, 65.8%, 57%; p<0.001). Increasing HbA1c quartiles were associated with higher daily mean blood glucose level (p<0.001) and higher levels of daily glucose variability indices, including mean amplitude of glycemic excursions (p<0.01). ConclusionsIn overweight/obese patients, HbA1c was associated with lower PPG contribution to “relative” hyperglycemia and greater glycemic variability. The present findings support the importance of postprandial period in glycemic exposure even before the appearance of diabetes.

A Higher-Complex Carbohydrate Diet in Gestational Diabetes Mellitus Achieves Glucose Targets and Lowers Postprandial Lipids: A Randomized Crossover Study

OBJECTIVEThe conventional diet approach to gestational diabetes mellitus (GDM) advocates carbohydrate restriction, resulting in higher fat (HF), also a substrate for fetal fat accretion and associated with maternal insulin resistance. Consequently, there is no consensus about the ideal GDM diet. We hypothesized that, compared with a conventional, lower-carbohydrate/HF diet (40% carbohydrate/45% fat/15% protein), consumption of a higher-complex carbohydrate (HCC)/lower-fat (LF) Choosing Healthy Options in Carbohydrate Energy (CHOICE) diet (60/25/15%) would result in 24-h glucose area under the curve (AUC) profiles within therapeutic targets and lower postprandial lipids.RESEARCH DESIGN AND METHODSUsing a randomized, crossover design, we provided 16 GDM women (BMI 34 ± 1 kg/m2) with two 3-day isocaloric diets at 31 ± 0.5 weeks (washout between diets) and performed continuous glucose monitoring. On day 4 of each diet, we determined postprandial (5 h) glucose, insulin, triglycerides (TGs), and free fatty acids (FFAs) following a controlled breakfast meal.RESULTSThere were no between-diet differences for fasting or mean nocturnal glucose, but 24-h AUC was slightly higher (∼6%) on the HCC/LF CHOICE diet (P = 0.02). The continuous glucose monitoring system (CGMS) revealed modestly higher 1- and 2-h postprandial glucose on CHOICE (1 h, 115 ± 2 vs. 107 ± 3 mg/dL, P ≤ 0.01; 2 h, 106 ± 3 vs. 97 ± 3 mg/dL, P = 0.001) but well below current targets. After breakfast, 5-h glucose and insulin AUCs were slightly higher (P < 0.05), TG AUC was no different, but the FFA AUC was significantly lower (∼19%; P ≤ 0.01) on the CHOICE diet.CONCLUSIONSThis highly controlled study randomizing isocaloric diets and using a CGMS is the first to show that liberalizing complex carbohydrates and reducing fat still achieved glycemia below current treatment targets and lower postprandial FFAs. This diet strategy may have important implications for preventing macrosomia.

Cystatin C and serum creatinine as predictors of kidney graft outcome

Serum cystatin C (Cys C) was evaluated as a predictor of kidney graft failure progression, and its predictive ability was compared to other markers of graft function. The following kidney graft markers were determined in 91 patients who came for regular checkups of kidney graft function to our outpatient service in February 2008: Cys C, serum creatinine (sCr), 24-h proteinuria and 24-h urinary creatinine clearance (CCr). Glomerular filtration rate (eGFR) was estimated using sCr-based and Cys C formula. Patients were regularly monitored until February 2013 or to graft failure. During follow-up, graft failure occurred in 21 recipients. The Cys C ≥2.65 mg/l discriminated patients with and without graft failure (sensitivity of 80.95% and specificity of 92.86%). According to c statistic, the highest performance was achieved for Cys C (0.874). In addition, Cys C area under the curve (AUC) was significantly better than CCr AUC (p = 0.007), 24-h proteinuria AUC (p = 0.03), eGFR estimated by the chronic kidney disease epidemiology collaboration (EPI) AUC (p = 0.05), but not better than sCr or eGFR AUCs calculated by other formulas. In the multivariable model, sCr, CCr, Cys C and eGFRs were predictors of graft failure. Combination of Cys C, sCr and logarithm of 24 h proteinuria (0.883) or Cys C, CCr and logarithm of 24-h proteinuria (0.884) had the highest AUC for predicting graft outcome that exceed insignificantly Cys C or sCr areas. The most reliable predictors of graft outcome were Cys C, sCr and proteinuria. Because Cys C is unavailable in many transplant centers, from the practical point of view, sCr remains the most sensitive predictor of graft outcome.

Effects of increased meal frequency on fat oxidation and perceived hunger

Consuming smaller, more frequent meals is often advocated as a means of controlling body weight, but studies demonstrating a mechanistic effect of this practice on factors associated with body weight regulation are lacking. The purpose of this study was to compare the effect of consuming three (3M) vs. six meals (6M) per day on 24-h fat oxidation and subjective ratings of hunger. Lean (body mass index <25 kg/m(2) ) subjects (7M, 8F) were studied in a whole-room calorimeter on two occasions in a randomized cross-over design. Subjects were provided isoenergetic, energy balanced diets with a 1- to 2-week washout between conditions. Hunger, fullness, and "desire to eat" ratings were assessed throughout the day using visual analog scales and quantified as area under the curve (AUC). There were no differences (P < 0.05) in 24-h energy expenditure (8.7 ± 0.3 vs. 8.6 ± 0.3 mj d(-1) ), 24-h respiratory quotient (0.85 ± 0.01 vs. 0.85 ± 0.01), or 24-h fat oxidation (82 ± 6 vs. 80 ± 7 g day(-1) ) between 3M and 6M, respectively. There was no difference in fullness 24-h AUC, but hunger AUC (41850 ± 2255 vs. 36612 ± 2556 mm.24 h, P = 0.03) and "desire to eat" AUC (47061 ± 1791 vs. 41170 ± 2574 mm.24 h, P = 0.03) were greater during 6M than 3M. We conclude that increasing meal frequency from three to six per day has no significant effect on 24-h fat oxidation, but may increase hunger and the desire to eat.

Insulin Sensitivity and Regional Fat Gain in Response to Overfeeding

Although insulin resistance and type 2 diabetes (T2DM) are associated with upper body fat distribution, it is unknown whether insulin resistance predisposes to upper body fat gain or whether upper body fat gain causes insulin resistance. Our objective was to determine whether insulin sensitivity predicts abdominal (subcutaneous and/or visceral) fat gain in normal weight adults. Twenty-eight (15 men) lean (BMI = 22.1 ± 2.5 kg/m(2)), healthy adults underwent ~8 weeks of overfeeding to gain ~4 kg fat. Body composition was assessed before and after overfeeding, using dual-energy X-ray absorptiometry (DXA) and abdominal computed tomography to measure total and regional (visceral, abdominal, and lower body subcutaneous) fat gain. We assessed insulin sensitivity with an intravenous glucose tolerance test (IVGTT) and the 24-h insulin area under the curve (AUC). We found a wide range of insulin sensitivity and a relatively narrow range of body fat distribution in this normal weight cohort. Participants gained 3.8 ± 1.7 kg of body fat (4.6 ± 2.2 kg body weight). The baseline 24-h AUC of insulin concentration was positively correlated with percent body fat (r = 0.43, P < 0.05). The contribution of leg fat gain to total fat gain ranged from 29 to 79%, whereas the contributions of abdominal subcutaneous fat and visceral fat gain to total fat gain ranged from 17 to 69% and -5 to 22%, respectively. Baseline insulin sensitivity, whether measured by an IVGTT (S(i)) or the 24-h AUC insulin, did not predict upper body subcutaneous or visceral fat gain in response to overfeeding. We conclude that reduced insulin sensitivity is not an obligate precursor to upper body fat gain.

Ingestion by Men of a Combined Dose of β-Carotene and Lycopene Does Not Affect the Absorption of β-Carotene but Improves That of Lycopene , ,

A double-blind study was conducted in 10 healthy men to investigate serum β-carotene and lycopene responses after ingestion of individual and combined doses of β-carotene (BC) and lycopene. On each dosing day, a baseline blood sample was drawn, followed by an oral dose of 0.11 mmol (60 mg) of either all-trans BC or all-trans lycopene or by a combined oral dose of 0.11 mmol each. Subjects were tested with each of the three doses. The dose type was randomized. Blood (10 mL) was drawn at 1, 3, 5, 7, 9, 12 and 24 h after dosing. At 2 and 4 wk after the first dose, the protocol was repeated with the other doses. After ingestion of the BC dose, serum BC concentrations significantly decreased from baseline at 1 and 3 h followed by a continuous increase from baseline that was significant at 12 and 24 h (P < 0.01). Serum lycopene concentrations significantly increased from baseline at 5 h after the lycopene dose (P < 0.008) and returned to baseline thereafter. Ingestion of a combined dose of BC and lycopene resulted in a significant increase in serum concentrations of both BC and lycopene at 24 h (P < 0.05). The 24-h area under the curve (AUC) for BC was not different when BC was ingested alone or with lycopene, whereas the 24-h AUC for lycopene was significantly greater when lycopene was ingested with BC than when ingested alone (P < 0.05). Our data suggest that ingestion of a combined dose of BC and lycopene has little effect on the absorption of BC but improves that of lycopene in men.