Insulin secretion rates can be accurately estimated from plasma C-peptide levels with a two-compartment model for C-peptide distribution and degradation. In previous studies, the kinetic parameters of C-peptide clearance were derived in each subject from the decay curve observed after bolus intravenous injection of biosynthetic human C-peptide. To determine whether standard parameters for C-peptide clearance could be defined and used to calculate insulin secretion without obtaining a decay curve in each subject, we analyzed 200 decay curves of biosynthetic human C-peptide obtained in normal, obese, and non-insulin-dependent diabetes mellitus subjects studied in our laboratory. This analysis showed that the volume of distribution and kinetic parameters of C-peptide distribution and metabolism vary by less than 30% in a population highly heterogeneous in terms of age, sex, degree of obesity, and degree of glucose tolerance. The volume of distribution correlated with the degree of obesity as quantified by body surface area (BSA). This dependence of C-peptide distribution volume on BSA was more marked in men than in women. The long half-life was slightly longer in elderly subjects than in younger adults. When effects of BSA, sex, and age were taken into account, the parameters of C-peptide kinetics were very similar in normal, obese, and diabetic subjects. Based on these findings, a simple procedure to derive standard parameters for C-peptide clearance taking into account degree of obesity, sex, and age was defined. These standard parameters resulted in estimations of mean insulin secretion rates, which differed in each subject by only 10-12% from those obtained with individual parameters. The approach of using standard rather than individual parameters did not systematically underestimate or overestimate insulin secretion so that group values for the fasting secretion rate, the mean 24-h secretion rate, and the number and the amplitude of secretory pulses obtained with standard parameters differed by only 1-2% from the values obtained with individual parameters. Furthermore, the accuracy of measurements based on standard parameters was not different from that associated with replicate determinations of the parameters of C-peptide clearance in the same subject. We conclude that it is possible to estimate insulin secretion rates from plasma C-peptide levels with standard parameters for C-peptide clearance rather than individually derived parameters without significant loss of accuracy.
Objective Serious discrepancies between glycemia measurements obtained with an Accutrend Sensor (Boehringer Mannheim GmbH, Mannheim, Germany) type analyzer (based on a glucose dehydrogenase enzymatic reaction) and measurements obtained in the laboratory by a reference method (hexokinase) have been found in an insulin-requiring, diabetic, continuous ambulatory peritoneal dialysis (CAPD) patient treated with icodextrin 7.5% (Extraneal; Baxter Healthcare SA, Castlebar, Ireland), a new osmotic agent for peritoneal dialysis. We therefore investigated the respective role of the Analyzer and of the glucose polymer in this hitherto undescribed problem. Design Glycemia was measured simultaneously on venous blood using a reference laboratory technique, and on capillary blood using the Accutrend Sensor glucose analyzer in three groups of CAPD patients: 6 patients on Extraneal for at least 1 week, 6 patients receiving their first Extraneal exchange, and 8 patients never exposed to Extraneal. In the first group of patients, glycemia was also measured with another analyzer (Glucocard; Menarini Diagnostics, Firenze, Italy) using a different enzymatic reaction (glucose oxidase). In a separate study, whole blood of a normal subject was spiked with concentrated solutions of glucose and icodextrin and some of its metabolites (maltose, maltotriose, maltopentaose). Once again, comparative measurements of glycemia were performed with the Accutrend Sensor, with two other kits using a glucose dehydrogenase enzyme reaction, and with the hexokinase reference method. Results In 6 CAPD patients treated with once-daily exchanges with Extraneal for a minimum of 7 consecutive days, we confirmed overestimation of glycemia by the Accutrend Sensor of 65 ± 26 mg/dL compared to reference values (p < 0.01), and of 69; I: 25 mg/dL (p < 0.001) compared to measurements obtained with the Glucocard monitor. In 6 other CAPD patients studied at the end of one single icodextrin exchange, overestimation of 61 ± 11 mg/dL was already present (p < 0.001). On the other hand, in 8 CAPD patients never treated with icodextrin, there was no discrepancy between the Accutrend Sensor readings and reference values. The measurements in spiked blood confirmed that only the Accutrend Sensor overestimates glycemia in the presence of maltose and glucose polymers. The overestimation decreased as the molecular size of the saccharides added to blood increased. There was no overestimation when other kits using a dehydrogenase enzyme were tested. Conclusion The overestimation observed is probably related to the presence of oligosaccharides (mainly maltose), derivatives of glucose polymers present in Extraneal and absorbed via the peritoneal route, in the blood of patients treated with icodextrin. The glucose dehydrogenase characterizing the Accutrend Sensor, an enzyme of the pyrroloquinolinequinone class, very likely reacts with the free reducing group of the glucose molecule located at the end of each saccharide chain. This would not be the case for the Glucocard monitor using glucose oxidase, for other kits using glucose dehydrogenase, and for the reference method based on hexokinase. The Accutrend Sensor type of analyzers are therefore not suitable for regular monitoring of glycemia in diabetic PD patients treated with icodextrin.
In this study of the humoral immune response after the SARS-CoV-2 mRNA vaccination, low seroconversion rates were noted in both kidney transplant recipients and dialysis patients after first dose administration. While in DP the seroconversion rate levelled up to 92.8% after a second dose of SARS-CoV-2 mRNA vaccination, KTR stayed behind with a seroconversion rate of 62.4%. Futhermore, vaccination with the mRNA-1273 vaccine (Moderna) resulted in both higher seroconversion rates and mean log-transformed antibody titer concentrations compared to BNT162b2 (Pfizer). Main textWith the roll-out of COVID-19 vaccines, it has become clear that vaccinating the majority of the population worldwide will be the most important element to control and manage the ongoing COVID-19 pandemic. Several reports have shown diminished immunogenicity of SARS-CoV-2 vaccines in both kidney transplant recipients (KTR) and dialysis patients (DP), as evidenced in a recent narrative review [1]. Furthermore, two recent articles have included comparisons between the immunogenicity of the mRNA-1273 (Moderna) versus the BNT162b2 (Pfizer) vaccine in these populations [2, 3]. Boyarsky et al. studied a cohort of solid organ transplant recipients, including KTR, and reported lower seroconversion rates after receiving the Pfizer vaccine [3]. Stumpf et al. also described lower seroconversion rates in KTR and DP receiving the Pfizer vaccine [2]. However, none of these articles reported the titers of anti-SARS-CoV-2 antibodies. Therefore, we here compared the immunogenicity of
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.