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Background and Aims The reliability of haemoglobin A1c (HbA1c) as a glycaemic marker in patients receiving haemodialysis (HD) remains unknown. To assess accuracy, we compared HbA1c and fructosamine levels with interstitial glucose levels measured by continuous glucose monitoring (CGM) in patients with type 2 diabetes receiving HD. Method The HD group (maintenance HD and type 2 diabetes) comprised 30 patients who completed the study period of 17 weeks; the control group (type 2 diabetes and an estimated glomerular filtration rate >60 mL/min/1.73 m2) comprised 36 individuals. CGM (Ipro2®, Medtronic) for periods up to seven days was performed five times (with four weeks intervals) during a 16-week period. HbA1c and fructosamine were measured at week 17. The mean sensor glucose from CGM was compared with the measured HbA1c, its estimated mean blood glucose (eMBGA1c) and fructosamine levels. Results In the HD group, the mean sensor glucose from CGM was 1.4 (95% confidence interval [CI]: 1.0–1.8) mmol/L higher than the eMBGA1c, whereas the difference was 0.1 mmol/L (95% CI: -0.1–[0.4]; P Conclusion HbA1c evaluated by CGM underestimates mean blood glucose levels in patients receiving maintenance HD; fructosamine appears to be more accurate. CGM-assessed blood glucose could complement or replace HbA1c in patients where HbA1c underestimates blood glucose levels.

The proton-dependent oligopeptide transporter (POT/PTR) family shares a highly conserved E1X1X2E2RFXYY (E1X1X2E2R) motif across all kingdoms of life. This motif is suggested to have a role in proton coupling and active transport in bacterial homologs. For the plant POT/PTR family, also known as the NRT1/PTR family (NPF), little is known about the role of the E1X1X2E2R motif. Moreover, nothing is known about the role of the X1 and X2 residues within the E1X1X2E2R motif. We used NPF2.11—a proton-coupled glucosinolate (GLS) symporter from Arabidopsis thaliana—to investigate the role of the E1X1X2E2K motif variant in a plant NPF transporter. Using liquid chromatography–mass spectrometry (LC-MS)-based uptake assays and two-electrode voltage clamp (TEVC) electrophysiology, we demonstrate an essential role for the E1X1X2E2K motif for accumulation of substrate by NPF2.11. Our data suggest that the highly conserved E1, E2 and K residues are involved in translocation of protons, as has been proposed for the E1X1X2E2R motif in bacteria. Furthermore, we show that the two residues X1 and X2 in the E1X1X2E2[K/R] motif are conserved as uncharged amino acids in POT/PTRs from bacteria to mammals and that introducing a positive or negative charge in either position hampers the ability to overaccumulate substrate relative to the assay medium. We hypothesize that introducing a charge at X1 and X2 interferes with the function of the conserved glutamate and lysine residues of the E1X1X2E2K motif and affects the mechanism behind proton coupling.

Background. Patients with end-stage renal disease (ESRD) have glucometabolic disturbances resulting in a high prevalence of prediabetes. The underlying pathophysiology remains unclear, but may prove important for the strategies employed to prevent progression to overt diabetes. Meal-induced release of the insulinotropic gut-derived incretin hormones and pancreatic hormones play a critical role in the maintenance of a normal postprandial glucose tolerance. Methods. We studied patients with ESRD and either normal (n = 10) or impaired (n= 10) glucose tolerance, and control subjects (n = 11). Plasma concentrations of glucose, insulin, glucagon, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and paracetamol were measured repeatedly during a standardized 4-h liquid meal including 1.5 g paracetamol (added for evaluation of gastric emptying). Results. Fasting glucose and postprandial glucose responses were comparable between groups (P > 0.082). Patients with ESRD exhibited higher fasting levels of GIP and glucagon compared with controls (P < 0.001). Baseline-corrected GLP-1 and glucagon responses were enhanced (P < 0.002), baseline-corrected insulin responses and insulin excursions were reduced (P < 0.035), and paracetamol excursions were delayed (P < 0.024) in patients with ESRD compared with controls. None of the variables differed between the two ESRD subgroups. Conclusions. Non-diabetic patients with ESRD were characterized by reduced postprandial insulin responses despite increased secretion of the insulinotropic incretin hormone GLP-1. Fasting levels and baseline-corrected responses of glucagon were elevated and gastric emptying was delayed in the ESRD patients. These perturbations seem to be caused by uraemia per se and may contribute to the disturbed glucose metabolism in ESRD patients.