Background: N^ε-(carboxymethyl)-lysine (CML) is formed in the human body by non-enzymatically driven reactions including glycation, oxidation, and lipoxidation. CML is a ubiquitous product of normal physiology, but its levels are increased under disease conditions like chronic kidney disease (CKD) and diabetes mellitus (DM). Free CML is eliminated from the human body mainly through kidney excretion, and its accumulation in the kidney tissue is linked to CKD pathogenesis. Aim: The main goal of this study was to evaluate the relative contribution of CKD and Type 2 DM (T2DM) to the accumulation of CML in patients’ sera. Methods: The study included 22 patients with CKD without DM, 55 with CKD and comorbid T2DM, and 21 with T2DM without CKD. Serum CML levels were measured by ELISA. The Kruskal-Wallis test was used to detect differences among groups. Spearman correlation analysis was performed, and the one-tailed Dunn test was considered to indicate statistical significance at p < 0.05. Results: The median serum CML levels (CKD, 658.4 ± 434.3 ng/mL; CKD + T2DM, 431.3 ± 327.9 ng/mL; T2DM, 273.9 ± 134.2 ng/mL) differed significantly (p < 0.05) among the three patient groups. A positive correlation was observed between serum CML and microalbuminuria (p = 0.004; r = 0.58), proteinuria (p = 0.002; r = 0.6), and age (p = 0.007; r = 0.52) only in the CKD patients. In all T2DM patients, independent of CKD status, serum CML correlated negatively (p < 0.05) with postprandial glucose and duration of diabetes, while its correlation with fasting glucose and HbA1c was negative only in the T2DM cohort without CKD. Conclusions: In patients with CKD, higher levels of CML were observed compared to those with T2DM. Serum CML correlated positively with proteinuria, albuminuria, and patient age in non-diabetic CKD patients, and negatively with blood glucose, HbA1c, and DM duration of T2DM in patients without CKD.

Diabetes mellitus (DM) is a metabolic disease of chronic insulin deficiency or resistance. The progression of DM is associated with long-term damage to macro- and micro-vascular body systems and causes serious health complications. Up to 40% of DM patients develop chronic kidney disease (CKD), mainly as a consequence of diabetic nephropathy (DN). Hence, strict glycemic control is recommended to slow down CKD progression. Hyperglycemia causes complications in diabetic patients through the glycation of various proteins. The interaction of glucose with the free NH2 groups of proteins results in the formation of the early glycation product fructosamine (FA). FA has a short half-life (1 to 2 weeks) and hence it has the potential of an early marker for glycemic control. Although long used in the clinical practice, the FA diagnostic and prognostic significance remains questionable. In this study, we tested the FA potential to serve as a glycemic marker in DM patients with DN. We found that DM patients have significantly higher serum FA levels than non-diabetics. Further, the serum FA level in diabetics correlates positively with the blood glucose concentration. Finally, the mean serum FA level was higher in DM patients with DN, compared to those without DN. These results establish FA as a promising marker for glycemic control in DN patients.

Recombinant human interferon-gamma (rhIFN-γ) produced in Escherichia coli (E. coli) undergoes structural and functional alterations as a result of two different but parallel processes—aggregation and non-enzymatic glycosylation (glycation). Finding approaches for their inhibition is of great importance for the quality of the rhIFN-γ. In this study we used arginine for this purpose. We found that arginine added to the E. coli culture medium, inhibits formation of fluorescent glycation adducts and imidazolone in the total bacterial protein but does not interfere with the early glycation stages. In addition, refolding and storage of rhIFN-γ in the presence of arginine led to delayed accumulation of N^ε-(carboxymethyl)lysine and structural stabilization of the recombinant protein.