Glucose variability in subjects with type 1 diabetes: the relationships with non-enzymatic glycation, albuminuria and renal function

摘要

Background and aim: Recent studies recognized increased glucose variability as an important factor in pathogenesis of diabetic chronic kidney disease (CKD). We evaluated the relationships between serum concentrations of glycation products, glycemic variability parameters, albuminuria and kidney function in subjects with type 1 diabetes at early and advanced stages of CKD.Materials and Methods: One hundred and forty eight patients with type 1 diabetes were included in the study. Ninety five 95 individuals had CKD C1-C2 and 53 subjects had CKD C3-5. Time in range (TIR), time below range (TBR), time above range (TAR) and a panel of GV parameters were calculated from continuous glucose monitoring system (CGMS) data. Serum concentrations of 1,5-anhydroglucitol (1,5-AG), glycated albumin (GA), and advanced glycation end products (AGEs) were determined by ELISA. Twenty subjects without disturbance of carbohydrate metabolism were acted as control.Results: In subjects with CKD stage 1-2, HbA1c was positively associated with average value of glucose obtained by CGMS, as well as with TAR, MAGE, LI, HBGI, CONGA, MAG and M-value. In patients with more advanced CKD stages these relationships were lost. Concentrations of GA and AGEs were elevated significantly in subjects with diabetes as compared to control (both P < 0.001). The concentrations in serum of 1,5-AG were reduced (P < 0.0001), reflecting increase in glucose variability. The levels of GA, but not AGEs, were associated negatively with 1,5-AG concentration. In patients with CKD C1-C2 stages, the estimated glomerular filtration rate (eGFR) showed inverse relationships with TBR and LBGI. Oppositely, in patients with CKD C3-C5 eGFR correlated negatively with mean glucose, TAR, MAGE, CONGA, HBGI and M-value and some GV parameters. In both groups albuminuria was associated positively with AGEs, GA, HbA1c, mean glucose, TAR, and glucose variability indices.Conclusions: We detected different patterns of relationships between eGFR and glucose variability parameters in subjects with T1DM at early and advanced CKD stages. In these patients, enhanced GV may contribute to albuminuria through acceleration of non-enzymatic glycation processes.