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

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Vadim V Klimontov1, Julia Рђ Semenova2, Alla K. Vigel3
1Laboratory of Endocrinology Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (RICEL – Branch of IC&G SB RAS), klimontov@mail.ru
2Laboratory of Endocrinology Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (RICEL – Branch of IC&G SB RAS), ekmxtyjr@yandex.ru
3Laboratory of Endocrinology Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (RICEL – Branch of IC&G SB RAS), endo-kray@mail.ru

Background and aim: Recent studies recognized increased glucose variability (GV) as an independent risk factor for chronic kidney disease (CKD) in diabetes. We aimed to assess the relationships between GV parameters, serum levels of glycation products, albuminuria and renal function in subjects with type 1 diabetes (T1D) at early and advanced stages of CKD.

Materials and Methods: We observed 148 T1D patients, including 95 individuals with CKD C1-C2 and 53 subjects had CKD C3-5. Time in range (TIR: 70-180 mg/dl), time below range (TBR), time above range (TAR) and a panel of GV parameters were derived from continuous glucose monitoring (CGM). Serum levels of 1,5-anhydroglucitol (1,5-AG), glycated albumin (GA) and advanced glycation end products (AGEs) were determined by ELISA and compared to control (20 healthy subjects).

Results: In patients with CKD C1-C2, HbA1c levels correlated positively with mean monitored glucose, 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 (p=0.004 and p<0.0001, respectively). The levels of 1,5-AG were reduced (p<0.0001), reflecting increase in GV. The levels of GA, but not AGEs, were associated negatively with 1,5-AG concentration. In CKD C1-C2 group, the estimated glomerular filtration rate (eGFR) showed inverse relationships with TBR and LBGI. Oppositely, in CKD C3-C5 patients 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 GV indices.

Conclusions: The results demonstrate different patterns of relationships between eGFR and GV parameters in patients with T1D at early and advanced CKD stages. In these patients, enhanced GV may contribute to albuminuria through acceleration of non-enzymatic glycation processes.
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Vadim Nimaev
Vadim Nimaev
3 years ago

As known excretion of 1.5-anhydroglucitol depends from renal threshold for glucose. What is your opinion about difference of this marker in patients with CKD 1-2 and CKD 3-5?

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