Association of FGF19, FGF21 and FGF23 with carbohydrate metabolism parameters and insulin resistance in patients with chronic kidney disease

Abstract

Insulin resistance (IR) is characterised by increased gluconeogenesis in the liver and the resistance of peripheral receptors to insulin. Several factors, including IR, type 2 diabetes, new-onset diabetes after transplant (NODAT) and secondary parathyroidism, are related to chronic kidney disease (CKD). These factors are associated with higher mortality due to the increased risk of cardiovascular complications. Many factors have been identified as potential markers of IR in CKD. These factors include fibroblast growth factors (FGFs), a subfamily of endocrine polypeptides. In this study, we examined the association of FGF19, FGF21 and FGF23 with selected parameters related to carbohydrate metabolism and insulin resistance in non diabetic patients with predialysis CKD and in non diabetic patients after renal transplantation.The study included 108 non diabetic subjects: 40 patients with predialysis CKD, 45 patients with CKD who had undergone renal transplantation, and 23 healthy subjects (control group).In patients who had undergone renal transplantation, concentrations of FGF23 were increased compared to the control group and patients with predialysis CKD. The highest and lowest FGF19 concentrations were observed in CKD patients and in patients who had undergone kidney transplantation, respectively. This difference was statistically significant. Leptin concentrations were higher in CKD patients compared to the control group and patients who had undergone kidney transplantation. There were no statistically significant differences in adiponectin concentrations, lean body mass or fat tissue mass between the studied groups. HOMA-IR and insulin levels were significantly increased in CKD patients and in patients who had undergone renal transplantation in comparison to the control group.The results of the study suggest the involvement of FGF in carbohydrate metabolism and insulin resistance in patients with predialysis CKD, as well as a correlation with kidney function. Highlights:• Insulin resistance is characterised by increased gluconeogenesis. • Chronic kidney disease (CKD) is associated with insulin resistance. • Fibroblast growth factors are involved in carbohydrate metabolism and insulin resistance in patients with predialysis CKD.

Fibroblast Growth Factor 23, Glucose Homeostasis, and Incident Diabetes: Findings of 2 Cohort Studies

“…The reduced strength of a given bone mineral density in (pre)diabetes could potentially trigger an increase in FGF23. Previous studies consistently report positive associations of FGF23 with markers of insulin resistance ( 6 , 31-33 ).…”