FGF21 and glycemic control in patients with T1D

Purpose: Fibroblast growth factor (FGF) 21 is a circulating hormone with an important role in metabolic regulation. FGF21 production in humans responds positively to glucose consumption and we hypothesize that serum FGF21 concentration is associated to glycemic control. Methods: We enrolled 31 patients with type 1 diabetes (T1D) based on their HbA1c (well-regulated (HbA1c <53 mmol/mol), (n = 18) or poorly-regulated (HbA1c >69 mmol/mol), (n = 13). Twelve patients (39%) were diagnosed with retinopathy. Twenty healthy individuals comparable for age and gender distribution were included as a reference group. Serum FGF21, intact FGF21, fibroblast activation protein (FAP), adiponectin, and C-Reactive Protein (CRP) were measured by immunoassays. Results: No correlation between FGF21 concentration and HbA1c was found. Patients with T1D had lower levels of circulating FGF21 as compared with the reference group, but the difference was nonsignificant (p = 0.12). Dividing the patients according to retinopathy, we found that T1D patients with retinopathy had significantly lower FGF21 concentrations (10.0 ng/L) as compared with the healthy reference group (37.1 ng/L), (p = 0.02). We found significantly higher levels of the FGF21 cleaving enzyme, FAP, in patients with T1D (97.2 μg/L) as compared with the healthy control group (78.5 μg/L), (p = 0.006). Interestingly, serum FAP levels correlated significantly with circulating FGF21 levels in T1D patients, but this correlation was not found in the healthy controls. Conclusions: We found no association between circulating FGF21 levels and HbA1c. T1D patients with retinopathy had significantly lower FGF21 levels as compared with healthy individuals, but it remains unclear if the lower levels of FGF21 are pathogenically related to the development of microvascular complications. Of note, serum FAP levels were significantly higher in all T1D patients as compared with the healthy individuals.