Prediabetes is Characterized by Higher FGF23 Levels and Higher Prevalence of Vitamin D Deficiency Compared to Normal Glucose Tolerance Subjects

Abstract

In the last years there is an increasing interest towards the bone as an endocrine organ and the role of bone and calcium-phosphate metabolism markers in a range of metabolic disturbances. The aim of the present study is to assess the changes of calcium phosphate metabolism markers in patients with prediabetes compared to normogycemic controls and their link to glucose disturbances and cardiovascular risk factors. In this study, 80 patients with mean age 50.4±10.6 years were included, divided into 2 age- and BMI-matched groups – group 1 with obesity without glycemic disturbances (n=41) and group 2 with obesity and prediabetes (n=39). Oral glucose tolerance test (OGTT) with measurement of immunoreactive insulin was performed in all participants and levels of PTH, 25(OH)D, FGF23, and Klotho were measured. We found significantly higher levels of FGF23 in patients with prediabetes compared to normal glucose tolerance subjects (10.4±10.7 vs. 5.8±7.3 pg/ml; p=0.03). FGF23 showed a weak positive correlation to fasting blood glucose (r=0.224; p=0.048) but not to blood glucose on the first and second hour of oral glucose tolerance test or insulin levels. There was extremely high prevalence of vitamin D deficiency in both groups. Lower levels of 25(OH)D were observed in prediabetes group, although without statistical significance (p=0.57). Patients with prediabetes have higher FGF23 levels and higher prevalence of vitamin D deficiency compared to normal glucose tolerance subjects. Elevated FGF23 levels seem to be correlated more to elevated fasting blood glucose levels than to insulin resistance state of the patients.

1ɑ,25‐Dihydroxyvitamin D3 promotes osteogenesis by down‐regulating FGF23 in diabetic mice

“…In vivo, we found that the blood glucose level increased accompanied with increased serum FGF23 concentration, which was consistent with the previous study conducted by Antoaneta Gateva et al 24 Also, we detected that DKK1, an inhibitor of the Wnt pathway, was significantly down‐regulated after treatment of 1,25D or FoxO1 knockout. It is known that Wnt/β‐catenin is a crucial signalling pathway in the process of bone formation.…”

Fibroblast Growth Factor 23 and Adverse Clinical Outcomes in Type 2 Diabetes: a Bitter-Sweet Symphony

“…Túñon et al found similar FGF23 levels in diabetic vs. non-diabetic patients; this could be explained by the fact that these patients had better kidney function as compared with the CRIC study [ 15 •]. On the other hand, a smaller cohort of prediabetic individuals with normal kidney function displayed significantly higher intact FGF23 levels than obese controls with normal glucose tolerance [ 16 ]. In a previous study, we assessed FGF23 in a general population cohort, which also included type 2 diabetes patients [ 20 ••].…”

Cytokines and Abnormal Glucose and Lipid Metabolism

“…In humans, serum FGF23 levels are elevated in individuals with obesity (212), MetS (144), prediabetes (213), and T2D (214). Moreover, FGF23 is associated positively with triglycerides, BMI, waist circumference, and fat mass, and negatively correlated with HDL and apolipoprotein A1 (144).…”