The relationship between serum FGF-23 concentration and insulin resistance, prediabetes and dyslipidemia in obese children and adolescents

Abstract

Background Obesity is known to cause metabolic disturbances including insulin resistance, dyslipidemia and alters bone mineralization. The effects of obesity on fibroblast growth factor 23 (FGF-23), which is important in bone mineralization, have not yet been clarified. Our aim was to investigate the association between FGF-23 concentration and obesity-associated dysmetabolism. Methods Subjects comprised 46 obese children and adolescents. The same number of age-matched, healthy controls were recruited. Markers of bone mineralization and glucose metabolism were measured. Thyroid function and insulin resistance were investigated in both groups. In obese subjects; an oral glucose tolerance test (OGTT) was performed and hemoglobin A1c and lipid fractions were measured. Bone mineral density and hepatic steatosis were investigated. Results Serum FGF-23, α-klotho and 1,25(OH)2D3 concentrations were significantly lower while fasting insulin, fasting glucose, C-peptide and alkaline phosphatase (ALP) concentrations and homeostasis model assessment of insulin resistance (HOMA-IR) were significantly higher in the obese group compared to controls. A significant negative correlation was observed between free tri-iodothyronine (fT3) and both FGF-23 and α-klotho in the obese group. Significant negative correlation was found between FGF-23 and C-peptide and a positive correlation was found between FGF-23 and high density lipoprotein-cholesterol (HDL-c) in the obese subjects with impaired glucose tolerance (IGT). Significant negative correlations were found between FGF-23 and both fasting insulin levels and C-peptide levels in the obese subjects with hepatic steatosis. Conclusions In our study, insulin resistance-associated hyperinsulinism and/or lower 1,25(OH)2D3 levels, both present in obese children and adolescents, may lead to decreased serum FGF-23 concentrations in obese subjects.

The Interplay Between Bone and Glucose Metabolism

“…Data in 1,179 middle aged subjects showed that FGF23 levels were positively and independently associated with visceral obesity (44). Conversely, significant negative correlations between FGF23 levels and both fasting insulin and C-peptide levels were described in obese children and adolescents with hepatic steatosis (45).…”

Lack of PTEN in osteocytes increases circulating phosphate concentrations by decreasing intact fibroblast growth factor 23 levels

“…A recent study on healthy volunteers demonstrated that the area under the curve of FGF23 levels was inversely associated with that of insulin after an oral glucose tolerance test 17 . Similarly, a negative correlation was observed between FGF23 and both C-peptide and fasting insulin in obese subjects 31 .…”

FGF-23 correlates with endocrine and metabolism dysregulation, worse cardiac and renal function, inflammation level, stenosis degree, and independently predicts in-stent restenosis risk in coronary heart disease patients underwent drug-eluting-stent PCI

“…(2) Secondly, according to the previous study by Kutluturk etc. [26], FGF-23 was correlated with insulin resistance, impaired glucose tolerance and dysregulation of cholesterol metabolism in obsess population suggesting the correlation of FGF-23 with high FBG level, insulin resistance, abnormal lipoprotein-cholesterol level and presence of hypercholesteremia in CHD patients. (3) Thirdly, FGF-23 was reported to decrease active vitamin D synthesis via decreasing 1α-hydroxylase expression, resulting in low level of anti-inflammation calcitriol in serum, meanwhile, high level of FGF-23 presented enhancing effect on inflammatory mediators and signaling (NF-κB signaling), which both amplifying inflammation [8].…”