Impaired response of FGF-23 to oral phosphate in patients with type 2 diabetes: a possible mechanism of atherosclerosis.
BACKGROUND
Fibroblast growth factor (FGF)-23, secreted from osteocytes/osteoblasts, plays major roles in phosphate (Pi)-mediated stimulation of PTH secretion and consequently in regulation of serum Pi. Osteocyte/osteoblast dysfunction develops in patients with type 2 diabetes mellitus (DM).


OBJECTIVE
Our objective was to examine whether increases in serum FGF-23 and PTH after oral Pi stimulation are impaired in type 2 DM.


METHODS
The subjects were 10 DM and 10 non-DM patients without chronic kidney disease stage 3-5. Serum FGF-23, intact PTH (iPTH), and Pi were measured serially after oral Pi administration at a daily dose of 2.0 g.


RESULTS
Pi administration caused significant increases of FGF-23 by 2 h and iPTH by 4 h in non-DM patients. These increases were attenuated in DM patients. After 2 d of Pi stimulation, serum FGF-23 and iPTH remained elevated in non-DM patients but not in DM. In all subjects, initial changes of serum FGF-23 (0-2 h) and iPTH (0-4 h) were positively correlated (r = 0.528) and showed significant negative correlations with later changes in serum Pi (2-4 h) (r = -0.457 and r = -0.673, respectively). Serum Pi (2-4 h) significantly increased in DM patients, consistent with the lack of change in serum FGF-23 and iPTH, whereas serum Pi did not change significantly in non-DM patients.


CONCLUSIONS
These results show that increases of serum FGF-23 and PTH in response to Pi stimulation are impaired in type 2 DM and that serum Pi is significantly increased thereafter. This may be a mechanism underlying advanced atherosclerosis in type 2 DM.
Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
Koichiro
K
Yoda
Yasuo
Y
Imanishi
Maki
M
Yoda
Takashi
T
Mishima
Mitsuru
M
Ichii
Shinsuke
S
Yamada
Katsuhito
K
Mori
Masanori
M
Emoto
Masaaki
M
Inaba
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000209:etiology*; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000008:administration & dosage*
D001786:Blood Glucose; C000717427:FGF23 protein, human; D010281:Parathyroid Hormone; D010710:Phosphates; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23