Acute hyperinsulinemia is followed by increased serum concentrations of fibroblast growth factor 23 in type 2 diabetes patients

Kristian Winthera, Mads Nybo*a, Birgitte Vindb, Susanne Møller Pedersena, Kurt Højlundb & Lars Melholt Rasmussenaa Department of Clinical Biochemistry and Pharmacologyb Department of Endocrinology, Odense University Hospital, Odense, DenmarkCorrespondence: Mads Nybo, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Sdr. Boulevard 29, DK-5000 Odense, Denmark. Tel: + 45 6541 1161. E-mail: mads.nybo@ouh.regionsyddanmark.dkAbstractBackground. Phosphate homeostasis is connected to glucose metabolism and is influenced by insulin, but the role of fibroblast growth factor 23 (FGF23) is unknown in this relation. Therefore, the levels of FGF23 and phosphate were investigated during a euglycemic-hyperinsulinemic clamp in healthy and type 2 diabetic individuals. Methods. The study population consisted of ten type 2 diabetic patients, ten weight-matched glucose-tolerant obese subjects, and ten healthy lean subjects. All subjects underwent a 4-h euglycemic-hyperinsulinemic clamp using physiological hyperinsulinemia (40 mU/min per m2) to determine glucose disposal rates. Blood samples for measurement of serum FGF23 and insulin, plasma phosphate and glucose, and HbA1c were drawn before and after insulin infusion. Results. The three groups did not differ in baseline levels of serum FGF23. Insulin infusion increased serum FGF23 in the diabetic group (p = 0.009), but not in the other groups. The increase in serum FGF23 correlated strongly with increase in insulin levels in the diabetic group (r = 0.83; p = 0.003). In the overall group insulin infusion suppressed plasma phosphate concentrations (p = 0.006), but with no differences between the groups. Conclusions. Physiological hyperinsulinemia is under euglycemic conditions followed by a significant increase in serum FGF23 concentrations in diabetic individuals, which correlated with change in insulin level. The interplay between insulin effects and FGF23 may be important for the understanding of phosphate metabolism in relation to type 2 diabetes and its vascular complications.