FokI polymorphism of the vitamin D receptor is closely related to a reduced insulin sensitivity in healthy adults

Background & aims: The “TT” genotype of the FokI polymorphism (rs2228570; T>C) of the vitamin D receptor has previously been associated with a higher risk of insulin resistance, metabolic syndrome and diabetes. The objective of this study was to compare the insulin sensitivity between the different genotypes of the FokI polymorphism after an oral glucose tolerance test (OGTT) in healthy adults. Methods: thirty-three previously genotyped subjects were selected randomly. Three groups of eleven participants were formed according to the allelic variants of the FokI polymorphism: “CC”, “CT” and “TT”. An oral glucose tolerance test was administrated and blood samples were drawn at baseline, 10, 20, 30, 60, 90, 120, 150 and 180 minutes. Plasma glucose, insulin and vitamin D concentrations were determined. Two OGTT derived indexes were computed: the Matsuda-DeFronzo insulin sensitivity index and an insulinogenic index. Results: no significant differences among study groups were found in any of the anthropometric and metabolic features, neither in vitamin D concentrations. Carriers of the “TT” genotype showed a substantial significant reduction of insulin sensitivity (≈40%) in contrast with the “CC+CT” group. Additionally, an inverse association was observed between the insulin sensitivity index and the number of copies of the “T” allele at 120 and 180 minutes (rho=-0.359, P=0.040; rho=-0.355, P=0.043, respectively). In contrast, no associations were found between any of the genotype models and the insulinogenic index. Conclusion: our results demonstrate a substantial reduction of insulin sensitivity in the carriers of the “TT” genotype. Since this decrement was observed in young non-obese subjects, the presence of the “TT” genotype suggests a considerable risk of impaired glucose metabolism in the carriers of this allelic variant.