Clinical implication of alterations in serum Klotho levels in patients with type 2 diabetes mellitus and its associated complications

Aim: To investigate the clinical significance of serum alpha-Klotho and beta-Klotho levels in patients with type 2 diabetes mellitus (T2DM) and its associated complications. Methods: Serum alpha-Klotho and beta-Klotho levels were measured using an ELISA kit in 817 individuals, including 127 with T2DM, 106 with diabetic nephropathy, 99 with diabetic retinopathy, 108 with diabetic neuropathy, 102 with diabetic foot disease, 135 with T2DM and more than one complication and 140 healthy controls. Results: Both alpha-Klotho and beta-Klotho levels were significantly decreased in the T2DM group and the groups with associated complications compared with the levels in control group. The differences between the T2DM group and the T2DM with complications groups were not significant, except between the diabetic nephropathy group and the other diabetic complications groups. In addition, alpha-Klotho and beta-Klotho levels were negatively correlated with serum fructosamine and HbA1c but were not associated with serum glucose in the model including all participants. Moreover, decreases in alpha-Klotho and beta-Klotho levels in the high glucose-exposed cell culture model, which was dependent on glucose exposure time, were confirmed. Conclusions: Levels of alpha-Klotho and beta-Klotho were downregulated in patients in the T2DM and complications groups. Our findings indicate that serum Klotho levels were associated with the development of T2DM, and long-term control of blood glucose will be beneficial in ameliorating changes to alpha-Klotho and beta-Klotho levels in patients with T2DM and complications. (C) 2018 Elsevier Inc. All rights reserved.