Soluble α-Klotho Levels, Glycemic Control and Renal Function in US Adults with Type 2 Diabetes

Aims: Soluble Klotho (s-Klotho) is associated with chronic kidney disease (CKD) and aging, but little is known on its relationship with chronic micro- and macro-vascular complications of type 2 diabetes and glycemic control. Here, we evaluate the association between s-Klotho levels, glycemic control and renal function in patients with type 2 diabetes (T2D).

Methods: This is a cross-sectional study including 2989 patients with T2D and available s-Klotho measurements from the 2007-2016 cycles of the National Health and Nutrition Examination Survey (mean ± SE, age: 60.0 ± 0.2 years, BMI 33.3 ± 0.2 kg/m, 46.7 ± 1.3% female). Determination of s-Klotho concentrations was performed with a sandwich ELISA test.

Results: Patients with higher s-Klotho levels were younger, more frequently female and had a lower prevalence of CKD and higher HbA1c levels. In multivariable linear regression models adjusting for age, race-ethnicity and BMI, both estimated glomerular filtration rate (B = 2.21, 95% CI 1.41-3.01, p < 0.001) and hemoglobin A1c (B = 37.38, 95% CI 28.91-45.86, p < 0.001) were positively associated with s-Klotho, while no significant association was found with cardiovascular disease. Results were confirmed when analyses were performed in men and women separately. No significant differences were identified between patients with an albuminuric or non-albuminuric CKD phenotype.

Conclusions: s-Klotho levels are dependent on kidney function and glycemic control in patients with T2D. Additional studies elucidating the mechanisms linking glycemic control and s-Klotho levels and exploring their predictive ability of clinically meaningful outcomes in patients with diabetes are needed.