Low levels of circulating anti-ageing hormone Klotho predict the onset and progression of diabetic retinopathy

Background: Klotho is a circulating anti-ageing hormone that predicts progression of cardiovascular and renal disease. The role of Klotho in diabetic retinopathy is unknown. Methods: We performed a single-centre observational study of 81 people (males 62%) with type 2 diabetes followed for a median of 44 months. Circulating levels of Klotho and other markers, were measured from stored samples. The primary outcome was progression of retinopathy defined as new onset retinopathy or step change in retinopathy grading. Results: During follow-up, 46 (57%) people reached the primary outcome. People with progression of retinopathy had lower levels of serum Klotho as compared to those without (median (interquartile range) 226.9 (171.1-394.0) vs 484.5 (221.8-709.9) pg/ml, p = 0.001). In multivariable logistic regression analyses, baseline Klotho level was the only variable independently associated with reduced risk of progression of retinopathy. Our results suggest that a halving of circulating Klotho levels increases the risk of retinopathy progression by 44%. Conclusion: In people with type 2 diabetes, lower circulating levels of the vascular protective hormone Klotho are associated with increased risk of progression of diabetic retinopathy. Klotho may be a novel biomarker and potential treatment target for diabetic eye disease.