P143 REDUCED LEVELS OF ANTI-AGEING HORMONE KLOTHO ARE ASSOCIATED WITH INCREASED AORTIC STIFFNESS IN PATIENTS WITH TYPE 2 DIABETES

Abstract

Background: Aortic Pulse Wave Velocity (Ao-PWV) predicts cardiovascular disease and renal dysfunction in Type 2 Diabetes (T2DM). Klotho is a circulating anti-ageing hormone that has direct cardio-renal protective effects in animal studies. We have previously demonstrated that circulating levels of Klotho are increased by Renin-angiotensin System inhibition (RASi), inversely associated with albuminuria and predict renal function decline in T2DM. The relationship between Klotho and Ao-PWV in diabetes is unknown. Methods: We investigated the correlation of serum Klotho levels and Ao-PWV in 92 patients with T2DM (61% male) all on RASi with preserved renal function in a cross-sectional study. Klotho levels were measured using a validated immunoassay and Ao-PWV by applanation tonometry (Sphygmocor system). Results: The mean age (range) of our cohort was 60.4 (40–82) years with an estimated GFR (using CKD-EPI equation) of 89.2 (46–143) ml/min. Median (interquartile range) Ao-PWV and circulating Klotho levels were 11.8 (10.3–13.6) m/s and 201.46 (154.64–280.17) pg/μl respectively. Patients with an Ao-PWV above the median were older (62.8 ± 9.9 vs 58.1 ± 8.2 years), had a higher SBP (160.9 ± 10.01 vs. 155.04 ± 11.7 mmHg) and lower Klotho levels (192.59 [120.27–255.45] pg/μl vs 219.92 [171.06–311.56] pg/μl), compared to those below the median (p = 0.05 for all).A 10% increase in circulating Klotho levels significantly reduced the odds of a patient being above the Ao-PWV median by 11% in a multivariable logistic regression analysis. Conclusion: There is an inverse association between Ao-PWV and circulating Klotho levels in T2DM. Treatments and strategies that that increase Klotho may attenuate aortic stiffness in diabetes.