SUN-578 Role of Linagliptin on CD34+ Endothelial Progenitor Cells and Arterial Stiffness in Renal Function Impaired Type 2 Diabetes Subjects

Abstract

Introduction: Endothelial Progenitor cells (EPCs) has been shown to be dysfunctional in both Type 2 Diabetes and Chronic Kidney Disease (CKD) leading to poor regeneration of endothelium and renal tubules. EPCs have been shown to be a robust cardiovascular disease (CVD) risk indicator. DPP4 inhibitor increase endogenous SDF1a which has been shown to increase CD34+ cells migration and thereby improve CVD risk. However, cellular mechanisms of DPP4i mediated improvement of CVD in patients with Type 2 Diabetes with established CKD is not established. Hypothesis: Linagliptin, a DPP4 inhibitor when added to insulin, metformin or both may recover endothelial function in a diabetic kidney disease (DKD) population. Methods: 31 subjects taking 1–2 grams of metformin and/or Insulin were enrolled in this 12 weeks, double blind, two-arm, randomized placebo matched trial, with 5 mg Linagliptin compared to placebo. Type 2 diabetes subjects (30–70 years old), HbA1c of 6.5–10%, and all stages of CKD were included. CD34+ cell number, migratory function, gene expression along with vascular parameters such as Arterial stiffness, biochemistry, resting energy expenditure and body composition were measured. Data were collected at week 0, 6 and 12. During trial HbA1C was maintained between 7–8% for all subjects. Every subject was used as their own control. A mixed model regression analysis was done with p value <0.05 considered significant. Results: A double positive CD34/CD184 cell count had a statistically significant increase (p<0.02) as determined by flow cytometry in treatment group though there was no statistically significant increase in CD34+ cell number, or colony formation units. Gene expression analysis on CD34+ cells showed reduced expression of TP53 (p<0.04). Arterial stiffness measures such as augmentation Index (p<0.04) along with augmentation pressure (p<0.02) were significantly reduced in the treatment group. A reduction in LDL: HDL ratio was noted in treatment group (p <0.04). No change in renal function was noted during the 12 week period.. We are currently analyzing urinary exosome based data to enquire further into renal function Conclusions: In DKD subjects, Linagliptin promotes an increase in CXCR4 expression on CD34+ progenitor cells with a concomitant improvement in arterial stiffness and LDL parameters within 12 weeks of intervention.