1292-P: Serum Thrombospondin-2 Level as a Novel Liver Fibrosis Biomarker That Changes with Liver Stiffness Improvement in Patients with Type 2 Diabetes

Abstract

Introduction: High baseline circulating thrombospondin-2 (TSP2) level was recently found to associate with both the development and progression of liver fibrosis in patients with co-existing nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes. Here, we investigated whether circulating TSP2 levels changed with improvement in liver fibrosis. Methods: Serum TSP2 levels were measured in all participants of the DISTINCTION study (NCT 03959501), a randomized 1:1 open-label intervention study, at baseline and after treatment with either 10mg dapagliflozin (N=30) or 100mg sitagliptin daily (N=30) for 24 weeks. Liver stiffness (LS) and controlled attenuation parameter (CAP) were measured using vibration-controlled transient elastography for evaluation of hepatic fibrosis and steatosis, respectively. Results: Among these 60 participants with similar clinical characteristics at baseline (mean HbA1c 8.9%, CAP 289 dB/m and LS 5.9 kPa), despite similar HbA1c lowering, treatment with dapagliflozin, but not sitagliptin, led to significant improvements in body weight (BW) (p=0.012), CAP (p=0.015) and LS (p=0.011) after 24 weeks. Serum TSP2 level significantly decreased from 3.07 to 2.90 ng/mL (p=0.012), whereas no significant change in TSP2 was observed with sitagliptin. In Pearson correlation analysis, change in serum TSP2 levels positively correlated with change in LS in the dapagliflozin group (r=0.388, p=0.034), but not with changes in BW, CAP or HbA1c after dapagliflozin treatment. Conclusion: Serum TSP2 level decreased with LS after dapagliflozin treatment, and was independent of improvements in BW, glycemic control and liver steatosis, further supporting the potential of serum TSP2 level as a novel liver fibrosis biomarker in type 2 diabetes. Disclosure J.H.C. Mak: None. H. Fong: None. Y. Wong: None. K.C. Tan: None. S. Lam: None. C. Lee: None.