Carotid Atherosclerosis Is Not Related to Hepatic Steatosis or Fibrosis in EDICT

Abstract

The prevalence of NAFLD has increased and is associated with type 2 diabetes, obesity, insulin resistance, and metabolic syndrome. In EDICT (Efficacy and Durability of Initial Combination Therapy) we compared the efficacy of Triple (pioglitazone/ exenatide/ metformin) versus Conventional (metformin, sulfonylurea/ insulin) Therapy in newly diagnosed T2D patients. During EDICT, liver function tests were obtained in all subjects (n=318) at baseline and annually for 6 years. Plasma AST and ALT decreased significantly (p<0.01) with Triple Therapy, but not with Conventional Therapy. Carotid intima media thickness (CIMT), a well-established measure of atherosclerotic cardiovascular disease, was obtained at baseline and study end. The increment in CIMT was less in Triple versus Conventional Therapy (+0.005±0.002 vs +0.015±0.002 mm, p<0.0001). EDICT initially was designed for 3 years and subsequently extended to 6 years. 68 patients entered the extension phase and received Fibroscan measurement at study end. 27/39 (69%) Conventional Therapy subjects had grade 2/3 steatosis compared to 9/29 (31%) in Triple Therapy (p=0.0003). 10/39 (26%) Conventional Therapy subjects had grade 3/4 fibrosis versus 2/29 (7%) in Triple Therapy (p=0.04). Severity of hepatic steatosis (CAP), (r=-0.42, p<0.001) and fibrosis (LSM) (r=-0.48, p<0.001) correlated inversely with Matsuda Index of insulin sensitivity. No correlation was observed between CIMT and CAP score (r=0.21, p>0.50) when Triple and Conventional Therapy groups were analyzed collectively (or individually). Similarly, no correlation was observed between CITM versus severity of hepatic fibrosis (r=0.18, p>0.50). CONCLUSION: Severity of atherosclerosis, measured by CIMT, is not related to hepatic steatosis or fibrosis.