Obesity (OB) and type 2 diabetes (T2D) are associated with NAFLD and a worse cardiometabolic profile. However, their independent contribution to steatosis, fibrosis, insulin resistance (IR) and atherogenic dyslipidemia are controversial. To this end, we examined the prevalence of NAFLD and hepatic fibrosis in 199 patients (64 with T2D, 135 without T2D) screened from outpatient endocrinology and primary care clinics. NAFLD/fibrosis was assessed by transient elastography (liver fat by controlled attenuation parameter/CAP; fibrosis by liver stiffness measurement/LSM) . Patients were divided into groups either with or without obesity (OB) or T2D. Within each group, patients were well matched for age, BMI, A1c and AST/ALT. The impact of obesity was best observed on the prevalence of steatosis, that increased from pts without OB or T2D (controls = C) to OB/no-T2D (OB) and OB/T2D (C: 40% vs. OB: 64% vs. OB/T2D: 86%, both p<0.vs. C) . The impact of T2D was best observed by the increasing prevalence of liver fibrosis (C: 4% vs. OB: 9% vs. OB/T2D: 25%; p=0.30, 0.01, respectively vs. C) . HOMA-IR (primarily hepatic IR, C: 2.5±0.3 vs. OB: 4.3±0.5 vs. OB/T2D: 6.0±0.6, p<0.vs. C) and adipo-IR (adipose tissue IR, C: 2.8±0.3 vs OB: 4.3±0.6 vs. OB/T2D: 5.4±0.6, p<0.vs. C) followed the worsening impact of OB and T2D. Finally, there was an independent, stepped worsening of HDL-C with obesity and T2D (C: 58±18 vs. OB: 50±vs. OB/T2D: 44±mg/dL; p<0.01) and a worsening trend of TG with T2D (C: 110±78 vs. OB: 110±62; p=0.98, and OB/T2D: 148±79 mg/dL; p<0.vs. C) . LDL-C did not follow this pattern as closely.
In conclusion, obesity and T2D increase the prevalence of NAFLD (more driven by OB) and hepatic fibrosis (more driven by T2D) . This is associated with a continuous worsening of IR and of atherogenic dyslipidemia. The clinical implication is that both factors need to be addressed for the prevention of cirrhosis and of cardiovascular disease in NASH.
A.Mathews: None. L.Mansour: None. M.A.Connelly: Employee; LabCorp. K.Y.Chun: None. D.Barb: None. K.Cusi: Consultant; Altimmune, Arrowhead Pharmaceuticals, Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Eli Lilly and Company, Fractyl Health, Inc., Genentech, Inc., Hanmi Pharm. Co., Ltd., Intercept Pharmaceuticals, Inc., Novo Nordisk. S.Kalavalapalli: None. E.Godinez: None. R.Lomonaco: None. R.E.Dillard: None. M.A.Gonzalez: None. S.A.Marangi: None. S.S.Shetty: None. S.Shrestha: None.
National Institutes of Health (R01DK120331-01A1 - R01DK120331-02)