Prediabetes with Obesity Is a Major Risk Factor for NAFLD and Liver Fibrosis

Clinical practice guidelines suggest that patients with prediabetes (preDM) are at a higher risk of NAFLD and liver fibrosis, among other high-risk groups. However, there is limited data available. The aim of this study was to examine the prevalence of liver steatosis and fibrosis in preDM in unselected patients attending their regular outpatient visits, unaware of having NAFLD. To this end, we recruited 711 middle-aged patients in whom elastography was performed to screen for liver fibrosis (liver stiffness measurement or LSM, 1º outcome) and for steatosis (CAP: ≥274 dB/m, 2º outcome). Among them, 127 had preDM, 254 T2DM and 330 were healthy controls (CON). The 3 groups were matched for age, gender and BMI. The prevalence of NAFLD (by CAP) was higher in T2DM (67%) and preDM (54%) vs. CON: 40% (both p<0.01 vs. CON). Overall, the OR 95% CI for steatosis in preDM vs. CON was 1.64, 1.05-2.58 (p<0.01). Steatosis also increased in preDM independent of obesity (non-obese [OB] CON: 26% vs. non-OB preDM: 38% vs. non-OB T2DM: 47%; p <0.05 vs. CON). The prevalence of any liver fibrosis (LSM ≥7.0 = ≥F1) was 3-fold higher among preDM vs. CON (6% and 2%, p=0.015), but significantly lower than in T2DM (17%; p<0.001). Moderate-to-severe fibrosis (≥F2) also happened more often in preDM 5% vs. CON 1% (in T2DM = 9%; both vs. CON p<0.01). Obesity led to a higher prevalence of NAFLD in T2DM (78%) and in preDM (71% vs. 26% in non-OB CON; p<0.01). Obesity increased the prevalence of liver fibrosis in preDM and T2DM (increasing from 1% [non-OB] to 13% [OB] and from 4% to 23%, respectively; both p <0.05) with the majority having F≥2 (10% and 13%, respectively). Prediabetes with obesity vs. CON with obesity had a 3-fold rate of liver fibrosis (3.35, 1.04-10.82; p<0.001). Conclusion: Prediabetes is associated with a high prevalence rate of NAFLD and liver fibrosis, both increasing significantly in the presence of obesity. Prediabetes deserves screening and fibrosis risk stratification to prevent cirrhosis, in particular, in the presence of obesity. Disclosure E.Godinez leiva: None. M.A.Gonzalez: None. L.Mansour: None. M.M.Calvet: None. D.Barb: None. A.Mathews: None. A.Sharma: None. K.Cusi: Consultant; Poxel SA, Altimmune, Arrowhead Pharmaceuticals, Inc., AstraZeneca, 89bio, Inc., Bristol-Myers Squibb Company, Lilly, Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Medscape, Myovant, Novo Nordisk, ProSciento, Quest Diagnostics, Sagimet, Sonic Incytes, Terns, Research Support; Echosens, Inventiva, LabCorp, Zydus. R.Lomonaco: None. S.Shrestha: None. S.A.Marangi: None. X.Chi: None. S.Kalavalapalli: None. S.S.Shetty: None. A.Ortiz rocha: None. E.Valdez saenz: None. Funding National Institutes of Health (R01120331-01A1)