Nonalcoholic fatty liver disease (NAFLD) increases overall and CVD mortality. We prospectively observed 774 T1D to assess impact of FLI (based on BMI, waist, GGT and triglycerides) on all-cause death and CVD (MI, stroke, amputation, revascularizations) risk. Over a 11-year follow-up, 57 subjects died (7.4%) and 49 CV events (6.7%) occurred among 736 T1D with retrievable incidence data. FLI was <30 in 515 T1D (66.5%) , ≥30-60 in 169 (21.8%) , ≥60 in 90 (11.6%) . Mortality increased with FLI: 3.9, 10.1, 22.2% (K-M p<0.0001) . In unadjusted Cox, risk of death in FLI ≥30-60 (HR 2.85, 95% CI 1.49-5.45, p=0.002) and in FLI ≥60 (6.07, 3.27-11.29, p<0.0001) increased respect to FLI <30. Adjusting for Steno Type 1 Risk Engine (ST1-RE: age, sex, DD, sBP, LDL-chol, A1c, ACR, GFR, smoking and exercise) , HRs was 1.52 (0.78-2.97, p=0.222) for FLI ≥30-60 and 3. (1.59-5.82, p=0.001) for FLI ≥60. Inclusion of prior CVD modified HRs slightly. FLI effect was confirmed in 733 T1D without prior CVD (noCVD) . Adjusting for EURODIAB Risk Engine (EURO-RE: age, A1c, WHR, ACR and HDL-chol) did not alter FLI effect (≥30-60: HR 1.24, 0.62-2.48; ≥60: 2.54, 1.30-4.95, p=0.007) even after inclusion of prior CVD, or by restricting the analysis to noCVD subjects. CVD incidence events increased with FLI: 3.5, 10.5, 17.2% (K-M p<0.0001) . In unadjusted Cox, HR was 3.24 (1.65-6.34, p=0.001) for FLI ≥30-60 and 5.41 (2.70-10.83, p<0.0001) for ≥60. After ST1-RE adjustment, HRs was 1.80 (0.90-3.61, p=0.096) for FLI ≥30-60 and 2.98 (1.45-6.13, p=0.003) for FLI ≥60, with trivial modification with prior CVD inclusion. FLI was not a significant predictor in noCVD subjects. EURO-RE adjustment instead of ST1-RE confirmed an independent FLI role (≥30-60: 1.49, 0.73-3.03; ≥60: 2.44, 1.1-5.09, p=0.017) , even after inclusion of prior CVD. This is the first prospective study to demonstrate that FLI is associated with higher all-cause mortality and increased risk of incident CV events in T1D.
M.Garofolo: Employee; Eli Lilly and Company. D.Lucchesi: None. E.Gualdani: None. P.Falcetta: Speaker's Bureau; Abbott Diabetes. M.Giambalvo: None. P.Francesconi: None. S.Del prato: Advisory Panel; Applied Therapeutics, Eli Lilly and Company, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Sanofi, Consultant; Menarini Group, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck & Co., Inc., Sanofi, Stock/Shareholder; Novo Nordisk A/S. G.Penno: Advisory Panel; Eli Lilly and Company.