| Summary: | Nonalcoholic fatty liver disease (NAFLD) is a growing health threat worldwide. Vitamin E supplementation is recommended for nonalcoholic steatohepatitis (NASH) patients, but only for non-diabetic subjects. We aimed to investigate whether serum vitamin E levels differently impact long-term prognosis in diabetic versus non-diabetic NAFLD individuals. A total of 2404 ultrasonographically defined NAFLD individuals from National Health and Nutrition Examination Survey (NHANES) III were stratified by their glycemic statuses into diabetic (<i>N</i> = 662), pre-diabetic (<i>N</i> = 836) and non-diabetic (<i>N</i> = 906), and the relationship between serum vitamin E levels and all-cause mortality was analyzed. The serum vitamin E concentrations were 31.1 ± 14.1, 26.7 ± 9.6, and 24.7 ± 9.8 µmol/L and vitamin E: total cholesterol ratios were 5.16 ± 1.70, 4.81 ± 1.46, and 4.80 ± 1.34 µmol/mmol in in diabetic, pre-diabetic, and non-diabetic groups, respectively. Of 2404 NAFLD subjects, 2403 have mortality information and 152 non-diabetic, 244 pre-diabetic, and 342 diabetic participants died over a median follow-up period of 18.8 years. Both serum vitamin E levels and vitamin E: total cholesterol ratios were negatively associated with all-cause mortality after adjusting for possible confounders in non-diabetic subjects (HR = 0.483, and 0.451, respectively, <i>p</i> < 0.005), but not in either diabetic or pre-diabetic subjects. In NAFLD individuals, both serum vitamin E and lipid-corrected vitamin E were (1) higher in the diabetic group; and (2) negatively associated with all-cause mortality only in the non-diabetic group. Further investigations are warranted to elucidate the underlying mechanism of this inverse association of serum vitamin E concentration with all-cause mortality in non-diabetic but not pre-diabetic or diabetic subjects.
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