Sex-specific differences in prevalence of nonalcoholic fatty liver disease in subjects with prediabetes and type 2 diabetes

Aims: To characterize the prevalence of NAFLD among subjects with NGT, prediabetes and type 2 diabetes (T2DM) by sex in adults with one or more cardio-metabolic risk factors, and to assess whether cardio-metabolic factors explained sex-related differences in NAFLD prevalence. Methods: The study sample encompasses 742 individuals with NGT, 553 with prediabetes, and 431 with T2DM. Results: Women with prediabetes and T2DM exhibited greater relative differences in waist circumference, HOMA-IR, hsCRP, and lipid profile than prediabetic and diabetic men when compared with their NGT counterparts. Formal tests for glucose tolerance status x sex interaction were statistically significant for waist circumference (P=0.008), HOMA-IR (P=0.03), total cholesterol (P=0.003), LDL (P=0.001), HDL (P=0.006), triglycerides (P<0.0001), and hsCRP (P<0.05). In a logistic regression analysis, prediabetic and diabetic women exhibited a higher OR for NAFLD than their male counterparts with test for glucose tolerance status x sex interaction being statistically significant. Conclusions: Prediabetic and diabetic women have higher OR of having NAFLD than men. Deterioration of glucose homeostasis in women is associated with a greater worsening in metabolic risk factors than men, which may explain the stronger impact of prediabetes and T2DM on NAFLD in women.