Insulin resistance is independently associated with liver aminotransferases in diabetic patients without ultrasound signs of nonalcoholic fatty liver disease

Background: It has been shown that elevated levels of alanine and aspartate aminotransferases (ALT and AST) are associated with insulin resistance and type 2 diabetes mellitus; however, the pattern of this association in diabetic patients with negative or mild steatosis is not well understood. The aim of this study was to assess the association between elevated liver enzymes and insulin resistance in diabetic subjects without ultrasound signs of nonalcoholic fatty liver disease (NAFLD) (i.e., with less than 30% steatosis). Methods: In a cross-sectional study, a total of 670 diabetic subjects without established causes of liver injury were included. Patients with evidence of NAFLD in ultrasonography were not included. Fasting blood samples were obtained and plasma glucose, insulin, glycosylated hemoglobin (HbA1c), C-peptide, alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lipid profile were measured. Three indices of insulin sensitivity/ insensitivity: Homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and McAuley were also calculated. Results: Elevated ALT was significantly (p<0.001) correlated with fasting insulin, C-peptide, HOMA-IR, QUICKI, McAuley, and waist circumference. The same correlations were also observed for AST, which in all cases were weaker than ALT. Multivariate regression analysis showed that, among the above-mentioned variables, only HOMA-IR and fasting insulin were independently correlated with both ALT and AST. This correlation was independent of body mass index (BMI) or waist circumference. Conclusion: In type 2 diabetes, in the absence of a detectable steatosis by ultrasonography, ALT and AST are associated with hyperinsulinemia and insulin resistance, independent of obesity. This finding possibly indicates that in diabetes a mild stage of steatosis is sufficient to mediate the association between insulin resistance and aminotransferases.