Eur J Clin Invest 2012; 42 (9): 974982 Abstract Background Parental history of type 2 diabetes (T2D) is associated with cardiometabolic risk. We aimed to investigate the associations of parental history of T2D with cardiometabolic biomarkers and to subsequently investigate to what extent these putative associations were explained by modifiable factors. Materials and methods Cross-sectionally, we analysed a random sample of 2001 participants without T2D (2070 years) from the European Prospective Investigation into Cancer and NutritionNetherlands (EPIC-NL). Plasma levels of 12 biomarkers total, HDL and LDL-cholesterol, triglycerides, HbA1c, gamma-glutamyltransferase (GGT), alanine aminotransferase (ALT), asparate aminotransferase (AST), albumin, uric acid, creatinine and high-sensitivity CRP (hs-CRP) were assessed according to categories of parental history of T2D. Results In age and sexadjusted analyses, offspring with parental history of T2D had significantly higher ALT [beta = 0.074; 95% confidence interval (95%CI), 0.023-0.126] and AST levels (beta = 0.033; 95%CI, 0.001 to 0.066) and a trend towards higher HbA1c (beta = 0.011; 95%CI, -0.001 to 0.024) and GGT (beta = 0.049; 95%CI, -0.015 to 0.112) levels. Adjustment for diet, smoking, alcohol intake, physical activity and educational level modestly attenuated the magnitude of these associations, but they remained significant for ALT and borderline significant for AST. After further adjustment for adiposity, additional attenuation was observed, but the association remained significant for ALT. Only maternal history of T2D was associated with higher ALT levels. T2D in both parents was associated with increased levels of all liver enzymes, but the association remained significant for GGT after adjustment for adiposity. Overall, the modifiable factors explained 21.2-45.4% of these associations. The contribution of adiposity was 18.2-38.9%. Conclusion We conclude that parental history of T2D was associated with higher non-fasting levels of liver enzymes in a general population without T2D. Adiposity substantially contributed to these associations. The contribution of diet and lifestyle factors was modest.