OBJECTIVEThere is dissociation between insulin resistance, overweight/obesity, and fatty liver as risk factors for type 2 diabetes, suggesting that different mechanisms are involved. Our aim was to 1) quantify risk of incident diabetes at follow-up with different combinations of these risk factors at baseline and 2) determine whether each is an independent risk factor for diabetes.RESEARCH DESIGN AND METHODSWe examined 12,853 subjects without diabetes from a South Korean occupational cohort, and insulin resistance (IR) (homeostasis model assessment-IR ≥75th centile, ≥2.0), fatty liver (defined by standard ultrasound criteria), and overweight/obesity (BMI ≥25 kg/m2) identified at baseline. Odds ratios (ORs) and 95% confidence intervals (CIs) for incident diabetes at 5-year follow-up were estimated using logistic regression.RESULTSWe identified 223 incident cases of diabetes from which 26 subjects had none of the three risk factors, 37 had one, 56 had two, and 104 had three. In the fully adjusted model, the OR and CI for diabetes were 3.92 (2.86–5.37) for IR, 1.62 (1.17–2.24) for overweight/obesity, and 2.42 (1.74–3.36) for fatty liver. The OR for the presence of all three factors in a fully adjusted model was 14.13 (8.99–22.21).CONCLUSIONSThe clustering of IR, overweight/obesity, and fatty liver is common and markedly increases the odds of developing type 2 diabetes, but these factors also have effects independently of each other and of confounding factors. The data suggest that treatment for each factor is needed to decrease risk of type 2 diabetes.