Interrelationship between Fatty Liver and Insulin Resistance in the Development of Type 2 Diabetes

Context: Although fatty liver and insulin resistance are known to be associated, the relationship between the two in the development of type 2 diabetes mellitus (T2DM) is unclear. Objective: We investigated the 5-yr risk of developing T2DM in individuals diagnosed with fatty liver using ultrasound and stratified by insulin sensitivity using quartiles of fasting insulin concentration. Design and Methods: We examined the clinical and laboratory data of 11,091 Koreans who had a medical evaluation including fasting insulin concentration and abdominal ultrasound at baseline and had a follow-up after 5 yr. Results: At baseline, 27% of the population had fatty liver. Almost half (47%) of the individuals with fatty liver had baseline insulin concentration in the highest quartile compared with 17% in those without fatty liver (P < 0.001). Regardless of baseline insulin concentration, individuals with fatty liver had significantly (P < 0.001) more baseline clinical and metabolic abnormalities, including higher glucose and triglyceride concentration and lower high-density lipoprotein cholesterol concentration. In addition, regardless of baseline insulin concentration, individuals with fatty liver had a significantly increased risk for incident T2DM compared with those without fatty liver [crude odds ratio, 5.05 (95% confidence interval, 2.08–12.29) in the lowest insulin quartile and 6.34 (3.58–11.21) in the highest quartile]. In individuals in the highest insulin quartile, the odds ratio for developing T2DM remained significant even after multivariate adjustment including baseline glucose concentration [2.42 (1.23–4.75)]. Conclusion: Although associated with insulin resistance, fatty liver diagnosed by ultrasound appears to independently increase the risk of T2DM.