Interrelationship between fatty liver and insulin resistance in the development of type 2 diabetes

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.

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.

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.

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)].

Although associated with insulin resistance, fatty liver diagnosed by ultrasound appears to independently increase the risk of T2DM.