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.

[1]  B. S. Mohammed,et al.  Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity , 2009, Proceedings of the National Academy of Sciences.

[2]  R. N. Bergman,et al.  Role of glucose and insulin resistance in development of type 2 diabetes mellitus: results of a 25-year follow-up study , 1992, The Lancet.

[3]  K. Sung,et al.  Impact of Nonalcoholic Fatty Liver Disease on Insulin Resistance in Relation to HbA1c Levels in Nondiabetic Subjects , 2010, The American Journal of Gastroenterology.

[4]  K-U. Lee,et al.  Fatty liver is an independent risk factor for the development of Type 2 diabetes in Korean adults , 2008, Diabetic medicine : a journal of the British Diabetic Association.

[5]  G. Reaven,et al.  Impact of degree of obesity on surrogate estimates of insulin resistance. , 2004, Diabetes care.

[6]  Jian-Gao Fan,et al.  Effects of nonalcoholic fatty liver disease on the development of metabolic disorders , 2007, Journal of gastroenterology and hepatology.

[7]  Erick M Remer,et al.  The utility of radiological imaging in nonalcoholic fatty liver disease. , 2002, Gastroenterology.

[8]  K. Sung,et al.  Utility of Homeostasis Model Assessment of β-Cell Function in Predicting Diabetes in 12,924 Healthy Koreans , 2009, Diabetes Care.

[9]  Norbert Stefan,et al.  Causes and metabolic consequences of Fatty liver. , 2008, Endocrine reviews.

[10]  G. Reaven.  Role of Insulin Resistance in Human Disease , 1988, Diabetes.

[11]  S. Haffner,et al.  Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of type 2 diabetes: the insulin resistance atherosclerosis study. , 2002, Diabetes.

[12]  T. Joh,et al.  Fatty liver predicts impaired fasting glucose and type 2 diabetes mellitus in Japanese undergoing a health checkup , 2010, Journal of gastroenterology and hepatology.

[13]  G. Reaven,et al.  The increase in plasma PAI-1 associated with insulin resistance may be mediated by the presence of hepatic steatosis. , 2010, Atherosclerosis.