The Role of Insulin Resistance in Nonalcoholic Fatty Liver Disease
Kristina M. Utzschneider and
Steven E. Kahn
Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, Veterans Affairs Puget Sound Health Care System and University of Washington, Seattle, Washington 98108
Address all correspondence and requests for reprints to: Kristina M. Utzschneider, M.D., Veterans Affairs Puget Sound Health Care System (151), 1660 South Columbian Way, Seattle, Washington 98108. E-mail: kutzschn{at}u.washington.edu.
Context: Insulin resistance is an almost universal finding innonalcoholic fatty liver disease (NAFLD). This review outlinesthe evidence linking insulin resistance and NAFLD, exploreswhether liver fat is a cause or consequence of insulin resistance,and reviews the current evidence for treatment of NAFLD.
Evidence Acquisition: Evidence from epidemiological, experimental,and clinical research studies investigating NAFLD and insulinresistance was reviewed.
Evidence Synthesis: Insulin resistance in NAFLD is characterizedby reductions in whole-body, hepatic, and adipose tissue insulinsensitivity. The mechanisms underlying the accumulation of fatin the liver may include excess dietary fat, increased deliveryof free fatty acids to the liver, inadequate fatty acid oxidation,and increased de novo lipogenesis. Insulin resistance may enhancehepatic fat accumulation by increasing free fatty acid deliveryand by the effect of hyperinsulinemia to stimulate anabolicprocesses. The impact of weight loss, metformin, and thiazolidinediones,all treatments aimed at improving insulin sensitivity, as wellas other agents such as vitamin E, have been evaluated in patientswith NAFLD and have shown some benefit. However, most interventionstudies have been small and uncontrolled.
Conclusion: Insulin resistance is a major feature of NAFLD that,in some patients, can progress to steatohepatitis. Treatmentsaimed at reducing insulin resistance have had some success,but larger placebo-controlled studies are needed to fully establishthe efficacy of these interventions and possibly others in reducingthe deleterious effects of fat accumulation in the liver.
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