HEPATIC STEATOSIS AND HEPATIC INSULIN RESISTANCE

Abstract

Hepatic steatosis, considered the first step in the pathophysiologic continuum of non-alcoholic fatty liver disease, is estimated to afflict 30% of the US population and over 75% of patients with Type 2 diabetes. Non-alcoholic fatty liver disease is already emerging as the most common cause of chronic liver disease worldwide [1], a trend that will only worsen in the coming decades. More so, NAFLD is thought to be an independent determinant of cardiovascular disease (CVD) [4], in addition to clustering in individuals who already have multiple cardiovascular risk factors, a relationship that leads to an increased risk of undesired outcomes in this patient population. NAFLD is therefore a complex problem with implications far beyond the liver. Obesity and the metabolic syndrome are commonly associated with NAFLD, in fact so closely that hepatic steatosis has been proposed to become one of the diagnostic criteria of the metabolic syndrome. Yet the mechanistic sequence of the association between NAFLD and insulin resistance (and diabetes) is not fully understood. Studies have shown that NAFLD predicts the incidence of diabetes independently of traditional risk factors, including obesity, peripheral insulin resistance and the metabolic syndrome [6], suggesting that NAFLD would have a direct causal effect on the development of diabetes, perhaps by promoting hepatic insulin resistance. Uncontrolled diabetes also promotes or worsens hepatic steatosis, thus fueling a vicious cycle that closely ties the two conditions together.