Nonalcoholic Fatty Liver Disease

Abstract

Insulin sensitivity (euglycemic clamp, insulin infusion rate: 40 mU ⅐ m ؊2 ⅐ min ؊1) was studied in 30 subjects with biopsy-proven nonalcoholic fatty liver disease (NAFLD), normal glucose tolerance, and a BMI <30 kg/m 2 . Of those 30 subjects, 9 had pure fatty liver and 21 had evidence of steatohepatitis. In addition, 10 patients with type 2 diabetes under good metabolic control and 10 healthy subjects were studied. Most NAFLD patients had central fat accumulation, increased triglycerides and uric acid, and low HDL cholesterol, irrespective of BMI. Glucose disposal during the clamp was reduced by nearly 50% in NAFLD patients, as well as in patients with normal body weight, to an extent similar to that of the type 2 diabetic patients. Basal free fatty acids were increased, whereas insulin-mediated suppression of lipolysis was less effective (؊69% in NAFLD vs. ؊84% in control subjects; P ‫؍‬ 0.003). Postabsorptive hepatic glucose production (HGP), measured by [6,6-2 H 2 ]glucose, was normal. In response to insulin infusion, HGP decreased by only 63% of basal in NAFLD vs. 84% in control subjects (P ‫؍‬ 0.002). Compared with type 2 diabetic patients, NAFLD patients were characterized by lower basal HGP, but with similarly reduced insulinmediated suppression of HGP. There was laboratory evidence of iron overload in many NAFLD patients, but clinical, histological, and biochemical data (including insulin sensitivity) were not correlated with iron status. Four subjects were heterozygous for mutation His63Asp of the HFE gene of familiar hemochromatosis. We concluded that NAFLD, in the presence of normoglycemia and normal or moderately increased body weight, is characterized by clinical and laboratory data similar to those found in diabetes and obesity. NAFLD may be considered an additional feature of the metabolic syndrome, with specific hepatic insulin resistance. Diabetes

Natural history of nonalcoholic fatty liver disease: A prospective follow‐up study with serial biopsies

“…NAFLD is commonly associated with components of metabolic syndrome2 and is an independent risk factor for cardiovascular disease 3, 4…”

Reply

“…On the other hand, there is firm evidence that obesity is associated with nonalcoholic fatty liver diseases (NAFLD). 4 Therefore, without considering the effect of higher fat mass, interpreting a harmful effect of decreased percent muscle mass on NAFLD as a result of decreased muscle mass seems to be inadequate.…”

“…In the Korean Longitudinal Study on Health and Aging, Lim et al defined sarcopenia using ASM/ height 2 or ASM/Wt of <1 SD below the sex-specific mean for young adults. 4 To examine the prevalence of SO, they also defined obesity as a visceral fat area 100 cm 2 . They concluded that subjects with SO defined by ASM/Wt were more insulin resistant and had a higher risk for metabolic syndrome than simply obese subjects.…”

“…They concluded that subjects with SO defined by ASM/Wt were more insulin resistant and had a higher risk for metabolic syndrome than simply obese subjects. 4 The European Working Group on Sarcopenia in Older People recently recommended using the presence of both low muscle mass and low muscle function (strength or performance) for the diagnosis of sarcopenia. 5 We agreed with the opinion that muscle strength does not depend solely on muscle mass, and the relationship between muscle mass and strength is not linear.…”

Diabetes in chronic liver disease: from old concepts to new evidence

“…The association between NAFLD and insulin resistance is even greater than that observed in alcoholic CLD, and some authors consider NAFLD as the hepatic manifestation of the metabolic syndrome [31]. However, the exact role of this metabolic impairment remains to be defined, and insulin resistance probably plays a bi-directional role in this type of liver disease.…”