BACKGROUND & AIMS:

Increased body iron, genetic hemochromatosis (GH) mutations, and nonalcoholic fatty liver disease (NAFLD) tend to cluster in carbohydrate-intolerant patients. In an attempt to further clarify the interrelationships among these conditions, we studied 42 carbohydrate-intolerant patients who were free of the common GH mutations C282Y and H63D, and had a serum iron saturation lower than 50%.

METHODS:

We measured body iron stores, and induced iron depletion to a level of near-iron deficiency (NID) by quantitative phlebotomy.

RESULTS:

In the 17 patients with clinical evidence of NAFLD, we could not demonstrate supranormal levels of body iron (1.6 +/- 0.2 vs. 1.4 +/- 0.2 g; P = 0.06). However, at NID, there was a 40%-55% improvement (P = 0.05-0.0001) of both fasting and glucose-stimulated plasma insulin concentrations, and near-normalization of serum alanine aminotransferase activity (from 61 +/- 5 to 32 +/- 2 IU/L; P < 0.001).

CONCLUSIONS:

These results reflect the insulin-sparing effect of iron depletion and indicate a key role of iron and hyperinsulinemia in the pathogenesis of NAFLD.