Effect of iron depletion in carbohydrate-intolerant patients with clinical evidence of nonalcoholic fatty liver disease.
OBJECTIVE
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.
Facchini
Francesco S
FS
Department of Medicine, University of California San Francisco and San Francisco General Hospital, San Francisco, California, USA. ffacchini@ecnea.org
Hua
Nancy W
NW
Stoohs
Riccardo A
RA
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D004040:Dietary Carbohydrates / Q000009:adverse effects*; D005234:Fatty Liver / Q000097:blood*; D005260:Female; D006432:Hemochromatosis / Q000097:blood / Q000235:genetics; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood; D007328:Insulin / Q000097:blood; D007501:Iron / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018962:Phlebotomy
D001786:Blood Glucose; D004040:Dietary Carbohydrates; D007328:Insulin; D007501:Iron; D000410:Alanine Transaminase