Factors affecting glucose tolerance in hereditary hemochromatosis.
OBJECTIVE
To determine insulin action and insulin secretory function in patients with hemochromatosis, and to find evidence for or against hypothesized pathogenetic mechanisms for the abnormal glucose metabolism associated with hemochromatosis. These mechanisms include decreased beta-cell secretion of insulin due to iron overload, insulin resistance and genetic factors.


METHODS
Prospective in vivo study.


METHODS
Seventeen subjects with hemochromatosis, of whom 4 had cirrhosis but not diabetes mellitus, 6 had diabetes mellitus and 7 had neither; 10 controls.


METHODS
Insulin sensitivity and insulin secretion were determined during an intravenous glucose tolerance test. Insulin secretion was measured as the acute insulin response to glucose (AIRg). Insulin sensitivity (Si) was quantified with the minimal-model method. Of the patients with hemochromatosis, 14 agreed to undergo a second metabolic study after treatment with venous phlebotomy.


RESULTS
All subjects with hereditary hemochromatosis had impaired glucose tolerance as measured by K(g) (rate of glucose disappearance). Subjects who were free of both diabetes mellitus and liver cirrhosis had a normal S1 and a decreased AIRg. In these subjects, phlebotomy treatment normalized serum ferritin levels, increased AIRg by 35% and normalized glucose tolerance (K(g)). Subjects with hemochromatosis and cirrhosis had a reduced Si and maintained a normal insulin secretion. Phlebotomy treatment did not change these parameters. Subjects with hemochromatosis and diabetes mellitus had both a reduced Si and AIRg, and these parameters were unaffected by phlebotomy treatment.


CONCLUSIONS
These results suggest that iron overload can impair insulin secretion and glucose tolerance early in hereditary hemochromatosis, before cirrhosis occurs. Phlebotomy treatment can reverse these defects. Impaired glucose tolerance resulting from insulin resistance in subjects with cirrhosis or diabetes mellitus is not affected by phlebotomy treatment.
Hramiak
I M
IM
Department of Medicine, University of Western Ontario, London. irene.hramiak@lhsc.on.ca
Finegood
D T
DT
Adams
P C
PC
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000737:chemistry / Q000378:metabolism*; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D003920:Diabetes Mellitus / Q000097:blood / Q000378:metabolism; D005293:Ferritins / Q000097:blood / Q000737:chemistry; D005951:Glucose Tolerance Test / Q000706:statistics & numerical data; D006442:Glycated Hemoglobin / Q000737:chemistry; D006432:Hemochromatosis / Q000097:blood / Q000150:complications* / Q000378:metabolism* / Q000503:physiopathology*; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D007501:Iron / Q000737:chemistry; D008099:Liver / Q000737:chemistry; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000378:metabolism; D008875:Middle Aged; D018962:Phlebotomy; D011446:Prospective Studies
D001786:Blood Glucose; D002096:C-Peptide; D005293:Ferritins; D006442:Glycated Hemoglobin; D007328:Insulin; D007501:Iron