Hereditary
hemochromatosis (HH) is associated with abnormal
glucose metabolism (AGM). We investigated the effect on
glucose metabolism of normalization of the markers of
iron overload by phlebotomy in subjects with HH. We prospectively studied 11 newly diagnosed subjects with HH and AGM using a standard 75-g oral
glucose tolerance test. Basal quantitative
insulin sensitivity check index (QUICKI) and stimulated oral
glucose insulin sensitivity index (OGIS)
insulin sensitivity was calculated from
glucose and
insulin data, whereas β-cell function was assessed using
C-peptide concentration after adjusting for ambient
insulin sensitivity. After normalization of
ferritin and
transferrin saturations by venesection for 12 (range, 8-16) months, subjects were studied again using the same methods. From 11 subjects with AGM at the time that HH was diagnosed, 7 had
impaired glucose tolerance (IGT) and 4 had
type 2 diabetes mellitus (T2DM). Normalization of the
iron stores (
ferritin and
transferrin) improved the
glucose tolerance status of 4 patients with IGT (to normal
glucose tolerance), whereas 2 of those with IGT progressed to T2DM. In 5 patients,
glucose tolerance status did not change (4 T2DM and 1 IGT). The area under the
insulin and the
C-peptide curve during the oral
glucose tolerance test and the hepatic
insulin extraction increased (P = .05), whereas no statistically significant changes occurred in
insulin sensitivity. However, the disposition index, a measure of the ability of
insulin release to compensate for
insulin resistance, improved significantly (P = .02). Normalization of
ferritin and
transferrin saturation by venesection in subjects with HH and AGM led to improvements in some, but not all, measures of insulin secretion and action. Most patients with AGM had an improvement in
glucose tolerance status, probably due to the augmented action of
insulin in peripheral tissues.