Diabetes in Hemochromatosis.

Diabetes in whites of European descent with hemochromatosis was first attributed to pancreatic siderosis. Later observations revealed that the pathogenesis of diabetes in hemochromatosis is multifactorial and its clinical manifestations are heterogeneous. Increased type 2 diabetes risk in hemochromatosis is associated with one or more factors, including abnormal iron homeostasis and iron overload, decreased insulin secretion, cirrhosis, diabetes in first-degree relatives, increased body mass index, insulin resistance, and metabolic syndrome. In p.C282Y homozygotes, serum ferritin, usually elevated at hemochromatosis diagnosis, largely reflects body iron stores but not diabetes risk. In persons with diabetes type 2 without hemochromatosis diagnoses, serum ferritin levels are higher than those of persons without diabetes, but most values are within the reference range. Phlebotomy therapy to achieve iron depletion does not improve diabetes control in all persons with hemochromatosis. The prevalence of type 2 diabetes diagnosed today in whites of European descent with and without hemochromatosis is similar. Routine iron phenotyping or genotyping of patients with type 2 diabetes is not recommended. Herein, we review diabetes in hemochromatosis and the role of iron in diabetes pathogenesis in whites of European descent with and without hemochromatosis.