Table 3.

Diabetes risk in HFE hemochromatosis.

Risk factors	Proposed mechanisms and pathophysiology
Increased iron entry into beta cells of islets	Increased transferrin saturation and transport via transferrin receptors Elevated nontransferrin bound iron in plasma and entry by incompletely described mechanisms Increased iron transport by divalent metal transporter 1
Decreased insulin secretion	Islet inflammation Beta-cell injury Pancreatic islet fibrosis
Cirrhosis	Associated with severe iron overload, pancreatic fibrosis Hyperglucagonemia PCSK7 rs236918 allele C
History of diabetes in first-degree relatives	Multiple genetic and acquired factors
Genetic markers	Multiple loci for type 2 diabetes Chromosome 6p loci for type 1 (autoimmune) diabetes