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Several authors have suggested a positive association between diabetes type 2 (DM2) and the C282Y and H63D mutations of the hereditary hemochromatosis gene but others have disputed it. There are also papers reporting an increased iron load in diabetes type 2 and a possible association with the pathogenesis of the disease. We therefore performed a study in 100 type 2 diabetics and 100 age and sex matched controls to assess the possibility that C282Y and H63D mutations constitute a risk factor for DM2 in Greece. We also evaluated the iron load in 500 diabetes type 2 patients and 423 age and sex matched controls. We did not find any differences in the allele frequencies of the above mutations between patients with diabetes type 2 and controls. The allele frequencies were estimated to be 0.0075 for the C282Y and 0.115 for the H63D mutation. Subjects with even one mutation (C282Y or H63D) had higher transferrin saturation compared to those with no such mutations. This seems to apply to both diabetics (49+/- 8,6 vs 44,5+/- 5,4, p&lt;0,01) and controls (49,3+/- 7,3 vs 42,6+/- 3,3 p&lt;0,01). Patients with DM2 had higher transferrin saturation compared to the general population. These differences were found among men (n=250, mean+/- SD 31,8+11 vs n=73, mean+/- SD 29,5+8, p=0,05) as well as among women (n=250, mean+/- SD 28.5+10 vs n=350, mean+/- SD 25.5+9.6, p=0.001). The DM2 patients had higher ferritin levels compared to controls. In conclusion, DM2 patients have increased iron load. The C282Y and H63D mutations contribute to increased iron load in both DM2 and controls. There was no difference in the frequency of C282Y and H63D alleles between DM2 and controls in the Hellenic population.

The role of Hemochromatosis C282Y and H63D mutations in the development of type 2 diabetes mellitus in Greece