title: Prevalence of hereditary haemochromatosis in late-onset type 1 diabetes mellitus: a retrospective study.
abstract: BACKGROUND
  Although genotyping studies suggest that hereditary haemochromatosis is one of the most common genetic disorders in white people, it is still thought of as an uncommon disease. Our aim was to test the hypothesis that hereditary haemochromatosis is a disease often overlooked in patients with late-onset type 1 diabetes mellitus, a late manifestation of untreated iron overload.
  
  
  METHODS
  We did a retrospective study in which we genotyped for the C282Y and H63D mutations in the haemochromatosis gene in 716 unselected Danish patients who developed type 1 diabetes mellitus after age 30 years and 9174 controls from the general Danish population. We also screened for hereditary haemochromatosis by assessment of transferrin saturation.
  
  
  RESULTS
  More patients with diabetes (n=9, relative frequency 1.26%, 95% CI 0.58-2.37) than controls (23, 0.25%, 0.16-0.38) were homozygous for C282Y (odds ratio 4.6, 2.0-10.1, p=0.0001). These patients had unrecognised signs of haemochromatosis. Transferrin saturation and ferritin concentrations ranged from 57% to 102% and 17 microg/L to 8125 microg/L, respectively. Frequency of compound heterozygosity (C282Y/H63D) did not differ between patients with diabetes (eight) and controls (131) (odds ratio 0.8, 95% CI 0.4-1.7). Positive and negative predictive values of transferrin saturation greater than 50%, in identification of C282Y homozygosity, were 0.26 and 1.00, respectively. A saturation of less than 50% therefore excluded C282Y homozygosity, whereas a saturation of more than 50% suggested C282Y homozygosity.
  
  
  CONCLUSIONS
  Measurement of transferrin saturation followed by genetic testing could prevent liver and heart problems and improve life expectancy in patients with diabetes. Population screening before the onset of diabetes might improve the outlook of patients even further, but will be less cost effective.
authors.affiliation: Departments of Haematology L, Herlev Hospital, University of Copenhagen, DK-2730, Herlev, Denmark.
authors.forename: C
authors.initials: C
authors.lastname: Ellervik
authors.forename: T
authors.initials: T
authors.lastname: Mandrup-Poulsen
authors.forename: B G
authors.initials: BG
authors.lastname: Nordestgaard
authors.forename: L E
authors.initials: LE
authors.lastname: Larsen
authors.forename: M
authors.initials: M
authors.lastname: Appleyard
authors.forename: M
authors.initials: M
authors.lastname: Frandsen
authors.forename: P
authors.initials: P
authors.lastname: Petersen
authors.forename: P
authors.initials: P
authors.lastname: Schlichting
authors.forename: T
authors.initials: T
authors.lastname: Saermark
authors.forename: A
authors.initials: A
authors.lastname: Tybjaerg-Hansen
authors.forename: H
authors.initials: H
authors.lastname: Birgens
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D003718:Denmark / Q000453:epidemiology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006432:Hemochromatosis / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008107:Liver Diseases / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D012189:Retrospective Studies; D014168:Transferrin / Q000378:metabolism*
chemical_list: D014168:Transferrin