May 23, 2001 Access past issues

Reviewed by: Michele Reyes, PhD1, Heidi Blanck, PhD1, and Giuseppina Imperatore, MD, PhD2

Affiliated agency:
¹Division of Nutrition and Physical Activity  
²Division of Diabetes Translation  
  National Center for Chronic Disease Prevention and Health Promotion  
  Centers for Disease Control and Prevention 

The Health Outcome

Hereditary hemochromatosis is a disease that is often overlooked in patients with late-onset type 1 diabetes mellitus, a possible late manifestation of untreated iron overload. Approximately one of every 200 to 400 people is affected, while one in 10 is a carrier, making this one of the most common of the known genetic disorders in the United States (1).  Hemochromatosis is characterized by lifelong excessive absorption of iron from the diet, with iron accumulating in body organs, eventually causing inflammation and damage and other serious health outcomes, such as diabetes.

The Finding

Retrospective case-control study among Danish adults:  716 patients diagnosed with type-1 diabetes compared to 9,174 controls (2).

Major findings:

• No statistically significant difference for genotype frequencies between the cases and controls, except for C282Y/C282Y. 
• Prevalence of the homozygous C282Y/C282Y genotype among patients with type-1 diabetes was 1.26% (95% CI = 0.58-2.37) compared to 0.25% (0.16-0.38) of controls, resulting in an OR = 4.6 (95% CI = 2.1-10.1). 
• No significant interaction between genotype and sex or age on risk of hemochromatosis.
• Diabetes patients (C282Y/C282Y) had unrecognized signs of hemochromatosis; but there was no examination of the 23 controls homozygous for C282Y.   
• Transferrin saturation (TS) values in C282Y/C282Y patients were higher than for all other genotypes. The Anova for all six genotype levels was P=0.01.  There was not significant interaction between genotype and sex or age in relation to TS.
• Compared TS values (>< 50%) by genotype (C282Y/C282Y vs. other) and demonstrated positive predictive value of 0.26, negative predictive value of 1.0%, sensitivity of 100% and specificity of 100%.  

Authors conclude that population screening for hemochromatosis before the onset of diabetes might improve the outlook of patients.  Measurement of TS followed by genetic testing could prevent liver and heart problems and improve the life expectancy of diabetic patients.

Public Health Implications

Early detection and treatment (phlebotomy) for iron overload due to hereditary hemochromatosis can lessen morbidity and mortality.  Recently diagnosed diabetics may contain an excess of persons with iron overload who might benefit from phlebotomy treatment, but additional data are still needed before proceeding to a screening recommendation. First, better epidemiologic data are needed to determine the proportion of newly diagnosed diabetics that can be attributed to hereditary hemochromatosis mutations.  Then, if this proportion is significant, controlled trials of screening and phlebotomy treatment may be merited, to determine whether such a screening approach is beneficial.  CDC currently recommends serum iron testing of people with 1) a close blood relative with hereditary hemochromatosis, 2) the unexplained symptoms compatible with hemochromatosis (severe weakness, fatigue, arthralgia, or abdominal pain), or 3) signs of diabetes, liver disease, heart problems, impotence, infertility, or amenorrhea.

References

1. Centers for Disease Control and Prevention, Nutrition and Physical Activity. Iron overload disease due to hereditary hemochromatosis (July 6, 2001).  [Cited December 2001 ]
2. Ellervik C, Mandrup-Poulsen T, Nordestgaard BG, et al. Prevalence of hereditary hemochromatosis in late-onset type 1 diabetes mellitus: a retrospective study. Lancet 2001 October 27;358:1405-9.
3. E-Journal Club abstraction template