Mortality and risk of diabetes, liver disease, and heart disease in individuals with haemochromatosis HFE C282Y homozygosity and normal concentrations of iron, transferrin saturation, or ferritin: prospective cohort study
Authors' conclusion
Haemochromatosis C282Y homozygotes with normal transferrin saturation and/or ferritin, not recommended for HFE genotyping according to most guidelines, had increased risk of diabetes. Furthermore, C282Y homozygotes with diabetes had higher mortality than non-carriers with diabetes, and 27.3% of all deaths among C282Y homozygotes were potentially attributable to diabetes. These results indicate that prioritising detection and treatment of diabetes in C282Y homozygotes may be relevant.
Study context
- Population
- Individuals from three Danish general population cohorts (Copenhagen City Heart Study, Copenhagen General Population Study, Danish General Suburban Population Study) genotyped for HFE C282Y and H63D; followed up to 27 years
- Participants
- 132,542 individuals
- Exposure
- HFE C282Y homozygotes vs non-carriers
- C282Y homozygotesn = 422
- Outcome
- Hospital contacts and deaths from national registers (diabetes, liver disease, heart disease; mortality)
- Follow-up
- Up to 27 years
Methodological detailsthree Danish general population cohorts
- Three Danish general population cohorts
Main finding
As reported in the abstract
Observational data: associations, not effects.
Further findings
| Outcome | HR (95% CI) | |
|---|---|---|
| Diabetes in C282Y homozygotes with normal iron markers at enrolmentC282Y homozygotesvs Non-carriersNormal transferrin saturation · single blood sample at study enrolment | 2.00 (1.04–3.84) | |
| Diabetes in C282Y homozygotes with normal iron markers at enrolmentC282Y homozygotesvs Non-carriersNormal ferritin · single blood sample at study enrolment | 3.76 (1.41–10.05) | |
| Diabetes in C282Y homozygotes with normal iron markers at enrolmentC282Y homozygotesvs Non-carriersNormal ferritin and transferrin saturation · single blood sample at study enrolment | 6.49 (2.09–20.18) | |
| All-cause mortality in individuals with diabetesWith diabetes | 1.94 (1.19–3.18) | |
| 0.050.21520Hazard ratio (log scale) |
Absolute 5-year risk of diabetes, by sex (range across age groups)
- C282Y homozygous women
- 0.54-4.3%
- Non-carrier women
- 0.37-3.0%
- C282Y homozygous men
- 0.86-6.8%
- Non-carrier men
- 0.60-4.80%
All-cause mortality in individuals with diabetes
- Mortality not increased in C282Y homozygotes without diabetes
Population attributable fraction of all deaths among C282Y homozygotes
- Diabetes
- 27.3% (95% CI 12.4% to 39.7%)
- Liver disease (3.1% to 24.3%)
- 14.4%
Diabetes or liver disease in other HFE genotypes
- Risk not increased in H63D heterozygotes, H63D homozygotes, C282Y heterozygotes, or C282Y/H63D compound heterozygotes
Original publication
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