Context Type 2 diabetes is a common manifestation of hemochromatosis, a disease
of iron overload. However, it is not clear whether higher iron stores predict
the development of type 2 diabetes in a healthy population.
Objective To examine plasma ferritin concentration and the ratio of the concentrations
of transferrin receptors to ferritin in relation to risk of type 2 diabetes.
Design, Setting, and Participants Prospective nested case-control study within the Nurses' Health Study
cohort. Of the 32 826 women who provided blood samples during 1989-1990
and were free of diagnosed diabetes, cardiovascular disease, and cancer, 698
developed diabetes during 10 years of follow-up. The controls (n = 716) were
matched to cases on age, race, and fasting status; and on body mass index
(BMI) for cases in the top BMI decile.
Main Outcome Measure Incident cases of type 2 diabetes.
Results Among cases, the mean (SD) concentration of ferritin was significantly
higher (109  vs 71.5 [68.7] ng/mL for controls; P<.001
for difference) and the mean (SD) ratio of transferrin receptors to ferritin
was significantly lower (102  vs 141 , respectively; P = .01). In conditional logistic regression stratified on the matching
factors and controlled for BMI and other diabetes risk factors, the multivariate
relative risks [RRs] of incident type 2 diabetes across increasing quintiles
of ferritin were 1.00, 1.09 (95% confidence interval [CI], 0.70-1.70), 1.26
(95% CI, 0.82-1.95), 1.30 (95% CI, 0.83-2.04), and 2.68 (95% CI, 1.75-4.11)
(P<.001 for trend). The RRs across increasing
quintiles of transferrin receptors to ferritin ratio were 2.44 (95% CI, 1.61-3.71),
1.00 (95% CI, 0.64-1.56), 1.13 (95% CI, 0.73-1.74), 0.99 (95% CI, 0.64-1.53),
and 1.00 (P = .01 for trend). Further adjustment
for an inflammatory marker (C-reactive protein) did not change the results
appreciably. The associations persisted within strata defined by levels of
BMI, menopausal status, alcohol consumption, and C-reactive protein.
Conclusion Higher iron stores (reflected by an elevated ferritin concentration
and a lower ratio of transferrin receptors to ferritin) are associated with
an increased risk of type 2 diabetes in healthy women independent of known
diabetes risk factors.