Body Iron Stores in Relation to Risk of Type 2 Diabetes in Apparently Healthy Women

Abstract

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 32826 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 [105] vs 71.5 [68.7] ng/mL for controls; PϽ.001 for difference) and the mean (SD) ratio of transferrin receptors to ferritin was significantly lower (102 [205] vs 141 [340], 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) (PϽ.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. ConclusionHigher 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.

Obesity modifies the association between diabetes and iron biomarkers and red cell indices in reproductive-aged women in the United States

“…The data overall point to a compromised iron status in diabetic women, characterized by increased risks of iron deficiency and anemia. Contrary to previous studies that linked higher SF levels with increased diabetes risk, 24,47 our study found decreased stored iron in women with diabetes. This discrepancy may be attributable to the younger average age of our participants compared to those in previous studies, acknowledging the age-related increases in diabetes risk and iron storage.…”

Moderate alcohol consumption alters both leucocyte gene expression profiles and circulating proteins related to immune response and lipid metabolism in men

“…Growing evidence has shown that even moderately increased Fe stores, represented by high-normal ferritin concentrations, are associated with insulin resistance ( 32 ) and type 2 diabetes. The results of the present randomised trial are in contrast with observational research that shows a positive association with alcohol consumption and ferritin concentrations ( 33 , 34 ) . Gene expression of ferritin in the leucocytes did not change between the treatments, probably because the protein is predominantly expressed in liver tissue.…”

Gestational Diabetes Mellitus in Relation to Maternal Dietary Heme Iron and Nonheme Iron Intake

“…Our findings, however, are largely consistent with existing literature reporting associations of dietary heme iron intake with risk of incident type 2 diabetes in men and nonpregnant women (6–8). In addition, our findings are supported by studies documenting increased risks of incident GDM (13) or type 2 diabetes (6,11) among individuals with increased levels of serum ferritin, a biological marker of body iron stores. Chen et al (13), in a prospective study of 1,456 healthy pregnant women, reported that maternal elevated serum ferritin concentrations were associated with a twofold increased GDM risk.…”