Iron Storage and Diabetes
Higher Iron Stores and Increased Risk of Type 2 Diabetes
What is the problem and what is known about it so far?
Excessive body iron stores has been shown to cause type 2 diabetes among patients with hemochromatosis, a disease of iron overload caused by a genetic defect in the regulation of iron absorption. It is not clear whether higher iron stores predict an increased risk of type 2 diabetes in healthy individuals. Formations of hydroxyl radicals assisted by iron are powerful chemicals that attack cell membranes, proteins and DNA. It has been hypothesized that hydroxyl radicals contribute to insulin resistance, decreased insulin secretion and ultimately the development of type 2 diabetes.
Why did the researchers do this particular study?
The purpose of the study was to test the hypothesis that higher iron stores can predict the development of type 2 diabetes independently of known diabetes risk factors
Who was studied?
This study used information collected in the Nurses' Health Study. During 1989-1990, 32,826 nurses who were free of diagnosed diabetes, cardiovascular disease, and cancer provided blood samples. By 2000, 698 had developed diabetes. Their findings were compared with nurses who had not developed diabetes (controls) but were similar to those that did with respect to age, race, fasting blood sugar at baseline, and body mass index (BMI) for very obese persons. The final study group included 698 cases and 716 controls.
How was the study done?
Incidence of diabetes was self-reported on follow-up questionnaires every 2 years and verified by a validated supplementary questionnaire regarding diabetes symptoms, diagnostic tests and treatments. Women with type 1 diabetes and diabetes only during pregnancy were excluded. The participants provided blood samples in 1989-1990. Concentrations of blood proteins that reflect body iron stores (ferritin and transferrin receptors) and metabolic markers of diabetes and inflammation were measured. The women provided information on family history of diabetes, body weight, cigarette smoking, physical activity, menopausal status, diet and use or nonuse of postmenopausal hormone therapy.
What did the researchers find?
Among women who developed diabetes during follow-up, the average ferritin concentration was 50% higher than the healthy controls. Adjustments for a marker of inflammation (CRP) and diabetes risk factors, including BMI, family history of diabetes, physical activity, smoking, alcohol use, menopausal status, and diet, did not change the results appreciably.
What were the limitations of the study?
One limitation to this study is that the ferritin concentration may not only reflect iron storage but also other body inflammation associated with insulin resistance and risk of type 2 diabetes. Researchers tried to reduce the likelihood that these factors were responsible for the results by adjusting for CRP in the analysis. Also the study design ensured that the high levels of ferritin were present before diabetes developed. Another confounding issue was obesity, which is an important risk factor for type 2 diabetes as it was not possible to fully assess its contribution to the findings. Lastly, because the controls were not uniformly screened for pre diabetes and the diagnostic criteria for type 2 diabetes were changed after 1998, some women classified as not having diabetes in 1990 would now be diagnosed as having diabetes using the new criteria.
What are the implications of the study?
The finding of the association between higher iron stores, as measured by a simple blood test, and increased risk for type 2 diabetes can help to identify a group of people at high-risk for developing type 2 diabetes who may benefit from early evaluation and lifestyle or therapeutic interventions.
Summarized by Cindy Huang, College of Medicine, University of Vermont.
Summarized from "Body Iron Stores in Relation to Risk of Type 2 Diabetes in Apparently Healthy Women". Jiang, Rui. et al. Journal of the American Medical Association, February 11, 2004, Volume 291, No. 6, Pages 711-717.
