A Prospective Study of Plasma Ferritin Level and Incident Diabetes: The Atherosclerosis Risk in Communities (ARIC) Study

Abstract

The authors performed a case-cohort study nested within the Atherosclerosis Risk in Communities (ARIC) Study to determine the association between plasma ferritin level and risk of type 2 diabetes mellitus. Persons with incident cases of type 2 diabetes diagnosed over an average follow-up period of 7.9 years (n = 599) were compared with a random sample of the cohort (n = 690). After adjustment for age, gender, menopausal status, ethnicity, center, smoking, and alcohol intake, the hazard ratio for diabetes, comparing the fifth quintile of ferritin with the first quintile, was 1.74 (95% confidence interval: 1.14, 2.65; p-trend < 0.001). After further adjustment for body mass index and components of the metabolic syndrome, the hazard ratio was 0.81 (95% confidence interval: 0.49, 1.34; p-trend = 0.87). From a causal perspective, there are two alternative interpretations of these findings. Elevated iron stores, reflected in elevated plasma ferritin levels, may induce baseline metabolic abnormalities that ultimately result in diabetes. Alternatively, elevated ferritin may be just one of several metabolic abnormalities related to the underlying process that ultimately results in diabetes, rather than a causal factor for diabetes. Longitudinal studies with repeated measurements of glucose and iron metabolism parameters are needed to establish the role of iron stores and plasma ferritin in diabetes development.

Effects of Cardiorespiratory Fitness on Serum Ferritin Concentration and Incidence of Type 2 Diabetes: Evidence from the Aerobics Center Longitudinal Study (ACLS)

“…These findings were consistent with those reported in the literature [3,4,13]. Our results relating to CRF levels included a 44% risk reduction for developing T2D among males with moderate CRF levels (HR: 0.56; 95% CI: 0.37,0.85) and 58% (HR: 0.42; 95% CI: 0.29,0.63) among males with high CRF when compared with those in the low CRF level group.…”

“…that an elevated SF level might be a cause for new onset of T2D [4]. The limitations of the study are related to the sample.…”

“…A number of studies indicate that increased SF concentrations are associated with an increased incidence of T2D development. SF may affect the glucose metabolic process that impairs the insulin effect and results in T2D [4]. It may also lead to impaired hepatic insulin extraction [5][6].…”

“…A number of studies suggest that SF is an important contributor to inducing the onset of T2D [1][2][3][4][8][9][10][11][12][13]. A study conducted in Finland found that males with high body iron stores were 2.4 times more likely to have diabetes than those with lower iron stores [11].…”

Insulin Sensitivity, Vascular Function, and Iron Stores in Voluntary Blood Donors

“…In subjects without overt iron overload, higher serum ferritin levels are significantly associated with biochemical evidence of decreased insulin sensitivity (5,6). However, epidemiological studies of the association between dietary iron intake or biomarkers of tissue iron stores and the risk of diabetes in populations without overt iron overload have yielded mixed findings (5,6,(13)(14)(15)(16). The inconsistencies in these reports may be partly attributable to the presence of inflammation or other unmeasured confounders that alter the relationship between dietary iron intake, biochemical markers of tissue iron stores, and metabolic effects of iron.…”