Diabetes and serum ferritin concentration among U.S. adults.

Ford, Earl S.; Cogswell, Mary E.

doi:10.2337/diacare.22.12.1978

Cited by 374 publications

(314 citation statements)

References 4 publications

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“…There were strong associations of clinically raised ferritin with diabetes, when compared with the whole group of those with normal ferritin, and also when compared with those in the lowest quartile of the ferritin distribution. Our sensitivity analysis showed that this was the case regardless of the cut-point of the upper limit of ferritin in women, in whom there is debate about whether the threshold should be 150 [3], 200 [20,21] or the same as in men at 300 ng/ml. We found that elevated ferritin was predictive of diabetes independently of a comprehensive range of risk factors and confounders, where previously only a limited number of confounders were accounted for.…”

Section: Discussionmentioning

confidence: 81%

“…Participants were classified into five groups according to their sex-specific serum ferritin concentrations, into quartiles of the normal range of ferritin in control participants (groups 1-4), and into a fifth category of clinically raised ferritin (group 5). We defined raised concentrations of ferritin as ≥300 ng/ml for men and ≥150 ng/ml for women, as previously described in an analysis of the Third National Health and Nutrition Examination Survey [3] and as currently defined by the US National Institutes of Health and National Library of Medicine. These cut-off values are close to the 95th percentile cut-off of 305 ng/ml in men and 165 ng/ml in women in the current study.…”

Section: Discussionmentioning

confidence: 99%

“…These two prospective studies reduce doubt about the temporal sequence which had affected previous cross-sectional or case-control studies [3][4][5][6][7], but several questions still remain unanswered.…”

Section: Introductionmentioning

confidence: 99%

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Elevated serum ferritin levels predict new-onset type 2 diabetes: results from the EPIC-Norfolk prospective study

et al. 2007

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Aims/hypothesis The aim of this study was to examine the association between baseline body iron stores and new-onset diabetes. Subjects and methods We studied the association between baseline serum ferritin concentration and type 2 diabetes in 360 clinically incident diabetes cases and 758 controls nested within the EPIC (European Prospective Investigation of Cancer)-Norfolk Cohort Study. Serum ferritin levels were categorised into five groups: sex-specific quartiles of the normal range of ferritin and a group with clinically raised ferritin below levels indicative of haemochromatosis. Results Baseline serum ferritin was higher among cases than control participants (geometric mean: men 96.6 vs 67.8 ng/ml, respectively, p<0.001; women 45.9 vs 34.8 ng/ ml, respectively, p=0.005). In analyses adjusted for known risk factors (age, BMI, sex, family history, physical activity, smoking habit) and dietary factors measured by 7-day food diary, the risk of diabetes was markedly elevated in participants with clinically raised ferritin compared with the lowest quartile (odds ratio [OR] 7.4, 95% CI 3.5-15.4). Further adjustment for potential confounding by inflammation (C-reactive protein, IL-6 and fibrinogen) had no material impact on the observed association, while adjustment for hepatic enzymes (alanine aminotransferase and γ glutamyl transferase) and adiponectin attenuated the magnitude of association, but it remained statistically significant (OR 3.2 [1.3-7.6]). Conclusions/interpretation Serum ferritin is an important and independent predictor of the development of diabetes. This finding may have important implications for understanding the aetiology of diabetes.

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

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Elevated serum ferritin levels predict new-onset type 2 diabetes: results from the EPIC-Norfolk prospective study

et al. 2007

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“…However, many researchers have supported a role for oxidative stress in the pathogenesis and complications of diabetes mellitus as a result of hyperglycemia. [33][34][35][36][37] In diabetes mellitus patients an increased blood glucose level may stimulate glycosylation of proteins, including hemoglobin, leading to an increase in the release of iron from hemoglobin and further production of free radicals causing oxidative stress. 34,35 A recent study in the United States found a high concentration of serum ferritin in patients having diabetes mellitus, suggesting that it may reflect increased body iron stores.…”

Section: Discussionmentioning

confidence: 99%

“…[33][34][35][36][37] In diabetes mellitus patients an increased blood glucose level may stimulate glycosylation of proteins, including hemoglobin, leading to an increase in the release of iron from hemoglobin and further production of free radicals causing oxidative stress. 34,35 A recent study in the United States found a high concentration of serum ferritin in patients having diabetes mellitus, suggesting that it may reflect increased body iron stores. 35 The fact that iron is a powerful pro-oxidant and that oxidative stress is increased in impaired glucose tolerance states suggests a possible role for oxidative stress in pathogenesis of diabetes mellitus and its complications, such as cirrhosis.…”

Section: Discussionmentioning

confidence: 99%

Risk factors for hepatocellular carcinoma: Synergism of alcohol with viral hepatitis and diabetes mellitus

et al. 2002

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Risk factors associated with hepatocellular carcinoma (HCC) are well documented, but the synergisms between these risk factors are not well examined. We conducted a hospital-based, case-control study among 115 HCC patients and 230 non-liver cancer controls. Cases and controls were pathologically diagnosed at The University of Texas M. D. Anderson Cancer Center and were matched by 5-year age groups, sex, and year of diagnosis. Information on risk factors was collected by personal interview and medical records review. Blood samples were tested for the presence of antibodies to hepatitis C virus antigen (anti-HCV), hepatitis B surface antigen (HBsAg), and antibodies to hepatitis B core antigen (anti-HBc). Conditional logistic regression was used to determine odds ratios (ORs) by the maximum likelihood method. Multivariate ORs and 95% confidence intervals (CIs) were 15.3 (4.3-54.4), 12.6 (2.5-63.1), 4.5 (1.4-14.8), and 4.3 (1.9-9.9) for anti-HCV, HBsAg, heavy alcohol consumption (>80 mL ethanol/d), and diabetes mellitus, respectively. Synergistic interactions on the additive model were observed between heavy alcohol consumption and chronic hepatitis virus infection (OR, 53.9; 95% CI, 7.0-415.7) and diabetes mellitus (OR, 9.9; 95% CI, 2.5-39.3). Independent of the effect of HCV, HBV, and diabetes mellitus, heavy alcohol consumption contributes to the majority of HCC cases (32%), whereas 22%, 16%, and 20% were explained by HCV, HBV, and diabetes mellitus, respectively. In conclusion, the significant synergy between heavy alcohol consumption, hepatitis virus infection, and diabetes mellitus may suggest a common pathway for hepatocarcinogenesis. Exploring the underlying mechanisms for such synergisms may indicate new HCC prevention strategies in highrisk individuals.

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

Jiang

Manson²,

Meigs³

et al. 2004

JAMA

523

402

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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.

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Diabetes and serum ferritin concentration among U.S. adults.

Abstract: Elevated serum ferritin concentration was associated with an increased risk of diabetes. We were unable to eliminate conclusively the possibility that the observed association reflected inflammation rather than excess body iron stores.

Cited by 374 publications

References 4 publications

Elevated serum ferritin levels predict new-onset type 2 diabetes: results from the EPIC-Norfolk prospective study

Elevated serum ferritin levels predict new-onset type 2 diabetes: results from the EPIC-Norfolk prospective study

Risk factors for hepatocellular carcinoma: Synergism of alcohol with viral hepatitis and diabetes mellitus

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

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