Objective: We investigated the risk of type 2 diabetes mellitus (T2DM) over a wide range of body iron stores. Methods: Prospective cohort of 1613 men in the Kuopio Ischemic Heart Disease Risk Factor study, aged 42-60 years, free of T2DM and hereditary hemochromatosis at baseline in [1984][1985][1986][1987][1988][1989]. Baseline serum ferritin (sF) and serum-soluble transferrin receptor (sTfR) concentrations were used to predict incident T2DM. T2DM was assessed by questionnaires, blood glucose measurements, and medication reimbursement register. Results: There were 331 cases of incident T2DM during the mean follow-up of 16.8 years (27 098 person-years). At baseline, subjects who later developed T2DM had average sF concentrations of 191 mg/l (S.D. 155) vs 151 mg/l (S.D. 119) among those who remained healthy, P!0.001. In a multivariate-adjusted logistic regression, each 100 mg/l increase in sF corresponded to an average of 14% increased (odds ratioZ1.14, 95% CI 1.03-1.26, PZ0.009) risk of developing T2DM. In a Cox regression, a markedly increased risk of developing T2DM was observed from the fourth sF quintile (185 mg/l, the median) upward (hazard ratio (HR) first vs fifth quintileZ1.5, 95% CI 1.0-2.2, P-trendZ0.05). In a corresponding Cox model in sTfR, the subjects in the third quintile (1840 mg/l, the median) had the least risk (HRZ0.63, 95% CI 0.42-0.97, PZ0.04). Conclusions: Body iron within the sF reference range is not an important determinant of T2DM risk, whereas high normal and above is associated with markedly increased risk. Iron depletion toward iron deficiency as assessed by sTfR is not protective against T2DM. A rule of thumb safe range could be 30-200 mg/l of sF.

These data suggest an inverse effect of serum 25(OH)D₃ concentration on the risk of incident pneumonia in the general ageing population.

Hepcidin is a peptide hormone with both paracrine and endocrine functions that help in maintaining body iron stores. Type 2 diabetes (T2D) is one of the sequelae of excess body iron stores; thus, iron regulatory hormone hepcidin may have a direct or at least an indirect role in the aetiopathogenesis of T2D. Both human and animal studies at molecular and genetic levels have attempted to establish a role for hepcidin in the development of T2D, and a few epidemiologic studies have also showed a link between hepcidin and T2D at population level, but the findings are still inconclusive. Recent data have suggested different pathways in which hepcidin could be associated with T2D with much emphasis on its primary or secondary role in insulin resistance. Some of the suggested pathways are via transcription modulator of hepcidin (STAT3); ferroportin 1 expression on the cells involved in iron transport; transmembrane protease 6 enzyme; and pro-inflammatory cytokines, interleukin (IL)-1, IL-6, tumor necrosis factor-α and IL-10. This review briefly reports the existing evidence on the possible links between hepcidin and T2D and concludes that more data are needed to confirm or refute hepcidin's role in the development of T2D. Examining this role could provide a further evidence base for iron in the aetiopathogenesis of T2D.

Background Studies of gender difference in type 2 diabetes have been inconclusive. We investigated gender difference in type 2 diabetes and the contribution of body iron, as assessed by serum ferritin to this difference. Methods We performed cross-sectional ( n = 1707) and prospective ( n = 1506) analyses in males and females aged 53-73 years in 1998-2001. Type 2 diabetes diagnosis was determined by questionnaire, blood glucose measurements and record linkage to type 2 diabetes registers. Gender difference in type 2 diabetes and serum ferritin contribution to the difference was examined in multivariable logistic and Cox regression models. Gender difference in fasting plasma glucose and insulin and homeostasis model assessment of insulin resistance was examined in linear regression analysis. Results In the cross-sectional analysis, a total of 201 type 2 diabetes cases were observed (males = 111 [55.2%] vs. female = 90 [44.8%], P = 0.032), and in adjusted models, males had higher odds of type 2 diabetes (OR = 1.61, 95% CI 1.10 to 2.34); higher fasting plasma glucose (β = 0.28, 95% CI 0.15 to 0.41), fasting plasma insulin (β = 0.73, 95% CI 0.26 to 1.19) and homeostasis model assessment of insulin resistance (β = 0.11, 95% CI 0.04 to 0.17). In the prospective analysis, males had increased risk of type 2 diabetes (HR = 1.46, 95% CI 1.03 to 2.07). With serum ferritin introduction (100  µg/L, log-transformed) into the models, the type 2 diabetes prevalence (OR = 1.35, 95% CI 0.91 to 1.99) and incidence (HR = 1.38, 95% CI 0.96 to 1.97) were appreciably attenuated. Conclusions These data suggest a gender difference in type 2 diabetes, with a higher prevalence and increased type 2 diabetes risk in males. Body iron explains about two-fifths and one-fifth of the gender difference in type 2 diabetes prevalence and incidence, respectively.

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