Body iron stores and the risk of type 2 diabetes in middle-aged men

Aregbesola, Alex; Voutilainen, Sari; Virtanen, Jyrki K.; Mursu, Jaakko; Tuomainen, Tomi‐Pekka

doi:10.1530/eje-13-0145

Cited by 55 publications

(46 citation statements)

References 39 publications

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“…Copper homeostasis and iron status are also related to GDM [61]–[63]. For example, high body iron stores, leading to unliganded iron, cause hydroxyl radical formation via Fenton chemistry and are significantly associated with a greater risk of T2DM [22], [64]–[67]. Here, 29 of the women were included in a vascular sub-study where there was a gradation of declining endothelial function of resistance blood vessels ex-vivo, poorest in the 12 of the 18 women with prior GDM studied here and less marked in those with UQ, compared with controls defined the same way [3].…”

Section: Discussionmentioning

confidence: 99%

Evidence That Multiple Defects in Lipid Regulation Occur before Hyperglycemia during the Prodrome of Type-2 Diabetes

et al. 2014

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BackgroundBlood-vessel dysfunction arises before overt hyperglycemia in type-2 diabetes (T2DM). We hypothesised that a metabolomic approach might identify metabolites/pathways perturbed in this pre-hyperglycemic phase. To test this hypothesis and for specific metabolite hypothesis generation, serum metabolic profiling was performed in young women at increased, intermediate and low risk of subsequent T2DM.MethodsParticipants were stratified by glucose tolerance during a previous index pregnancy into three risk-groups: overt gestational diabetes (GDM; n = 18); those with glucose values in the upper quartile but below GDM levels (UQ group; n = 45); and controls (n = 43, below the median glucose values). Follow-up serum samples were collected at a mean 22 months postnatally. Samples were analysed in a random order using Ultra Performance Liquid Chromatography coupled to an electrospray hybrid LTQ-Orbitrap mass spectrometer. Statistical analysis included principal component (PCA) and multivariate methods.FindingsSignificant between-group differences were observed at follow-up in waist circumference (86, 95%CI (79–91) vs 80 (76–84) cm for GDM vs controls, p<0.05), adiponectin (about 33% lower in GDM group, p = 0.004), fasting glucose, post-prandial glucose and HbA1c, but the latter 3 all remained within the ‘normal’ range. Substantial differences in metabolite profiles were apparent between the 2 ‘at-risk’ groups and controls, particularly in concentrations of phospholipids (4 metabolites with p≤0.01), acylcarnitines (3 with p≤0.02), short- and long-chain fatty acids (3 with p< = 0.03), and diglycerides (4 with p≤0.05).InterpretationDefects in adipocyte function from excess energy storage as relatively hypoxic visceral and hepatic fat, and impaired mitochondrial fatty acid oxidation may initiate the observed perturbations in lipid metabolism. Together with evidence from the failure of glucose-directed treatments to improve cardiovascular outcomes, these data and those of others indicate that a new, quite different definition of type-2 diabetes is required. This definition would incorporate disturbed lipid metabolism prior to hyperglycemia.

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Section: Discussionmentioning

confidence: 99%

Evidence That Multiple Defects in Lipid Regulation Occur before Hyperglycemia during the Prodrome of Type-2 Diabetes

et al. 2014

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“…Several longitudinal studies have previously shown an association between incident diabetes and higher baseline ferritin levels [10, 12–16, 29]. …”

Section: Discussionmentioning

confidence: 99%

Serum ferritin levels and the development of metabolic syndrome and its components: a 6.5-year follow-up study

Hämäläinen

Saltevo

Kautiainen

et al. 2014

Diabetol Metab Syndr

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BackgroundThe aim of this study was to investigate the relationship between changes in serum ferritin concentrations and the development of metabolic syndrome (MetS) and its components over a 6.5 year follow-up period in Finnish adults.MethodsAdults born in Pieksämäki, Finland, in 1942, 1947, 1952, 1957, and 1962 (n = 1294) were invited to health checkups between 1997 and 1998 and 2003 and 2004. All of the required variables for both checkups were available from 691 (53%) subjects (289 men and 402 women). MetS was defined by the National Cholesterol Education Program criteria.ResultsDuring the 6.5-year follow-up period, 122 (18%) subjects developed incident cases of MetS. Increases in serum ferritin levels were significantly higher in both women and men with incident MetS compared with women and men without MetS (p = 0.04, p = 0.03). Also, serum ferritin levels increased significantly less in women in whom the criteria for MetS resolved during the follow-up period (p = 0.01). Increases in serum ferritin levels were significantly lower in women in whom the glucose criterion for MetS resolved, and higher in women for whom the waist criterion developed (p = 0.01 and p <0.001, respectively). Serum ferritin levels decreased significantly more in men in whom the triglyceride criterion for MetS resolved during the follow-up period (p = 0.01). There was a clear and significant correlation between change in serum ferritin level and change in waist circumference both in men and women (p <0.001, p <0.01). In addition, correlations between change in serum ferritin level and change in plasma triglyceride as well as glucose levels were strongly positive in men (p <0.001). There was negative correlation between change in serum ferritin and plasma high density cholesterol level both in men and women.ConclusionsIncreases in serum ferritin over a 6,5 year period are associated with development of MetS in both men and women. Whereas, lower increases in serum ferritin over the same timeframe are associated with resolution of hypertriglyceridemia in men and hyperglycemia in women. Increases in waist circumference was positively correlated with increases in serum ferritin in both men and women.

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“…To our knowledge, the sTfR-F has not yet been investigated for associations with any glycemic or insulin outcomes, except for a small correlation study in 110 female T2DM patients from Kuwait (39). Importantly, the sTfR-F-index may not be confused with the sTfR-F-ratio, which lacks the log 10 -transformation of ferritin in the denominator and that has been investigated for association with T2DM in several studies, all reporting inverse associations (11,13,37,40,41). This ratio in our as in other studies (11,13) showed an extremely strong correlation (Pearson rZK0.97) with ferritin, questioning its additional value.…”

Section: Stfr and Stfr-f-indexmentioning

confidence: 99%

Biomarkers of iron metabolism are independently associated with impaired glucose metabolism and type 2 diabetes: the KORA F4 study

Huth

Beuerle

Zierer

et al. 2015

European Journal of Endocrinology

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Objective: Iron has been suggested to play a role in the etiology of type 2 diabetes mellitus (T2DM). Except for ferritin, evidence is sparse for other markers of iron metabolism that are regulated differently and might act through independent pathways. We therefore investigated the associations of serum ferritin, transferrin, soluble transferrin receptor (sTfR), transferrin saturation (TSAT), sTfR-to-log 10 ferritin (sTfR-F) index, and iron with impaired glucose metabolism (IGM/'prediabetes'), T2DM, and four continuous glucose and insulin traits. Design and methods: Data from 2893 participants of the population-based Cooperative Health Research in the Region of Augsburg (KORA) F4 study (Germany) was investigated through regression analysis. The results were adjusted for sociodemographic, life-style, and obesity measures as well as metabolic, inflammatory, and other iron biomarkers following a step-wise approach. Non-linearity was tested by adding a non-linear spline component to the model. Results: Ferritin and transferrin were positively associated with IGM (fourth vs first sex-specific quartile: ferritin odds ratio (OR)Z2.08 (95% CI 1.43-3.04) and transferrin ORZ1.89 (95% CI 1.32-2.70)), T2DM (ferritin ORZ1.98 (95% CI 1.22-3.22) and transferrin ORZ2.42 (95% CI 1.54-3.81)), and fasting as well as 2-h glucose. TSAT (ORZ0.55 (95% CI 0.34-0.88)) and iron (ORZ0.61 (95% CI 0.38-0.97)) were inversely associated with T2DM, sTfR-F-index was inversely associated with IGM (ORZ0.67 (95% CI 0.48-0.95)). There was no strong evidence for non-linear relationships. Conclusions:The observed associations of several markers of iron metabolism with hyperglycemia and insulin resistance suggest that iron stores as well as iron-related metabolic pathways contribute to the pathogenesis of IGM and T2DM. Moreover, TSAT levels are decreased in T2DM patients.

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Body iron stores and the risk of type 2 diabetes in middle-aged men

Cited by 55 publications

References 39 publications

Evidence That Multiple Defects in Lipid Regulation Occur before Hyperglycemia during the Prodrome of Type-2 Diabetes

Evidence That Multiple Defects in Lipid Regulation Occur before Hyperglycemia during the Prodrome of Type-2 Diabetes

Serum ferritin levels and the development of metabolic syndrome and its components: a 6.5-year follow-up study

Biomarkers of iron metabolism are independently associated with impaired glucose metabolism and type 2 diabetes: the KORA F4 study

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