Do high ferritin levels confer lower cardiovascular risk in men with Type 2 diabetes?

Hermans, Michel P.; Ahn, Sylvie A.; Amoussou-Guenou, K. Daniel; Baldé, NM; Rousseau, Michel F.

doi:10.1111/j.1464-5491.2010.02979.x

Cited by 9 publications

(9 citation statements)

References 28 publications

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“…Hermans et al . reported lower prevalence of coronary artery disease, cerebrovascular disease and peripheral artery disease in men with Type 2 diabetes who had high serum ferritin . In diabetic microangiopathy, however, Canturk et al .…”

Section: Introductionmentioning

confidence: 95%

“…The relationship between serum ferritin and diabetic complications has been controversial. Hermans et al reported lower prevalence of coronary artery disease, cerebrovascular disease and peripheral artery disease in men with Type 2 diabetes who had high serum ferritin [13]. In diabetic microangiopathy, however, Canturk et al reported a significant association between serum ferritin and diabetic retinopathy [5].…”

Section: Introductionmentioning

confidence: 99%

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Association between serum ferritin and microalbuminuria in Type 2 diabetes in Taiwan

Hsu

Huang²,

Chang

et al. 2013

Diabet. Med.

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Aims Serum ferritin has been found closely related with diabetes and glucose metabolism, but its impact on diabetic nephropathy remains unknown. This study aimed to explore the association between serum ferritin and microalbuminuria in Type 2 diabetes. Methods Eight hundred and fifty‐one subjects with Type 2 diabetes were selected from a cohort participating in a glycaemic control study in Taiwan in 2008. We used urine albumin:creatinine ratio to define microalbuminuria; serum ferritin was divided into quartiles for analysis. Logistic regression and trend tests were used to delineate the association between serum ferritin and microalbuminuria. Results Subjects with diabetes with higher ferritin tended to have more metabolic disorders, higher high‐sensitivity C‐reactive protein and higher prevalence of microalbuminuria. Compared with those in the lowest quartile, subjects with diabetes in the highest ferritin quartile were 55% (P = 0.029) more likely to have microalbuminuria. After controlling for demographics, metabolic profiles and other inflammatory markers, the association between serum ferritin levels and microalbuminuria remained significant (P for trend < 0.001). This independent relationship was not changed either for those who had better glycaemic control or those who had not used an angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker. Conclusions The current study shows hyperferritinemia may be an independent risk factor of nephropathy in patients with Type 2 diabetes.

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Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Association between serum ferritin and microalbuminuria in Type 2 diabetes in Taiwan

Hsu

Huang²,

Chang

et al. 2013

Diabet. Med.

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“…Consistent with free fatty acids having a regulatory role in ferritin expression, the ferritin concentration has been noted to be elevated in adipocytes (29), in obesity (11,12), hyperlipidemia (30), and type II diabetes (31), and in myelinated neuronal tissue (32). Interestingly, total blood iron is not increased nearly as much as the ferritin concentration in type II diabetes (31), suggesting that the lipid, and not iron, is driving ferritin expression. Our finding that caprylate also binds ferritin makes it likely that a range of fatty acids or fatty acid-like endogenous substances bind this same ferritin site; it is certainly possible that it is not optimized for arachidonate.…”

Section: Discussionmentioning

confidence: 87%

“…Interestingly, the searched‐for associations have been inconsistent at best. For example, cardiovascular risk in type II diabetes was found to be paradoxically lower in those with high ferritin levels (31) or simply unassociated with serum ferritin levels (34). Finally, the results of an interventional clinical trial of the “iron‐heart” hypothesis of cardiovascular disease was largely negative (33).…”

Section: Discussionmentioning

confidence: 99%

Ferritin couples iron and fatty acid metabolism

Liu

Cheung-Lau

et al. 2012

FASEB j.

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A physiological relationship between iron, oxidative injury, and fatty acid metabolism exists, but transduction mechanisms are unclear. We propose that the iron storage protein ferritin contains fatty acid binding sites whose occupancy modulates iron uptake and release. Using isothermal microcalorimetry, we found that arachidonic acid binds ferritin specifically and with 60 μM affinity. Arachidonate binding by ferritin enhanced iron mineralization, decreased iron release, and protected the fatty acid from oxidation. Cocrystals of arachidonic acid and horse spleen apoferritin diffracted to 2.18 Å and revealed specific binding to the 2-fold intersubunit pocket. This pocket shields most of the fatty acid and its double bonds from solvent but allows the arachidonate tail to project well into the ferrihydrite mineralization site on the ferritin L-subunit, a structural feature that we implicate in the effects on mineralization by demonstrating that the much shorter saturated fatty acid, caprylate, has no significant effects on mineralization. These combined effects of arachidonate binding by ferritin are expected to lower both intracellular free iron and free arachidonate, thereby providing a previously unrecognized mechanism for limiting lipid peroxidation, free radical damage, and proinflammatory cascades during times of cellular stress.

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“…So far, only one cross-sectional study of 424 people has tested this hypothesis. The authors reported an apparently paradoxical decreased prevalence of macroangiopathy in men with T2D and increased serum ferritin levels but adjustment for covariates was not performed (7)].…”

Section: Introductionmentioning

confidence: 99%

Decreased iron stores are associated with cardiovascular disease in patients with type 2 diabetes both cross-sectionally and longitudinally

et al. 2018

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Do high ferritin levels confer lower cardiovascular risk in men with Type 2 diabetes?

Cited by 9 publications

References 28 publications

Association between serum ferritin and microalbuminuria in Type 2 diabetes in Taiwan

Association between serum ferritin and microalbuminuria in Type 2 diabetes in Taiwan

Ferritin couples iron and fatty acid metabolism

Decreased iron stores are associated with cardiovascular disease in patients with type 2 diabetes both cross-sectionally and longitudinally

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