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

Suárez‐Ortegón, Milton Fabian; McLachlan, Stela; Price, Anna H.; Fernández-Balsells, Mercè; Franch-Nadal, Josep; Mata-Cases, Manel; Puente, Joan Barrot-de la; Mundet-Tudurí, Xavier; Mauricio, Dı́dac; Ricart, Wifredo; Strachan, Mark W. J.; Price, Jackie F.; Fernández‐Real, José‐Manuel

doi:10.1016/j.atherosclerosis.2018.03.028

Cited by 14 publications

(13 citation statements)

References 24 publications

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“…The disruption of iron homeostasis can guide tissue iron overload, which has been proven to contribute to the generation of ROS and oxidative stress [9]. Body iron stores, expressed as serum ferritin, have been proposed to be a contributor of atherosclerosis [16], although the epidemiological association is yet to be fully understood [20,21]. The confirmation for this hypothesis is that high serum ferritin levels are associated with oxidative stress, an event implicated in lipoprotein oxidation [9], such as oxLDL [16], Figure 2 shows a diagram that summarizes the possible relationship between oxLDL ferritin-oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, most prior studies were conducted between US and European populations [8,10,14,22,23,25]. There is little evidence in Asian populations [11,12,16,21], and there is scarce information regarding iron metabolism on Mexican and South American populations [26]. Caucasians and Asians have been shown to maintain different serum ferritin levels, suggesting a possible difference in the homeostasis of ferritin between populations [26,27].…”

Section: Discussionmentioning

confidence: 99%

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Increased serum ferritin is associated with oxidized low-density lipoprotein in prediabetes patients: A pilot study

Martínez-Soto

Candia-Plata

López-Soto

et al. 2021

Heliyon

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This pilot study aimed to determine if increased serum ferritin (SF) is associated with cardiovascular risk factors in patients with prediabetes. Methods: Eighteen patients with prediabetes and 36 subjects without prediabetes (control), non-white Hispanic, non-indigenous origin, Mexican mestizo descent were included. Participants had no inflammation, or vascular complications. SF and metabolic markers were evaluated in both groups. Results: SF and oxidized low-density lipoprotein (oxLDL) were increased in prediabetes subjects. Moreover, in prediabetes and control groups as a whole, natural logarithm (ln)-SF correlated with oxLDL and ln-oxLDL/LDL after adjustment for sex, ln-age, ln-fasting plasma glucose (FPG), ln-body mass index, ln-triglyceride (TG), total cholesterol (TC), and high-density lipoproteins. Finally, ln-SF was an independent contributor to ln-oxLDL/LDL ratio in control and prediabetes subjects (β ¼ 0.2915) after the introduction of potential confounders such as FPG, TC, TG, and hypertension. Conclusions: The results of this study indicate that hyperferritinemia is associated with oxLDL, considered one of the main cardiovascular risk factors, which allows us to suggest that an increase in SF could contribute to the progression of prediabetes, prior to the appearance of diabetes. Further research is required to establish a causal relationship of iron disruption metabolism in oxLDL generation under prediabetes conditions.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Increased serum ferritin is associated with oxidized low-density lipoprotein in prediabetes patients: A pilot study

Martínez-Soto

Candia-Plata

López-Soto

et al. 2021

Heliyon

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“…While ferritin levels greater than 1000 ng/mL in serum was described as an overall marker for diseases [44], levels lower than 30 ng/mL were postulated to be an indicator for iron deficiency [45]. Decreased serum ferritin levels were also correlated with a higher risk for cardiovascular diseases in patients with type 2 diabetes [46].…”

Section: Discussionmentioning

confidence: 99%

An In Vitro Barrier Model of the Human Submandibular Salivary Gland Epithelium Based on a Single Cell Clone of Cell Line HTB-41: Establishment and Application for Biomarker Transport Studies

et al. 2020

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The blood–saliva barrier (BSB) consists of the sum of the epithelial cell layers of the oral mucosa and salivary glands. In vitro models of the BSB are inevitable to investigate and understand the transport of salivary biomarkers from blood to saliva. Up to now, standardized, cell line-based models of the epithelium of the submandibular salivary gland are still missing for this purpose. Therefore, we established epithelial barrier models of the submandibular gland derived from human cell line HTB-41 (A-253). Single clone isolation resulted in five different clones (B2, B4, B9, D3, and F11). Clones were compared to the parental cell line HTB-41 using measurements of the transepithelial electrical resistance (TEER), paracellular marker permeability assays and analysis of marker expression for acinar, ductal, and myoepithelial cells. Two clones (B9, D3) were characterized to be of acinar origin, one clone (F11) to be of myoepithelial origin and one isolation (B4) derived from two cells, to be presumably a mixture of acinar and ductal origin. Clone B2, presumably of ductal origin, showed a significantly higher paracellular barrier compared to other clones and parental HTB-41. The distinct molecular identity of clone B2 was confirmed by immunofluorescent staining, qPCR, and flow cytometry. Experiments with ferritin, a biomarker for iron storage, demonstrated the applicability of the selected model based on clone B2 for transport studies. In conclusion, five different clones originating from the submandibular gland cell line HTB-41 were successfully characterized and established as epithelial barrier models. Studies with the model based on the tightest clone B2 confirmed its suitability for transport studies in biomarker research.

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“…In contrast, a recent large sample study from UK shown that low iron status was associated with CVD risk in T2DM, suggesting that low iron status seems to be harmful for cardiovascular health in T2DM. However, the underlying mechanisms are still unclear [10]. The European Prospective Investigation into Cancer and Nutrition-Potsdam study concluded that high SF levels are associated with high risk of T2DM that is independent of established diabetes risk factors [17].…”

Section: Discussionmentioning

confidence: 99%

“…Recent meta-analysis showed that increased ferritin levels were independently and positively associated with the presence of MetS, with an odds ratio of higher than 1.73 [9]. However, a recent large sample study from UK shown that low iron status was associated with CVD risk in T2DM, suggesting that low iron status seems to be harmful for cardiovascular health in T2DM [10].…”

Section: Introductionmentioning

confidence: 99%

Serum ferritin, an early marker of cardiovascular risk: a study in Chinese men of first-degree relatives with family history of type 2 diabetes

Liu

Yin

et al. 2019

BMC Cardiovasc Disord

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Background Ferritin is one of the key proteins that regulate iron homeostasis and is widely available clinical biomarker of iron status. This study aimed to discuss the influence of serum ferritin (SF) on cardiovascular risk factors in the first-degree relatives with family history of type 2 diabetes (FHD). Methods This cross-sectional study included 232 men. Anthropometric measurements and blood samples were analyzed. The people were divided into four groups according to median SF (102.8 ng/ml) and people with or without FHD. Group A (FHD–and low SF), group B (FHD–and high SF), group C (FHD+ and low SF), and group D (FHD+ and high SF). Results The subjects in different categories of SF concentrations showed significant differences in BMI (SF main effect: P = 0.010), WC ( P = 0.030), SBP ( P < 0.001), FPG ( P < 0.001), PPG-2 h ( P < 0.001), FINS ( P < 0.001), and HOMA-IR ( P = 0.015; all: 2-way ANOVA). There was a significant difference in SBP (FHD main effect: P = 0.003), DBP ( P = 0.006), and FINS ( P = 0.013, all: 2-way ANOVA) between the groups with or without FHD. The interaction term between SF and FHD was significant for SBP ( P = 0.011), DBP ( P = 0.012), and PPG-2 h ( P = 0.022). Logistic analysis showed that accumulation of CVD risk factors, which were ≥ 2 items and ≥ 3 items in group D were 7.546 and 3.343 times higher compared with group A ( P < 0.05). Conclusions The increased SF levels increased the risk of cardiovascular risk factors and the occurrence of insulin resistance in first-degree relatives with FHD.

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

Abstract: Low iron status was associated with CVD risk in T2D. This pattern was consistent in populations at different cardiovascular risk. Low iron status seems to be harmful for cardiovascular health in T2D and it may be a target for intervention.

Cited by 14 publications

References 24 publications

Increased serum ferritin is associated with oxidized low-density lipoprotein in prediabetes patients: A pilot study

Increased serum ferritin is associated with oxidized low-density lipoprotein in prediabetes patients: A pilot study

An In Vitro Barrier Model of the Human Submandibular Salivary Gland Epithelium Based on a Single Cell Clone of Cell Line HTB-41: Establishment and Application for Biomarker Transport Studies

Serum ferritin, an early marker of cardiovascular risk: a study in Chinese men of first-degree relatives with family history of type 2 diabetes

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