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      Relationship between iron status markers and insulin resistance: an exploratory study in subjects with excess body weight

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          Abstract

          Background

          Controversy exists on the relationship between iron metabolism and cardiometabolic risk. The aim of this study was to determine if there is a link between dysmetabolic iron and cardiometabolic markers in subjects with excess body weight.

          Methods

          Cross-sectional study with fifty participants presenting overweight or obesity and at least another metabolic syndrome factor. Determinations: anthropometry, body composition, blood pressure, lipids, glucose, insulin, leptin, areas under the curve (AUC) for glucose and insulin after an oral glucose tolerance test, hs-C reactive protein (hs-CRP), blood count, ferritin, transferrin, transferrin saturation (TSAT), soluble transferrin receptor (sTfR). Gender-adjusted linear correlations and two independent samples t tests were used.

          Results

          Ferritin was positively correlated with insulin-AUC ( r = 0.547, p = 0.008) and TSAT was negatively correlated with waist-hip ratio ( r =  − 0.385, p = 0.008), insulin ( r =  − 0.551, p < 0.001), and insulin resistance (HOMA-IR, r =  − 0.586, p < 0.001). Subjects with TSAT ≤ 20% had higher insulin ( p = 0.012) and HOMA-IR ( p = 0.003) compared to those with TSAT > 20%. In conclusion, the observed results suggest that iron transport and storage are altered in subjects with overweight/obesity, at the same time that they exhibit the characteristic features of insulin resistance. Nevertheless, this occurs without iron overload or deficiency. These results should be validated in wider cohorts since they suggest that iron transport and storage should be assessed when performing the clinical evaluation of subjects with excess body weight.

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          Most cited references23

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          Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19·2 million participants

          Summary Background Underweight and severe and morbid obesity are associated with highly elevated risks of adverse health outcomes. We estimated trends in mean body-mass index (BMI), which characterises its population distribution, and in the prevalences of a complete set of BMI categories for adults in all countries. Methods We analysed, with use of a consistent protocol, population-based studies that had measured height and weight in adults aged 18 years and older. We applied a Bayesian hierarchical model to these data to estimate trends from 1975 to 2014 in mean BMI and in the prevalences of BMI categories (<18·5 kg/m2 [underweight], 18·5 kg/m2 to <20 kg/m2, 20 kg/m2 to <25 kg/m2, 25 kg/m2 to <30 kg/m2, 30 kg/m2 to <35 kg/m2, 35 kg/m2 to <40 kg/m2, ≥40 kg/m2 [morbid obesity]), by sex in 200 countries and territories, organised in 21 regions. We calculated the posterior probability of meeting the target of halting by 2025 the rise in obesity at its 2010 levels, if post-2000 trends continue. Findings We used 1698 population-based data sources, with more than 19·2 million adult participants (9·9 million men and 9·3 million women) in 186 of 200 countries for which estimates were made. Global age-standardised mean BMI increased from 21·7 kg/m2 (95% credible interval 21·3–22·1) in 1975 to 24·2 kg/m2 (24·0–24·4) in 2014 in men, and from 22·1 kg/m2 (21·7–22·5) in 1975 to 24·4 kg/m2 (24·2–24·6) in 2014 in women. Regional mean BMIs in 2014 for men ranged from 21·4 kg/m2 in central Africa and south Asia to 29·2 kg/m2 (28·6–29·8) in Polynesia and Micronesia; for women the range was from 21·8 kg/m2 (21·4–22·3) in south Asia to 32·2 kg/m2 (31·5–32·8) in Polynesia and Micronesia. Over these four decades, age-standardised global prevalence of underweight decreased from 13·8% (10·5–17·4) to 8·8% (7·4–10·3) in men and from 14·6% (11·6–17·9) to 9·7% (8·3–11·1) in women. South Asia had the highest prevalence of underweight in 2014, 23·4% (17·8–29·2) in men and 24·0% (18·9–29·3) in women. Age-standardised prevalence of obesity increased from 3·2% (2·4–4·1) in 1975 to 10·8% (9·7–12·0) in 2014 in men, and from 6·4% (5·1–7·8) to 14·9% (13·6–16·1) in women. 2·3% (2·0–2·7) of the world’s men and 5·0% (4·4–5·6) of women were severely obese (ie, have BMI ≥35 kg/m2). Globally, prevalence of morbid obesity was 0·64% (0·46–0·86) in men and 1·6% (1·3–1·9) in women. Interpretation If post-2000 trends continue, the probability of meeting the global obesity target is virtually zero. Rather, if these trends continue, by 2025, global obesity prevalence will reach 18% in men and surpass 21% in women; severe obesity will surpass 6% in men and 9% in women. Nonetheless, underweight remains prevalent in the world’s poorest regions, especially in south Asia. Funding Wellcome Trust, Grand Challenges Canada.
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            Assessing iron status: beyond serum ferritin and transferrin saturation.

            The increasing prevalence of multiple comorbidities among anemic patients with chronic kidney disease has made the use of serum ferritin and transferrin saturation more challenging in diagnosing iron deficiency. Because serum ferritin is an acute-phase reactant and because the inflammatory state may inhibit the mobilization of iron from reticuloendothelial stores, the scenario of patients with serum ferritin >800 ng/ml, suggesting iron overload, and transferrin saturation <20%, suggesting iron deficiency, has become more common. This article revisits the basis for the Kidney Disease Outcomes Quality Initiative recommendations regarding the use of serum ferritin and transferrin saturation in guiding iron therapy, then explores some of the newer alternative markers for iron status that may be useful when serum ferritin and transferrin saturation are insufficient. These newer tests include reticulocyte hemoglobin content, percentage of hypochromic red cells, and soluble transferrin receptor, all of which have shown some promise in limited studies. Finally, the role of hepcidin, a hepatic polypeptide, in the pathophysiology of iron mobilization is reviewed briefly.
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              Obesity as an Emerging Risk Factor for Iron Deficiency

              Iron homeostasis is affected by obesity and obesity-related insulin resistance in a many-facetted fashion. On one hand, iron deficiency and anemia are frequent findings in subjects with progressed stages of obesity. This phenomenon has been well studied in obese adolescents, women and subjects undergoing bariatric surgery. On the other hand, hyperferritinemia with normal or mildly elevated transferrin saturation is observed in approximately one-third of patients with metabolic syndrome (MetS) or nonalcoholic fatty liver disease (NAFLD). This constellation has been named the “dysmetabolic iron overload syndrome (DIOS)”. Both elevated body iron stores and iron deficiency are detrimental to health and to the course of obesity-related conditions. Iron deficiency and anemia may impair mitochondrial and cellular energy homeostasis and further increase inactivity and fatigue of obese subjects. Obesity-associated inflammation is tightly linked to iron deficiency and involves impaired duodenal iron absorption associated with low expression of duodenal ferroportin (FPN) along with elevated hepcidin concentrations. This review summarizes the current understanding of the dysregulation of iron homeostasis in obesity.
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                Author and article information

                Contributors
                Journal
                PeerJ
                PeerJ
                peerj
                peerj
                PeerJ
                PeerJ Inc. (San Diego, USA )
                2167-8359
                31 July 2020
                2020
                : 8
                : e9528
                Affiliations
                [1 ]Department of Metabolism and Nutrition, Institute of Food Science and Technology and Nutrition (ICTAN-CSIC) , Madrid, Spain
                [2 ]Madrid Institute for Rural, Agricultural and Food Research and Development (IMIDRA) , Madrid, Spain
                [3 ]Department of Biology, Universidad Autónoma de Madrid (UAM) , Madrid, Spain, España
                Article
                9528
                10.7717/peerj.9528
                7397981
                32821534
                f2c2cb20-3262-4e33-a071-da6c9b1980cf
                ©2020 Vaquero et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.

                History
                : 23 January 2020
                : 21 June 2020
                Funding
                Funded by: Spanish Ministry of Economy and Competitiveness
                Award ID: AGL201455102-JIN
                Funded by: European Social Fund (ESF)
                Funded by: Unit of Information Resources for Research (URICI)
                This study was funded by the Spanish Ministry of Economy and Competitiveness (MINNECO-FEDER, grant: AGL2014 55102-JIN). Angélica Gallego-Narbón was funded by the Youth Employment Initiative (YEI) from the European Social Fund (ESF). Support for the publication fee was provided by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Biochemistry
                Diabetes and Endocrinology
                Nutrition
                Public Health

                iron,ferritin,tranferrin,insulin resistance,obesity
                iron, ferritin, tranferrin, insulin resistance, obesity

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