Prevalence of Body Iron Excess in the Metabolic Syndrome

Bozzini, Claudia; Girelli, Domenico; Olivieri, Oliviero; Martinelli, Nicola; Bassi, Antonella; Matteis, Giovanna De; Tenuti, Ilaria; Lotto, Valentina; Friso, Simonetta; Pizzolo, Francesca; Corrocher, Roberto

doi:10.2337/diacare.28.8.2061

Cited by 183 publications

(149 citation statements)

References 33 publications

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“…Indeed, in 1998, iron stores, expressed as serum ferritin concentration, were proposed to be a component of the MetS (10,11), and increased prevalence of excess iron in the body was observed in subjects with the syndrome (12). Insulin resistance measured using gold-standard methodologies (euglycemichyperinsulinemic clamp) was associated with total body iron stores, even in the presence of normal glucose tolerance (11).…”

Section: Inherited Versus Acquired Iron Overload Syndromesmentioning

confidence: 99%

Mechanisms Linking Glucose Homeostasis and Iron Metabolism Toward the Onset and Progression of Type 2 Diabetes

2015

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OBJECTIVEThe bidirectional relationship between iron metabolism and glucose homeostasis is increasingly recognized. Several pathways of iron metabolism are modified according to systemic glucose levels, whereas insulin action and secretion are influenced by changes in relative iron excess. We aimed to update the possible influence of iron on insulin action and secretion and vice versa. RESEARCH DESIGN AND METHODSThe mechanisms that link iron metabolism and glucose homeostasis in the main insulin-sensitive tissues and insulin-producing b-cells were revised according to their possible influence on the development of type 2 diabetes (T2D). RESULTSThe mechanisms leading to dysmetabolic hyperferritinemia and hepatic overload syndrome were diverse, including diet-induced alterations in iron absorption, modulation of gluconeogenesis, heme-mediated disruption of circadian glucose rhythm, impaired hepcidin secretion and action, and reduced copper availability. Glucose metabolism in adipose tissue seems to be affected by both iron deficiency and excess through interaction with adipocyte differentiation, tissue hyperplasia and hypertrophy, release of adipokines, lipid synthesis, and lipolysis. Reduced heme synthesis and dysregulated iron uptake or export could also be contributing factors affecting glucose metabolism in the senescent muscle, whereas exercise is known to affect iron and glucose status. Finally, iron also seems to modulate b-cells and insulin secretion, although this has been scarcely studied. CONCLUSIONSIron is increasingly recognized to influence glucose metabolism at multiple levels. Body iron stores should be considered as a potential target for therapy in subjects with T2D or those at risk for developing T2D. Further research is warranted.Iron levels help to modulate the clinical manifestations of numerous systemic diseases. The importance of adequate amounts of iron for health and well-being in humans is well known. Iron is involved in binding and transporting oxygen and regulating cell growth and differentiation, as well as electron transport, DNA synthesis, and many important metabolic processes (1).From a clinical standpoint, assessing serum ferritin concentrations is a useful measure of iron storage. Ferritin is also an acute-phase reactant and, as such, is

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Section: Inherited Versus Acquired Iron Overload Syndromesmentioning

confidence: 99%

Mechanisms Linking Glucose Homeostasis and Iron Metabolism Toward the Onset and Progression of Type 2 Diabetes

2015

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“…To our knowledge, this study is the first to investigate the prevalence and the nature of gonadal dysfunction in men with the dysmetabolic iron overload syndrome, a situation which is observed in about 10-20% of overweight individuals in Europe (14). Data on the frequency of hypogonadism based on BT are scarce in men with the metabolic syndrome or type 2 diabetes.…”

Section: Discussionmentioning

confidence: 99%

Liver iron overload is associated with elevated SHBG concentration and moderate hypogonadotrophic hypogonadism in dysmetabolic men without genetic haemochromatosis

Gautier

Lainé

Massart

et al. 2011

European Journal of Endocrinology

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Aims: To assess the relation between moderate iron overload on sex hormone binding globulin (SHBG) levels and gonadotroph function in men with dysmetabolic iron overload syndrome and the effects of phlebotomy. Methods: The relationship between magnetic resonance imaging assessed liver iron concentration (LIC) and plasma ferritin levels with total testosterone, bioavailable testosterone (BT), SHBG and LH levels, were studied in 50 men with moderate dysmetabolic iron excess, in the absence of genetic haemochromatosis, who were randomised to phlebotomy therapy or to normal care. Results: Four patients (8%) had low total testosterone (!10.4 nmol/l) and 13 patients (26%) had low BT (!2.5 nmol/l). In the entire population, those with LIC above the median (90 mmol/l) had a higher mean SHBG (PZ0.028), lower LH (PZ0.039) than those with LIC below the median. In multivariable analysis (adjusted for age, and fasting insulin) LIC was significantly associated with SHBG (positively) and LH (negatively). Patients in the highest quartile of SHBG had higher LIC (PZ0.010) and higher ferritinaemia (PZ0.012) than those in the three other quartiles. Iron depletion by venesection did not significantly improve any hormonal levels. Conclusions: Hypogonadism is not infrequent in men with dysmetabolic iron overload syndrome. Liver iron excess is associated with increased plasma SHBG and moderate hypogonadotrophic hypogonadism. Phlebotomy therapy needs further investigation in symptomatic hypogonadal men with dysmetabolic iron excess.

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“…In metabolic liver diseases, hepatic iron overlord was seen in nonalcoholic fatty liver disease patients in several regions [24][25][26]. Iron overlord was also related to development of insulin resistance [25] and several kinds of metabolic syndrome indexes like body mass index, while triglycerides are significantly associated with ferritin values [27]. Although Jeju groundwaters do not have a free radical scavenging or antioxidative ability, S1 and S2 (but not S3) may be able to reduce free radicals during oxidation of ferrous ions, and are beneficial to lipid metabolism after multiple-daily intake.…”

Section: Discussionmentioning

confidence: 99%

Beneficial effects of natural Jeju groundwaters on lipid metabolism in high-fat diet-induced hyperlipidemic rats

Wang

Jin

et al. 2014

Nutr Res Pract

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BACKGROUND:Groundwater is believed to possess many beneficial effects due to its natural source of various minerals. In this study, we examined the effects of natural Jeju groundwater S1 (Samdasoo TM ), S2 and S3 pumped up from different locations of Jeju Island, Korea, along with local tap water, on body weight gain, serum lipids and lipoproteins, and liver histopathology in high-fat diet-induced hyperlipidemic rats. MATERIALS/METHODS: Rats were randomly and equally divided into 6 groups. Different water samples were supplied to the hyperlipidemic rats as their daily drinking water and the widely-used anti-hyperlipidemic drug simvastatin was used as a positive control. Body weight, serum lipids and lipoproteins were measured weekly. Liver weight, liver index and liver histopathology were examined after the execution of the rats. RESULTS: After drinking Jeju groundwaters for two months, S2 but not S3 significantly reduced weight growth and serum triglycerides levels and increased high density lipoprotein-C (HDL-C) without affecting total cholesterol or LDL-C. S1 and particularly S2 significantly reduced the severity of liver hypertrophy and steatosis. All Groundwaters had much higher contents of vanadium (S3>S2>S1>>tap water) whereas S1 and S2 but not S3 markedly blocked autoxidation of ferrous ions. CONCLUSION: Jeju Groundwater S1 and particularly S2 exhibit protective effects against hyperlipidemia and fatty liver and hypothesize that the beneficial effect of Jeju Groundwaters may be contributed from blockade of autoxidation of ferrous ions rather than their high contents of vanadium.

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Prevalence of Body Iron Excess in the Metabolic Syndrome

Cited by 183 publications

References 33 publications

Mechanisms Linking Glucose Homeostasis and Iron Metabolism Toward the Onset and Progression of Type 2 Diabetes

Mechanisms Linking Glucose Homeostasis and Iron Metabolism Toward the Onset and Progression of Type 2 Diabetes

Liver iron overload is associated with elevated SHBG concentration and moderate hypogonadotrophic hypogonadism in dysmetabolic men without genetic haemochromatosis

Beneficial effects of natural Jeju groundwaters on lipid metabolism in high-fat diet-induced hyperlipidemic rats

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