Association between serum ferritin and the insulin resistance syndrome in a representative population

Wrede, Christian; Buettner, Roland; Bollheimer, Leo Cornelius; Schölmerich, J; Palitzsch, Klaus‐Dieter; Hellerbrand, Claus

doi:10.1530/eje.1.02083

Cited by 136 publications

(115 citation statements)

References 30 publications

(29 reference statements)

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“…One of these 5 had diagnoses and laboratory values consistent with metabolic syndrome, a condition associated with moderately increased ferritin levels in Northern European populations, 22 including our own. There were 35 patients who were not homozygotes or compound heterozygotes for HFE mutations.…”

Section: Resultsmentioning

confidence: 82%

Screening for hemochromatosis by measuring ferritin levels: a more effective approach

Waalen

Felitti

Gelbart

et al. 2008

Blood

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Because the penetrance of HFE hemochromatosis is low, traditional population screening measuring the transferrin saturation is unlikely to be cost-effective because the majority of subjects detected neither have clinical disease nor are likely to develop it. Three independent studies show that only patients with serum ferritin concentrations more than 1000 g/L are at risk for cirrhosis, one of the main morbidities of hemochromatosis. Among 29 699 white subjects participating in the Scripps/Kaiser hemochromatosis study, only 59 had serum ferritin levels more than 1000 g/L; 24 had homozygous mutant or compound heterozygous mutant HFE genotypes. In all but 5 of the other subjects, the causes of elevated ferritin were excessive alcohol intake, cancer, or liver disease. Screening for hemochromatosis with serum ferritin levels will detect the majority of patients who will be clinically affected and may detect other clinically significant disease in patients who IntroductionAt one time, hereditary hemochromatosis was regarded as the "poster child" for genetic screening for a common, treatable disease. However, enthusiasm for screening for hemochromatosis waned after several large controlled studies showed that the penetrance of the homozygous state for the HFE C282Y mutation is much lower than had previously been thought. These studies showed that the nonspecific symptoms attributed to iron overload in C282Y homozygotes were equally prevalent in controls, leading to a more specific definition of penetrance based on the presence of liver disease. Although there may be disagreement of whether the penetrance in males is of the order of 2% as shown by our studies 1 and those of others, 2,3 or whether it approaches 5% as suggested by the prevalence of cirrhosis found by others, 4,5 it is clear that earlier penetrance estimates of 95% 6 or 43% 7 on which calculation of the cost-effectiveness of screening strategies were based are no longer tenable.Because such cost estimates are based on the number of patients who may be helped by therapy, the low penetrance of hemochromatosis makes screening much more expensive than had originally been estimated. Accordingly, strategies aimed at lowering the expense of screening, such as performing less costly unsaturated iron binding capacity measurements rather than transferrin saturation determinations, 8 or focusing on "at-risk" groups 9-12 have been proposed to bring population screening closer to cost-effectiveness. Although such approaches may decrease somewhat the cost per case found, the majority of detected subjects will not have a clinical phenotype, nor will they be fated to develop one in the future. As a result, many essentially normal patients will be subjected to further extensive and often expensive examinations from which they will not benefit.What is needed is a means of limiting screening to subjects who are not only at high risk of being homozygous for the C282Y mutation (which occurs almost exclusively in persons of European ancestry) but who also are at increased ris...

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Section: Resultsmentioning

confidence: 82%

Screening for hemochromatosis by measuring ferritin levels: a more effective approach

Waalen

Felitti

Gelbart

et al. 2008

Blood

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“…It is found in one third to half of patients with NAFLD and ranges from mild elevations to rarely 10001500 ng/mL [17] . Serum ferritin concentrations increase with the number of features of the MetS [21] . Transferrin saturation (TfS) is typically in the upper range of normal or mildly elevated (45%50%) which is distinct from hereditary hemochromatosis, where hyperferritinemia is accompanied by markedly elevated TfS and usually TfS is elevated before the development of hyperferritinemia in early stages of hemochromatosis [22] .…”

Section: What Is the Iron Phenotype Of Nafld?mentioning

confidence: 98%

“…However, glucose metabolism and iron homeostasis appear to be functionally inter connected, due to the fact that gluconeogenetic signals regulate iron homeostasis via hepcidin [34] while iron loading or deficiency directly affect circulating glucose concentrations in mammals most likely via its effects on citric acid cycle enzyme activities [35,36] , thereby also affecting lipid profiles [37] . Ferritin concentrations were associated with an increased rate of diabetes and gestational diabetes [3843] , with BMI [44] , visceral fat mass [45] , serum glucose levels and insulin sensitivity [46] , blood pressure [47] , the MetS [21,48] , the polycystic ovary syndrome (PCOS) [49] and cholesterol [50] . Higher parameters of iron storage clustered with metabolic risk markers in a study of obese [51] and healthy lean adolescents [52] .…”

Section: Ir and Associated Metabolic Conditionsmentioning

confidence: 99%

Dysregulation of iron and copper homeostasis in nonalcoholic fatty liver

Aigner

Weiss

Datz

2014

WJH

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Elevated iron stores as indicated by hyperferritinemia with normal or mildly elevated transferrin saturation and mostly mild hepatic iron deposition are a characteristic finding in subjects with non-alcoholic fatty liver disease (NAFLD). Excess iron is observed in approximately one third of NAFLD patients and is commonly referred to as the "dysmetabolic iron overload syndrome". Clinical evidence suggests that elevated body iron stores aggravate the clinical course of NAFLD with regard to liver-related and extrahepatic disease complications which relates to the fact that excess iron catalyses the formation of toxic hydroxylradicals subsequently resulting in cellular damage. Iron removal improves insulin sensitivity, delays the onset of type 2 diabetes mellitus, improves pathologic liver function tests and likewise ameliorates NAFLD histology. Several mechanisms contribute to pathologic iron accumulation in NAFLD. These include impaired iron export from hepatocytes and mesenchymal Kupffer cells as a consequence of imbalances in the concentrations of iron regulatory factors, such as hepcidin, cytokines, copper or other dietary factors. This review summarizes the knowledge about iron homeostasis in NAFLD and the rationale for its therapeutic implications.

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“…To further complicate the picture, associations have been made between insulin resistance and serum ferritin, in which the severity of insulin resistance syndrome has been correlated to increasing serum ferritin levels (Wrede, 2006). Several studies have attempted to understand the relationships among iron overload, insulin resistance, and CHC (D'Souza et al, 2005;Palekar and Harrison, 2005); both Hernandez et al (2000) and Lecube et al (2004) found that the presence of diabetes mellitus was the primary risk factor for increased ferritin levels in patients with CHC.…”

Section: Ironmentioning

confidence: 99%

Assessment of Increased Serum Aminotransferases in a Managed Atlantic Bottlenose Dolphin (Tursiops Truncatus) Population

Venn‐Watson

Smith

Jensen

2008

Journal of Wildlife Diseases

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ABSTRACT:Nonspecific chronic hepatitis and increased activities of serum aminotransferases have been reported in cetaceans (dolphins, porpoises, and whales). We identified bottlenose dolphins in our current population with episodic increases in serum aminotransferases, specifically alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and we hypothesized that hematologic and serum biochemical changes in these animals may provide clues as to potential causes of liver disease in cetaceans. A retrospective case-control study involving 1,288 blood samples collected during 1998-2006 from 18 dolphins (six cases and 12 age-and sex-matched healthy controls) was conducted to compare eosinophil and platelet counts; and serum proteins, albumin, globulins, bilirubin, gamma glutamyltransferase (GGT), cholesterol, triglycerides, glucose, iron, and erythrocyte sedimentation rates. Bottlenose dolphins with increased ALT and AST activities were more likely to have higher serum globulins, bilirubin, GGT, iron, glucose, triglycerides, and cholesterol levels, greater erythrocyte sedimentation rates, and lower platelet counts compared to healthy controls. Our findings suggest that dolphins with chronic increases in aminotransferases may have a chronic hepatitis involving iron overload with similar etiologies and pathophysiology compared to terrestrial mammals. Areas for future research include predisposing metabolic risk factors; associations between iron overload and a diabetes-like condition; and a potential overlap syndrome involving autoimmune responses that may or may not be associated with viral infection.

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Association between serum ferritin and the insulin resistance syndrome in a representative population

Cited by 136 publications

References 30 publications

Screening for hemochromatosis by measuring ferritin levels: a more effective approach

Screening for hemochromatosis by measuring ferritin levels: a more effective approach

Dysregulation of iron and copper homeostasis in nonalcoholic fatty liver

Assessment of Increased Serum Aminotransferases in a Managed Atlantic Bottlenose Dolphin (Tursiops Truncatus) Population

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