Hyperferritinemia Is Associated with Insulin Resistance and Fatty Liver in Patients without Iron Overload

Abstract

ObjectiveDuring the last 10 years we have experienced an increasing number of referrals due to hyperferritinemia. This is probably due to increased awareness of hereditary hemochromatosis, and the availability of a genetic test for this condition. Most of these referred patients were over-weight middle-aged men with elevated ferritin levels, but without the hemochromatosis-predisposing gene mutations. We evaluated the relationship between hyperferritinemia and the metabolic syndrome in 40 patients.MethodsForty consecutive patients referred for hyperferritinemia were investigated. The examination programme included medical history, clinical investigation and venous blood samples drawn after an overnight fast. This resulted in 34 patients with unexplained hyperferritinemia, which were further examined. Liver biopsy was successfully performed in 29 subjects. Liver iron stores were assessed morphologically, and by quantitative phlebotomy in 16 patients.ResultsThe majority of the patients had markers of the metabolic syndrome, and 18 patients (52%) fulfilled the IDF-criteria for the metabolic syndrome. Mean body mass index was elevated (28,8±4,2), mean diastolic blood pressure was 88,5±10,5 mmHg, and mean fasting insulin C-peptide 1498±539 pmol/l. Liver histology showed steatosis and nuclear glycogen inclusions in most patients (19 out of 29). Only four patients had increased iron stores by histology, of which two could be explained by alcohol consumption. Fourteen of 16 patients normalized ferritin levels after phlebotomy of a cumulative blood amount corresponding to normal iron stores. Ferritin levels were significantly related to insulin C-peptide level (p<0.002) and age (p<0.002).ConclusionThe present results suggest that liver steatosis and insulin resistance but not increased iron load is frequently seen in patients referred for suspected hemochromatosis on the basis of hyperferritinemia. The ferritin level seems to be positively associated to insulin resistance.

Serum Ferritin Level is an Independent Predictor of Insulin Resistance in Non-diabetic Men Aged Between 30-69 Years: Korean National Health and Nutrition Examination Survey 2008-2010

“…In men, ferritin level was independently associated with HOMA-IR in the entire model analyzed (p<0.05; Many previous studies suggested that the association between ferritin and insulin resistance is mediated by body fat content, 17 systemic inflammation 6 or nonalcoholic fatty liver disease. 24 However, our study suggested that elevated ferritin level might be an independent risk factor of insulin resistance aside from the mediators suggested in previous studies. Reduction of iron stores by blood donation or phlebotomy have been reported to improve insulin sensitivity, 25,26 which also supports that iron overload might be a primary cause of insulin resistance.…”

Evaluation of Serum-Free Iron and Glycated Hemoglobin in Uncontrolled Type-Ii Diabetic Patients

“…Increased glycation of proteins as a result of poor glycemic control triggers the increased release of free iron from glycated proteins like hemoglobin which generates a vicious cycle of hyperglycemia, glycation of hemoglobin, and increase in levels of free iron [18]. The relationship between free iron and Type-2 diabetes is bidirectional [24].…”

“…The mechanisms for insulin resistance include the possibility of iron overload causing resistance directly or through hepatic dysfunction. Patients with unexplained hepatic iron overload mostly found to be insulin resistant, which suggests a common etiologic link among hepatic iron, hepatic dysfunction, and insulin resistance [18]. This study was aimed to determine serum free iron in person with diabetes and healthy individuals.…”

Hyperferritinemia in patients with nonalcoholic fatty liver disease

“…Brudevold et al 17 assessed the relationship between MetS and HPF in 40 patients consecutively referred for investigation of this disorder in 2001. Among the 29 subjects who underwent hepatic biopsy, 19 had steatosis and four had iron overload; 52% met criteria for MetS according to IDF criteria.…”