Elevated serum ferritin levels and increased body iron stores are now recognized as features that sometimes occur in the insulin resistance syndrome (IRS; also known as the metabolic syndrome) and type 2 diabetes mellitus. A key component of IRS is abdominal obesity. Other metabolic risk factors may also accompany IRS, including atherogenic dyslipidemia, hypertension, a pro-thrombotic state, and a pro-inflammatory state. Some persons are genetically predisposed to IRS. Acquired factors, such as excess body fat and physical inactivity, can elicit IRS in some persons. The incidence of IRS is increasing, and it is estimated about 25% of adult Americans have IRS. Approximately 15% of individuals with IRS have increased ferritin levels. Increased hepatic iron has been found in as many as one-third of patients with non-alcoholic fatty liver disease (NAFLD). NAFLD, a manifestation of IRS, is characterized by hepatic insulin resistance. The molecular mechanisms underlying the interrelationship between insulin resistance, NAFLD, and iron metabolism remain unclear.

Clinical manifestations

In 1997, Moirand et al. described a new syndrome of moderate hepatic iron overload with normal transferrin saturation. It is now considered that most of these patients, and those in a subsequent study by the same group, had IRS with iron overload. In the first study, Moirand et al. described 65 patients who had been referred for further evaluation of suspected iron overload. These patients were referred either for an evaluation of fatigue and arthralgias or hyperferritinemia.