Iron Excess, Early Glucose Intolerance and Impaired Insulin Secretion in Idiopathic Haemochromatosis

Abstract. The relationship between iron storage and glucose metabolism was studied in 21 relatives of 4 patients with idiopathic haemochromatosis and in 10 healthy control subjects. In all individuals, plasma iron and iron binding capacity were measured and liver function was assessed. In addition, intravenous and oral glucose tolerance tests (IVGTT, OGTT), as well as tolbutamide (TTT) and insulin tolerance tests (ITT), were performed. Serum insulin (IRI) was measured. Liver biopsies were performed on the 21 relatives only.
In the relatives of patients with haemochromatosis, glucose tolerance was impaired and insulin secretion in response to hyperglycaemia diminished and/or delayed. Glucose intolerance increased with age but did not depend on abnormal liver function or excessive iron storage. Insulin release in response to tolbutamide was normal and insulin tolerance test failed to reveal insulin resistance.
The results suggest that:
1. There is an early glucose intolerance in healthy relatives of patients suffering from idiopathic haemochromatosis.
2. The glucose intolerance seems unrelated to measurable anomalies in iron metabolism.
3. The delayed insulin secretion in response to glucose resembles that observed in common maturity-onset diabetes mellitus.
4. The results obtained are compatible with the hypothesis that haemochromatosis and diabetes mellitus might be two distinct but genetically linked entities.