To investigate the development of diabetes mellitus in patients with thalassemia major, plasma glucose and immunoreactive insulin (IRI) levels following oral glucose and intravenous tolbutamide and glucose disappearance rates following intravenous insulin were measured in 10 patients before and during five years on a high transfusion program (HTP). Plasma immunoreactive glucagon (IRG) levels following oral glucose, intravenous insulin, and arginine were measured during the sixth year. Serial percutaneous liver biopsies were performed on seven patients.
The oral glucose tolerance tests (OGTT) and mean peak IRI levels were normal in nine of 10 patients before HTP. After HTP was begun a progressive deterioration of OGTT occurred despite normal IRI levels. Following tolbutamide, the mean per cent fall in plasma glucose in the patients before HTP was significantly less than in controls (p < 0.01) and similar to that of controls during five years of HTP in spite of higher than normal peak IRI levels.
Of seven survivors after six years of HTP, three had normal OGTT and four had chemical diabetes; mean peak IRI levels were normal, but fasting IRG levels were significantly higher than in controls (p < 0.05). In all seven patients, plasma IRG failed to increase following insulin-induced hypoglycemia and was significantly higher than in controls after arginine (p < 0.01); after oral glucose, plasma IRG fell significantly below that of fasting only in the patients with chemical diabetes (p < 0.03). Following intravenous insulin, the mean per cent fall in glucose before and during HTP was significantly less than in controls (p < 0.01). Hemosiderosis and cirrhosis were present in all biopsied patients. Four patients died; two had chemical and two had nonketotic insulin-dependent diabetes.
These data suggest that diabetes mellitus occurs frequently in patients with thalassemia on HTP and that insulin resistance and hyperglucagonemia, possibly due to cirrhosis, are important etiologic factors.