THE ROLE OF INSULIN RESISTANCE IN THE PATHOGENESIS OF MYOTONIC MUSCULAR DYSTROPHY

Abstract

A study of glucose, insulin, lipids and lipoproteins in myotonic dystrophy (MyD) has shown elevation of fasting plasma insulin, triglycerides and very low density lipoproteins (VLDL) but no significant difference from normal in the fasting plasma glucose, total cholesterol or low and high density lipoproteins. Elevation of the total triglyceride and VLDL levels showed a direct relationship to hyperinsulinaemia. Insulin binding to cultured MyD fibroblasts under optimal conditions was significantly reduced but there was no difference in receptor affinity between MyD and control cells. In contrast to insulin binding, LDL binding to MyD fibroblasts was normal although there was a tendency to reduced LDL binding at 37° C that may reflect mildly reduced lipid metabolism. The alterations in lipids and insulin in MyD are compatible with insulin resistance. Laboratory and clinical findings in MyD were compared with other inherited insulin-resistant diseases. MyD showed marked similarity to a group of disorders that have mild insulin resistance and mildly elevated plasma insulin in contrast to others with severe hyperinsulinaemia and insulin resistance. It is suggested that at least some clinical features of MyD may be due to diminished overall effect of insulin or other trophic factors on cell metabolism.