Glucose Intolerance in Myotonic Dystrophy

Abstract

Abnormality of carbohydrate metabolism is often observed in myotonic dystrophy. Hyperinsulinemia and impaired glucose metabolism in the skeletal muscle have also been reported in myotonic dystrophy 1 (DM1); thus, insulin resistance could be the primary pathophysiology leading to glucose intolerance in DM1. One of the molecular mechanisms of insulin resistance is an aberrant expression of the low-signaling IR-A in the muscle resulting from abnormal splicing caused by altered RNA binding due to the CUG expansion in the DMPK gene. It is also suggested that DMPK itself affects insulin action, and reduced DMPK causes insulin resistance. Fasting hyperinsulinemia and hypersecretion of insulin on glucose loading are observed in DM1 patients from early period before the onset of diabetes, and these may be risk of developing diabetes. Myotonic dystrophy patients have some factors for deterioration of glucose intolerance other than genetic-based insulin resistance: reduced lean body mass, relatively increased body fat, and low physical activity with progression of myopathy. Concerning treatment, it is reasonable to use insulin-sensitizing drugs such as pioglitazone and metformin. However, most of patients, especially with long duration of diabetes, need to use other medicines including insulin for keeping adequate glycemic control. In clinical practice, the goals of glycemic control should be determined individually in light of the patient’s important comorbidities. Since myotonic dystrophy is one of the important comorbidities, further studies will be needed to answer how we determine the goals of glycemic control and how we should treat in safe the individuals with progressed myopathy.