Abnormal regulation of monocyte insulin-binding affinity after glucose ingestion in patients with myotonic dystrophy.

Insulin insensitivity of uncertain etiology often exists in myotonic muscular dystrophy, a multitissue, autosomal dominant disorder hypothesized to be a hereditary membrane disease. The present studies show that monocytes from patients with myotonic dystrophy fail to demonstrate the normally observed qualitative increase in insulin-binding affinity after oral glucose loading. Monocytes from 10 normal volunteers developed a significantly increased insulin-binding affinity by 2 hr after glucose ingestion (mean +/- SEM, 11.7 +/- 2.7 ng/ml compared to basal 50% insulin displacement value of 23.3 +/- 2.2 ng/ml, P less than 0.005). This increase was maintained at 5 hr (13.5 +/- 2.7 ng/ml, P less than 0.05). In contrast, no significant increase in monocyte insulin-binding affinity occurred in cells from nine myotonic dystrophy patients at 2 and 5 hr after glucose loading (50% insulin displacement values: basal, 14.2 +/- 2.8 ng/ml; 2 hr, 16.7 +/- 1.7 ng/ml; 5 hr, 10.8 +/- 2.1 ng/ml). These alterations document the presence of abnormalities in the insulin receptor or receptor-associated processes that modulate insulin binding. A hereditary plasma membrane defect may underlie these findings. This abnormality may have an etiologic role in the decreased insulin sensitivity that frequently afflicts patients with myotonic dystrophy.