Changes in muscle glucose metabolism in type 1 diabetes

Patients with type 1 diabetes are characterized by an average 40% reduction in the insulin sensitivity. In newly diagnosed patients, insulin resistance is due to insulin deficiency and its metabolic consequences. After the beginning of insulin therapy, insulin sensitivity transiently improves, but deteriorates again after 6-9 months of insulin therapy. Insulin resistance is mainly due to a reduction in glucose uptake by muscle tissue. There are similar relative reductions in both oxidative and nonoxidative glucose disposal. When glucose disposal is determined under similar plasma glucose and insulin concentrations, glucose oxidation, the activity of pyruvate dehydrogenase and glycogen synthase are all reduced. If glucose disposal rate in diabetic patients is normalized by glucose mass action, both oxidative and nonoxidative glucose disposal and glycogen synthase activity become normal. As the normalization of glucose disposal occurs in the face of unchanged muscle glucose-6-phosphate concentrations, this suggest that reduced glucose disposal is secondary to reduced glucose transport in type 1 diabetes.