Abstract
In normal individuals hypoglycemic counterregulation is a multifactorial, redundant process that involves reduction of insulin secretion, increasing glucagon secretion, adrenergic activation, and increased growth hormone and cortisol secretion. Metabolically, these lead to increased glucose production, initially through glycogenolysis and later through gluconeogenesis, decreased muscle glucose oxidation and storage and increased release and use of alternative fuels, primarily free fatty acids. They also lead to hypoglycemic symptoms and hunger which increase food intake. These systems are designed to provide as much glucose as possible for brain glucose use. In patients with type 1 diabetes there are multiple impairments of these responses. Insulin does not decrease. Glucagon secretion is decreased or absent. Recovery from hypoglycemia is therefore dependent on the adrenergic response. Hypoglycemia increases plasma levels of both epinephrine and norepinephrine. These catechols are released primarily from the adrenal medulla. However, it is well documented that hypoglycemic increases muscle sympathetic nerve activity, and that both α and β adrenergic activity increase. Increased β-activity increases free fatty acid release which increase glucose production and decrease glucose utilization. The increased activitys primary role is to counteract β-adrenergic vasodilation. It may also reduce neurogenic and neuroglycopenic symptoms. Lastly, there is evidence that both cardiac and adrenergic sensitivity are altered in type 1 diabetes. It is hoped that this information can be used in the future to help develop ways to protect patients with type 1 diabetes from hypoglycemia and its adverse effects.
Keywords: muscle sympathetic nerve activity, epinephrine, type 1 diabetes, antecedent hypoglycemia, ACTH
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