EVALUATION OF HYPOGLYCEMIC COUNTERREGULATION USING A MODIFICATION OF THE ANDRES GLUCOSE CLAMP

The glucose clamp, developed by Andres for the quantification of insul in action and secretion, was modified to study counterregulatory mecha nisms against hypoglycemia, thereby overcoming the technical difficult ies in producing a standardized, reproducible hypoglycemic stimulus. N ormal subjects are exquisitely sensitive to small decrements in glucos e; levels within the normal range cause suppression of endogenous insu lin (almost-equal-to 4.0 mM) and activation of glucagon and epinephrin e (almost-equal-to 3.5 mM) secretion. The glucose threshold for hormon e release is modified by multiple factors, including age, gender, and the level of insulin per se. If glucose continues to fall toward 3.0 m M, the hormonal response is intensified and symptoms appear. The windo w between the appearance of symptoms triggering carbohydrate ingestion and the earliest signs of neuroglycopenia are surprisingly narrow. Su btle neuroelectrophysiological changes in cortical and brain stem func tion are evident at 2.9 mM. Insulin-dependent diabetes mellitus (IDDM) patients must rely heavily on their ability to secrete epinephrine to overcome a defective glucagon response. Unfortunately, this defense m echanism may diminish as disease duration increases, and may become fu rther impaired by iatrogenic hypoglycemia accompanying insulin treatme nt. Commonly, the glucose level triggering adrenergic responses is shi fted downward during intensive insulin therapy of IDDM. This may help explain why such patients release epinephrine and experience symptoms of hypoglycemia at a lower glucose level.