Impact of activated glucose counterregulation on insulin requirements in insulin-dependent diabetes mellitus.

The glucose counterregulatory system is one of the most important homeostatic systems in physiology, since it normally prevents hypoglycaemia or, should it occur for any reason such as insulin administration, limits the severity of hypoglycaemia and ultimately may restore normoglycaemia. In normal nondiabetic subjects, activation of counterregulation does not result in overt hyperglycaemia in the post-absorptive state, because the pancreatic beta-cell increases insulin secretion. On the contrary, in subjects with insulin-dependent diabetes mellitus (IDDM) whose pancreatic B-cell cannot respond to an increase in plasma glucose, activated counterregulation may easily result in overt hyperglycaemia. There are two different circumstances under which counterregulation may contribute to excessive hyperglycaemia in IDDM, namely nonhypoglycaemic nocturnal activation of counterregulation (dawn phenomenon), and hypoglycaemic activation of counterregulation (Somogyi phenomenon). The dawn phenomenon is an increase in insulin requirements which occurs between 04.00 and 08.00 h in the absence of preceding hypoglycaemia and concomitant hypoinsulinemia. It is caused by a decrease in hepatic and extrahepatic sensitivity to insulin induced by the nocturnal secretion of growth hormone. The dawn phenomenon may contribute importantly to fasting hyperglycaemia in IDDM, because usually plasma insulin concentration following the pre-supper insulin injection decreases after 04.00 h, i.e. a time at which plasma insulin concentration should instead increase to maintain normoglycaemia. The Somogyi phenomenon is best defined as hyperglycaemia following hypoglycaemia and is caused by the insulin resistance induced by hypoglycaemic-activation of counterregulation. Although insulin resistance following hypoglycaemia is a constant event in IDDM, post-hypoglycaemic hyperglycaemia is not the rule. For example, if the responses of counterregulatory hormones to nocturnal hypoglycaemia are blunted, or plasma insulin concentration following hypoglycaemia is inappropriately high, post-hypoglycaemic insulin resistance is not powerful enough to result in overt hyperglycaemia in the fasting state. However, post-breakfast plasma glucose may be exaggerately elevated following nocturnal hypoglycaemia even in the case that fasting plasma glucose is only modestly increased. It is important to prevent nocturnal hypoglycaemia, not only to protect brain function, but also to prevent insulin resistance which may easily result in exaggerated hyperglycaemia and initiate the vicious circle "hypoglycaemia-hyperglycaemia-increase in insulin dose-risk for subsequent hypoglycaemia", and so on.