ABSTRACT
When blood glucose concentrations fall too low to support normal brain function, confusion, abnormal behaviors, coma, and seizures may ensue. It is not surprising that hypoglycemia, low blood glucose, ranks with blindness and renal failure as a fear for patients with Type 1 diabetes (1) and is widely believed to be a major limitation to the ability to achieve targets for glycemic control (2). The major trial that demonstrated unequivocally the link between lower mean blood glucose concentrations and reduced risk of longterm vascular complications (The Diabetes Control and Complications Trial, or DCCT) showed a three-fold increase in hypoglycemic episodes severe enough to render the patient incapable of self-management in those randomly assigned to receive intensive diabetes therapy (3). The negative associations shown between risk of hypoglycemia and mean glycated hemoglobin (HbA1c, a measure of mean blood glucose concentrations over about 2 months) are compatible with the logical assumption that running blood glucose concentrations lower increases the risk of overshooting into frank hypoglycemia (4). In the DCCT, there was also a direct association between the use of intensive insulin therapy and the risk of severe hypoglycemia, irrespective of HbA1c achieved (Fig. 1) (5). Although more modern methods of diabetes management can achieve improved mean blood glucose concentrations without increasing the risk of severe hypoglycemia (6-8), expectations have also increased. Patients and professionals now expect to achieve the more rigorous glucose targets needed in the fight against long-term complications but, at the same time, are far less accepting
of the lifestyle restrictions imposed on people using insulin therapy than before. Despite major improvements in treatment regimens (6-9), the introduction of designer insulins with (slightly) more physiological action profiles (e.g., 10,11) and advances in home blood glucose monitoring (12,13), severe hypoglycemia remains a major problem in the appropriate management of insulin-deficient diabetes mellitus. Furthermore, avoiding intensified insulin therapy and not maintaining near-normoglycemia does not provide protection against severe hypoglycemia; all insulin deficient diabetic patients are at risk.
