Perspectives in Diabetes Hypoglycemia Begets Hypoglycemia in IDDM

I atrogenic hypoglycemia causes recurrent physical morbidity, and some mortality, as well as recurrent or persistent psychological morbidity in patients with IDDM (1). The frequency of iatrogenic hypoglycemia is substantially higher during effective intensive therapy of IDDM. Even in the highly structured Diabetes Control and Complications Trial the frequency of severe hypoglycemia was increased more than threefold in intensively treated IDDM (2). Given the demonstration that effective intensive therapy makes a difference (it reduced the development and progression of retinopathy, nephropathy, and neuropathy in the Diabetes Control and Complications Trial [2]), and assuming that this finding will lead to more widespread attempts to keep plasma glucose concentrations as close to the nondiabetic range as possible, iatrogenic hypoglycemia will almost assuredly become an even greater problem for patients with IDDM. Because current insulin replacement regimens are far from perfect, absolute or relative insulin excess must occur from time to time in IDDM. This occurs, for example, when insulin doses are excessive or ill-timed, after missed meals or snacks, during an overnight fast, and during or after unusual physical activity. However, it has become increasingly clear that the risk of iatrogenic hypoglycemia is not determined by insulin excess alone but rather by the interplay of insulin excess and compromised glucose counterregulation (1).