Blood glucose levels of approximately 10 mg/dL are associated with deep coma, dilatation of pupils, pale skin, shallow respiration, slow pulse and hypotonia, what had in the past been termed the “medullary phase” of hypoglycemia. If glucose is administered before this level has been attained, the patient can be restored to normal, retracing the aforementioned steps in reverse order. However, once this state is reached, and particularly if it persists for more than a few minutes, recovery is delayed for a period of days or weeks and may be incomplete as noted below.
The EEG is altered as the blood glucose falls, but the correlations are imprecise. There is diffuse slowing in the theta or delta range. During recovery, sharp waves may appear and coincide in some cases with seizures.
The major clinical differences between hypoglycemic and hypoxic encephalopathy lie in the setting and the mode of evolution of the neurologic disorder. The effects of hypoglycemia usually unfold more slowly, over a period of 30 to 60 min, rather than in a few seconds or minutes. The recovery phase and sequelae of the two conditions are quite similar.
A large dose of insulin, which produces intense hypoglycemia, even of relatively brief duration (30 to 60 min), is more dangerous than a series of less-severe hypoglycemic episodes from smaller doses of insulin, possibly because the former impairs or exhausts essential enzymes, a condition that cannot then be overcome by large quantities of intravenous glucose. Reflecting the benignity of repeated minor occurrences, the Diabetes Control and Complications Trial have demonstrated that recurrent hypoglycemic episodes in the course of treatment of diabetes over many years are very well tolerated and do not lead to cognitive decline.
A severe and prolonged episode of hypoglycemia may result in permanent impairment of intellectual function as well as other neurologic residua, like those that follow severe anoxia. We also have observed states of protracted coma, as well as relatively pure Korsakoff amnesia. However, one should not be hasty in prognosis, for we have observed slow improvement to continue for 1 to 2 years.
Recurrent hypoglycemia from an islet cell tumor may masquerade for some time as an episodic confusional psychosis or convulsive illness; diagnosis then awaits the demonstration of low blood glucose or hyperinsulinism in association with the neurologic symptoms. We saw a man in the emergency department whose main complaint was episodic inability to dial a touchtone telephone and a mild mental fogginess; he was found to have an insulinoma.
Functional or reactive hypoglycemia is the most ambiguous of all syndromes related to low blood glucose. This condition is usually idiopathic but may precede the onset of diabetes mellitus. The rise of insulin in response to a carbohydrate meal is delayed but then causes an excessive fall in blood glucose, to 30 to 40 mg/dL. The symptoms are malaise, fatigue, nervousness, headache and tremor, which may be difficult to distinguish from anxious depression. Not surprisingly, the term functional hypoglycemia has been much abused, being applied indiscriminately to a variety of complaints that would now be called chronic fatigue syndrome or an anxiety syndrome. In fact, a syndrome attributable to functional or reactive hypoglycemia is infrequent and its diagnosis requires the finding of an excessive reaction to insulin, low blood glucose during the symptomatic period, and a salutary response to oral glucose.