Hypoglycemia Causes

Hypoglycemia has conventionally been classified into two categories: fasting (or postabsorptive) hypoglycemia and reactive (or postprandial) hypoglycemia. However, with very rare exceptions, all patients with clinically important hypoglycemia have a disorder that causes fasting hypoglycemia. In some cases hypoglycemia also develops in these patients shortly after meals, but the differential diagnosis remains that of fasting hypoglycemia.

Although once widely used for the diagnosis of reactive hypoglycemia, the oral glucose tolerance test is unreliable and should not be used to diagnose suspected hypoglycemia. Patients given the diagnosis of reactive hypoglycemia based on this test rarely have hypoglycemia during daily life (after ordinary meals or during spontaneous symptoms).

The major causes of fasting hypoglycemia are outlined in Box 304-1. Hypoglycemia occurs when glucose use exceeds glucose production. Fasting hypoglycemia in patients with the various forms of hyperinsulinism and in those with tumors secreting insulin-like hormones is due to suppressed hepatic glucose production coupled with inappropriately high rates of glucose utilization. Impaired hepatic glucose production with ongoing obligate glucose utilization (e.g., by the brain) is believed to be the predominant mechanism of fasting hypoglycemia attributable to drugs, hormonal deficits, hepatic dysfunction, chronic renal failure, and the childhood hypoglycemic disorders. Clearly, accelerated glucose utilization in conditions such as vigorous exercise and pregnancy could exacerbate fasting hypoglycemia attributable to any of the disorders listed. However, accelerated glucose utilization alone seldom results in fasting hypoglycemia because of the normal capacity to increase glucose production.

By far the most common cause of hypoglycemia is therapy of diabetes mellitus with insulin or sulfonylureas. Although hypoglycemia is a major therapeutic limitation in diabetes, it seldom presents a diagnostic problem. These drugs may also be used to produce factitious hypoglycemia, however, especially among medical personnel and others with knowledge of diabetes. Ethanol inhibits gluconeogenesis but not glycogenolysis. Thus it causes hypoglycemia only when hepatic glycogen is depleted in fasting or malnourished individuals. Salicylates cause hypoglycemia in children by an unknown mechanism. Pentamidine and quinine stimulate insulin release and presumably cause hypoglycemia by this means. A number of other drugs have been associated with hypoglycemia, but in most cases other potential causes of hypoglycemia were present and a clear causal relationship was not established.

Renal insufficiency is a major factor associated with hypoglycemia in hospitalized patients. The mechanisms are not known, although the majority of patients who develop hypoglycemia are malnourished. The development of renal failure in diabetes mellitus often reduces insulin requirements and increases the risk of hypoglycemia. Hepatic disease can cause hypoglycemia as a result of inadequate glucose production. Because the liver is normally able to increase glucose output several-fold, only severe hepatic dysfunction causes hypoglycemia. Hypoglycemia in patients with cardiac failure or sepsis is probably a result of impaired hepatic and renal function. Hypoglycemia has rarely been attributed to malnutrition without other disorders.