Some of the most common etiologies of postprandial hypoglycemia (which is also known as “reactive hypoglycemia”) include the following eiologies

Alimentary. Postprandial Hypoglycemia of gastrointestinal tract origin (sometimes called the “dumping syndrome”) most often occurs after gastric surgery and results from unusually swift or complete gastric emptying of ingested carbohydrate into the duodenum, resulting in abnormally high blood glucose levels and temporary hypoglycemia after hastily produced insulin has overcome the initial hyperglycemia. Initial blood glucose elevation is definitely greater than that of a normal person.

Diabetic. Some persons with subclinical or early diabetes mellitus of the NDDG type II (noninsulin-dependent) category may develop mild and transitory hypoglycemia 3-5 hours after eating. This seems to be an early manifestation of their disease, which often disappears as the disease progresses. The exact incidence in diabetics is unclear but is probably low. However, because of the large number of diabetic persons, it may be a relatively frequent cause of postprandial hypoglycemia. Initial elevation of blood glucose values may or may not be higher than in normal persons, but the 2-hour postprandial value is elevated. The rise in plasma insulin after eating tends to be delayed, and the insulin peak (when finally achieved) may be somewhat elevated, resulting in the hypoglycemic episode.

Functional. Some patients develop symptoms of hypoglycemia after eating without known cause. This most often occurs 3-4 hours postprandially (range, 1-5 hours). In some cases symptoms can be correlated with acceptably low blood glucose values, in which case many physicians make a diagnosis of functional hypoglycemia (although there is controversy on this point, to be discussed later with the 5-hour OGTT). In other cases, probably the majority, symptoms cannot be adequately correlated with acceptably low blood glucose values. Either the OGTT serum glucose value is low but no symptoms occur, or (less commonly) symptoms occur at a relatively normal glucose level. In these cases some have used the diagnosis of “idiopathic postprandial syndrome.” Perhaps a better term would be “pseudohypoglycemia.” The peak blood glucose elevation after eating is not higher than in a normal person, and the 2-hour value is also normal.

Other. A few patients with insulinoma or alcoholism may develop postprandial hypoglycemia, although fasting hypoglycemia is much more common.

Laboratory tests

The first consideration is to rule out a fasting hypoglycemia, especially when hypoglycemic symptoms occur several hours after food intake. Self-administered hypoglycemic agents are also possible, although for some reason this is not often mentioned when associated with postprandial symptoms. The best test would be a blood glucose measurement drawn at the same time that symptoms were present. Because symptoms in daily life usually occur at times when blood specimens cannot be obtained, the traditional laboratory procedure in postprandial hypoglycemia has been the 5-hour OGTT. In alimentary hypoglycemia the classic OGTT pattern is a peak value within 1 hour that is above OGTT reference limits, followed by a swift fall to hypoglycemic levels (usually between 1 and 3 hours after glucose). In diabetic hypoglycemia, there is an elevated 2-hour postprandial value, followed by hypoglycemia during the 3-5 hours postglucose time interval. In functional hypoglycemia, there is a normal OGTT peak and 2-hour level, followed by hypoglycemia during the 2 to 4-hour postglucose time interval (Fig.).

Representative oral glucose tolerance curves.

Representative oral glucose tolerance curves.

Unfortunately, diagnosis has not been as simple as the classic OGTT findings just mentioned would imply. Many investigators have found disturbing variability in OGTT curves, which often change when testing is repeated over a period of time and may change when testing is repeated on a day-to-day basis. In some cases this is related to factors known to influence the OGTT, such as inadequate carbohydrate preparation, but in other cases there is no obvious cause for OGTT discrepancies. Another major problem is disagreement regarding what postprandial blood glucose value to accept as indicative of hypoglycemia. Most investigators use 50 mg/100 ml (2.76 mmol/L) of plasma glucose as the dividing line. However, there is considerable controversy in the literature on this point. In some cases it is not clear whether serum or whole blood was assayed (reference values for whole blood are 15% less than those for serum or plasma). An additional problem involves the concept of chemical hypoglycemia versus clinical hypoglycemia. A number of studies have shown that a certain percentage of clinically normal persons may have OGTT curves compatible with functional hypoglycemia without developing any symptoms. In some instances asymptomatic OGTT serum levels as low as 30 mg/100 ml (1.65 mmol/L) were observed. Moreover, in some studies continuous blood glucose monitoring systems disclosed hypoglycemic dips not evident in standard OGTT specimens. On the other hand, some persons with symptoms compatible with hypoglycemia do not develop OGTT values below reference limits. To make matters more confusing, some studies have found that when the 5-hour OGTT was repeated after it had initially displayed a hypoglycemic dip, a substantial number of the repeat OGTT results became normal (about 65% of cases in one report). Finally, several studies have indicated that hypoglycemic values found during an OGTT usually disappear when an ordinary meal is substituted for the carbohydrate dose. Since actual patients do not usually ingest pure carbohydrate meals, this casts doubt on the reliability and usefulness of the OGTT in the diagnosis of functional hypoglycemia. One study found that patients with symptoms of functional hypoglycemia had an increase in the plasma epinephrine level of at least 250 pg/ml over baseline at the time of the OGTT lowest (“nadir”) serum glucose level, regardless of the actual value, whereas those who did not develop symptoms had an epinephrine increase at the time of the glucose nadir that was less than 250 pg/ml.

In summary, the diagnosis of postprandial hypoglycemia is clouded by controversy, especially the category of functional hypoglycemia. Probably the least debatable diagnosis would be one established by a serum glucose level less than 50 mg/100 ml obtained less than 5 hours after a regular meal while the patient is having hypoglycemic symptoms. A 5-hour OGTT could be done with a regular meal instead of the pure glucose dose. This would also help to exclude alimentary or diabetic etiologies.