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DEFINITION

• Symptomatic hypoglycemia due to low blood glucose (<70 mg/dL) occurring within 2-5 h after food intake, in the absence of hypoglycemic medications.
• Also referred to as reactive hypoglycemia
• Highly disputed and controversial entity

EPIDEMIOLOGY

• Experts consider that in most cases, postprandial symptoms are not due to hypoglycemia
• 10% of normal subjects have a blood glucose concentration <50 mg/dL four to six hours following oral glucose tolerance test
• An unproven observation is that patients with pre-diabetes or early, mild type 2 diabetes, may have postprandial hypoglycemia due to delayed but exaggerated insulin secretion. 
• Postprandial hypoglycemia is more common in very lean people, or after extreme weight reduction.
• Prevalence and incidence figures are virtually impossible to determine since symptoms are non-specific and blood glucose is rarely measured during symptoms.
• Can be seen after bariatric surgery, due to dumping syndrome or beta cell hyperplasia.

DIAGNOSIS

• Whipple's triad: symptoms compatible with hypoglycemia, documentation of low blood glucose concentration, and resolution of symptoms after treating the hypoglycemia.
• After an overnight fast, administer type of food intake thought to induce hypoglycemia. Hold all nonessential medications. Observe patient for signs and symptoms of hypoglycemia, with written log. Avoid treatment, if possible, until test completed.
• Measure plasma glucose, before ingestion and every 30 minutes up to 300 minutes after eating meal. Some experts recommend also sending insulin, C-peptide, and proinsulin for analysis if plasma glucose < 60 mg/dL (3.3 mmol/L) (Cryer).
•  Mixed meal tests (10 kcal/kg, 45% carbohydrate, 15% protein, and 40% fat) have been used for diagnosis but standards for interpretation have not been established.
• Oral glucose tolerance test is not recommended (Cryer).
• Factious hypoglycemia should always be considered and may be excluded with a detailed medication history and screening for sulfonylureas in urine.
•  Insulin autoantibodies may be helpful in selected populations where these antibodies are more prevalent (i.e. Asian)

SIGNS AND SYMPTOMS

• Autonomic symptoms: sweating, palpitations, shaking, hunger, anxiety, weakness, tremor, or perspiration,
• Rarely if ever a cause of mental status changes or death.  
• Neuroglycopenic symptoms (confusion, drowsiness, speech difficulty) are probably not due to postprandial hypoglycemia.

CLINICAL TREATMENT

• Diet is main treatment, and can be a simple diagnostic as well as therapeutic modality.
• Patient should ingest a small carbohydrate-containing snack (15-30 gm) anticipating the time symptoms usually occur (such as late morning or mid-afternoon). This will keep blood glucose from going low and if effective, it is an easy to implement and consistent with the diagnosis of postprandial hypoglycemia (Brun).
• Avoid high carbohydrate meals, rapidly absorbable sugars and drinks rich in glucose or sucrose.
• Avoid drinks combining sugar with alcohol, especially in fasting state.
• Some experts recommend, without proven efficacy, adding protein or soluble dietary fibers to meals, to slow gastric emptying and reduce insulin response. 
• If symptoms persist, a number of medications have been tried: 1) alpha-glucosidase inhibitors (acarbose, miglitol) to delay starch and sucrose digestion or 2) metformin, 500 to 850 mg orally, taken with meals.
• In exceptional cases, the somatostatin analogue octreotide has been used.
• Diazoxide is not recommended due to side effects including water retention, hypertrichosis, and digestive disorders.

FOLLOW UP

• Encourage dietary management as long as patient experiences symptoms.
• Not a progressive disorder.
• Rarely if ever a cause of mental status changes or death.
• Usually responds well to diet modification.
• Medication may be needed in extreme cases.

EXPERT COMMENTS

• As indicated above, postprandial hypoglycemia is a controversial entity, difficult to prove and of unclear mechanism. Most experts question whether it is a real disease.
• Since the adrenergic symptoms are identical to those of simple anxiety, and caused by the same hormones (catecholamines) underlying anxiety, depression or psychiatric illness may be misattributed to hypoglycemia.
• Must rule out fasting hypoglycemia, which is an important diagnosis to establish. 
• Blood glucose frequently dips below baseline, and normal counter-regulatory hormones (epinephrine, glucagon) bring glucose back to baseline. The controversy is whether, or how often, this process causes symptoms.
• For most patients, simple dietary treatment alone is sufficient.

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