Hypoglycemia after Gastric Bypass

Hyperinsulinemic hypoglycemia is a complication of gastric bypass surgery and may occur anywhere from 6 months to 8 years after surgery. The definition, diagnostic criteria, pathophysiology mechanisms, and treatment will be reviewed.

Definition of hypoglycemia

Hypoglycemia is defined as a low plasma glucose (< 50–55 mg/dl) in the presence of symptoms compatible with neuroglycopenia that are ameliorated by a glycemic load (Whipple’s triad).

Diagnosis of post gastric hypoglycemia

  1. Fulfillment of Whipple’s triad
  2. Concomitantly elevated insulin (> 3 μU/ml) and C-peptide (> 0.6 ng/ml) ***
  3. Negative oral hypoglycemic agent screen or exposure to exogenous insulin.

*** It is worth knowing that c-peptide has a biological half life of approximately 30 minutes, as such, in the postprandial period, c-peptide may still be elevated in “normal” patients (even if endogenous insulin which has a half life of a few minutes is appropriately suppressed). A liquid mixed-meal test which requires the measurement of c-peptide levels is also fraught with challenges in interpreting c-peptide levels.

Differential diagnoses of hypoglycemia after gastric bypass surgery

The differential diagnoses of hypoglycemia after gastric bypass surgery include dumping syndrome (both early and late dumping),hyperinsulinemic hypoglycemia and rarely, insulinoma)

Dumping Syndrome

Dumping syndrome occurs in up to 50% of post gastric bypass patients. Ingestion of simple sugars is the usual trigger for this syndrome in the post gastric period.

Early dumping – This occurs as a result of rapid emptying of food into the jejunum because of the surgically altered gastrointestinal anatomy. Patients present with vasomotor symptoms (flushing, tachycardia and diaphoresis), colicky bdominal discomfort, and diarrhea. Early dumping occurs soon after the gastric bypass surgery but improves over time.

Late dumping – This is a form of “reactive hypoglycemia,” which occurs at least one to three hours after meal ingestion. It occurs as a consequence of the rapid release of insulin in response to hyperglycemia. Late dumping occurs as a result of absorption of simple sugars from the proximal small intestine.

Treatment : Patients with either early or late dumping respond to nutrition modification, which involves the ingestion of frequent, small and low-carbohydrate meals. Pharmacotherapeutic options include acarbose and somatostatin

Post-RYGB hypoglycemia (hyperinsulinemic hypoglycemia)

Presents several months to years (usually > 1 year) after gastric bypass surgery. The underlying mechanism is pancreatic nesidioblastosis.

Pancreatic nesidioblastosis is characterized by islet cell enlargement and increased budding of β-cells from ductal epithelium. This condition may also in patients with no history of gastric bypass surgery.

Treatment : This condition responds suboptimally to carbohydrate restriction alone. Pharmacotherapies include α-glucosidase inhibitor acarbose, octreotide, verapamil, and diazoxide.

For patients with debilitating symptoms and a positive selective arterial calcium-stimulated test, partial pancreatectomy may lead to significant amelioration of symptoms. In some instances, RYGB may have to be reversed (restoration of normal intestinal anatomy)

Insulinoma

Although insulinomas typically cause fasting hypoglycemia, postprandial hypoglycemia may occur in up to 10% of patients.

Treatment of hypoglycemia after gastric bypass

DrugMechanism of Action
DiazoxideDiminishes insulin secretion. It causes marked edema and hirsutism
OctreotideOctreotide is an analog of somatostatin (exhibits growth hormone-inhibitory function). Although octreotide inhibits growth hormone secretion, in large doses, it also inhibits the secretion of thyroid-stimulating hormone (TSH), insulin, and glucagon. Variable efficacy in patients with hyperinsulinemic hypoglycemia.
EverolimusEverolimus is an inhibitor of the mammalian (mechanistic) target of rapamycin (mTOR)
Verapamil A calcium channel blocker with reported efficacy in the management of hypoglycemia. Limited by its hypotensive effects.

References

Cryer PE, Axelrod L, Grossman AB, Heller SR, Montori VM, Seaquist ER, Service FJ; Endocrine Society. Evaluation and management of adult hypoglycemic disorders: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2009 Mar;94(3):709-28.

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