HORMONAL MECHANISMS
There are multiple theories regarding the etiology of b-cell hyperplasia following bariatric surgery. The specific causes for NIPHS after gastric bypass remain under investigation.2
The most common theory is that b-cell hyperplasia may occur as a result of the surgical procedure itself and not due to obesity. The rapid delivery of food to the distal ileum after gastric bypass surgery may result in elevated production of incretin hormones (eg, GLP-1 and GIP), which increase b-cell proliferation, insulin secretion, and insulin sensitivity.7
Roux-en-Y gastric bypass also impairs ghrelin secretion. Ghrelin normally acts to suppress insulin secretion and directly opposes the action of insulin. Reduced levels of ghrelin may increase the likelihood of hypoglycemia. Other hormones that may contribute to the metabolic effects of bariatric surgery include peptide YY, oxyntomodulin, and others as yet unidentified.5,6
CLINICAL MANIFESTATIONS
NIPHS is characterized by moderate to severe postprandial hypoglycemia. Symptoms include confusion, diaphoresis, tremulousness, anxiety, weakness, blurred vision, and disorientation, as well as more severe neuroglycopenic symptoms, such as cognitive impairment, seizures, and loss of consciousness.5
These symptoms do not typically manifest until several months after gastric bypass surgery. (By contrast, symptoms experienced with dumping syndrome typically manifest shortly after the procedure.) Of note, hypoglycemic symptoms of NIPHS do not typically improve after dietary modifications aimed at reducing carbohydrate intake.2
DIAGNOSIS
Diagnosis of NIPHS is based on hypoglycemic/neuroglycopenic signs and symptoms without fasting hypoglycemia; endogenous hyperinsulinemia in the presence of hypoglycemia; negative localization studies for insulinoma (using triple-phase spiral CT); and positive selective arterial calcium stimulation test.4,6
If fasting hypoglycemia is reported or suspected, the patient should be evaluated for insulinoma using a 72-hour fast. During it, glucose, insulin, C-peptide, and pro-insulin levels should be tested every six hours; results will be normal in patients with NIPHS.5
The use of OGTT is controversial, as patients can experience variable degrees of postprandial hyperinsulinism and symptomatic hypoglycemia during the test. There are no guidelines on whether to perform OGTT in the work-up for NIPHS. In research protocols, it is common to perform a five-hour OGTT; subjects consume a mixed meal containing 50 g of carbohydrates, then their glucose, insulin, and C-peptide levels are tested every 30 to 60 minutes (or sooner if hypoglycemic symptoms occur).
Elevated insulin and C-peptide levels in the setting of hypoglycemia are characteristic findings in patients with NIPHS.5,9 In the setting of hypoglycemia, a cortisol level > 20 mg/dL is considered an appropriate adrenal response and excludes adrenal insufficiency. Triple-phase CT of the abdomen should be performed to rule out insulinoma if strongly suspected and if work-up for NIPHS is negative.5
The selective arterial calcium stimulation test is employed to confirm the diagnosis of NIPHS and to guide the extent of pancreatic resection, in an effort to minimize postoperative complications of insulin-dependent diabetes and exocrine insufficiency. In this procedure, the splenic, gastroduodenal, superior mesenteric, and hepatic arteries that supply the pancreas are selectively injected with calcium gluconate. After injection of calcium, the insulin level is measured within each artery.4,5,7 The selective arterial calcium stimulation test can also be used to localize an insulinoma. NIPHS is distinguished from insulinoma by a diffuse increase in insulin secreted from multiple segments of the arteries that supply the pancreas, following calcium stimulation.4,5,7
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