Visualizing Beta Cells in Patients With Hyperinsulinemic Hypoglycemia After Bariatric Surgery

Hyperinsulinaemic hypoglycemia after bariatric surgery. Overweight and obesity are an increasing health problem globally and in the Netherlands, about 15% of the population in the Netherlands is obese. Obesity is associated with increased risk of morbidity, such as cardiovascular disease and type 2 diabetes (T2D). Weight loss is the most important intervention in obese patients, reducing obesity related morbidity and increasing life expectancy. Non-invasive weight loss interventions such as diet, lifestyle or medication only have a moderate effect which is short lived. Weight reducing surgery, i.e. bariatric surgery, is the only intervention that leads to persistent weight loss and is superior above conventional treatment. The most performed and preferred bariatric surgery is Roux-en-Y Gastric Bypass (RYGB), which is a food restrictive and malabsorptive procedure. Besides weight loss, metabolic improvement in T2D patients is an additional result after RYGB.

A frequent late complication of RYGB is the dumping syndrome and a rare late complication is hyperinsulinaemic hypoglycemia (HH). Reported incidences of dumping syndrome range from 20 to 70% of the patients. Dumping is a condition where food enters the small bowel too rapidly and can be divided into early and late dumping. Early dumping is due to rapid gastric emptying and comprises intestinal and vasomotor symptoms within minutes after food ingestion. Late dumping occurs 1 to 3 hours after a meal and the symptoms are partly caused by hypoglycemia.

Reported incidences of HH range from 0.2 to 1% after RYGB and is observed after gastric bypass procedures only. In HH plasma glucose concentrations reach values below 50 mg/dL (2.8 mmol/L) and adrenergic and neuroglucopenic symptoms occur, often occurring after a meal. After a meal or glucose challenge an early large glucose peak followed by an insulin peak is observed in HH patients. Additionally, an increased postprandial GLP1 level compared to RYGB controls without HH was observed. Low plasma glucose levels are also found in asymptomatic patients after RYGB in 30 to 50% of the patients.

The underlying mechanism of HH is not completely understood and several potential causes have been proposed, including, 1) An inappropriate increase of beta cell mass and function, that is persisting despite the increased insulin sensitivity after RYGB, 2) late dumping syndrome, i.e. an inappropriate insulin secretion following rapid food entry into the small intestine, 3) an inappropriate counter-regulatory glucagon response and 4) post-RYGB an increase in the incretin secretion (GLP1 and GIP).

Besides stimulation of the postprandial insulin secretion, GLP1 may induce beta cell hypertrophy or an increase in the number of beta cells by inhibiting apoptosis and increasing replication. Nesidioblastosis (beta cell hypertrophy, islet hyperplasia and increased beta cell mass) is associated with HH after RYGB in some cases, however, nesidioblastosis was not found in these patients and an overexpression of GLP1-receptors in individual islets was not found.