The Effect of Gastric Bypass Surgery on Glucose Metabolism, Gestational Weight Gain and Fetal Growth in Subsequent Pregnancy

Background Post-prandial hypoglycemia Roux-en-Y Gastric Bypass (RYGB) is a well-established treatment of severe obesity and is performed in women most often during their reproductive years. RYGB is a hormonal, malabsorptive as well as a restrictive surgical procedure, leading to complications such as vitamin deficiencies and postprandial hypoglycemia, which are exaggerated during pregnancy. Hypoglycemia usually does not occur until one year post surgery and evolves gradually with non-specific symptoms, causing delayed diagnosis. Symptoms of hypoglycemia include autonomic symptoms (palpitations, lightheadedness, sweating) and neuroglycopenic symptoms (confusion, decreased attentiveness, seizure, loss of consciousness). While severe hypoglycemia is estimated with a frequency of 0.2 % following RYGB, the frequency of mild to moderate hypoglycemia is unknown due to a lack of recognition of symptoms.

Insulin sensitivity increases due to weight loss and the resulting changes in insulin and glucagon response are a possible underlying mechanism for postprandial hypoglycemia. In pregnant women, insulin sensitivity changes from early to late pregnancy. Whilst usually attenuated in late pregnancy, the incretin response is reinforced in subjects with RYGB. These factors make it difficult to predict the risk of hypoglycemia in pregnancies following RYGB.

Studies have shown that plasma insulin concentration is inappropriately elevated during the hypoglycemic episodes and that fasting hypoglycemia is uncommon, suggesting that hypoglycemia is primarily associated with postprandial dysregulation of insulin secretion. Beta-cell diameter has been shown to correlate with pre-operative Body Mass Index (BMI). Accordingly, hypertrophy of the beta-cells in the pancreas has previously been proposed as an explanation of hyperinsulinemic hypoglycemia. However, pancreatic resection has not provided a cure for hypoglycemia following RYGB. In a recent study, administration of a Glucagon Like Peptide-1 (GLP-1) receptor antagonist was shown to eliminate postprandial hypoglycemia in patients with symptomatic hypoglycemia following RYGB. In this study altered gastro-intestinal function was suggested to contribute to the altered glucose metabolism in combination with dysregulation of insulin secretion. Hence, there is no general consensus on the subject.

No evidence-based guidelines for the diagnosis of postprandial hypoglycemia or investigation of glucose-metabolism in RYGB patients exist. Continuous Glucose Monitoring (CGM) has proven to provide high detection rates for hypoglycemia under real life conditions and can therefore be used as an important tool for screening of hypoglycemia. Currently, the preferred method for diagnosis of postprandial hypoglycemia is the mixed meal test (MMT), as it provides a more physiological stimulus compared to the oral glucose tolerance test (OGTT). While the OGTT consists of ingestion of a liquid containing 75 g glucose, the MMT consists of a liquid meal of 55 % carbohydrate, 25 % protein and 20 % fat. Both tests are performed after fasting with blood samples drawn during the test measuring glucose, insulin and c-peptide.

Knowledge of predictive factors for postprandial hypoglycemia in pregnancy will be an important tool for improving dietary management and quality of life in women with RYGB.