Introduction and Objective: Rates of nutrient delivery to the small intestine is one of major determinants of prandial glucose homeostasis. Rapid and accentuated rise in prandial blood glucose accompanying hyperinsulinemia is the hallmark of gastric bypass surgery (GB). However, it is unclear to what extent the rate of enteral nutrient flux due to rerouted gut after this procedure contributes to changes in prandial glycemia or islet-cell hormonal response. Here, the effects of rapid vs. slow nutrient ingestion on prandial glucose metabolism after GB is examined.Methods: Nine non-diabetic subjects with history of GB (>5 years, BMI of 30 3 kg/m2 and age of 54 3) underwent two study visits separated by 5-10 days. An isocaloric isovolumic liquid mixed meal (50-gram whey protein + 50-gram glucose) was given orally once over 5 minutes (SHORT) and once over 30 min (divided into 7 equal aliquots taken every 5 min; LONG).Results: Fasting levels of glucose, islet hormones, and insulin sensitivity and clearance were similar between 2 experiments. Despite a right shift of prandial glucose curve as a result of extended period of nutrient ingestion, the areas under the prandial glucose, insulin or glucagon curves did not differ between the LONG and SHORT studies. Beta-cell glucose sensitivity was also similar between the two studies. However, insulin sensitivity measured by OGIS (oral glucose insulin sensitivity) was diminished during LONG vs. SHORT studies (p<0.05). This was associated with a larger insulinogenic index [(Ins30-Ins0)/(Glu30-Glu0)] during LONG compared to SHORT (p<0.05) likely due to a lower trend of metabolic clearance of insulin during LONG studies (p=0.1).Conclusion: The findings presented here are not compatible with the established assumption that increased beta-cell responsiveness to glucose following GB is due to faster nutrient flux. Instead, in this model, OGIS, which more closely estimates peripheral (muscle) insulin sensitivity, seems to be regulated by the rate of nutrient delivery to the gut.
A. Alamari: None. A. Gastaldelli: Advisory Panel; Boehringer-Ingelheim. Consultant; Boehringer-Ingelheim, Novo Nordisk, Merck Sharp & Dohme Corp, Regeneron Pharmaceuticals. Other Relationship; Pfizer Inc, Madrigal Pharmaceuticals, Inc, Echosens, Eli Lilly and Company. Speaker’s Bureau; Merck Sharp & Dohme Corp, Eli Lilly and Company, Novo Nordisk. M. Salehi: Advisory Panel; Vognex, Amylyx.
National Institutes of Health DK105379 (MS)
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