Calorie Restriction & Short-term Effects of Gastric Bypass
Objective. Roux-en-Y gastric bypass (RYGB) and restrictive weight loss interventions, such as gastric banding (GB) and very-low-calorie diets (VLCD) directly impact glucose metabolism, possibly by calorie restriction and/or altered secretion of gut hormones. We aimed to establish the direct endocrine and metabolic effects of RYGB compared to restrictive interventions in obese glucose-tolerant (NGT) subjects and subjects with type 2 diabetes (T2DM).
Design. Controlled, nonrandomized observational trial.
Patients and Measurements. Four groups of obese females received a mixed meal at baseline and 3 weeks after intervention; NGT-GB (n = 11), NGT-RYGB (n = 16), T2DM-RYGB (n = 15) and T2DM-VLCD (n = 12). Normal weight controls (n = 12) were studied once.
Results. At baseline, all obese subjects were hyperinsulinemic. T2DM was associated with hyperglycaemia and decreased GLP-1 levels. RYGB and VLCD reduced glucose levels to a similar extent in T2DM, insulin levels decreased only after VLCD. Comparison of restrictive intervention vsRYGB showed a more pronounced decrease in glucose and insulin AUC after restriction. In NGT and T2DM subjects, RYGB increased GLP-1 and PYY levels and decreased ghrelin levels, whereas VLCD and GB only increased GIP levels.
Conclusions. These data indicate that deterioration of glucose metabolism in T2DM is associated with a decline of GLP-1 levels. Calorie restriction facilitates glucose metabolism and blunts hyperinsulinemia in obese (diabetic) humans. Additional duodenal exclusion through RYGB induces gut hormone release and hyperinsulinemia but does not improve postprandial glucose levels any further. Our data thus strongly suggest that calorie restriction underlies the short-term metabolic benefits of RYGB in obese T2DM patients.
Even though the pathogenesis of obesity and type 2 diabetes is incompletely understood, current scientific knowledge suggests that metabolic, neuroendocrine and inflammatory adaptations to overnutrition and inactivity are involved. Calorie restriction effectively improves glucose metabolism on the short term. Roux-en-Y gastric bypass surgery (RYGB) has also been shown to improve glucose metabolism within weeks, before significant weight loss has occurred. This suggests that gastrointestinal rearrangements and/or concomitant calorie restriction per se exert direct beneficial effects on metabolism.
Various reports have suggested that gut hormones, that is, glucagon-like-polypeptide-1 (GLP-1), glucose-dependent-insulinotropic-peptide (GIP), peptide YY (PYY) and ghrelin, are critical mediators of the benefits of bariatric surgery. GLP-1 and PYY, secreted by L-cells primarily located in de distal ileum, inhibit food intake and enhance glucose-dependent insulin secretion. Exaggerated postprandial GLP-1 and PYY secretion, driven by expedited nutrient delivery to L-cells, is hypothesized to confer the metabolic effects after RYGB. GIP, produced by K-cells in the duodenum, facilitates glucose-induced insulin release and promotes glucose uptake and fat storage in adipocytes. RYGB was reported to either increase or decrease GIP. Ghrelin is an orexigenic hormone, which is released by endocrine cells in the stomach in the absence of food and is suppressed by food intake. Although much debated, some evidence suggests that ghrelin levels remain suppressed after RYGB, which possibly adds to the anorexigenic effect of this procedure. Finally, fatty acid entry into the proximal gut appears to play an important role in the control of endogenous glucose production via neural pathways in healthy (nondiabetic) rats.
In view of these multiple effects of hormones released by distinct gut segments in response to the presence or absence of food, it is conceivable that gastrointestinal rearrangements modifying food intake and/or the processing of nutrients do indeed have significant effects on postprandial hormone release and metabolism. However, RYGB also limits calorie intake to a substantial extent, and calorie restriction per se beneficially impacts postprandial metabolism. The relative contributions of calorie restriction vs the endocrine corollaries of bypass surgery to the metabolic benefits of RYGB remain elusive.
To clarify this issue, we conducted a clinical trial comparing the postprandial glucose, insulin and gut hormone response to GB/caloric restriction or RYGB in obese individuals with normal glucose tolerance and equally obese subjects with T2DM (trial no NCT01167959). We hypothesized that gastric bypass surgery would increase postprandial gut hormone release to elevate insulin levels and lower glucose levels in response to a meal to a greater extent than calorie restriction per se. To identify effects that are independent of fat loss, we examined the endocrine and metabolic response to a mixed meal 3 weeks after intervention, when body weight loss was insignificant.
Abstract and Introduction
Abstract
Objective. Roux-en-Y gastric bypass (RYGB) and restrictive weight loss interventions, such as gastric banding (GB) and very-low-calorie diets (VLCD) directly impact glucose metabolism, possibly by calorie restriction and/or altered secretion of gut hormones. We aimed to establish the direct endocrine and metabolic effects of RYGB compared to restrictive interventions in obese glucose-tolerant (NGT) subjects and subjects with type 2 diabetes (T2DM).
Design. Controlled, nonrandomized observational trial.
Patients and Measurements. Four groups of obese females received a mixed meal at baseline and 3 weeks after intervention; NGT-GB (n = 11), NGT-RYGB (n = 16), T2DM-RYGB (n = 15) and T2DM-VLCD (n = 12). Normal weight controls (n = 12) were studied once.
Results. At baseline, all obese subjects were hyperinsulinemic. T2DM was associated with hyperglycaemia and decreased GLP-1 levels. RYGB and VLCD reduced glucose levels to a similar extent in T2DM, insulin levels decreased only after VLCD. Comparison of restrictive intervention vsRYGB showed a more pronounced decrease in glucose and insulin AUC after restriction. In NGT and T2DM subjects, RYGB increased GLP-1 and PYY levels and decreased ghrelin levels, whereas VLCD and GB only increased GIP levels.
Conclusions. These data indicate that deterioration of glucose metabolism in T2DM is associated with a decline of GLP-1 levels. Calorie restriction facilitates glucose metabolism and blunts hyperinsulinemia in obese (diabetic) humans. Additional duodenal exclusion through RYGB induces gut hormone release and hyperinsulinemia but does not improve postprandial glucose levels any further. Our data thus strongly suggest that calorie restriction underlies the short-term metabolic benefits of RYGB in obese T2DM patients.
Introduction
Even though the pathogenesis of obesity and type 2 diabetes is incompletely understood, current scientific knowledge suggests that metabolic, neuroendocrine and inflammatory adaptations to overnutrition and inactivity are involved. Calorie restriction effectively improves glucose metabolism on the short term. Roux-en-Y gastric bypass surgery (RYGB) has also been shown to improve glucose metabolism within weeks, before significant weight loss has occurred. This suggests that gastrointestinal rearrangements and/or concomitant calorie restriction per se exert direct beneficial effects on metabolism.
Various reports have suggested that gut hormones, that is, glucagon-like-polypeptide-1 (GLP-1), glucose-dependent-insulinotropic-peptide (GIP), peptide YY (PYY) and ghrelin, are critical mediators of the benefits of bariatric surgery. GLP-1 and PYY, secreted by L-cells primarily located in de distal ileum, inhibit food intake and enhance glucose-dependent insulin secretion. Exaggerated postprandial GLP-1 and PYY secretion, driven by expedited nutrient delivery to L-cells, is hypothesized to confer the metabolic effects after RYGB. GIP, produced by K-cells in the duodenum, facilitates glucose-induced insulin release and promotes glucose uptake and fat storage in adipocytes. RYGB was reported to either increase or decrease GIP. Ghrelin is an orexigenic hormone, which is released by endocrine cells in the stomach in the absence of food and is suppressed by food intake. Although much debated, some evidence suggests that ghrelin levels remain suppressed after RYGB, which possibly adds to the anorexigenic effect of this procedure. Finally, fatty acid entry into the proximal gut appears to play an important role in the control of endogenous glucose production via neural pathways in healthy (nondiabetic) rats.
In view of these multiple effects of hormones released by distinct gut segments in response to the presence or absence of food, it is conceivable that gastrointestinal rearrangements modifying food intake and/or the processing of nutrients do indeed have significant effects on postprandial hormone release and metabolism. However, RYGB also limits calorie intake to a substantial extent, and calorie restriction per se beneficially impacts postprandial metabolism. The relative contributions of calorie restriction vs the endocrine corollaries of bypass surgery to the metabolic benefits of RYGB remain elusive.
To clarify this issue, we conducted a clinical trial comparing the postprandial glucose, insulin and gut hormone response to GB/caloric restriction or RYGB in obese individuals with normal glucose tolerance and equally obese subjects with T2DM (trial no NCT01167959). We hypothesized that gastric bypass surgery would increase postprandial gut hormone release to elevate insulin levels and lower glucose levels in response to a meal to a greater extent than calorie restriction per se. To identify effects that are independent of fat loss, we examined the endocrine and metabolic response to a mixed meal 3 weeks after intervention, when body weight loss was insignificant.
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