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Gastric bypass surgery has a weight-loss independent effect on post-challenge serum glucose levels.

ABSTRACT: BACKGROUND:Gastric bypass surgery seems to have an effect on glucose metabolism beyond what is mediated through weight reduction. The magnitude of this effect on fasting and post-challenge glucose levels remains unknown. RESULTS:Morbidly obese subjects without known diabetes performed a 75 g oral glucose tolerance test before and after either gastric bypass surgery (n = 64) or an intensive lifestyle intervention programme (n = 55), ClinicalTrials.gov identifier NCT00273104. The age-adjusted effects of the therapeutic procedures and percentage weight change on fasting and 2-h glucose levels at 1 year were explored using multiple linear regression analysis. Mean (SD) serum fasting and 2-h glucose levels at baseline did not differ between the surgery and lifestyle groups. Weight-loss after surgical treatment and lifestyle intervention was 30 (8) and 9 (10) % (p < 0.001). At 1 year, fasting and 2-h glucose levels were significantly lower in the surgery group than in the lifestyle group, 4.7 (0.4) versus 5.4 (0.7) mmol/l and 3.4 (0.8) versus 6.0 (2.4) mmol/l, respectively (both p < 0.001). Gastric bypass and weight-loss had both independent glucose-lowering effects on 2-h glucose levels [B (95 % CI) 1.4 (0.6-2.3) mmol/l and 0.4 (0.1-0.7) mmol/l per 10 % weight-loss, respectively]. Fasting glucose levels were determined by weight change [0.2 (0.1-0.3) mmol/l per 10 % weight-loss] and not by type of treatment. CONCLUSIONS:Gastric bypass surgery has a clinically relevant glucose-lowering effect on post-challenge glucose levels which is seemingly not mediated through weight-loss alone.

SUBMITTER: Hofso D

PROVIDER: S-EPMC4546335 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Gastric bypass surgery has a weight-loss independent effect on post-challenge serum glucose levels.

Hofsø Dag D Birkeland Kåre I KI Holst Jens J JJ Bollerslev Jens J Sandbu Rune R Røislien Jo J Hjelmesæth Jøran J

Diabetology & metabolic syndrome 20150822

<h4>Background</h4>Gastric bypass surgery seems to have an effect on glucose metabolism beyond what is mediated through weight reduction. The magnitude of this effect on fasting and post-challenge glucose levels remains unknown.<h4>Results</h4>Morbidly obese subjects without known diabetes performed a 75 g oral glucose tolerance test before and after either gastric bypass surgery (n = 64) or an intensive lifestyle intervention programme (n = 55), ClinicalTrials.gov identifier NCT00273104. The ag ...[more]

PMID: 26300987

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Project description:Roux-en-Y gastric bypass surgery (RYGB) leads to improved glycemic control in individuals with severe obesity beyond the effects of weight loss alone. Here, We addressed the potential contribution of gut microbiota in mediating this favourable surgical outcome by using an established preclinical model of RYGB. 16S rRNA sequencing revealed that RYGB-treated Zucker fatty rats had altered fecal composition of various bacteria at the phylum and species levels, including lower fecal abundance of an unidentified Erysipelotrichaceae species, compared with both sham-operated (Sham) and body weight-matched to RYGB-treated (BWM) rats. Correlation analysis further revealed that fecal abundance of this unidentified Erysipelotrichaceae species linked with multiple indices of glycemic control uniquely in RYGB-treated rats. Sequence alignment of this Erysipelotrichaceae species identified Longibaculum muris to be the most closely related species, and its fecal abundance positively correlated with oral glucose intolerance in RYGB-treated rats. In fecal microbiota transplant experiments, the improved oral glucose tolerance of RYGB-treated compared with BWM rats could partially be transferred to recipient germfree mice, independently of body weight. Unexpectedly, providing L. muris as a supplement to RYGB recipient mice further improved oral glucose tolerance, while administering L. muris alone to chow-fed or Western style diet-challenged conventionally raised mice had minimal metabolic impact. Taken together, our findings provide evidence that the gut microbiota contributes to weight loss-independent improvements in glycemic control after RYGB and demonstrate how correlation of a specific gut microbiota species with a host metabolic trait does not imply causation. IMPORTANCE Metabolic surgery remains the most effective treatment modality for severe obesity and its comorbidities, including type 2 diabetes. Roux-en-Y gastric bypass (RYGB) is a commonly performed type of metabolic surgery that reconfigures gastrointestinal anatomy and profoundly remodels the gut microbiota. While it is clear that RYGB is superior to dieting when it comes to improving glycemic control, the extent to which the gut microbiota contributes to this effect remains untested. In the present study, we uniquely linked fecal Erysipelotrichaceae species, including Longibaculum muris, with indices of glycemic control after RYGB in genetically obese and glucose-intolerant rats. We further show that the weight loss-independent improvements in glycemic control in RYGB-treated rats can be transmitted via their gut microbiota to germfree mice. Our findings provide rare causal evidence that the gut microbiota contributes to the health benefits of metabolic surgery and have implications for the development of gut microbiota-based treatments for type 2 diabetes.

Dataset Information

Gastric bypass surgery has a weight-loss independent effect on post-challenge serum glucose levels.

Publications

Gastric bypass surgery has a weight-loss independent effect on post-challenge serum glucose levels.

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