Dataset Information

Improvement in insulin resistance after gastric bypass surgery is correlated with a decline in plasma 2-hydroxybutyric acid.

ABSTRACT:

Background

Gastric bypass surgery for weight reduction often corrects dysglycemia in diabetic patients, but a full understanding of the underlying biochemical pathways continues to be investigated.

Objectives

To explore the effects of weight loss by surgical and dietary interventions on plasma metabolites using both targeted and discovery-oriented metabolomics platforms.

Setting

An academic medical center in the United States.

Methods

Improvement in homeostatic model assessment for insulin resistance (HOMA-IR), as an index of insulin resistance, was compared at 6 months in 11 patients that underwent Roux-en-Y gastric bypass against 11 patients that were matched for weight loss in the Weight Loss Maintenance (WLM) program. Metabolites in plasma were evaluated by nontargeted gas chromatography/mass spectrometry for the potential detection of >1100 biochemical markers.

Results

Among multiple metabolites detected, 2-hydroxybutyric acid (2-HBA) declined most significantly after 6 months in comparing patients that underwent Roux-en-Y gastric bypass with those in WLM (P < .001), corresponding with declines in HOMA-IR (P?=?.025). Baseline levels of 2-HBA for all patients were correlated with preintervention levels of HOMA-IR (R²?=?.565, P < .001). Moreover, the changes in 2-HBA after 6 months were correlated with changes in HOMA-IR (R²?=?.399, P?=?.0016).

Conclusions

Correlation between insulin resistance and 2-HBA suggests the utility of the latter as an excellent biomarker for tracking glycemic improvement, and offers further insight into the pathways that control diabetes. This is the first report of a decline in 2-HBA in response to bariatric surgery.

SUBMITTER: Shantavasinkul PC

PROVIDER: S-EPMC6153057 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Improvement in insulin resistance after gastric bypass surgery is correlated with a decline in plasma 2-hydroxybutyric acid.

Shantavasinkul Prapimporn Chattranukulchai PC Muehlbauer Michael J MJ Bain James R JR Ilkayeva Olga R OR Craig Damian M DM Newgard Christopher B CB Svetkey Laura P LP Shah Svati H SH Torquati Alfonso A

Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery 20180417 8

<h4>Background</h4>Gastric bypass surgery for weight reduction often corrects dysglycemia in diabetic patients, but a full understanding of the underlying biochemical pathways continues to be investigated.<h4>Objectives</h4>To explore the effects of weight loss by surgical and dietary interventions on plasma metabolites using both targeted and discovery-oriented metabolomics platforms.<h4>Setting</h4>An academic medical center in the United States.<h4>Methods</h4>Improvement in homeostatic model ...[more]

PMID: 29805089

Similar Datasets

Project description:Background/objectivesRoux-en-Y gastric bypass (RYGB) surgery improves insulin sensitivity (SI) and β-cell function in obese non-diabetic subjects. Exercise also improves SI and may be an effective adjunct therapy to RYGB surgery. However, the mechanisms by which exercise or weight loss improve peripheral SI after RYGB surgery are unclear. We hypothesized that microRNAs (miRNAs) mediate at least some of the regulatory processes driving such mechanisms. Consequently, this work aimed at profiling plasma miRNAs in participants of the Physical Activity Following Surgery Induced Weight Loss study (clinicaltrials.gov identifier: NCT00692367), to assess whether miRNA levels track with improvements in SI and cardiometabolic risk factors.Subjects/methodsNinety-four miRNAs implicated in metabolism were profiled in plasma samples from 22 severely obese subjects who were recruited 1-3 months after RYGB surgery and followed for 6 months of RYGB surgery-induced weight loss, with (exercise program (EX), N=11) or without (CON, N=11) an exercise training intervention. The subjects were selected, considering a priori sample size calculations, among the participants in the parent study. Mixed-effect modeling for repeated measures and partial correlation analysis was implemented in the R environment for statistical analysis.ResultsMirroring results in the parent trial, both groups experienced significant weight loss and improvements in cardiometabolic risk. In the CON group, weight loss significantly altered the pattern of circulating miR-7, miR-15a, miR-34a, miR-106a, miR-122 and miR-221. In the EX group, a distinct miRNA signature was altered: miR-15a, miR-34a, miR-122, miR-135b, miR-144, miR-149 and miR-206. Several miRNAs were significantly associated with improvements in acute insulin response, SI, and other cardiometabolic risk factors.ConclusionsThese findings present novel insights into the RYGB surgery-induced molecular changes and the effects of mild exercise to facilitate and/or maintain the benefits of a 'comprehensive' weight-loss intervention with concomitant improvements in cardiometabolic functions. Notably, we show a predictive value for miR-7, miR-15a, miR-106b and miR-135b.

Project description:Type 2 diabetes (T2D) is a challenging health concern worldwide. A lifestyle intervention to treat T2D is difficult to adhere, and the effectiveness of approved medications such as metformin, thiazolidinediones (TZDs), and sulfonylureas are suboptimal. On the other hand, bariatric procedures such as Roux-en-Y gastric bypass (RYGB) are being recognized for their remarkable ability to achieve diabetes remission, although the underlying mechanism is not clear. Recent evidence points to branched-chain amino acids (BCAAs) as a potential contributor to glucose impairment and insulin resistance. RYGB has been shown to effectively lower plasma BCAAs in insulin-resistant or T2D patients that may help improve glycemic control, but the underlying mechanism for BCAA reduction is not understood. Hence, we attempted to explore the mechanism by which RYGB reduces BCAAs. To this end, we randomized diet-induced obese (DIO) mice into three groups that underwent either sham or RYGB surgery or food restriction to match the weight of RYGB mice. We also included regular chow-diet-fed healthy mice as an additional control group. Here, we show that compared to sham surgery, RYGB in DIO mice markedly lowered serum BCAAs most likely by rescuing BCAA breakdown in both liver and white adipose tissues. Importantly, the restored BCAA metabolism following RYGB was independent of caloric intake. Fasting insulin and HOMA-IR were decreased as expected, and serum valine was strongly associated with insulin resistance. While gut hormones such as glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are postulated to mediate various surgery-induced metabolic benefits, mice lacking these hormonal signals (GLP-1R/Y2R double KO) were still able to effectively lower plasma BCAAs and improve glucose tolerance, similar to mice with intact GLP-1 and PYY signaling. On the other hand, mice deficient in fibroblast growth factor 21 (FGF21), another candidate hormone implicated in enhanced glucoregulatory action following RYGB, failed to decrease plasma BCAAs and normalize hepatic BCAA degradation following surgery. This is the first study using an animal model to successfully recapitulate the RYGB-led reduction of circulating BCAAs observed in humans. Our findings unmasked a critical role of FGF21 in mediating the rescue of BCAA metabolism following surgery. It would be interesting to explore the possibility of whether RYGB-induced improvement in glucose homeostasis is partly through decreased BCAAs.

Dataset Information

Improvement in insulin resistance after gastric bypass surgery is correlated with a decline in plasma 2-hydroxybutyric acid.

Background

Objectives

Setting

Methods

Results

Conclusions

Publications

Improvement in insulin resistance after gastric bypass surgery is correlated with a decline in plasma 2-hydroxybutyric acid.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets