Dataset Information

Differential metabolic impact of gastric bypass surgery versus dietary intervention in obese diabetic subjects despite identical weight loss.

ABSTRACT: Glycemic control is improved more after gastric bypass surgery (GBP) than after equivalent diet-induced weight loss in patients with morbid obesity and type 2 diabetes mellitus. We applied metabolomic profiling to understand the mechanisms of this better metabolic response after GBP. Circulating amino acids (AAs) and acylcarnitines (ACs) were measured in plasma from fasted subjects by targeted tandem mass spectrometry before and after a matched 10-kilogram weight loss induced by GBP or diet. Total AAs and branched-chain AAs (BCAAs) decreased after GBP, but not after dietary intervention. Metabolites derived from BCAA oxidation also decreased only after GBP. Principal components (PC) analysis identified two major PCs, one composed almost exclusively of ACs (PC1) and another with BCAAs and their metabolites as major contributors (PC2). PC1 and PC2 were inversely correlated with pro-insulin concentrations, the C-peptide response to oral glucose, and the insulin sensitivity index after weight loss, whereas PC2 was uniquely correlated with levels of insulin resistance (HOMA-IR). These data suggest that the enhanced decrease in circulating AAs after GBP occurs by mechanisms other than weight loss and may contribute to the better improvement in glucose homeostasis observed with the surgical intervention.

SUBMITTER: Laferrere B

PROVIDER: S-EPMC3656497 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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Differential metabolic impact of gastric bypass surgery versus dietary intervention in obese diabetic subjects despite identical weight loss.

Laferrère Blandine B Reilly David D Arias Sara S Swerdlow Nicholas N Gorroochurn Prakash P Bawa Baani B Bose Mousumi M Teixeira Julio J Stevens Robert D RD Wenner Brett R BR Bain James R JR Muehlbauer Michael J MJ Haqq Andrea A Lien Lillian L Shah Svati H SH Svetkey Laura P LP Newgard Christopher B CB

Science translational medicine 20110401 80

Glycemic control is improved more after gastric bypass surgery (GBP) than after equivalent diet-induced weight loss in patients with morbid obesity and type 2 diabetes mellitus. We applied metabolomic profiling to understand the mechanisms of this better metabolic response after GBP. Circulating amino acids (AAs) and acylcarnitines (ACs) were measured in plasma from fasted subjects by targeted tandem mass spectrometry before and after a matched 10-kilogram weight loss induced by GBP or diet. Tot ...[more]

PMID: 21525399

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Project description:Background. Differential gene expression in adipose tissue during diet-induced weight loss followed by a weight stability period is not well characterized. Markers of these processes may provide a deeper understanding of the underlying mechanisms. Objective. To identify differentially expressed genes in human adipose tissue during weight loss and weight maintenance after weight loss. Design. RNA from subcutaneous abdominal adipose tissue from nine obese subjects was obtained and analyzed at baseline, after weight reduction on a low calorie diet (LCD), and after a period of group therapy in order to maintain weight stability. Results. Subjects lost 18.8 + 5.4% of their body weight during the LCD and maintained this weight during group therapy. Insulin sensitivity (HOMA) improved after weight loss with no further improvement during weight maintenance. Cyclin-dependent kinase inhibitor 2B (CDKN2B) and JAZF zinc finger 1 (JAZF1), associated with type 2 diabetes, were downregulated. We could also confirm the downregulation of candidates for obesity and related traits, such as tenomodulin (TNMD) and matrix metallopeptidase 9 (MMP9), with weight loss. The expression of other candidates, such as cell death-inducing DFFA-like effector A (CIDEA) and stearoyl-CoA desaturase (SCD) were upregulated during weight loss but returned to baseline levels during weight maintenance. Conclusion. Genes in the adipose tissue are differentially expressed during weight loss and weight maintenance after weight loss. Genes that show sustained regulation may be of potential interest as markers of the beneficial effects of weight loss whereas others seem to be primarily involved in the process of weight loss itself. Nine participants were prescribed a low calorie diet (LCD) containing 1200 kcal/day for approximately three months (101 ± 26 days). Following the weight reduction phase the participants attended a six month follow-up period (167 ± 37 days). By protocol design, subjects were eligible to enter the study if they had lost at least 10% of their initial body weight during the LCD-period and maintained this weight (+5%) after group therapy. Subcutaneous adipose tissue samples were obtained at three time-points: (i) at baseline, (ii) after weight reduction when subjects were no longer losing weight, and (iii) after the group therapy weight maintenance phase.

Project description:Background/Objetives: Obesity and obesity related co-morbidities are well-recognized risks for cardiovascular (CV) disease and mortality. Weight loss improves CV risk factors and the efficacy of bariatric surgery in decreasing CV mortality is now well-established. Our aim was to assess CV risk progression and occurrence of CV events in a cohort of patients that underwent Roux-en-Y gastric bypass (RYGB) for obesity treatment in a single academic public center. Subjects and Methods: Ten year CV risk was estimated using the Framingham Equation at baseline and 2 years after RYGB surgery in our patients cohort (n = 260). In the subgroup with a follow-up time longer than 4 years after surgery (n = 185; mean 5.4 ± 0.1 years), CV risk adjusted for the time length after RYGB was similarly estimated and the occurrence of CV events for outcome adjudication was monitored during the same time period by reviewing the hospital patients' record, the electronic national health system patient register and our center outpatient clinic records. Results: Ten year CV risk was significantly reduced 2 years after surgery when compared to baseline, with reductions of 1.65 ± 0.25% in the risk of CV disease. Patients with prior type 2 diabetes and aged 50 years or older experienced a significantly superior CV risk reduction, with diabetic patients experiencing a reduction of their 10-year CV disease risk of 3.58 ± 1.11% vs. a reduction of 1.31 ± 0.20% in non-diabetic patients and with the 10-year risk of CV disease dropping 3.41 ± 0.75% in patients older than 50 vs. a reduction of 0.99 ± 0.18 in patients up to 50 years. For the subgroup of patients with a longer follow-up time, baseline CV risk estimation predicted the occurrence of 6.08 ± 0.56 cardiovascular disease (CVD) events, 3.87 ± 0.39 coronary heart disease (CHD) events, 1.49 ± 0.22 myocardial infarctions (MI), 0.71 ± 0.09 strokes, 0. 28 ± 0.05 deaths from CHD and 0.35 ± 0.05 deaths from CVD. No CV events were adjudicated in this subgroup during follow-up. Conclusions: RYGB significantly improves CV risk and prevents the occurrence of CV events. For similar weight loss, diabetic and elder patients experience a superior CV risk improvement and may have additional CV benefits after bariatric surgery.

Dataset Information

Differential metabolic impact of gastric bypass surgery versus dietary intervention in obese diabetic subjects despite identical weight loss.

Publications

Differential metabolic impact of gastric bypass surgery versus dietary intervention in obese diabetic subjects despite identical weight loss.

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