Differential Metabolic Impact of Gastric Bypass Surgery Versus Dietary Intervention in Obese Diabetic Subjects Despite Identical Weight Loss

Laferrère, Blandine; Reilly, David; Arias, Sara; Swerdlow, Nicholas J.; Gorroochurn, Prakash; Bawa, Baani; Bose, Mousumi; Teixeira, Júlio; Stevens, Robert; Wenner, Brett R.; Bain, James R.; Muehlbauer, Michael J.; Haqq, Andrea M.; Lien, Lillian F.; Shah, Svati H.; Svetkey, Laura P.; Newgard, Christopher B.

doi:10.1126/scitranslmed.3002043

Cited by 340 publications

(351 citation statements)

References 33 publications

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“…with insulin sensitivity (20,21). Moreover, significantly different acylcarnitine profiles were observed among subjects with normal glucose tolerance, prediabetic states, or type 2 diabetes in a German study (22).…”

Section: Discussionmentioning

confidence: 99%

Early Prediction of Developing Type 2 Diabetes by Plasma Acylcarnitines: A Population-Based Study

et al. 2016

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OBJECTIVEAcylcarnitines were suggested as early biomarkers even prior to insulin resistance in animal studies, but their roles in predicting type 2 diabetes were unknown. Therefore, we aimed to determine whether acylcarnitines could independently predict type 2 diabetes by using a targeted metabolic profiling approach. RESEARCH DESIGN AND METHODSA population-based prospective study was conducted among 2,103 communityliving Chinese individuals aged 50-70 years from Beijing and Shanghai with a mean follow-up duration of 6 years. Fasting glucose, glycohemoglobin, and insulin were determined at baseline and in a follow-up survey. Baseline plasma acylcarnitines were profiled by liquid chromatography-tandem mass spectrometry. RESULTSOver the 6-year period, 507 participants developed diabetes. A panel of acylcanitines, especially with long chain, was significantly associated with increased risk of type 2 diabetes. The relative risks of type 2 diabetes per SD increase of the predictive model score were 2.48 (95% CI 2.20-2.78) for the conventional and 9.41 (95% CI 7.62-11.62) for the full model including acylcarnitines, respectively. Moreover, adding selected acylcarnitines substantially improved predictive ability for incident diabetes, as area under the receiver operator characteristic curve improved to 0.89 in the full model compared with 0.73 in the conventional model. Similar associations were obtained when the predictive models were established separately among Beijing or Shanghai residents. CONCLUSIONSA panel of acylcarnitines, mainly involving mitochondrial lipid dysregulation, significantly improved predictive ability for type 2 diabetes beyond conventional risk factors. These findings need to be replicated in other populations, and the underlying mechanisms should be elucidated.The escalating global epidemic of type 2 diabetes has contributed considerably to socioeconomic burdens in both developed and developing countries (1). To understand biological mechanisms and improve clinical predictions, it is essential to identify novel biomarkers to enhance the capability to predict early pathophysiological changes (2). As a largely preventable disease, early prediction is the key to control the epidemic trend of type 2 diabetes, particularly in those countries with

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Section: Discussionmentioning

confidence: 99%

Early Prediction of Developing Type 2 Diabetes by Plasma Acylcarnitines: A Population-Based Study

et al. 2016

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“…Furthermore, this metabolic signature predicted improvement in insulin resistance with moderate weight loss independent of the amount of weight lost (13) . In a separate study of subjects undergoing GBP further evidence emerged to support the important role of BCAA in insulin resistance (14) . It is well established that glycemic control improves more after GBP compared with equivalent diet-induced weight loss in patients with morbid obesity and type-2 diabetes mellitus.…”

Section: Metabolomicsmentioning

confidence: 99%

The relationship between BMI and metabolomic profiles: a focus on amino acids

et al. 2012

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The role of metabolomics in the field of nutrition is continuing to grow and it has the potential to assist in the understanding of metabolic regulation and explain how minor perturbations can have a multitude of biochemical endpoints. It is this development, which creates the potential to provide the knowledge necessary to facilitate a more targeted approach to nutrition. In recent years, there has been interest in applying metabolomics to examine alterations in the metabolic profile according to weight gain/obesity. Emerging from these studies is the strong evidence that alterations in the amino acid (AA) profiles are associated with obesity. Several other studies have also shown a relationship between branched-chain amino acids (BCAA), obesity and insulin resistance. The present review focuses on the proposed link between AA and in particular BCAA, obesity and insulin resistance. In conclusion, a wealth of information is accumulating to support the role of AA, and in particular of the BCAA, in obesity. Metabolomics: Amino acids: BMI: Branched-chain amino acidsObesity is now considered as a major global health problem, and the WHO has demonstrated that obesity levels have reached epidemic proportions worldwide with approximately 2 . 3 billion adults predicted to be overweight or obese by the year 2015(1) . It is well recognised that obesity plays a central role in insulin resistance, the metabolic syndrome and type-2 diabetes mellitus. Despite many years of research the exact mechanisms underlying the role of obesity in the development of these disorders and diseases are still not fully elucidated. However, in recent years, the application of 'omic' technologies to studies comparing lean and obese subjects has enhanced our understanding of this research area. This review will focus on the literature, which has utilised metabolomic techniques to investigate the altered metabolic profile in obesity and the subsequent effect on insulin resistance. MetabolomicsMetabolomics is the comprehensive study of metabolites in biofluids, tissues or cellular extracts. The metabolic profile of a sample may be assessed using a variety of techniques including Proton NMR spectroscopy, LC-MS and GC-MS. The role of metabolomics in the field of nutrition is continuing to grow and its utility in a number of studies has been demonstrated (2,3) . Earlier applications of metabolomics in this field compared metabolic profiles of lean and obese subjects (Table 1). Pietiläinen et al.(4) investigated whether acquired obesity was associated with changes in global serum lipid profiles independent of genetic factors in young adult monozygotic twins. In this study, fourteen healthy monozygotic pairs discordant for obesity (10-25 kg weight Abbreviations: AA, amino acid; BCAA, branched-chain amino acid; GBP, gastric bypass surgery; HF, high fat.

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“…These metabolites are prognostic of obesity intervention outcomes (40) and show favorable responses to therapeutic procedures such as gastric bypass (41). These strong associations of BCAA with human disease argue for a better understanding of the mechanisms that drive changes in their circulating levels and for testing the therapeutic impact of new methods for altering BCAA metabolism (42).…”

Section: Bt2 (S)-cppmentioning

confidence: 99%

Benzothiophene Carboxylate Derivatives as Novel Allosteric Inhibitors of Branched-chain α-Ketoacid Dehydrogenase Kinase

Tso

Gui

et al. 2014

Journal of Biological Chemistry

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Background: Branched-chain amino acids (BCAA) are elevated in maple syrup urine disease, obesity, and type 2 diabetes. Results: We show that benzothiophene carboxylate derivatives are allosteric inhibitors of branched-chain ␣-ketoacid dehydrogenase kinase (BDK). Conclusion: These BDK inhibitors robustly augment BCAA oxidation in mice, resulting in lower plasma BCAA. Significance: The BDK inhibitors are potentially useful for treatment of the above disorders.

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Differential Metabolic Impact of Gastric Bypass Surgery Versus Dietary Intervention in Obese Diabetic Subjects Despite Identical Weight Loss

Cited by 340 publications

References 33 publications

Early Prediction of Developing Type 2 Diabetes by Plasma Acylcarnitines: A Population-Based Study

Early Prediction of Developing Type 2 Diabetes by Plasma Acylcarnitines: A Population-Based Study

The relationship between BMI and metabolomic profiles: a focus on amino acids

Benzothiophene Carboxylate Derivatives as Novel Allosteric Inhibitors of Branched-chain α-Ketoacid Dehydrogenase Kinase

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