Metabolites and diabetes remission after weight loss.
Metabolites and diabetes remission after weight loss.
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DOI：
10.1038/s41387-021-00151-6
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发表时间：
2021-02-24
影响因子：
6.1
通讯作者：
Laferrère B
中科院分区：
文献类型：
--
作者：
Kwee LC;Ilkayeva O;Muehlbauer MJ;Bihlmeyer N;Wolfe B;Purnell JQ;Xavier Pi-Sunyer F;Chen H;Bahnson J;Newgard CB;Shah SH;Laferrère B
在体重减轻量和代谢改善方面，对体重减轻干预措施的反应存在明显的异质性。我们试图确定预测2型糖尿病缓解的生物标志物，以及参与减肥手术纵向评估（LABS）和展望未来（糖尿病健康行动）研究的重度肥胖患者的体重减轻量。使用嵌套设计对干预前血液样本中的135种代谢物进行了基于靶向质谱的分析，用于5年内糖尿病缓解（n = 93个LABS，n = 80个Look AHEAD; n = 87个缓解者）和5年时极端体重减轻（n = 151个LABS; n = 75个体重减轻）。主成分分析（PCA）用于降维，PCA衍生的代谢物因子与糖尿病缓解和体重减轻的相关性进行了测试。对代谢标志物进行了测试，以获得临床模型的增量改善，包括DiaRem评分。两种代谢物因素与糖尿病缓解相关：一种主要由支链氨基酸（BCAA）和酪氨酸组成（比值比（95%置信区间）[OR（95% CI）] = 1.4 [1.0-1.9]，p = 0.045），甜菜碱和胆碱组（OR [95%CI] = 0.7 [0.5-0.9]，p = 0.02）。经多次检验调整后，这些结果无显著性。在临床模型中纳入这两个因素，模型拟合和性能得到了适度的改善：在构建的临床模型中，C统计量从0.87改善到0.90（p = 0.02），而净重新分类指数显示与DiaRem评分相比预测有所改善（NRI = 0.26，p = 0.0013）。5年时无与体重减轻相关的代谢物因素。BCAA和三甲胺-N-氧化物（TMAO）-微生物组相关途径中代谢物的基线水平与重度肥胖个体减肥干预后的持续糖尿病缓解独立且递增相关。这些代谢物可以作为临床上有用的生物标志物，以识别从减肥干预措施中受益最大的个体。
There is marked heterogeneity in the response to weight loss interventions with regards to weight loss amount and metabolic improvement. We sought to identify biomarkers predictive of type 2 diabetes remission and amount of weight loss in individuals with severe obesity enrolled in the Longitudinal Assessment of Bariatric Surgery (LABS) and the Look AHEAD (Action for Health in Diabetes) studies. Targeted mass spectrometry-based profiling of 135 metabolites was performed in pre-intervention blood samples using a nested design for diabetes remission over five years (n = 93 LABS, n = 80 Look AHEAD; n = 87 remitters), and for extremes of weight loss at five years (n = 151 LABS; n = 75 with high weight loss). Principal components analysis (PCA) was used for dimensionality reduction, with PCA-derived metabolite factors tested for association with both diabetes remission and weight loss. Metabolic markers were tested for incremental improvement to clinical models, including the DiaRem score. Two metabolite factors were associated with diabetes remission: one primarily composed of branched chain amino acids (BCAA) and tyrosine (odds ratio (95% confidence interval) [OR (95% CI)] = 1.4 [1.0–1.9], p = 0.045), and one with betaine and choline (OR [95% CI] = 0.7 [0.5–0.9], p = 0.02).These results were not significant after adjustment for multiple tests. Inclusion of these two factors in clinical models yielded modest improvements in model fit and performance: in a constructed clinical model, the C-statistic improved from 0.87 to 0.90 (p = 0.02), while the net reclassification index showed improvement in prediction compared to the DiaRem score (NRI = 0.26, p = 0.0013). No metabolite factors associated with weight loss at five years. Baseline levels of metabolites in the BCAA and trimethylamine-N-oxide (TMAO)-microbiome-related pathways are independently and incrementally associated with sustained diabetes remission after weight loss interventions in individuals with severe obesity. These metabolites could serve as clinically useful biomarkers to identify individuals who will benefit the most from weight loss interventions.
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影响因子：
9.1
作者：
Dutton GR;Lewis CE
通讯作者：
Lewis CE
影响因子：
2.9
作者：
Arterburn DE;Bogart A;Sherwood NE;Sidney S;Coleman KJ;Haneuse S;O'Connor PJ;Theis MK;Campos GM;McCulloch D;Selby J
通讯作者：
Selby J
影响因子：
44.5
作者：
Gregg, Edward W.;Jakicic, John M.;Lewis, Cora E.;Regensteiner, Judith G.;Pi-Sunyer, Xavier;Wing, Rena R.;Curtis, Jeffrey M.;Yanovski, Susan Z.;Evans, Mary;Lang, Wei;Neiberg, Rebecca H.;Ribisl, Paul M.;Gregg, Edward W.;Jakicic, John M.;Blackburn, George;Bloomquist, Paul;Bray, George A.;Clark, Jeanne M.;Coday, Mace;Curtis, Jeff Rey M.;Egan, Caitlin;Evans, Mary;Foreyt, John P.;Foster, Gary D.;Hazuda, Helen P.;Hill, James O.;Horton, Edward S.;Hubbard, Van S.;Ery, Robert W. Jeff;Johnson, Karen C.;Abbas;Kitabchi;Knowler, William C.;Kriska, Andrea;Lang, Wei;Lewis, Cora E.;Montez, Maria G.;Nathan, David M.;Neiberg, Rebecca H.;Patricio, Jennifer;Peters, Anne;Pi-Sunyer, Xavier;Pownall, Henry;Redmon, Bruce;Regensteiner, Judith G.;Rejeski, W. Jack;Ribisl, Paul M.;Ord, Monika Saff;Stewart, Kerry;Trence, Dace;Wadden, Thomas A.;Wing, Rena R.;Yanovski, Susan Z.
通讯作者：
Yanovski, Susan Z.
影响因子：
5.8
作者：
Laferrere, Blandine;Teixeira, Julio;Olivan, Blanca
通讯作者：
Olivan, Blanca
影响因子：
16.9
作者：
Courcoulas, Anita P.;King, Wendy C.;Yanovski, Susan Z.
通讯作者：
Yanovski, Susan Z.