Distinctive Metabolomics Patterns Associated With Insulin Resistance and Type 2 Diabetes Mellitus.
Distinctive Metabolomics Patterns Associated With Insulin Resistance and Type 2 Diabetes Mellitus.
复制标题
DOI：
10.3389/fmolb.2020.609806
复制
发表时间：
2020
影响因子：
5
通讯作者：
Aljada A
中科院分区：
文献类型：
--
作者：
Gu X;Al Dubayee M;Alshahrani A;Masood A;Benabdelkamel H;Zahra M;Li L;Abdel Rahman AM;Aljada A
肥胖与胰岛素抵抗（IR）和2型糖尿病（T2 DM）风险增加相关，2型糖尿病是一种与代谢失调相关的多因素疾病，可在葡萄糖耐量受损的糖尿病前期个体中预防。强调代谢途径的代谢组学方法对我们理解这种异质性疾病至关重要。本研究旨在表征与IR和T2 DM相关的血清代谢组学指纹和多代谢物特征。在这里，我们使用了非靶向的高性能化学同位素标记（CIL）液相色谱-质谱（LC-MS），以确定候选生物标志物IR和T2 DM的血清从30名正常体重的成年人，26名肥胖的成年人，和16名新诊断为T2 DM的成年人。在检测到的3633个峰对中，62%被识别或匹配。与瘦型组相比，肥胖组有78种代谢产物上调，111种代谢产物下调，而与肥胖组相比，T2 DM组有459种代谢产物上调，166种代谢产物下调。几种代谢产物被鉴定为IR潜在生物标志物，包括氨基酸（Asn、Gln和His）、蛋氨酸（Met）亚砜、2-甲基-3-羟基-5-甲酰基吡啶-4-羧酸酯、5-羟色胺、L-2-氨基-3-氧代丁酸和4，6-二羟基喹啉。T2 DM与42种代谢物的失调相关，包括氨基酸、氨基酸代谢物和二肽。总之，这些初步数据已将IR和T2 DM代谢组学组确定为IR的潜在新型生物标志物，并确定了与T2 DM相关的代谢物，具有可能的诊断和治疗应用。在前瞻性队列中进一步研究以证实这些关联是必要的。
Obesity is associated with an increased risk of insulin resistance (IR) and type 2 diabetes mellitus (T2DM) which is a multi-factorial disease associated with a dysregulated metabolism and can be prevented in pre-diabetic individuals with impaired glucose tolerance. A metabolomic approach emphasizing metabolic pathways is critical to our understanding of this heterogeneous disease. This study aimed to characterize the serum metabolomic fingerprint and multi-metabolite signatures associated with IR and T2DM. Here, we have used untargeted high-performance chemical isotope labeling (CIL) liquid chromatography-mass spectrometry (LC-MS) to identify candidate biomarkers of IR and T2DM in sera from 30 adults of normal weight, 26 obese adults, and 16 adults newly diagnosed with T2DM. Among the 3633 peak pairs detected, 62% were either identified or matched. A group of 78 metabolites were up-regulated and 111 metabolites were down-regulated comparing obese to lean group while 459 metabolites were up-regulated and 166 metabolites were down-regulated comparing T2DM to obese groups. Several metabolites were identified as IR potential biomarkers, including amino acids (Asn, Gln, and His), methionine (Met) sulfoxide, 2-methyl-3-hydroxy-5-formylpyridine-4-carboxylate, serotonin, L-2-amino-3-oxobutanoic acid, and 4,6-dihydroxyquinoline. T2DM was associated with dysregulation of 42 metabolites, including amino acids, amino acids metabolites, and dipeptides. In conclusion, these pilot data have identified IR and T2DM metabolomics panels as potential novel biomarkers of IR and identified metabolites associated with T2DM, with possible diagnostic and therapeutic applications. Further studies to confirm these associations in prospective cohorts are warranted.
登录
查看更多内容
影响因子：
5.9
作者：
Abboud, Kahlile Youssef;Reis, Sabrina Karen;Prada, Patricia Oliveira
通讯作者：
Prada, Patricia Oliveira
影响因子：
9.8
作者：
CAMPBELL, PJ;MANDARINO, LJ;GERICH, JE
通讯作者：
GERICH, JE
影响因子：
4.1
作者：
Dahabiyeh, Lina A.;Malkawi, Abeer K.;Rahman, Anas M. Abdel
通讯作者：
Rahman, Anas M. Abdel
影响因子：
4.4
作者：
DiBattista, Alicia;McIntosh, Nathan;Britz-McKibbin, Philip
通讯作者：
Britz-McKibbin, Philip
影响因子：
64.8
作者：
Fu, Suneng;Yang, Ling;Li, Ping;Hofmann, Oliver;Dicker, Lee;Hide, Winston;Lin, Xihong;Watkins, Steven M.;Ivanov, Alexander R.;Hotamisligil, Goekhan S.
通讯作者：
Hotamisligil, Goekhan S.