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Plasma metabolomic profiles in association with type 2 diabetes risk and prevalence in Chinese adults.

Published on Jan 1, 2016in Metabolomics3.167
· DOI :10.1007/s11306-015-0890-8
Danxia Yu16
Estimated H-index: 16
(Vandy: Vanderbilt University),
Steven C. Moore41
Estimated H-index: 41
+ 5 AuthorsXiao-Ou Shu100
Estimated H-index: 100
(Vandy: Vanderbilt University)
Abstract
Metabolomic studies have identified several metabolites associated with type 2 diabetes (T2D) in populations of European ancestry. East Asians, a population of particular susceptibility to T2D, were generally not included in previous studies. We examined the associations of plasma metabolites with risk and prevalence of T2D in 976 Chinese men and women (40–74 years of age) who were participants of two prospective cohort studies and had no cardiovascular disease or cancer at baseline. Sixty-eight prevalent and 73 incident T2D cases were included. Non-targeted metabolomics was conducted that detected 689 metabolites with known identities and 690 unknown metabolites. Multivariable logistic and Cox regressions were used to evaluate the associations of standardized metabolites with diabetes risk and prevalence. We identified 36 known metabolites and 10 unknown metabolites associated with prevalent and/or incident T2D at false discovery rate <0.05. The known metabolites are involved in metabolic pathways of glycolysis/gluconeogenesis, branched-chain amino acids, other amino acids, fatty acids, glycerophospholipids, androgen, and bradykinin. Six metabolites showed independent associations with incident T2D: 1,5-anhydroglucitol, mannose, valine, 3-methoxytyrosine, docosapentaenoate (22:5n3), and bradykinin-hydroxy-pro(3). Each standard deviation increase in these metabolites was associated with a 40–150 % change in risk of developing diabetes (30–80 % after further adjustment for glucose). Risk prediction was significantly improved by adding these metabolites in addition to known T2D risk factors, including central obesity and glucose. These findings suggest that hexoses, branched-chain amino acids, and yet to be validated novel plasma metabolites may improve risk prediction and mechanistic understanding of T2D in Chinese populations.
  • References (55)
  • Citations (23)
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References55
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#1Xiao-Ou Shu (Vandy: Vanderbilt University)H-Index: 100
#2Honglan Li (SJTU: Shanghai Jiao Tong University)H-Index: 9
Last. Yong-Bing Xiang (SJTU: Shanghai Jiao Tong University)H-Index: 57
view all 8 authors...
The Shanghai Men’s Health Study (SMHS) is a population-based cohort study of 61 480 men aged 40–74 years, launched in 2002 in urban Shanghai to investigate the contribution of lifestyle/environmental factors and genetic susceptibility to cancer and other non-communicable diseases (NCDs). At baseline, trained interviewers collected detailed information on personal and dietary habits, occupational/medical history and physical activity, and took anthropometric measurements (response rate: 74%). Blo...
50 CitationsSource
#1Therese TillinH-Index: 20
#2Alun D. HughesH-Index: 65
Last. Nish ChaturvediH-Index: 69
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Aims/hypothesis South Asian individuals have an increased risk of diabetes compared with Europeans that is unexplained by obesity and traditional or established metabolic measures. Circulating amino acids (AAs) may provide additional explanatory insights. In a unique cohort of European and South Asian men, we compared cross-sectional associations between AAs, metabolic and obesity traits, and longitudinal associations with incident diabetes.
76 CitationsSource
#1C W Ma Ronald (CUHK: The Chinese University of Hong Kong)H-Index: 51
#2Xu(林旭) Lin (CAS: Chinese Academy of Sciences)H-Index: 1
Last. Weiping Jia (SJTU: Shanghai Jiao Tong University)H-Index: 55
view all 3 authors...
Summary The prevalence of diabetes in China has increased substantially over recent decades, with more than 100 million people estimated to be affected by the disease presently. During this period there has been an increase in the rates of obesity and a reduction in physical activity. Many of the changes in lifestyle and diet are a result of increased economic development and urbanisation. In addition to an increasingly westernised diet, the traditional Chinese diet also plays a part, with the q...
61 CitationsSource
#1C N Chan Juliana (CUHK: The Chinese University of Hong Kong)H-Index: 77
#2Yuying Zhang (CUHK: The Chinese University of Hong Kong)H-Index: 9
Last. Guang Ning (SJTU: Shanghai Jiao Tong University)H-Index: 8
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Summary China has a large burden of diabetes: in 2013, one in four people with diabetes worldwide were in China, where 11·6% of adults had diabetes and 50·1% had prediabetes. Many were undiagnosed, untreated, or uncontrolled. This epidemic is the result of rapid societal transition that has led to an obesogenic environment against a backdrop of traditional lifestyle and periods of famine, which together puts Chinese people at high risk of diabetes and multiple morbidities. Societal determinants ...
92 CitationsSource
#1Christopher J. Lynch (PSU: Pennsylvania State University)H-Index: 43
#2Sean H. AdamsH-Index: 34
Branched-chain amino acid (BCAA) levels are increased in individuals with obesity and are associated with worse metabolic health and future insulin resistance. In this Review, Christopher Lynch and Sean Adams discuss whether and how impaired BCAA metabolism might occur in obesity and how perturbations in BCAA levels reflect the insulin resistant and type 2 diabetes mellitus pathophenotypes.
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#1Jared R. Mayers (MIT: Massachusetts Institute of Technology)H-Index: 14
#2Chen Wu (Harvard University)H-Index: 38
Last. Brian M. Wolpin (Harvard University)H-Index: 48
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Elevated plasma levels of branched chain amino acids detected prior to pancreatic cancer diagnosis may result from whole body tissue breakdown occurring during the early stages of this disease.
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Modulation of the kallikrein-kinin system (KKS) has been shown to have beneficial effects on glucose homeostasis and several other physiological responses relevant to the progression of type 2 diabetes mellitus (T2D). The importance of bradykinin and its receptors in mediating these responses is well documented, but the role of tissue kallikrein-1, the protease that generates bradykinin in situ, is much less understood. We developed and tested DM199, recombinant human tissue kallikrein-1 protein...
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Metabolic profiling, or metabolomics, has developed into a mature science in recent years. It has major applications in the study of metabolic disorders. This review addresses issues relevant to the choice of the metabolomics platform, study design and data analysis in diabetes research, and presents recent advances using metabolomics in the identification of markers for altered metabolic pathways, biomarker discovery, challenge studies, metabolic markers of drug efficacy and off-target effects....
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#1Barbara S. Connolly (McMaster University)H-Index: 7
#2Anthony E. Lang (U of T: University of Toronto)H-Index: 126
Importance Parkinson disease is the second most common neurodegenerative disease worldwide. Although no available therapies alter the underlying neurodegenerative process, symptomatic therapies can improve patient quality of life. Objective To provide an evidence-based review of the initial pharmacological management of the classic motor symptoms of Parkinson disease; describe management of medication-related motor complications (such as motor fluctuations and dyskinesia), and other medication a...
458 CitationsSource
#1Steven C. Moore (NIH: National Institutes of Health)H-Index: 41
#2Charles E. Matthews (NIH: National Institutes of Health)H-Index: 53
Last. Amanda J. Cross (NIH: National Institutes of Health)H-Index: 48
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A high body mass index (BMI) is a major risk factor for several chronic diseases, but the biology underlying these associations is not well-understood. Dyslipidemia, inflammation, and elevated levels of growth factors and sex steroid hormones explain some of the increased disease risk, but other metabolic factors not yet identified may also play a role. In order to discover novel metabolic biomarkers of BMI, we used non-targeted metabolomics to assay 317 metabolites in blood samples from 947 par...
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#1Yue Sun (Capital Medical University)
#2Hao-Yu Gao (Capital Medical University)
Last. Yuxiang Yan (Capital Medical University)H-Index: 12
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OBJECTIVE: Metabolic signatures have emerged as valuable signaling molecules in the biochemical process of type 2 diabetes (T2D). To summarize and identify metabolic biomarkers in T2D, we performed a systematic review and meta-analysis of the associations between metabolites and T2D using high-throughput metabolomics techniques. METHODS: We searched relevant studies from MEDLINE (PubMed), Embase, Web of Science, and Cochrane Library as well as Chinese databases (Wanfang, Vip, and CNKI) inception...
Source
#1Hyung-Suk Yoon (VUMC: Vanderbilt University Medical Center)
#2Jae Jeong Yang (VUMC: Vanderbilt University Medical Center)H-Index: 1
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Abstract Background and aims Dyslipidemia has been identified as a major risk factor for cardiovascular disease. We aimed to identify metabolites and metabolite modules showing novel association with lipids among Bogalusa Heart Study (BHS) participants using untargeted metabolomics. Methods and Results Untargeted ultrahigh performance liquid chromatography-tandem mass spectroscopy was used to quantify serum metabolites of 1 243 BHS participants (816 whites and 427 African-Americans). The associa...
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