000			03928nam a22005177a 4500
008			220124s20212021 xxu||||| |||| 00| 0 eng d
022			_a0149-5992
024			_a10.2337/dc21-0451 [doi]
024			_adc21-0451 [pii]
024			_aPMC8669540 [pmc]
040			_aOvid MEDLINE(R)
099			_a34702783
245			_aLongitudinal Plasma Lipidome and Risk of Type 2 Diabetes in a Large Sample of American Indians With Normal Fasting Glucose: The Strong Heart Family Study.
251			_aDiabetes Care. 44(12):2664-2672, 2021 12.
252			_aDiabetes Care. 44(12):2664-2672, 2021 12.
252			_zDiabetes Care. 44(12):2664-2672, 2021 Dec.
253			_aDiabetes care
260			_c2021
260			_fFY2022
260			_p2021 Dec
265			_sppublish
266			_d2022-01-25
268			_aDiabetes Care. 44(12):2664-2672, 2021 Dec.
501			_aAvailable online from MWHC library: 1995 - present, Available in print through MWHC library: 1999 - 2006
520			_aCONCLUSIONS: Lipid dysregulation occurs many years preceding T2D, and novel molecular lipids (both baseline level and longitudinal change over time) are significantly associated with risk of T2D beyond traditional risk factors. Our findings shed light on the mechanisms linking dyslipidemia to T2D and may yield novel therapeutic targets for early intervention tailored to American Indians. Copyright (c) 2021 by the American Diabetes Association.
520			_aOBJECTIVE: Comprehensive assessment of alterations in lipid species preceding type 2 diabetes (T2D) is largely unknown. We aimed to identify plasma molecular lipids associated with risk of T2D in American Indians.
520			_aRESEARCH DESIGN AND METHODS: Using untargeted liquid chromatography-mass spectrometry, we repeatedly measured 3,907 fasting plasma samples from 1,958 participants who attended two examinations (~5.5 years apart) and were followed up to 16 years in the Strong Heart Family Study. Mixed-effects logistic regression was used to identify lipids associated with risk of T2D, adjusting for traditional risk factors. Repeated measurement analysis was performed to examine the association between change in lipidome and change in continuous measures of T2D, adjusting for baseline lipids. Multiple testing was controlled by false discovery rate at 0.05.
520			_aRESULTS: Higher baseline level of 33 lipid species, including triacylglycerols, diacylglycerols, phosphoethanolamines, and phosphocholines, was significantly associated with increased risk of T2D (odds ratio [OR] per SD increase in log2-transformed baseline lipids 1.50-2.85) at 5-year follow-up. Of these, 21 lipids were also associated with risk of T2D at 16-year follow-up. Aberrant lipid profiles were also observed in prediabetes (OR per SD increase in log2-transformed baseline lipids 1.30-2.19 for risk lipids and 0.70-0.78 for protective lipids). Longitudinal changes in 568 lipids were significantly associated with changes in continuous measures of T2D. Multivariate analysis identified distinct lipidomic signatures differentiating high- from low-risk groups.
546			_aEnglish
650			_a*Diabetes Mellitus, Type 2
650			_a*Lipidomics
650			_aAmerican Indians or Alaska Natives
650			_aFasting
650			_aGlucose
650			_aHumans
650			_aRisk Factors
651			_aMedStar Health Research Institute
657			_aJournal Article
700			_aHoward, Barbara V
700			_aUmans, Jason G
700			_aZhu, Jianhui
790			_aCole SA, DeFelice B, Fiehn O, Fretts AM, Howard BV, Huo Z, Lee ET, Miao G, Pedrosa D, Umans JG, Wohlgemuth G, Zeng W, Zhang Y, Zhao J, Zhu J
856			_uhttps://dx.doi.org/10.2337/dc21-0451 _zhttps://dx.doi.org/10.2337/dc21-0451
858			_yHoward, Barbara V _uhttps://orcid.org/0000-0002-4216-7859 _zhttps://orcid.org/0000-0002-4216-7859
942			_cART _dArticle
999			_c10939 _d10939