Longitudinal Plasma Lipidome and Risk of Type 2 Diabetes in a Large Sample of American Indians With Normal Fasting Glucose: The Strong Heart Family Study.

MedStar author(s):
Citation: Diabetes Care. 44(12):2664-2672, 2021 12.PMID: 34702783Institution: MedStar Health Research InstituteForm of publication: Journal ArticleMedline article type(s): Journal ArticleSubject headings: *Diabetes Mellitus, Type 2 | *Lipidomics | American Indians or Alaska Natives | Fasting | Glucose | Humans | Risk FactorsYear: 2021Local holdings: Available online from MWHC library: 1995 - present, Available in print through MWHC library: 1999 - 2006ISSN:
  • 0149-5992
Name of journal: Diabetes careAbstract: CONCLUSIONS: 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.OBJECTIVE: 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.RESEARCH 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.RESULTS: 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.All authors: Cole 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 JOriginally published: Diabetes Care. 44(12):2664-2672, 2021 Dec.Fiscal year: FY2022Digital Object Identifier: ORCID: Date added to catalog: 2022-01-25
Holdings
Item type Current library Collection Call number Status Date due Barcode
Journal Article MedStar Authors Catalog Article 34702783 Available 34702783

Available online from MWHC library: 1995 - present, Available in print through MWHC library: 1999 - 2006

CONCLUSIONS: 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.

OBJECTIVE: 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.

RESEARCH 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.

RESULTS: 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.

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