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0149-5992
10.2337/dc21-0451 [doi]
dc21-0451 [pii]
PMC8669540 [pmc]
Ovid MEDLINE(R)
34702783
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.
Diabetes Care. 44(12):2664-2672, 2021 12.
Diabetes Care. 44(12):2664-2672, 2021 12.
Diabetes Care. 44(12):2664-2672, 2021 Dec.
Diabetes care
2021
FY2022
2021 Dec
ppublish
2022-01-25
Diabetes Care. 44(12):2664-2672, 2021 Dec.
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.
English
*Diabetes Mellitus, Type 2
*Lipidomics
American Indians or Alaska Natives
Fasting
Glucose
Humans
Risk Factors
MedStar Health Research Institute
Journal Article
Howard, Barbara V
Umans, Jason G
Zhu, Jianhui
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 J
https://dx.doi.org/10.2337/dc21-0451
https://dx.doi.org/10.2337/dc21-0451
Howard, Barbara V
https://orcid.org/0000-0002-4216-7859
https://orcid.org/0000-0002-4216-7859
ART
Article
0
0
0
0
Article
authcat
authcat
2022-01-25
0
34702783
34702783
2022-01-25
2022-01-25
ART
10939
10939