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Nontargeted and Targeted Metabolomic Profiling Reveals Novel Metabolite Biomarkers of Incident Diabetes in African Americans.
Chen, Zsu-Zsu; Pacheco, Julian Avila; Gao, Yan; Deng, Shuliang; Peterson, Bennet; Shi, Xu; Zheng, Shuning; Tahir, Usman A; Katz, Daniel H; Cruz, Daniel E; Ngo, Debby; Benson, Mark D; Robbins, Jeremy M; Guo, Xiuqing; Del Rocio Sevilla Gonzalez, Magdalena; Manning, Alisa; Correa, Adolfo; Meigs, James B; Taylor, Kent D; Rich, Stephen S; Goodarzi, Mark O; Rotter, Jerome I; Wilson, James G; Clish, Clary B; Gerszten, Robert E.
Afiliación
  • Chen ZZ; Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Boston, MA.
  • Pacheco JA; Harvard School of Medicine, Boston, MA.
  • Gao Y; Broad Institute of MIT and Harvard, Boston, MA.
  • Deng S; University of Mississippi Medical Center, Jacksonville, MS.
  • Peterson B; Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA.
  • Shi X; Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA.
  • Zheng S; Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA.
  • Tahir UA; Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA.
  • Katz DH; Harvard School of Medicine, Boston, MA.
  • Cruz DE; Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA.
  • Ngo D; Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA.
  • Benson MD; Harvard School of Medicine, Boston, MA.
  • Robbins JM; Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA.
  • Guo X; Harvard School of Medicine, Boston, MA.
  • Del Rocio Sevilla Gonzalez M; Division of Pulmonary, Critical Care, and Sleep Medicine, Beth Israel Deaconess Medical Center, Boston, MA.
  • Manning A; Harvard School of Medicine, Boston, MA.
  • Correa A; Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA.
  • Meigs JB; Harvard School of Medicine, Boston, MA.
  • Taylor KD; Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA.
  • Rich SS; The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA.
  • Goodarzi MO; Harvard School of Medicine, Boston, MA.
  • Rotter JI; Broad Institute of MIT and Harvard, Boston, MA.
  • Wilson JG; Division of General Internal Medicine, Massachusetts General Hospital, Boston, MA.
  • Clish CB; Harvard School of Medicine, Boston, MA.
  • Gerszten RE; Broad Institute of MIT and Harvard, Boston, MA.
Diabetes ; 71(11): 2426-2437, 2022 11 01.
Article en En | MEDLINE | ID: mdl-35998269
Nontargeted metabolomics methods have increased potential to identify new disease biomarkers, but assessments of the additive information provided in large human cohorts by these less biased techniques are limited. To diversify our knowledge of diabetes-associated metabolites, we leveraged a method that measures 305 targeted or "known" and 2,342 nontargeted or "unknown" compounds in fasting plasma samples from 2,750 participants (315 incident cases) in the Jackson Heart Study (JHS)-a community cohort of self-identified African Americans-who are underrepresented in omics studies. We found 307 unique compounds (82 known) associated with diabetes after adjusting for age and sex at a false discovery rate of <0.05 and 124 compounds (35 known, including 11 not previously associated) after further adjustments for BMI and fasting plasma glucose. Of these, 144 and 68 associations, respectively, replicated in a multiethnic cohort. Among these is an apparently novel isomer of the 1-deoxyceramide Cer(m18:1/24:0) with functional geonomics and high-resolution mass spectrometry. Overall, known and unknown metabolites provided complementary information (median correlation ρ = 0.29), and their inclusion with clinical risk factors improved diabetes prediction modeling. Our findings highlight the importance of including nontargeted metabolomics methods to provide new insights into diabetes development in ethnically diverse cohorts.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Glucemia / Diabetes Mellitus Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Diabetes Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Glucemia / Diabetes Mellitus Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Diabetes Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos