Dataset Information

Nontargeted and Targeted Metabolomic Profiling Reveals Novel Metabolite Biomarkers of Incident Diabetes in African Americans.

ABSTRACT: 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.

SUBMITTER: Chen ZZ

PROVIDER: S-EPMC9630088 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Nontargeted and Targeted Metabolomic Profiling Reveals Novel Metabolite Biomarkers of Incident Diabetes in African Americans.

Chen Zsu-Zsu ZZ Pacheco Julian Avila JA Gao Yan Y Deng Shuliang S Peterson Bennet B Shi Xu X Zheng Shuning S Tahir Usman A UA Katz Daniel H DH Cruz Daniel E DE Ngo Debby D Benson Mark D MD Robbins Jeremy M JM Guo Xiuqing X Del Rocio Sevilla Gonzalez Magdalena M Manning Alisa A Correa Adolfo A Meigs James B JB Taylor Kent D KD Rich Stephen S SS Goodarzi Mark O MO Rotter Jerome I JI Wilson James G JG Clish Clary B CB Gerszten Robert E RE

Diabetes 20221101 11

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 c ...[more]

PMID: 35998269

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Project description:Background and objectivesNovel biomarkers that more accurately reflect kidney function and predict future CKD are needed. The human metabolome is the product of multiple physiologic or pathophysiologic processes and may provide novel insight into disease etiology and progression. This study investigated whether estimated kidney function would be associated with multiple metabolites and whether selected metabolomic factors would be independent risk factors for incident CKD.Design, setting, participants, & measurementsIn total, 1921 African Americans free of CKD with a median of 19.6 years follow-up among the Atherosclerosis Risk in Communities Study were included. A total of 204 serum metabolites quantified by untargeted gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry was analyzed by both linear regression for the cross-sectional associations with eGFR (specified by the Chronic Kidney Disease Epidemiology Collaboration equation) and Cox proportional hazards model for the longitudinal associations with incident CKD.ResultsForty named and 34 unnamed metabolites were found to be associated with eGFR specified by the Chronic Kidney Disease Epidemiology Collaboration equation with creatine and 3-indoxyl sulfate showing the strongest positive (2.8 ml/min per 1.73 m(2) per +1 SD; 95% confidence interval, 2.1 to 3.5) and negative association (-14.2 ml/min per 1.73 m(2) per +1 SD; 95% confidence interval, -17.0 to -11.3), respectively. Two hundred four incident CKD events with a median follow-up time of 19.6 years were included in the survival analyses. Higher levels of 5-oxoproline (hazard ratio, 0.70; 95% confidence interval, 0.60 to 0.82) and 1,5-anhydroglucitol (hazard ratio, 0.68; 95% confidence interval, 0.58 to 0.80) were significantly related to lower risk of incident CKD, and the associations did not appreciably change when mutually adjusted.ConclusionsThese data identify a large number of metabolites associated with kidney function as well as two metabolites that are candidate risk factors for CKD and may provide new insights into CKD biomarker identification.

Dataset Information

Nontargeted and Targeted Metabolomic Profiling Reveals Novel Metabolite Biomarkers of Incident Diabetes in African Americans.

Publications

Nontargeted and Targeted Metabolomic Profiling Reveals Novel Metabolite Biomarkers of Incident Diabetes in African Americans.

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