Changes in metabolomics profiles over ten years and subsequent risk of developing type 2 diabetes: Results from the Nurses' Health Study

Summary: Background: Metabolomics profiles were consistently associated with type 2 diabetes (T2D) risk, but evidence on long-term metabolite changes and T2D incidence is lacking. We examined the associations of 10-year plasma metabolite changes with subsequent T2D risk. Methods: We conducted a nes...

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Main Authors: Clemens Wittenbecher, Marta Guasch-Ferré, Danielle E. Haslam, Courtney Dennis, Jun Li, Shilpa N. Bhupathiraju, Chih-Hao Lee, Qibin Qi, Liming Liang, A. Heather Eliassen, Clary Clish, Qi Sun, Frank B Hu
Format: Article
Language:English
Published: Elsevier 2022-01-01
Series:EBioMedicine
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Online Access:http://www.sciencedirect.com/science/article/pii/S2352396421005934
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author Clemens Wittenbecher
Marta Guasch-Ferré
Danielle E. Haslam
Courtney Dennis
Jun Li
Shilpa N. Bhupathiraju
Chih-Hao Lee
Qibin Qi
Liming Liang
A. Heather Eliassen
Clary Clish
Qi Sun
Frank B Hu
author_facet Clemens Wittenbecher
Marta Guasch-Ferré
Danielle E. Haslam
Courtney Dennis
Jun Li
Shilpa N. Bhupathiraju
Chih-Hao Lee
Qibin Qi
Liming Liang
A. Heather Eliassen
Clary Clish
Qi Sun
Frank B Hu
author_sort Clemens Wittenbecher
collection DOAJ
description Summary: Background: Metabolomics profiles were consistently associated with type 2 diabetes (T2D) risk, but evidence on long-term metabolite changes and T2D incidence is lacking. We examined the associations of 10-year plasma metabolite changes with subsequent T2D risk. Methods: We conducted a nested T2D case-control study (n=244 cases, n=244 matched controls) within the Nurses' Health Study. Repeated metabolomics profiling (170 targeted metabolites) was conducted in participant blood specimens from 1989/1990 and 2000/2001, and T2D occurred between 2002 and 2008. We related 10-year metabolite changes (Δ-values) to subsequent T2D risk using conditional logistic models, adjusting for baseline metabolite levels and baseline levels and concurrent changes of BMI, diet quality, physical activity, and smoking status. Findings: The 10-year changes of thirty-one metabolites were associated with subsequent T2D risk (false discovery rate-adjusted p-values [FDR]<0.05). The top three high T2D risk-associated 10-year changes were (odds ratio [OR] per standard deviation [SD], 95%CI): Δisoleucine (2.72, 1.97-3.79), Δleucine (2.53, 1.86-3.47), and Δvaline (1.93, 1.52-2.44); other high-risk-associated metabolite changes included alanine, tri-/diacylglycerol-fragments, short-chain acylcarnitines, phosphatidylethanolamines, some vitamins, and bile acids (ORs per SD between 1.31and 1.82). The top three low T2D risk-associated 10-year metabolite changes were (OR per SD, 95% CI): ΔN-acetylaspartic acid (0.54, 0.42-0.70), ΔC20:0 lysophosphatidylethanolamine (0.68, 0.56-0.82), and ΔC16:1 sphingomyelin (0.68, 0.56-0.83); 10-year changes of other sphingomyelins, plasmalogens, glutamine, and glycine were also associated with lower subsequent T2D risk (ORs per SD between 0.66 and 0.78). Interpretation: Repeated metabolomics profiles reflecting the long-term deterioration of amino acid and lipid metabolism are associated with subsequent risk of T2D.
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spelling doaj.art-fe53d695028b482da66d0eb1fd421ad12022-12-21T23:27:32ZengElsevierEBioMedicine2352-39642022-01-0175103799Changes in metabolomics profiles over ten years and subsequent risk of developing type 2 diabetes: Results from the Nurses' Health StudyClemens Wittenbecher0Marta Guasch-Ferré1Danielle E. Haslam2Courtney Dennis3Jun Li4Shilpa N. Bhupathiraju5Chih-Hao Lee6Qibin Qi7Liming Liang8A. Heather Eliassen9Clary Clish10Qi Sun11Frank B Hu12Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA; Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam Rehbruecke, Nuthetal, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany; Corresponding authors at: Department of Nutrition, Harvard T.H. Chan School of Public Health, 655 Huntington Avenue, Boston, MA 02115, USA.Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, MA, USADepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, MA, USABroad Institute of MIT and Harvard, Cambridge, MA, USADepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USADepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, MA, USADepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA; Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Boston, MA, USADepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA; Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USADepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USADepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USABroad Institute of MIT and Harvard, Cambridge, MA, USADepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USADepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA; Corresponding authors at: Department of Nutrition, Harvard T.H. Chan School of Public Health, 655 Huntington Avenue, Boston, MA 02115, USA.Summary: Background: Metabolomics profiles were consistently associated with type 2 diabetes (T2D) risk, but evidence on long-term metabolite changes and T2D incidence is lacking. We examined the associations of 10-year plasma metabolite changes with subsequent T2D risk. Methods: We conducted a nested T2D case-control study (n=244 cases, n=244 matched controls) within the Nurses' Health Study. Repeated metabolomics profiling (170 targeted metabolites) was conducted in participant blood specimens from 1989/1990 and 2000/2001, and T2D occurred between 2002 and 2008. We related 10-year metabolite changes (Δ-values) to subsequent T2D risk using conditional logistic models, adjusting for baseline metabolite levels and baseline levels and concurrent changes of BMI, diet quality, physical activity, and smoking status. Findings: The 10-year changes of thirty-one metabolites were associated with subsequent T2D risk (false discovery rate-adjusted p-values [FDR]<0.05). The top three high T2D risk-associated 10-year changes were (odds ratio [OR] per standard deviation [SD], 95%CI): Δisoleucine (2.72, 1.97-3.79), Δleucine (2.53, 1.86-3.47), and Δvaline (1.93, 1.52-2.44); other high-risk-associated metabolite changes included alanine, tri-/diacylglycerol-fragments, short-chain acylcarnitines, phosphatidylethanolamines, some vitamins, and bile acids (ORs per SD between 1.31and 1.82). The top three low T2D risk-associated 10-year metabolite changes were (OR per SD, 95% CI): ΔN-acetylaspartic acid (0.54, 0.42-0.70), ΔC20:0 lysophosphatidylethanolamine (0.68, 0.56-0.82), and ΔC16:1 sphingomyelin (0.68, 0.56-0.83); 10-year changes of other sphingomyelins, plasmalogens, glutamine, and glycine were also associated with lower subsequent T2D risk (ORs per SD between 0.66 and 0.78). Interpretation: Repeated metabolomics profiles reflecting the long-term deterioration of amino acid and lipid metabolism are associated with subsequent risk of T2D.http://www.sciencedirect.com/science/article/pii/S2352396421005934MetabolomicsType 2 diabetesLipidsAmino acidsRepeated measurementsChange analysis
spellingShingle Clemens Wittenbecher
Marta Guasch-Ferré
Danielle E. Haslam
Courtney Dennis
Jun Li
Shilpa N. Bhupathiraju
Chih-Hao Lee
Qibin Qi
Liming Liang
A. Heather Eliassen
Clary Clish
Qi Sun
Frank B Hu
Changes in metabolomics profiles over ten years and subsequent risk of developing type 2 diabetes: Results from the Nurses' Health Study
EBioMedicine
Metabolomics
Type 2 diabetes
Lipids
Amino acids
Repeated measurements
Change analysis
title Changes in metabolomics profiles over ten years and subsequent risk of developing type 2 diabetes: Results from the Nurses' Health Study
title_full Changes in metabolomics profiles over ten years and subsequent risk of developing type 2 diabetes: Results from the Nurses' Health Study
title_fullStr Changes in metabolomics profiles over ten years and subsequent risk of developing type 2 diabetes: Results from the Nurses' Health Study
title_full_unstemmed Changes in metabolomics profiles over ten years and subsequent risk of developing type 2 diabetes: Results from the Nurses' Health Study
title_short Changes in metabolomics profiles over ten years and subsequent risk of developing type 2 diabetes: Results from the Nurses' Health Study
title_sort changes in metabolomics profiles over ten years and subsequent risk of developing type 2 diabetes results from the nurses health study
topic Metabolomics
Type 2 diabetes
Lipids
Amino acids
Repeated measurements
Change analysis
url http://www.sciencedirect.com/science/article/pii/S2352396421005934
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