The association of serum sulfur amino acids and related metabolites with incident diabetes: a prospective cohort study
Aim Plasma total cysteine (tCys) is associated with fat mass and insulin resistance, whereas taurine is inversely related to diabetes risk. We investigated the association of serum sulfur amino acids (SAAs) and related amino acids (AAs) with incident diabetes. Methods Serum AAs were measured at base...
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| Veröffentlicht in: | European journal of nutrition 2022-09, Vol.61 (6), p.3161-3173 |
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| creator | Elshorbagy, Amany K. Turner, Cheryl Bastani, Nasser Refsum, Helga Kwok, Timothy |
| description | Aim
Plasma total cysteine (tCys) is associated with fat mass and insulin resistance, whereas taurine is inversely related to diabetes risk. We investigated the association of serum sulfur amino acids (SAAs) and related amino acids (AAs) with incident diabetes.
Methods
Serum AAs were measured at baseline in 2997 subjects aged ≥ 65 years. Diabetes was recorded at baseline and after 4 years. Logistic regression evaluated the association of SAAs [methionine, total homocysteine (tHcy), cystathionine, tCys, and taurine] and related metabolites [serine, total glutathione (tGSH), glutamine, and glutamic acid] with diabetes risk.
Results
Among 2564 subjects without diabetes at baseline, 4.6% developed diabetes. Each SD increment in serum tCys was associated with a 68% higher risk (95% CI 1.27, 2.23) of diabetes [OR for upper vs. lower quartile 2.87 (1.39, 5.91)], after full adjustments (age, sex, other AAs, adiposity, eGFR, physical activity, blood pressure, diet and medication); equivalent ORs for cystathionine were 1.33 (1.08, 1.64) and 1.68 (0.85, 3.29). Subjects who were simultaneously in the upper tertiles of both cystathionine and tCys had a fivefold risk [OR = 5.04 (1.55, 16.32)] of diabetes compared with those in the lowest tertiles. Higher serine was independently associated with a lower risk of developing diabetes [fully adjusted OR per SD = 0.68 (0.54, 0.86)]. Glutamic acid and glutamine showed positive and negative associations, respectively, with incident diabetes in age- and sex-adjusted analysis, but only the glutamic acid association was independent of other confounders [fully adjusted OR per SD = 1.95 (1.19, 3.21); for upper quartile = 7.94 (3.04, 20.75)]. tGSH was inversely related to diabetes after adjusting for age and sex, but not other confounders. No consistent associations were observed for methionine, tHcy or taurine.
Conclusion
Specific SAAs and related metabolites show strong and independent associations with incident diabetes. This suggests that perturbations in the SAA metabolic pathway may be an early marker for diabetes risk. |
| doi_str_mv | 10.1007/s00394-022-02872-5 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2649995752</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2649995752</sourcerecordid><originalsourceid>FETCH-LOGICAL-c375t-deda86b1e141e5ea935d5e763468e0ea66baba0c266f9d968ad59f9900075f943</originalsourceid><addsrcrecordid>eNp9kUtv1TAQRi0EoqXlD7BAltiwCfgROzG7quIlVeqmrK1JPOG6SuKLxynqv6_pLUXqgoVlyz7zeUaHsTdSfJBCdB9JCO3aRihVV9-pxjxjx7LVtrFKmuePZ9EdsVdE10IIpa18yY60aaXplTpmN1c75ECUxgglppWniRPmbeG0zdOWOSxxTRzGGIjDGnjGGQoGvmCBIc2xIPHfsex4XCuDa-EhwoD1-hMHvs-J9jiWeIN8TLuUC6eyhdtT9mKCmfD1w37Cfnz5fHX-rbm4_Pr9_OyiGXVnShMwQG8HibKVaBCcNsFgZ3VrexQI1g4wgBiVtZMLzvYQjJucq5N2ZnKtPmHvD7m1kV8bUvFLpBHnGVZMG3llW-ec6Yyq6Lsn6HXa8lq786oTQhprha6UOlBjnYwyTn6f4wL51kvh_1jxByu-WvH3VrypRW8fordhwfBY8ldDBfQBoPq0_sT87-__xN4BlgmZEw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2700156603</pqid></control><display><type>article</type><title>The association of serum sulfur amino acids and related metabolites with incident diabetes: a prospective cohort study</title><source>MEDLINE</source><source>SpringerNature Journals</source><creator>Elshorbagy, Amany K. ; Turner, Cheryl ; Bastani, Nasser ; Refsum, Helga ; Kwok, Timothy</creator><creatorcontrib>Elshorbagy, Amany K. ; Turner, Cheryl ; Bastani, Nasser ; Refsum, Helga ; Kwok, Timothy</creatorcontrib><description>Aim
Plasma total cysteine (tCys) is associated with fat mass and insulin resistance, whereas taurine is inversely related to diabetes risk. We investigated the association of serum sulfur amino acids (SAAs) and related amino acids (AAs) with incident diabetes.
Methods
Serum AAs were measured at baseline in 2997 subjects aged ≥ 65 years. Diabetes was recorded at baseline and after 4 years. Logistic regression evaluated the association of SAAs [methionine, total homocysteine (tHcy), cystathionine, tCys, and taurine] and related metabolites [serine, total glutathione (tGSH), glutamine, and glutamic acid] with diabetes risk.
Results
Among 2564 subjects without diabetes at baseline, 4.6% developed diabetes. Each SD increment in serum tCys was associated with a 68% higher risk (95% CI 1.27, 2.23) of diabetes [OR for upper vs. lower quartile 2.87 (1.39, 5.91)], after full adjustments (age, sex, other AAs, adiposity, eGFR, physical activity, blood pressure, diet and medication); equivalent ORs for cystathionine were 1.33 (1.08, 1.64) and 1.68 (0.85, 3.29). Subjects who were simultaneously in the upper tertiles of both cystathionine and tCys had a fivefold risk [OR = 5.04 (1.55, 16.32)] of diabetes compared with those in the lowest tertiles. Higher serine was independently associated with a lower risk of developing diabetes [fully adjusted OR per SD = 0.68 (0.54, 0.86)]. Glutamic acid and glutamine showed positive and negative associations, respectively, with incident diabetes in age- and sex-adjusted analysis, but only the glutamic acid association was independent of other confounders [fully adjusted OR per SD = 1.95 (1.19, 3.21); for upper quartile = 7.94 (3.04, 20.75)]. tGSH was inversely related to diabetes after adjusting for age and sex, but not other confounders. No consistent associations were observed for methionine, tHcy or taurine.
Conclusion
Specific SAAs and related metabolites show strong and independent associations with incident diabetes. This suggests that perturbations in the SAA metabolic pathway may be an early marker for diabetes risk.</description><identifier>ISSN: 1436-6207</identifier><identifier>EISSN: 1436-6215</identifier><identifier>DOI: 10.1007/s00394-022-02872-5</identifier><identifier>PMID: 35415822</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adipose tissue ; Amino Acids ; Amino Acids, Sulfur ; Blood pressure ; Body fat ; Chemistry ; Chemistry and Materials Science ; Cohort analysis ; Cystathionine ; Cysteine ; Diabetes ; Diabetes Mellitus ; Glutamates ; Glutamic acid ; Glutamine ; Glutathione ; Homocysteine ; Humans ; Insulin ; Insulin resistance ; Metabolic pathways ; Metabolites ; Methionine ; Nutrition ; Original Contribution ; Physical activity ; Prospective Studies ; Serine ; Sulfur ; Taurine</subject><ispartof>European journal of nutrition, 2022-09, Vol.61 (6), p.3161-3173</ispartof><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany 2022</rights><rights>2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.</rights><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany 2022.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-deda86b1e141e5ea935d5e763468e0ea66baba0c266f9d968ad59f9900075f943</citedby><cites>FETCH-LOGICAL-c375t-deda86b1e141e5ea935d5e763468e0ea66baba0c266f9d968ad59f9900075f943</cites><orcidid>0000-0002-8624-860X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00394-022-02872-5$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00394-022-02872-5$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35415822$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Elshorbagy, Amany K.</creatorcontrib><creatorcontrib>Turner, Cheryl</creatorcontrib><creatorcontrib>Bastani, Nasser</creatorcontrib><creatorcontrib>Refsum, Helga</creatorcontrib><creatorcontrib>Kwok, Timothy</creatorcontrib><title>The association of serum sulfur amino acids and related metabolites with incident diabetes: a prospective cohort study</title><title>European journal of nutrition</title><addtitle>Eur J Nutr</addtitle><addtitle>Eur J Nutr</addtitle><description>Aim
Plasma total cysteine (tCys) is associated with fat mass and insulin resistance, whereas taurine is inversely related to diabetes risk. We investigated the association of serum sulfur amino acids (SAAs) and related amino acids (AAs) with incident diabetes.
Methods
Serum AAs were measured at baseline in 2997 subjects aged ≥ 65 years. Diabetes was recorded at baseline and after 4 years. Logistic regression evaluated the association of SAAs [methionine, total homocysteine (tHcy), cystathionine, tCys, and taurine] and related metabolites [serine, total glutathione (tGSH), glutamine, and glutamic acid] with diabetes risk.
Results
Among 2564 subjects without diabetes at baseline, 4.6% developed diabetes. Each SD increment in serum tCys was associated with a 68% higher risk (95% CI 1.27, 2.23) of diabetes [OR for upper vs. lower quartile 2.87 (1.39, 5.91)], after full adjustments (age, sex, other AAs, adiposity, eGFR, physical activity, blood pressure, diet and medication); equivalent ORs for cystathionine were 1.33 (1.08, 1.64) and 1.68 (0.85, 3.29). Subjects who were simultaneously in the upper tertiles of both cystathionine and tCys had a fivefold risk [OR = 5.04 (1.55, 16.32)] of diabetes compared with those in the lowest tertiles. Higher serine was independently associated with a lower risk of developing diabetes [fully adjusted OR per SD = 0.68 (0.54, 0.86)]. Glutamic acid and glutamine showed positive and negative associations, respectively, with incident diabetes in age- and sex-adjusted analysis, but only the glutamic acid association was independent of other confounders [fully adjusted OR per SD = 1.95 (1.19, 3.21); for upper quartile = 7.94 (3.04, 20.75)]. tGSH was inversely related to diabetes after adjusting for age and sex, but not other confounders. No consistent associations were observed for methionine, tHcy or taurine.
Conclusion
Specific SAAs and related metabolites show strong and independent associations with incident diabetes. This suggests that perturbations in the SAA metabolic pathway may be an early marker for diabetes risk.</description><subject>Adipose tissue</subject><subject>Amino Acids</subject><subject>Amino Acids, Sulfur</subject><subject>Blood pressure</subject><subject>Body fat</subject><subject>Chemistry</subject><subject>Chemistry and Materials Science</subject><subject>Cohort analysis</subject><subject>Cystathionine</subject><subject>Cysteine</subject><subject>Diabetes</subject><subject>Diabetes Mellitus</subject><subject>Glutamates</subject><subject>Glutamic acid</subject><subject>Glutamine</subject><subject>Glutathione</subject><subject>Homocysteine</subject><subject>Humans</subject><subject>Insulin</subject><subject>Insulin resistance</subject><subject>Metabolic pathways</subject><subject>Metabolites</subject><subject>Methionine</subject><subject>Nutrition</subject><subject>Original Contribution</subject><subject>Physical activity</subject><subject>Prospective Studies</subject><subject>Serine</subject><subject>Sulfur</subject><subject>Taurine</subject><issn>1436-6207</issn><issn>1436-6215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><recordid>eNp9kUtv1TAQRi0EoqXlD7BAltiwCfgROzG7quIlVeqmrK1JPOG6SuKLxynqv6_pLUXqgoVlyz7zeUaHsTdSfJBCdB9JCO3aRihVV9-pxjxjx7LVtrFKmuePZ9EdsVdE10IIpa18yY60aaXplTpmN1c75ECUxgglppWniRPmbeG0zdOWOSxxTRzGGIjDGnjGGQoGvmCBIc2xIPHfsex4XCuDa-EhwoD1-hMHvs-J9jiWeIN8TLuUC6eyhdtT9mKCmfD1w37Cfnz5fHX-rbm4_Pr9_OyiGXVnShMwQG8HibKVaBCcNsFgZ3VrexQI1g4wgBiVtZMLzvYQjJucq5N2ZnKtPmHvD7m1kV8bUvFLpBHnGVZMG3llW-ec6Yyq6Lsn6HXa8lq786oTQhprha6UOlBjnYwyTn6f4wL51kvh_1jxByu-WvH3VrypRW8fordhwfBY8ldDBfQBoPq0_sT87-__xN4BlgmZEw</recordid><startdate>20220901</startdate><enddate>20220901</enddate><creator>Elshorbagy, Amany K.</creator><creator>Turner, Cheryl</creator><creator>Bastani, Nasser</creator><creator>Refsum, Helga</creator><creator>Kwok, Timothy</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7RQ</scope><scope>7RV</scope><scope>7TS</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-8624-860X</orcidid></search><sort><creationdate>20220901</creationdate><title>The association of serum sulfur amino acids and related metabolites with incident diabetes: a prospective cohort study</title><author>Elshorbagy, Amany K. ; Turner, Cheryl ; Bastani, Nasser ; Refsum, Helga ; Kwok, Timothy</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-deda86b1e141e5ea935d5e763468e0ea66baba0c266f9d968ad59f9900075f943</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Adipose tissue</topic><topic>Amino Acids</topic><topic>Amino Acids, Sulfur</topic><topic>Blood pressure</topic><topic>Body fat</topic><topic>Chemistry</topic><topic>Chemistry and Materials Science</topic><topic>Cohort analysis</topic><topic>Cystathionine</topic><topic>Cysteine</topic><topic>Diabetes</topic><topic>Diabetes Mellitus</topic><topic>Glutamates</topic><topic>Glutamic acid</topic><topic>Glutamine</topic><topic>Glutathione</topic><topic>Homocysteine</topic><topic>Humans</topic><topic>Insulin</topic><topic>Insulin resistance</topic><topic>Metabolic pathways</topic><topic>Metabolites</topic><topic>Methionine</topic><topic>Nutrition</topic><topic>Original Contribution</topic><topic>Physical activity</topic><topic>Prospective Studies</topic><topic>Serine</topic><topic>Sulfur</topic><topic>Taurine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Elshorbagy, Amany K.</creatorcontrib><creatorcontrib>Turner, Cheryl</creatorcontrib><creatorcontrib>Bastani, Nasser</creatorcontrib><creatorcontrib>Refsum, Helga</creatorcontrib><creatorcontrib>Kwok, Timothy</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Career & Technical Education Database</collection><collection>Proquest Nursing & Allied Health Source</collection><collection>Physical Education Index</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of nutrition</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Elshorbagy, Amany K.</au><au>Turner, Cheryl</au><au>Bastani, Nasser</au><au>Refsum, Helga</au><au>Kwok, Timothy</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The association of serum sulfur amino acids and related metabolites with incident diabetes: a prospective cohort study</atitle><jtitle>European journal of nutrition</jtitle><stitle>Eur J Nutr</stitle><addtitle>Eur J Nutr</addtitle><date>2022-09-01</date><risdate>2022</risdate><volume>61</volume><issue>6</issue><spage>3161</spage><epage>3173</epage><pages>3161-3173</pages><issn>1436-6207</issn><eissn>1436-6215</eissn><abstract>Aim
Plasma total cysteine (tCys) is associated with fat mass and insulin resistance, whereas taurine is inversely related to diabetes risk. We investigated the association of serum sulfur amino acids (SAAs) and related amino acids (AAs) with incident diabetes.
Methods
Serum AAs were measured at baseline in 2997 subjects aged ≥ 65 years. Diabetes was recorded at baseline and after 4 years. Logistic regression evaluated the association of SAAs [methionine, total homocysteine (tHcy), cystathionine, tCys, and taurine] and related metabolites [serine, total glutathione (tGSH), glutamine, and glutamic acid] with diabetes risk.
Results
Among 2564 subjects without diabetes at baseline, 4.6% developed diabetes. Each SD increment in serum tCys was associated with a 68% higher risk (95% CI 1.27, 2.23) of diabetes [OR for upper vs. lower quartile 2.87 (1.39, 5.91)], after full adjustments (age, sex, other AAs, adiposity, eGFR, physical activity, blood pressure, diet and medication); equivalent ORs for cystathionine were 1.33 (1.08, 1.64) and 1.68 (0.85, 3.29). Subjects who were simultaneously in the upper tertiles of both cystathionine and tCys had a fivefold risk [OR = 5.04 (1.55, 16.32)] of diabetes compared with those in the lowest tertiles. Higher serine was independently associated with a lower risk of developing diabetes [fully adjusted OR per SD = 0.68 (0.54, 0.86)]. Glutamic acid and glutamine showed positive and negative associations, respectively, with incident diabetes in age- and sex-adjusted analysis, but only the glutamic acid association was independent of other confounders [fully adjusted OR per SD = 1.95 (1.19, 3.21); for upper quartile = 7.94 (3.04, 20.75)]. tGSH was inversely related to diabetes after adjusting for age and sex, but not other confounders. No consistent associations were observed for methionine, tHcy or taurine.
Conclusion
Specific SAAs and related metabolites show strong and independent associations with incident diabetes. This suggests that perturbations in the SAA metabolic pathway may be an early marker for diabetes risk.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>35415822</pmid><doi>10.1007/s00394-022-02872-5</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-8624-860X</orcidid></addata></record> |
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| subjects | Adipose tissue Amino Acids Amino Acids, Sulfur Blood pressure Body fat Chemistry Chemistry and Materials Science Cohort analysis Cystathionine Cysteine Diabetes Diabetes Mellitus Glutamates Glutamic acid Glutamine Glutathione Homocysteine Humans Insulin Insulin resistance Metabolic pathways Metabolites Methionine Nutrition Original Contribution Physical activity Prospective Studies Serine Sulfur Taurine |
| title | The association of serum sulfur amino acids and related metabolites with incident diabetes: a prospective cohort study |
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