Glycolysis/gluconeogenesis- and tricarboxylic acid cycle–related metabolites, Mediterranean diet, and type 2 diabetes
Glycolysis/gluconeogenesis and tricarboxylic acid (TCA) cycle metabolites have been associated with type 2 diabetes (T2D). However, the associations of these metabolites with T2D incidence and the potential effect of dietary interventions remain unclear. We aimed to evaluate the association of basel...
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| Veröffentlicht in: | The American journal of clinical nutrition 2020-04, Vol.111 (4), p.835-844 |
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| creator | Guasch-Ferré, Marta Santos, José L Martínez-González, Miguel A Clish, Clary B Razquin, Cristina Wang, Dong Liang, Liming Li, Jun Dennis, Courtney Corella, Dolores Muñoz-Bravo, Carlos Romaguera, Dora Estruch, Ramón Santos-Lozano, José Manuel Castañer, Olga Alonso-Gómez, Angel Serra-Majem, Luis Ros, Emilio Canudas, Sílvia Asensio, Eva M Fitó, Montserrat Pierce, Kerry Martínez, J Alfredo Salas-Salvadó, Jordi Toledo, Estefanía Hu, Frank B Ruiz-Canela, Miguel |
| description | Glycolysis/gluconeogenesis and tricarboxylic acid (TCA) cycle metabolites have been associated with type 2 diabetes (T2D). However, the associations of these metabolites with T2D incidence and the potential effect of dietary interventions remain unclear.
We aimed to evaluate the association of baseline and 1-y changes in glycolysis/gluconeogenesis and TCA cycle metabolites with insulin resistance and T2D incidence, and the potential modifying effect of Mediterranean diet (MedDiet) interventions.
We included 251 incident T2D cases and 638 noncases in a nested case-cohort study within the PREDIMED Study during median follow-up of 3.8 y. Participants were allocated to MedDiet + extra-virgin olive oil, MedDiet + nuts, or control diet. Plasma metabolites were measured using a targeted approach by LC–tandem MS. We tested the associations of baseline and 1-y changes in glycolysis/gluconeogenesis and TCA cycle metabolites with subsequent T2D risk using weighted Cox regression models and adjusting for potential confounders. We designed a weighted score combining all these metabolites and applying the leave-one-out cross-validation approach.
Baseline circulating concentrations of hexose monophosphate, pyruvate, lactate, alanine, glycerol-3 phosphate, and isocitrate were significantly associated with higher T2D risk (17–44% higher risk for each 1-SD increment). The weighted score including all metabolites was associated with a 30% (95% CI: 1.12, 1.51) higher relative risk of T2D for each 1-SD increment. Baseline lactate and alanine were associated with baseline and 1-y changes of homeostasis model assessment of insulin resistance. One-year increases in most metabolites and in the weighted score were associated with higher relative risk of T2D after 1 y of follow-up. Lower risks were observed in the MedDiet groups than in the control group although no significant interactions were found after adjusting for multiple comparisons.
We identified a panel of glycolysis/gluconeogenesis-related metabolites that was significantly associated with T2D risk in a Mediterranean population at high cardiovascular disease risk. A MedDiet could counteract the detrimental effects of these metabolites. This trial was registered at controlled-trials.com as ISRCTN35739639. |
| doi_str_mv | 10.1093/ajcn/nqaa016 |
| format | Article |
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We aimed to evaluate the association of baseline and 1-y changes in glycolysis/gluconeogenesis and TCA cycle metabolites with insulin resistance and T2D incidence, and the potential modifying effect of Mediterranean diet (MedDiet) interventions.
We included 251 incident T2D cases and 638 noncases in a nested case-cohort study within the PREDIMED Study during median follow-up of 3.8 y. Participants were allocated to MedDiet + extra-virgin olive oil, MedDiet + nuts, or control diet. Plasma metabolites were measured using a targeted approach by LC–tandem MS. We tested the associations of baseline and 1-y changes in glycolysis/gluconeogenesis and TCA cycle metabolites with subsequent T2D risk using weighted Cox regression models and adjusting for potential confounders. We designed a weighted score combining all these metabolites and applying the leave-one-out cross-validation approach.
Baseline circulating concentrations of hexose monophosphate, pyruvate, lactate, alanine, glycerol-3 phosphate, and isocitrate were significantly associated with higher T2D risk (17–44% higher risk for each 1-SD increment). The weighted score including all metabolites was associated with a 30% (95% CI: 1.12, 1.51) higher relative risk of T2D for each 1-SD increment. Baseline lactate and alanine were associated with baseline and 1-y changes of homeostasis model assessment of insulin resistance. One-year increases in most metabolites and in the weighted score were associated with higher relative risk of T2D after 1 y of follow-up. Lower risks were observed in the MedDiet groups than in the control group although no significant interactions were found after adjusting for multiple comparisons.
We identified a panel of glycolysis/gluconeogenesis-related metabolites that was significantly associated with T2D risk in a Mediterranean population at high cardiovascular disease risk. A MedDiet could counteract the detrimental effects of these metabolites. This trial was registered at controlled-trials.com as ISRCTN35739639.</description><identifier>ISSN: 0002-9165</identifier><identifier>EISSN: 1938-3207</identifier><identifier>DOI: 10.1093/ajcn/nqaa016</identifier><identifier>PMID: 32060497</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Aged ; Aged, 80 and over ; Alanine ; Cardiovascular diseases ; Case-Control Studies ; Citric Acid Cycle ; Cohort Studies ; Diabetes ; Diabetes mellitus ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Type 2 - diet therapy ; Diabetes Mellitus, Type 2 - metabolism ; Diabetes Mellitus, Type 2 - physiopathology ; Diet ; Diet, Mediterranean ; Female ; Gluconeogenesis ; Glycerol ; Glycolysis ; glycolysis metabolites ; Health risks ; Hexose ; Homeostasis ; Humans ; Insulin ; Insulin resistance ; Lactic acid ; Male ; Metabolites ; metabolomics ; Middle Aged ; Nuts ; Oils & fats ; Olive oil ; Original Research Communications ; Pyruvic acid ; Regression analysis ; Regression models ; Risk ; Tricarboxylic acid cycle ; tricarboxylic acid cycle metabolites ; type 2 diabetes</subject><ispartof>The American journal of clinical nutrition, 2020-04, Vol.111 (4), p.835-844</ispartof><rights>2020 American Society for Nutrition.</rights><rights>Copyright © The Author(s) 2020. 2020</rights><rights>Copyright © The Author(s) 2020.</rights><rights>Copyright American Society for Clinical Nutrition, Inc. Apr 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4726-bebdcf0ab966fe42af02f6ef5a7a22dfa71b3190ed50abc4f50d51e145337c473</citedby><cites>FETCH-LOGICAL-c4726-bebdcf0ab966fe42af02f6ef5a7a22dfa71b3190ed50abc4f50d51e145337c473</cites><orcidid>0000-0003-2700-7459 ; 0000-0003-3519-8638 ; 0000-0002-7684-2787 ; 0000-0001-8259-9245</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32060497$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Guasch-Ferré, Marta</creatorcontrib><creatorcontrib>Santos, José L</creatorcontrib><creatorcontrib>Martínez-González, Miguel A</creatorcontrib><creatorcontrib>Clish, Clary B</creatorcontrib><creatorcontrib>Razquin, Cristina</creatorcontrib><creatorcontrib>Wang, Dong</creatorcontrib><creatorcontrib>Liang, Liming</creatorcontrib><creatorcontrib>Li, Jun</creatorcontrib><creatorcontrib>Dennis, Courtney</creatorcontrib><creatorcontrib>Corella, Dolores</creatorcontrib><creatorcontrib>Muñoz-Bravo, Carlos</creatorcontrib><creatorcontrib>Romaguera, Dora</creatorcontrib><creatorcontrib>Estruch, Ramón</creatorcontrib><creatorcontrib>Santos-Lozano, José Manuel</creatorcontrib><creatorcontrib>Castañer, Olga</creatorcontrib><creatorcontrib>Alonso-Gómez, Angel</creatorcontrib><creatorcontrib>Serra-Majem, Luis</creatorcontrib><creatorcontrib>Ros, Emilio</creatorcontrib><creatorcontrib>Canudas, Sílvia</creatorcontrib><creatorcontrib>Asensio, Eva M</creatorcontrib><creatorcontrib>Fitó, Montserrat</creatorcontrib><creatorcontrib>Pierce, Kerry</creatorcontrib><creatorcontrib>Martínez, J Alfredo</creatorcontrib><creatorcontrib>Salas-Salvadó, Jordi</creatorcontrib><creatorcontrib>Toledo, Estefanía</creatorcontrib><creatorcontrib>Hu, Frank B</creatorcontrib><creatorcontrib>Ruiz-Canela, Miguel</creatorcontrib><title>Glycolysis/gluconeogenesis- and tricarboxylic acid cycle–related metabolites, Mediterranean diet, and type 2 diabetes</title><title>The American journal of clinical nutrition</title><addtitle>Am J Clin Nutr</addtitle><description>Glycolysis/gluconeogenesis and tricarboxylic acid (TCA) cycle metabolites have been associated with type 2 diabetes (T2D). However, the associations of these metabolites with T2D incidence and the potential effect of dietary interventions remain unclear.
We aimed to evaluate the association of baseline and 1-y changes in glycolysis/gluconeogenesis and TCA cycle metabolites with insulin resistance and T2D incidence, and the potential modifying effect of Mediterranean diet (MedDiet) interventions.
We included 251 incident T2D cases and 638 noncases in a nested case-cohort study within the PREDIMED Study during median follow-up of 3.8 y. Participants were allocated to MedDiet + extra-virgin olive oil, MedDiet + nuts, or control diet. Plasma metabolites were measured using a targeted approach by LC–tandem MS. We tested the associations of baseline and 1-y changes in glycolysis/gluconeogenesis and TCA cycle metabolites with subsequent T2D risk using weighted Cox regression models and adjusting for potential confounders. We designed a weighted score combining all these metabolites and applying the leave-one-out cross-validation approach.
Baseline circulating concentrations of hexose monophosphate, pyruvate, lactate, alanine, glycerol-3 phosphate, and isocitrate were significantly associated with higher T2D risk (17–44% higher risk for each 1-SD increment). The weighted score including all metabolites was associated with a 30% (95% CI: 1.12, 1.51) higher relative risk of T2D for each 1-SD increment. Baseline lactate and alanine were associated with baseline and 1-y changes of homeostasis model assessment of insulin resistance. One-year increases in most metabolites and in the weighted score were associated with higher relative risk of T2D after 1 y of follow-up. Lower risks were observed in the MedDiet groups than in the control group although no significant interactions were found after adjusting for multiple comparisons.
We identified a panel of glycolysis/gluconeogenesis-related metabolites that was significantly associated with T2D risk in a Mediterranean population at high cardiovascular disease risk. A MedDiet could counteract the detrimental effects of these metabolites. This trial was registered at controlled-trials.com as ISRCTN35739639.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Alanine</subject><subject>Cardiovascular diseases</subject><subject>Case-Control Studies</subject><subject>Citric Acid Cycle</subject><subject>Cohort Studies</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Diabetes Mellitus, Type 2 - diet therapy</subject><subject>Diabetes Mellitus, Type 2 - metabolism</subject><subject>Diabetes Mellitus, Type 2 - physiopathology</subject><subject>Diet</subject><subject>Diet, Mediterranean</subject><subject>Female</subject><subject>Gluconeogenesis</subject><subject>Glycerol</subject><subject>Glycolysis</subject><subject>glycolysis metabolites</subject><subject>Health risks</subject><subject>Hexose</subject><subject>Homeostasis</subject><subject>Humans</subject><subject>Insulin</subject><subject>Insulin resistance</subject><subject>Lactic acid</subject><subject>Male</subject><subject>Metabolites</subject><subject>metabolomics</subject><subject>Middle Aged</subject><subject>Nuts</subject><subject>Oils & fats</subject><subject>Olive oil</subject><subject>Original Research Communications</subject><subject>Pyruvic acid</subject><subject>Regression analysis</subject><subject>Regression models</subject><subject>Risk</subject><subject>Tricarboxylic acid cycle</subject><subject>tricarboxylic acid cycle metabolites</subject><subject>type 2 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Muñoz-Bravo, Carlos ; Romaguera, Dora ; Estruch, Ramón ; Santos-Lozano, José Manuel ; Castañer, Olga ; Alonso-Gómez, Angel ; Serra-Majem, Luis ; Ros, Emilio ; Canudas, Sílvia ; Asensio, Eva M ; Fitó, Montserrat ; Pierce, Kerry ; Martínez, J Alfredo ; Salas-Salvadó, Jordi ; Toledo, Estefanía ; Hu, Frank B ; Ruiz-Canela, Miguel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4726-bebdcf0ab966fe42af02f6ef5a7a22dfa71b3190ed50abc4f50d51e145337c473</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Alanine</topic><topic>Cardiovascular diseases</topic><topic>Case-Control Studies</topic><topic>Citric Acid Cycle</topic><topic>Cohort Studies</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>Diabetes Mellitus, Type 2 - diet therapy</topic><topic>Diabetes 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diabetes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Guasch-Ferré, Marta</creatorcontrib><creatorcontrib>Santos, José L</creatorcontrib><creatorcontrib>Martínez-González, Miguel A</creatorcontrib><creatorcontrib>Clish, Clary B</creatorcontrib><creatorcontrib>Razquin, Cristina</creatorcontrib><creatorcontrib>Wang, Dong</creatorcontrib><creatorcontrib>Liang, Liming</creatorcontrib><creatorcontrib>Li, Jun</creatorcontrib><creatorcontrib>Dennis, Courtney</creatorcontrib><creatorcontrib>Corella, Dolores</creatorcontrib><creatorcontrib>Muñoz-Bravo, Carlos</creatorcontrib><creatorcontrib>Romaguera, Dora</creatorcontrib><creatorcontrib>Estruch, Ramón</creatorcontrib><creatorcontrib>Santos-Lozano, José Manuel</creatorcontrib><creatorcontrib>Castañer, Olga</creatorcontrib><creatorcontrib>Alonso-Gómez, Angel</creatorcontrib><creatorcontrib>Serra-Majem, Luis</creatorcontrib><creatorcontrib>Ros, Emilio</creatorcontrib><creatorcontrib>Canudas, 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Olga</au><au>Alonso-Gómez, Angel</au><au>Serra-Majem, Luis</au><au>Ros, Emilio</au><au>Canudas, Sílvia</au><au>Asensio, Eva M</au><au>Fitó, Montserrat</au><au>Pierce, Kerry</au><au>Martínez, J Alfredo</au><au>Salas-Salvadó, Jordi</au><au>Toledo, Estefanía</au><au>Hu, Frank B</au><au>Ruiz-Canela, Miguel</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Glycolysis/gluconeogenesis- and tricarboxylic acid cycle–related metabolites, Mediterranean diet, and type 2 diabetes</atitle><jtitle>The American journal of clinical nutrition</jtitle><addtitle>Am J Clin Nutr</addtitle><date>2020-04-01</date><risdate>2020</risdate><volume>111</volume><issue>4</issue><spage>835</spage><epage>844</epage><pages>835-844</pages><issn>0002-9165</issn><eissn>1938-3207</eissn><abstract>Glycolysis/gluconeogenesis and tricarboxylic acid (TCA) cycle metabolites have been associated with type 2 diabetes (T2D). However, the associations of these metabolites with T2D incidence and the potential effect of dietary interventions remain unclear.
We aimed to evaluate the association of baseline and 1-y changes in glycolysis/gluconeogenesis and TCA cycle metabolites with insulin resistance and T2D incidence, and the potential modifying effect of Mediterranean diet (MedDiet) interventions.
We included 251 incident T2D cases and 638 noncases in a nested case-cohort study within the PREDIMED Study during median follow-up of 3.8 y. Participants were allocated to MedDiet + extra-virgin olive oil, MedDiet + nuts, or control diet. Plasma metabolites were measured using a targeted approach by LC–tandem MS. We tested the associations of baseline and 1-y changes in glycolysis/gluconeogenesis and TCA cycle metabolites with subsequent T2D risk using weighted Cox regression models and adjusting for potential confounders. We designed a weighted score combining all these metabolites and applying the leave-one-out cross-validation approach.
Baseline circulating concentrations of hexose monophosphate, pyruvate, lactate, alanine, glycerol-3 phosphate, and isocitrate were significantly associated with higher T2D risk (17–44% higher risk for each 1-SD increment). The weighted score including all metabolites was associated with a 30% (95% CI: 1.12, 1.51) higher relative risk of T2D for each 1-SD increment. Baseline lactate and alanine were associated with baseline and 1-y changes of homeostasis model assessment of insulin resistance. One-year increases in most metabolites and in the weighted score were associated with higher relative risk of T2D after 1 y of follow-up. Lower risks were observed in the MedDiet groups than in the control group although no significant interactions were found after adjusting for multiple comparisons.
We identified a panel of glycolysis/gluconeogenesis-related metabolites that was significantly associated with T2D risk in a Mediterranean population at high cardiovascular disease risk. A MedDiet could counteract the detrimental effects of these metabolites. This trial was registered at controlled-trials.com as ISRCTN35739639.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>32060497</pmid><doi>10.1093/ajcn/nqaa016</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0003-2700-7459</orcidid><orcidid>https://orcid.org/0000-0003-3519-8638</orcidid><orcidid>https://orcid.org/0000-0002-7684-2787</orcidid><orcidid>https://orcid.org/0000-0001-8259-9245</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0002-9165 |
| ispartof | The American journal of clinical nutrition, 2020-04, Vol.111 (4), p.835-844 |
| issn | 0002-9165 1938-3207 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7138680 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Aged Aged, 80 and over Alanine Cardiovascular diseases Case-Control Studies Citric Acid Cycle Cohort Studies Diabetes Diabetes mellitus Diabetes mellitus (non-insulin dependent) Diabetes Mellitus, Type 2 - diet therapy Diabetes Mellitus, Type 2 - metabolism Diabetes Mellitus, Type 2 - physiopathology Diet Diet, Mediterranean Female Gluconeogenesis Glycerol Glycolysis glycolysis metabolites Health risks Hexose Homeostasis Humans Insulin Insulin resistance Lactic acid Male Metabolites metabolomics Middle Aged Nuts Oils & fats Olive oil Original Research Communications Pyruvic acid Regression analysis Regression models Risk Tricarboxylic acid cycle tricarboxylic acid cycle metabolites type 2 diabetes |
| title | Glycolysis/gluconeogenesis- and tricarboxylic acid cycle–related metabolites, Mediterranean diet, and type 2 diabetes |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-31T01%3A42%3A51IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Glycolysis/gluconeogenesis-%20and%20tricarboxylic%20acid%20cycle%E2%80%93related%20metabolites,%20Mediterranean%20diet,%20and%20type%202%20diabetes&rft.jtitle=The%20American%20journal%20of%20clinical%20nutrition&rft.au=Guasch-Ferr%C3%A9,%20Marta&rft.date=2020-04-01&rft.volume=111&rft.issue=4&rft.spage=835&rft.epage=844&rft.pages=835-844&rft.issn=0002-9165&rft.eissn=1938-3207&rft_id=info:doi/10.1093/ajcn/nqaa016&rft_dat=%3Cproquest_pubme%3E2389727001%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2389727001&rft_id=info:pmid/32060497&rft_oup_id=10.1093/ajcn/nqaa016&rft_els_id=S0002916522010711&rfr_iscdi=true |