Glycemic dysregulations are associated with worsening cognitive function in older participants at high risk of cardiovascular disease: two-year follow-up in the PREDIMED-Plus study

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• dc.contributor.author Gómez Martínez, Carlos
• dc.contributor.author Castañer, Olga
• dc.contributor.author Torre Fornell, Rafael de la
• dc.contributor.author Goday Arno, Alberto
• dc.contributor.author Cuenca Royo, Aida Ma, 1981-
• dc.contributor.author Salas Salvadó, Jordi
• dc.date.accessioned 2021-12-09T07:01:49Z
• dc.date.available 2021-12-09T07:01:49Z
• dc.date.issued 2021
• dc.description.abstract Introduction: Type 2 diabetes has been linked to greater cognitive decline, but other glycemic parameters such as prediabetes, diabetes control and treatment, and HOMA-IR and HbA1c diabetes-related biomarkers have shown inconsistent results. Furthermore, there is limited research assessing these relationships in short-term studies. Thus, we aimed to examine 2-year associations between baseline diabetes/glycemic status and changes in cognitive function in older participants at high risk of cardiovascular disease. Methods: We conducted a 2-year prospective cohort study (n=6,874) within the framework of the PREDIMED-Plus study. The participants (with overweight/obesity and metabolic syndrome; mean age 64.9 years; 48.5% women) completed a battery of 8 cognitive tests, and a global cognitive function Z-score (GCF) was estimated. At baseline, participants were categorized by diabetes status (no-diabetes, prediabetes, and <5 or ≥5-year diabetes duration), and also by diabetes control. Furthermore, insulin resistance (HOMA-IR) and glycated hemoglobin (HbA1c) levels were measured, and antidiabetic medications were recorded. Linear and logistic regression models, adjusted by potential confounders, were fitted to assess associations between glycemic status and changes in cognitive function. Results: Prediabetes status was unrelated to cognitive decline. However, compared to participants without diabetes, those with ≥5-year diabetes duration had greater reductions in GCF (β=-0.11 (95%CI -0.16;-0.06)], as well as in processing speed and executive function measurements. Inverse associations were observed between baseline HOMA-IR and changes in GCF [β=-0.0094 (95%CI -0.0164;-0.0023)], but also between HbA1c levels and changes in GCF [β=-0.0085 (95%CI -0.0115, -0.0055)], the Mini-Mental State Examination, and other executive function tests. Poor diabetes control was inversely associated with phonologic fluency. The use of insulin treatment was inversely related to cognitive function as measured by the GCF [β=-0.31 (95%CI -0.44, -0.18)], and other cognitive tests. Conclusions: Insulin resistance, diabetes status, longer diabetes duration, poor glycemic control, and insulin treatment were associated with worsening cognitive function changes in the short term in a population at high cardiovascular risk. Clinical trial registration: http://www.isrctn.com/ISRCTN89898870, identifier ISRCTN: 89898870.
• dc.description.sponsorship This work was supported by the official Spanish Institutions for funding scientific biomedical research, CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN) and Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigación para la Salud (FIS), which is co-funded by the European Regional Development Fund (six coordinated FIS projects leaded by JS-S and JVid, including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI14/00972, PI14/00728, PI14/01471, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926, PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, PI19/01332, PI20/01802, PI20/00138, PI20/01532, PI20/00456, PI20/00339, PI20/00557, PI20/00886, PI20/01158); the Especial Action Project entitled: Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-Plus grant to JS-S; the European Research Council (Advanced Research Grant 2014–2019; agreement #340918) granted to MM; the Recercaixa (agreement #2013ACUP00194) grant to JS-S; grants from the Consejería de Salud de la Junta de Andalucía (PI0458/2013, PS0358/2016, PI0137/2018); the PROMETEO/2017/017 grant from the Generalitat Valenciana; the SEMERGEN grant; The Horizon 2020 PRIME study (Prevention and Remediation of Insulin Multimorbidity in Europe; grant agreement #847879); JJ holds the Miguel Servet-II contract (CPII19/00015) awarded by the Instituto de Salud Carlos III (co-funded by the European Social Fund “Investing in your future”); JK was supported by the ‘FOLIUM’ programme within the FUTURMed project from the Fundación Instituto de Investigación Sanitaria Illes Balears (financed by 2017annual plan of the sustainable tourism tax and at 50% with charge to the ESF Operational Program 2014–2020 of the Balearic Islands); AÁ-S received a post-doctoral grant from the Generalitat Valenciana (APOSTD/2020/164); CG receives a predoctoral grant from the University of Rovira i Virgili (2020PMF-PIPF-37); We thank CERCA Programme/Generalitat de Catalunya for institutional support and partial support was also provided by SLT006/17/00246, funded by the Department of Health of the Generalitat de Catalunya by the calls “Acció instrumental de programes de recerca orientats en l’àmbit de la recerca i la innovació en salut” and “Pla estratègic de recerca i innovació en salut (PERIS)”; JS-S, senior author of this article, is partially supported by ICREA under the ICREA Academia program; None of the funding sources took part in the design, collection, analysis, interpretation of the data, or writing the report, or in the decision to submit the manuscript for publication.
• dc.format.mimetype application/pdf
• dc.identifier.citation Gómez-Martínez C, Babio N, Júlvez J, Becerra-Tomás N, Martínez-González MÁ, Corella D. Glycemic dysregulations are associated with worsening cognitive function in older participants at high risk of cardiovascular disease: two-year follow-up in the PREDIMED-Plus study. Front Endocrinol (Lausanne). 2021;12:754347. DOI: 10.3389/fendo.2021.754347
• dc.identifier.doi http://dx.doi.org/10.3389/fendo.2021.754347
• dc.identifier.issn 1664-2392
• dc.identifier.uri http://hdl.handle.net/10230/49157
• dc.language.iso eng
• dc.publisher Frontiers
• dc.relation.ispartof Front Endocrinol (Lausanne). 2021;12:754347
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/340918
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/847879
• dc.rights © 2021 Gómez-Martínez, Babio, Júlvez, Becerra-Tomás, Martínez-González, Corella, Castañer, Romaguera, Vioque, Alonso-Gómez, Wärnberg, Martínez, Serra-Majem, Estruch, Tinahones, Lapetra, Pintó, Tur, López-Miranda, Bueno-Cavanillas, Gaforio, Matía-Martín, Daimiel, Martín-Sánchez, Vidal, Vázquez, Ros, Dalsgaard, Sayón-Orea, Sorlí, de la Torre, Abete, Tojal-Sierra, Barón-López, Fernández-Brufal, Konieczna, García-Ríos, Sacanella, Bernal-López, Santos-Lozano, Razquin, Alvarez-Sala, Goday, Zulet, Vaquero-Luna, Diez-Espino, Cuenca-Royo, Fernández-Aranda, Bulló and Salas-Salvadó. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does n
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Cognitive function
• dc.subject.keyword Diabetes duration
• dc.subject.keyword Glycated (glycosylated) hemoglobin
• dc.subject.keyword Insulin resistance
• dc.subject.keyword Prediabetes
• dc.subject.keyword Type 2 diabetes
• dc.title Glycemic dysregulations are associated with worsening cognitive function in older participants at high risk of cardiovascular disease: two-year follow-up in the PREDIMED-Plus study
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion