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

Carlos Gómez-Martínez; Nancy Babio; Jordi Júlvez; Nerea Becerra-Tomás; Miguel Á Martínez-González; Dolores Corella; Olga Castañer; Dora Romaguera; Jesús Vioque; Ángel M Alonso-Gómez; Julia Wärnberg; José A Martínez; Luís Serra-Majem; Ramón Estruch; Francisco J Tinahones; José Lapetra; Xavier Pintó; Josep A Tur; José López-Miranda; Aurora Bueno-Cavanillas; José J Gaforio; Pilar Matía-Martín; Lidia Daimiel; Vicente Martín-Sánchez; Josep Vidal; Clotilde Vázquez; Emilio Ros; Søren Dalsgaard; Carmen Sayón-Orea; José V Sorlí; Rafael de la Torre; Itziar Abete; Lucas Tojal-Sierra; Francisco J Barón-López; Noelia Fernández-Brufal; Jadwiga Konieczna; Antonio García-Ríos; Emilio Sacanella; M Rosa Bernal-López; José M Santos-Lozano; Cristina Razquin; Andrea Alvarez-Sala; Albert Goday; M Angeles Zulet; Jessica Vaquero-Luna; Javier Diez-Espino; Aida Cuenca-Royo; Fernando Fernández-Aranda; Mònica Bulló; Jordi Salas-Salvadó

doi:10.3389/fendo.2021.754347

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

Carlos Gómez-Martínez, Nancy Babio, Jordi Júlvez, Nerea Becerra-Tomás, Miguel Á Martínez-González, Dolores Corella, Olga Castañer, Dora Romaguera, Jesús Vioque, Ángel M Alonso-Gómez, Julia Wärnberg, José A Martínez, Luís Serra-Majem, Ramón Estruch, Francisco J Tinahones, José Lapetra, Xavier Pintó, Josep A Tur, José López-Miranda, Aurora Bueno-CavanillasJosé J Gaforio, Pilar Matía-Martín, Lidia Daimiel, Vicente Martín-Sánchez, Josep Vidal, Clotilde Vázquez, Emilio Ros, Søren Dalsgaard, Carmen Sayón-Orea, José V Sorlí, Rafael de la Torre, Itziar Abete, Lucas Tojal-Sierra, Francisco J Barón-López, Noelia Fernández-Brufal, Jadwiga Konieczna, Antonio García-Ríos, Emilio Sacanella, M Rosa Bernal-López, José M Santos-Lozano, Cristina Razquin, Andrea Alvarez-Sala, Albert Goday, M Angeles Zulet, Jessica Vaquero-Luna, Javier Diez-Espino, Aida Cuenca-Royo, Fernando Fernández-Aranda, Mònica Bulló, Jordi Salas-Salvadó

15 Citations (Scopus)

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.

Original language	English
Article number	754347
Journal	Frontiers in Endocrinology
Volume	12
ISSN	1664-2392
DOIs	https://doi.org/10.3389/fendo.2021.754347
Publication status	Published - 29 Oct 2021
Externally published	Yes

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Gómez-Martínez, C., Babio, N., Júlvez, J., Becerra-Tomás, N., Martínez-González, M. Á., Corella, D., Castañer, O., Romaguera, D., Vioque, J., Alonso-Gómez, Á. M., Wärnberg, J., Martínez, J. A., Serra-Majem, L., Estruch, R., Tinahones, F. J., Lapetra, J., Pintó, X., Tur, J. A., López-Miranda, J., ... Salas-Salvadó, J. (2021). 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. Frontiers in Endocrinology, 12, Article 754347. https://doi.org/10.3389/fendo.2021.754347

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. / Gómez-Martínez, Carlos; Babio, Nancy; Júlvez, Jordi et al.
In: Frontiers in Endocrinology, Vol. 12, 754347, 29.10.2021.

Research output: Contribution to journal › Journal article › Research › peer-review

Gómez-Martínez, C, Babio, N, Júlvez, J, Becerra-Tomás, N, Martínez-González, MÁ, Corella, D, Castañer, O, Romaguera, D, Vioque, J, Alonso-Gómez, ÁM, Wärnberg, J, Martínez, JA, Serra-Majem, L, Estruch, R, Tinahones, FJ, Lapetra, J, Pintó, X, Tur, JA, López-Miranda, J, Bueno-Cavanillas, A, Gaforio, JJ, Matía-Martín, P, Daimiel, L, Martín-Sánchez, V, Vidal, J, Vázquez, C, Ros, E, Dalsgaard, S, Sayón-Orea, C, Sorlí, JV, de la Torre, R, Abete, I, Tojal-Sierra, L, Barón-López, FJ, Fernández-Brufal, N, Konieczna, J, García-Ríos, A, Sacanella, E, Bernal-López, MR, Santos-Lozano, JM, Razquin, C, Alvarez-Sala, A, Goday, A, Zulet, MA, Vaquero-Luna, J, Diez-Espino, J, Cuenca-Royo, A, Fernández-Aranda, F, Bulló, M & Salas-Salvadó, J 2021, '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', Frontiers in Endocrinology, vol. 12, 754347. https://doi.org/10.3389/fendo.2021.754347

@article{3b427226b2fe44b496ade3d959f52f1c,

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",

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.",

author = "Carlos G{\'o}mez-Mart{\'i}nez and Nancy Babio and Jordi J{\'u}lvez and Nerea Becerra-Tom{\'a}s and Mart{\'i}nez-Gonz{\'a}lez, \{Miguel {\'A}\} and Dolores Corella and Olga Casta{\~n}er and Dora Romaguera and Jes{\'u}s Vioque and Alonso-G{\'o}mez, \{{\'A}ngel M\} and Julia W{\"a}rnberg and Mart{\'i}nez, \{Jos{\'e} A\} and Lu{\'i}s Serra-Majem and Ram{\'o}n Estruch and Tinahones, \{Francisco J\} and Jos{\'e} Lapetra and Xavier Pint{\'o} and Tur, \{Josep A\} and Jos{\'e} L{\'o}pez-Miranda and Aurora Bueno-Cavanillas and Gaforio, \{Jos{\'e} J\} and Pilar Mat{\'i}a-Mart{\'i}n and Lidia Daimiel and Vicente Mart{\'i}n-S{\'a}nchez and Josep Vidal and Clotilde V{\'a}zquez and Emilio Ros and S{\o}ren Dalsgaard and Carmen Say{\'o}n-Orea and Sorl{\'i}, \{Jos{\'e} V\} and \{de la Torre\}, Rafael and Itziar Abete and Lucas Tojal-Sierra and Bar{\'o}n-L{\'o}pez, \{Francisco J\} and Noelia Fern{\'a}ndez-Brufal and Jadwiga Konieczna and Antonio Garc{\'i}a-R{\'i}os and Emilio Sacanella and Bernal-L{\'o}pez, \{M Rosa\} and Santos-Lozano, \{Jos{\'e} M\} and Cristina Razquin and Andrea Alvarez-Sala and Albert Goday and Zulet, \{M Angeles\} and Jessica Vaquero-Luna and Javier Diez-Espino and Aida Cuenca-Royo and Fernando Fern{\'a}ndez-Aranda and M{\`o}nica Bull{\'o} and Jordi Salas-Salvad{\'o}",

note = "Copyright {\textcopyright} 2021 G{\'o}mez-Mart{\'i}nez, Babio, J{\'u}lvez, Becerra-Tom{\'a}s, Mart{\'i}nez-Gonz{\'a}lez, Corella, Casta{\~n}er, Romaguera, Vioque, Alonso-G{\'o}mez, W{\"a}rnberg, Mart{\'i}nez, Serra-Majem, Estruch, Tinahones, Lapetra, Pint{\'o}, Tur, L{\'o}pez-Miranda, Bueno-Cavanillas, Gaforio, Mat{\'i}a-Mart{\'i}n, Daimiel, Mart{\'i}n-S{\'a}nchez, Vidal, V{\'a}zquez, Ros, Dalsgaard, Say{\'o}n-Orea, Sorl{\'i}, de la Torre, Abete, Tojal-Sierra, Bar{\'o}n-L{\'o}pez, Fern{\'a}ndez-Brufal, Konieczna, Garc{\'i}a-R{\'i}os, Sacanella, Bernal-L{\'o}pez, Santos-Lozano, Razquin, Alvarez-Sala, Goday, Zulet, Vaquero-Luna, Diez-Espino, Cuenca-Royo, Fern{\'a}ndez-Aranda, Bull{\'o} and Salas-Salvad{\'o}.",

year = "2021",

month = oct,

day = "29",

doi = "10.3389/fendo.2021.754347",

language = "English",

volume = "12",

journal = "Frontiers in Endocrinology",

issn = "1664-2392",

publisher = "Frontiers Media S.A.",

}

TY - JOUR

T1 - Glycemic Dysregulations Are Associated With Worsening Cognitive Function in Older Participants at High Risk of Cardiovascular Disease

T2 - Two-Year Follow-up in the PREDIMED-Plus Study

AU - Gómez-Martínez, Carlos

AU - Babio, Nancy

AU - Júlvez, Jordi

AU - Becerra-Tomás, Nerea

AU - Martínez-González, Miguel Á

AU - Corella, Dolores

AU - Castañer, Olga

AU - Romaguera, Dora

AU - Vioque, Jesús

AU - Alonso-Gómez, Ángel M

AU - Wärnberg, Julia

AU - Martínez, José A

AU - Serra-Majem, Luís

AU - Estruch, Ramón

AU - Tinahones, Francisco J

AU - Lapetra, José

AU - Pintó, Xavier

AU - Tur, Josep A

AU - López-Miranda, José

AU - Bueno-Cavanillas, Aurora

AU - Gaforio, José J

AU - Matía-Martín, Pilar

AU - Daimiel, Lidia

AU - Martín-Sánchez, Vicente

AU - Vidal, Josep

AU - Vázquez, Clotilde

AU - Ros, Emilio

AU - Dalsgaard, Søren

AU - Sayón-Orea, Carmen

AU - Sorlí, José V

AU - de la Torre, Rafael

AU - Abete, Itziar

AU - Tojal-Sierra, Lucas

AU - Barón-López, Francisco J

AU - Fernández-Brufal, Noelia

AU - Konieczna, Jadwiga

AU - García-Ríos, Antonio

AU - Sacanella, Emilio

AU - Bernal-López, M Rosa

AU - Santos-Lozano, José M

AU - Razquin, Cristina

AU - Alvarez-Sala, Andrea

AU - Goday, Albert

AU - Zulet, M Angeles

AU - Vaquero-Luna, Jessica

AU - Diez-Espino, Javier

AU - Cuenca-Royo, Aida

AU - Fernández-Aranda, Fernando

AU - Bulló, Mònica

AU - Salas-Salvadó, Jordi

N1 - Copyright © 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.

PY - 2021/10/29

Y1 - 2021/10/29

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85119078569

U2 - 10.3389/fendo.2021.754347

DO - 10.3389/fendo.2021.754347

M3 - Journal article

C2 - 34777250

SN - 1664-2392

VL - 12

JO - Frontiers in Endocrinology

JF - Frontiers in Endocrinology

M1 - 754347

ER -

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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