TY - JOUR
T1 - Associations between plasma kynurenines and cognitive function in individuals with normal glucose metabolism, prediabetes and type 2 diabetes
T2 - the Maastricht Study
AU - Bakker, Lieke
AU - Ramakers, Inez H G B
AU - van Boxtel, Martin P J
AU - Schram, Miranda T
AU - Stehouwer, Coen D A
AU - van der Kallen, Carla J H
AU - Dagnelie, Pieter C
AU - van Greevenbroek, Marleen M J
AU - Wesselius, Anke
AU - Midttun, Øivind
AU - Ueland, Per M
AU - Verhey, Frans R J
AU - Eussen, Simone J P M
AU - Köhler, Sebastian
N1 - Funding Information:
The research in this paper was supported by the European Regional Development Fund as part of OP-ZUID, the province of Limburg, the Dutch Ministry of Economic Affairs (grant no. 31O.041), Stichting the Weijerhorst (Maastricht, the Netherlands), the Pearl String Initiative Diabetes (Amsterdam, the Netherlands), the Cardiovascular Center (Maastricht, the Netherlands), Cardiovascular Research Institute (CARIM; Maastricht, the Netherlands), School for Public Health and Primary Care (CAPHRI; Maastricht, the Netherlands), School for Nutrition, Toxicology and Metabolism (NUTRIM; Maastricht, the Netherlands), Stichting Annadal (Maastricht, the Netherlands) and Health Foundation Limburg (Maastricht, the Netherlands) and by unrestricted grants from Janssen-Cilag B.V. (Tilburg, the Netherlands), Novo Nordisk Farma B.V. (Alphen aan den Rijn, the Netherlands) and Sanofi-Aventis B.V. (Gouda, the Netherlands). The study funders were not involved in the design of the study; the collection, analysis, and interpretation of data; writing the report; and did not impose any restrictions regarding the publication of the report.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/11
Y1 - 2021/11
N2 - AIMS/HYPOTHESIS: Studies investigating associations between kynurenines and cognitive function have generally been small, restricted to clinical samples or have found inconsistent results, and associations in the general adult population, and in individuals with type 2 diabetes in particular, are not clear. Therefore, the aim of the present study was to investigate cross-sectional associations between plasma kynurenines and cognitive function in a cohort of middle-aged participants with normal glucose metabolism, prediabetes (defined as impaired fasting glucose and/or impaired glucose tolerance) and type 2 diabetes.METHODS: Plasma kynurenines were quantified in 2358 participants aged 61 ± 8 years. Cross-sectional associations of kynurenines with cognitive impairment and cognitive domain scores were investigated using logistic, multiple linear and restricted cubic spline regression analyses adjusted for several confounders.RESULTS: Effect modification by glucose metabolism status was found for several associations with cognitive impairment, hence analyses were stratified. In individuals with prediabetes, 3-hydroxykynurenine (OR per SD 0.59 [95% CI 0.37, 0.94]) and 3-hydroxyanthranilic acid (0.67 [0.47, 0.96]) were associated with lower odds of cognitive impairment after full adjustment. In individuals with type 2 diabetes, kynurenine (0.80 [0.66, 0.98]), 3-hydroxykynurenine (0.82 [0.68, 0.99]), kynurenic acid (0.81 [0.68, 0.96]), xanthurenic acid (0.73 [0.61, 0.87]) and 3-hydroxyanthranilic acid (0.73 [0.60, 0.87]) were all associated with lower odds of cognitive impairment. Kynurenic acid (β per SD 0.07 [95% CI 0.02, 0.13]) and xanthurenic acid (0.06 [0.01, 0.11]) were also associated with better executive function/attention. No associations were observed in individuals with normal glucose metabolism.CONCLUSIONS/INTERPRETATION: Several kynurenines were cross-sectionally associated with lower odds of cognitive impairment and better cognitive functioning in type 2 diabetes, while less widespread associations were seen in prediabetes. Low levels of kynurenines might be involved in the pathway of type 2 diabetes and cognitive decline but this needs further studies.
AB - AIMS/HYPOTHESIS: Studies investigating associations between kynurenines and cognitive function have generally been small, restricted to clinical samples or have found inconsistent results, and associations in the general adult population, and in individuals with type 2 diabetes in particular, are not clear. Therefore, the aim of the present study was to investigate cross-sectional associations between plasma kynurenines and cognitive function in a cohort of middle-aged participants with normal glucose metabolism, prediabetes (defined as impaired fasting glucose and/or impaired glucose tolerance) and type 2 diabetes.METHODS: Plasma kynurenines were quantified in 2358 participants aged 61 ± 8 years. Cross-sectional associations of kynurenines with cognitive impairment and cognitive domain scores were investigated using logistic, multiple linear and restricted cubic spline regression analyses adjusted for several confounders.RESULTS: Effect modification by glucose metabolism status was found for several associations with cognitive impairment, hence analyses were stratified. In individuals with prediabetes, 3-hydroxykynurenine (OR per SD 0.59 [95% CI 0.37, 0.94]) and 3-hydroxyanthranilic acid (0.67 [0.47, 0.96]) were associated with lower odds of cognitive impairment after full adjustment. In individuals with type 2 diabetes, kynurenine (0.80 [0.66, 0.98]), 3-hydroxykynurenine (0.82 [0.68, 0.99]), kynurenic acid (0.81 [0.68, 0.96]), xanthurenic acid (0.73 [0.61, 0.87]) and 3-hydroxyanthranilic acid (0.73 [0.60, 0.87]) were all associated with lower odds of cognitive impairment. Kynurenic acid (β per SD 0.07 [95% CI 0.02, 0.13]) and xanthurenic acid (0.06 [0.01, 0.11]) were also associated with better executive function/attention. No associations were observed in individuals with normal glucose metabolism.CONCLUSIONS/INTERPRETATION: Several kynurenines were cross-sectionally associated with lower odds of cognitive impairment and better cognitive functioning in type 2 diabetes, while less widespread associations were seen in prediabetes. Low levels of kynurenines might be involved in the pathway of type 2 diabetes and cognitive decline but this needs further studies.
KW - 3-HYDROXYKYNURENINE
KW - ABNORMALITIES
KW - ALZHEIMERS-DISEASE
KW - BIOMARKERS
KW - Cognition
KW - Cognitive impairment
KW - DEMENTIA
KW - EDUCATION
KW - Glucose metabolism status
KW - INFLAMMATION
KW - INSULIN-RESISTANCE
KW - Kynurenines
KW - Metabolites
KW - PARTICIPANTS AGED 24-81
KW - PATHWAY METABOLITES
KW - Population-based cohort study
KW - Prediabetes
KW - Type 2 diabetes mellitus
U2 - 10.1007/s00125-021-05521-4
DO - 10.1007/s00125-021-05521-4
M3 - Article
C2 - 34409496
SN - 0012-186X
VL - 64
SP - 2445
EP - 2457
JO - Diabetologia
JF - Diabetologia
IS - 11
ER -