Association between urinary metabolomics and cognitive performance in Asians with type 2 diabetes

BackgroundThere is an ongoing quest for novel biomarkers which may serve as therapeutic targets in cognitive impairment, alongside a growing appreciation of urinary metabolomics as a promising non-invasive approach to identify metabolic signature of Alzheimer's disease and other causes of dementia.ObjectiveWe studied whether urine metabolomics were associated with mild cognitive impairment (MCI) and cognitive performance in a diabetic milieu.MethodsWe implemented a cross-sectional study on 1053 patients who had Type 2 diabetes (T2D). Urinary metabolites were quantitated by nuclear magnetic resonance (NMR). We evaluated cognitive performance by administering Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Criteria for mild cognitive impairment (MCI) were met if patients scored > 1.5 standard deviations (SDs) less than the mean RBANS score for total index or any of the cognitive domains.ResultsThe average age was 65.1 ± 7.9. Four metabolites were associated with RBANS total score after multiple testing correction by Benjamini-Hochberg (BH) procedure in the adjusted analyses: sucrose (β = -1.17 (95%CI -1.71, -0.62)), 4-hydroxyhippurate (β = -0.92 (-1.42, -0.42)), trans-aconitate (β = -0.93 (-1.46, -0.40)), and tryptophan (β = -0.82 (-1.33, -0.32)). Sucrose was associated with MCI (OR = 2.19 (1.44, 3.32). Sucrose, trans-aconitate, 4-hydroxyhippurate, and 4-deoxythreonate were associated with delayed memory. Hypoxanthine, sucrose and tryptophan were related to visuo-spatial/constructional function.ConclusionsOur study identified several urinary metabolites which were differentially linked to cognitive performance in T2D. Future investigations are warranted to confirm the findings.