Serum oxidized low density lipoprotein serves as a mediator for the inverse relationship between serum d-ribose and cognitive performance in type 2 diabetic patients

Abstract

Chronic hyperglycemia, proinflammatory state, and oxidative stress are implicated in the etiology of mild cognitive impairment (MCI) in type 2 diabetes mellitus (T2DM) patients. However, roles and mechanisms of the diabetes-related dys-regulation of serum d-ribose in the pathogenesis remain unclear. This study was to assess: 1) changes of serum d-ribose in T2DM patients with or without MCI compared with healthy controls; and 2) associations of serum d-ribose with key biomarkers of ribosylation [advanced glycation end products (AGEs) and receptor for advanced glycation end products (RAGE)], inflammation (IL-6 and NF-κB) and oxidative stress [oxidized low density lipoproteins (ox-LDL), advanced oxidation protein products (AOPP), total thiol, and non-protein thiol)]. A cross-sectional study was conducted with 1564 initial participants including 362 T2DM patients. Based on their fasting blood glucose concentrations and Montreal cognitive assessment (MoCA) scores, we selected 89 participants and divided them into three groups: 27 healthy controls, 26 T2DM patients with normal cognition, 36 T2DM patients with MCI. All participants were gone through standard anthropometric tests and biochemical examinations of serum clinical profiles and concentrations of d-ribose, AGE, RAGE, IL-6, NF-κB, ox-LDL, AOPP, total thiol, and non-protein thiol. Serum concentrations of d-ribose, ox-LDL, and AOPP were greater (P < 0.05) in the T2DM-MCI patients than that in the T2DM or controls. Serum d-ribose exhibited a positive correlation (P < 0.05) with serum AGEs, RAGE, ox-LDL, and fasting blood glucose, but a negative correlation (P < 0.05) with MoCA score. This negative relationship remained (P < 0.05) after adjusting various covariates, and was found to be mediated (P < 0.05) by serum ox-LDL. In conclusion, our results reveal serum ox-LDL as a potential mediator for the inverse relationship between the elevation of serum d-ribose concentration and the decline of cognitive performance in the T2DM-MCI patients.

Keywords: Advanced glycation end products; Inflammation; Mild cognitive impairment; Oxidative stress; Type 2 diabetes mellitus; d-ribose.