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Serum oxidized low density lipoprotein serves as a mediator for the inverse relationship between serum d-ribose and
Yanhui Lu1, Hua Jiang1, Huijing Zhang1
1School of Nursing, Peking University, Beijing, China.
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.
Insights
Elevated serum d-ribose is linked to cognitive decline in type 2 diabetes mellitus (T2DM) patients with mild cognitive impairment (MCI). Oxidized low-density lipoproteins (ox-LDL) may mediate this relationship, highlighting a potential therapeutic target.
Area of Science:
- Endocrinology
- Neuroscience
- Biochemistry
Background:
- Type 2 diabetes mellitus (T2DM) is associated with chronic hyperglycemia, inflammation, and oxidative stress, contributing to mild cognitive impairment (MCI).
- The specific role of serum d-ribose dysregulation in T2DM-related MCI pathogenesis is not well understood.
Purpose of the Study:
- To investigate serum d-ribose levels in T2DM patients with and without MCI compared to healthy controls.
- To examine the association of serum d-ribose with biomarkers of ribosylation, inflammation, and oxidative stress.
Main Methods:
- A cross-sectional study involving 89 participants (27 healthy controls, 26 T2DM normal cognition, 36 T2DM-MCI).
- Measurements included serum d-ribose, advanced glycation end products (AGEs), receptor for advanced glycation end products (RAGE), IL-6, NF-κB, oxidized low-density lipoproteins (ox-LDL), advanced oxidation protein products (AOPP), total thiol, and non-protein thiol.
- Cognitive function assessed using the Montreal Cognitive Assessment (MoCA).
Main Results:
- Serum d-ribose, ox-LDL, and AOPP were significantly higher in T2DM-MCI patients compared to T2DM or controls.
- Serum d-ribose positively correlated with AGEs, RAGE, ox-LDL, and fasting blood glucose.
- Serum d-ribose negatively correlated with MoCA scores, with ox-LDL identified as a mediator.
Conclusions:
- Elevated serum d-ribose is associated with mild cognitive impairment in T2DM patients.
- Serum ox-LDL may mediate the inverse relationship between d-ribose levels and cognitive function decline in T2DM-MCI.
- Targeting ox-LDL could be a strategy to mitigate cognitive impairment in T2DM.
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