Inverted U-shaped correlation between serum low-density lipoprotein cholesterol levels and cognitive functions of patients with type 2 diabetes mellitus

Zhang, Haoqiang; Zhu, Wenwen; Niu, Tong; Wang, Zheng; An, Ke; Cao, Wuyou; Shi, Jijing; Wang, Shaohua

doi:10.1186/s12944-021-01534-5

Cited by 11 publications

(3 citation statements)

References 49 publications

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“…Previous studies showed U-shaped or reverse U-shaped relationships between some adverse health events and lipid levels ( 16 , 17 ), similar to the present study between cumRC and fragility fracture risk, suggesting a possible dual effect of lipid metabolism on bone metabolism. On the one hand, it has been found that increased lipids accumulate beneath the vascular intima and perivascular space in the bones, and the inflammatory bioactive lipids induce bone loss; particularly, oxidized LDL-C plays a significant role in bone loss.…”

Section: Discussionsupporting

confidence: 90%

Cumulative exposure to remnant cholesterol and the risk of fragility fractures: a longitudinal cohort study

Hou,

Zhang,

Guo

et al. 2023

Front. Endocrinol.

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ObjectiveTo investigate the association between cumulative remnant cholesterol (cumRC) and the risk of new-onset fragility fractures.MethodsThis study included individuals who participated in the 2006, 2008, and 2010 Kailuan health examinations. Baseline characteristics were compared between groups according to cumRC quartiles. The incidence density was calculated, and the log-rank test was used to compare the cumulative incidence. Cox proportional hazards models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI), and restricted cubic spline was used to examine the possibly non-linear relation between cumRC and the risk of fragility fractures. Additional analyses were performed with stratification by age (≥ or <65 years).ResultsA total of 43,839 individuals were included in this study. During the median follow-up period of 10.97 years, a total of 489 fragility fractures occurred. Multivariable Cox proportional hazards regression model 3 showed that the Q1 and Q4 groups versus the Q2 group were associated with a higher HR of fragility fracture (HR 1.61, 95% CI: 1.23–2.11; HR 1.38, 95% CI: 1.06–1.81), and restricted cubic spline regression analysis showed a non-linear relationship between cumRC level and the risk of fragility fractures (POverall association < 0.001, PNon-linear association = 0.001). The association was significant in the age group <65 years but not in the age group ≥65 years. The sensitivity analyses were consistent with the main results.ConclusionsBoth too high and too low cumRC levels were associated with a greater risk of fragility fractures, and this association was more significant in young and middle-aged people.

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Section: Discussionsupporting

confidence: 90%

Cumulative exposure to remnant cholesterol and the risk of fragility fractures: a longitudinal cohort study

Hou,

Zhang,

Guo

et al. 2023

Front. Endocrinol.

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“…Despite observing elevated LDL-C levels in patients with DPN, compared to those in the control group, there is no statistical significance. Similarly, slightly increased LDL-C levels were found in diabetic patients with and without cognitive dysfunction, another neuronal complication in the central nervous system [ 5 ]. However, no significant difference in LDL-C levels was found in overall patients with cognitive impairment.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, our further exploration with 497 individuals showed that LDL-C levels have a U-shaped association with cognitive performance. Elevated LDL-C levels may impair executive function, while LDL-C deficiency could affect visual spatial function [ 5 ]. Besides central nervous system damage, diabetic patients exhibiting severe lipid metabolic disorders are at a higher risk of DPN than those without lipid disorders [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

The mediating role of HbA1c in the association between elevated low-density lipoprotein cholesterol levels and diabetic peripheral neuropathy in patients with type 2 diabetes mellitus

et al. 2023

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Background Increased levels of low-density lipoprotein cholesterol (LDL-C) have been identified as one potential risk factor for diabetic peripheral neuropathy (DPN) in patients. The current study seeks to clarify the link between LDL-C, hyperglycemia, and DPN in patients with type 2 diabetes mellitus (T2DM). Methods Here, a total of 120 T2DM individuals were recruited. These volunteers with T2DM were divided into 2 groups, based on the presence or absence of peripheral neuropathy. Additionally, their baseline characteristics were compared. Association among LDL-C and glycosylated hemoglobin (HbA1c) levels and DPN, particularly with respect to specific nerve conduction velocity were analyzed. To identify factors influencing DPN, regression was performed. Furthermore, mediation analysis was employed to evaluate the indirect, direct and total effects of LDL-C on specific nerve conduction velocity, with HbA1c serving as a mediator. Results Compared to 55 patients without DPN, 65 patients with DPN demonstrated elevated levels of LDL-C and HbA1c. Both LDL-C and HbA1c have been found to be associated with reduced the motor fiber conduction velocities of Ulnar (or the Common peroneal) nerve in diabetic patients. HbA1c is one of the known risk factors for DPN in individuals with T2DM. Further mediation analysis revealed that the effect of LDL-C on the Ulnar (or the Common peroneal) nerve motor fiber conduction velocities are fully mediated by HbA1c in patients with T2DM. Conclusions The impact of elevated LDL-C levels upon the Ulnar (or the Common peroneal) nerve motor fiber conduction velocities in patients with T2DM was found to be entirely mediated by increased HbA1c levels.

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Impact and Interrelationships of Striatal Proteins, EPHB2, OPRM1, and PER2 on Mild Cognitive Impairment

Campomayor,

Kim,

Lee

et al. 2024

Mol Neurobiol

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With the global increase in life expectancy, there has been a rise in the incidence of cognitive impairments attributed to diverse etiologies. Notably, approximately 50% of individuals diagnosed with mild cognitive impairment (MCI) progress to dementia within 3 years. However, the precise mechanisms underlying MCI remain elusive. Therefore, this study aimed to elucidate potential mechanisms implicated in MCI utilizing Per2 knockout (KO) mice, which have previously been shown to have cognitive deficits. Behavioral (Y-maze, Barnes maze) and molecular (electrophysiology, RNA sequencing, western blot, and immunofluorescence) experiments were conducted in Per2 KO and wild-type (WT) mice. Per2 KO mice exhibited impaired spatial working memory in the Y-maze and Barnes maze. However, there were no significant group differences in hippocampal long-term potentiation (LTP) between Per2 KO and WT mice, whereas striatal LTP in Per2 KO mice was lower compared to WT mice. In RNA sequencing analysis, 58 genes were downregulated and 64 genes were upregulated in the striatum of Per2 KO mice compared to WT mice. Among the differentially expressed genes, four genes (Chrm2, EphB2, Htr1b, Oprm1) were identified. Optimal expression levels of EPHB2 and OPRM1 were found to significantly enhance cognitive performance in mice. Additionally, Per2 KO mice exhibited reduced EPHB2-NMDAR-LTP and OPRM-mTOR signaling, along with elevated amyloid beta (Aβ) levels, when compared to WT mice. However, these alterations were reversed upon administration of morphine treatment. Striatal OPRM1-mTOR signaling, EPHB2-NMDAR-LTP signaling, and Aβ expression levels may exert a combined effect on MCI under the control of Per2 expression.

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Inverted U-shaped correlation between serum low-density lipoprotein cholesterol levels and cognitive functions of patients with type 2 diabetes mellitus

Cited by 11 publications

References 49 publications

Cumulative exposure to remnant cholesterol and the risk of fragility fractures: a longitudinal cohort study

Cumulative exposure to remnant cholesterol and the risk of fragility fractures: a longitudinal cohort study

The mediating role of HbA1c in the association between elevated low-density lipoprotein cholesterol levels and diabetic peripheral neuropathy in patients with type 2 diabetes mellitus

Impact and Interrelationships of Striatal Proteins, EPHB2, OPRM1, and PER2 on Mild Cognitive Impairment

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