LDL-C plays a causal role on T2DM: a Mendelian randomization analysis

Pan, Wenwei; Sun, Weiju; Yang, Shuo; Zhuang, He; Jiang, Huijie; Ju, Hong; Wang, Donghua; Han, Ying

doi:10.18632/aging.102763

Cited by 20 publications

(19 citation statements)

References 51 publications

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“…These disparities also suggested that race and ethnicity might not be the major influencing factor. A Mendelian random analysis (47) reported that LDL-c played a causal role in T2DM with the elevated LDL-c significantly increased the risk of T2DM, which made the effects of LDL-c on T2DM confusing compared to our results.…”

Section: Discussioncontrasting

confidence: 65%

Gender differences of relationship between serum lipid indices and type 2 diabetes mellitus: a cross-sectional survey in Chinese elderly adults

Guo¹,

Li²,

Fang³

et al. 2021

Ann Transl Med

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Background: To investigate the gender differences of the relationships between clinical serum lipid indices and type 2 diabetes mellitus (T2DM) in Chinese elderly adults.Methods: Between 2014 and 2016, participants selected from three communities in an urban district of Shanghai were measured for serum lipid indices of low-density lipoprotein cholesterol (LDL-c), highdensity lipoprotein cholesterol (HDL-c), total cholesterol (TC), and triglyceride (TG). Age and multivariate adjusted logistic regression models were utilized to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of serum lipid indices on T2DM prevalence.Results: In total, 4,023 male and 3,862 female participants were included in this study, with the T2DM prevalence proportions of 13.03% and 11.73%, respectively. In association analysis, the serum levels of LDL-c, HDL-c, TC were significant between non-T2DM individuals and T2DM patients in men, but the HDL-c and TG in women. LDL-c/HDL-c, TG/HDL-c, and TC/HDL-c ratios were associated with the T2DM prevalence only in women. In the multivariate analysis, a higher serum LDL-c level was positively associated with a reduced risk of T2DM prevalence in men with OR (95% CI) of 0.57 (0.39-0.85) (P=0.006).Higher ratios of LDL-c/HDL-c, TG/HDL-c, and TC/HDL-c were all more likely associated with the decreased risks of T2DM prevalence with the ORs ranging from 0.45 to 0.62 in men (all P<0.05), but not in women.Conclusions: High LDL-c concentration was significantly associated with a lower T2DM prevalence in men. A gender difference of the associations between the lipid ratios and T2DM prevalence was observed for LDL-c/HDL-c and TC/HDL-c ratios, which might be validated in female T2DM prevalence in the future.

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Section: Discussioncontrasting

confidence: 65%

Gender differences of relationship between serum lipid indices and type 2 diabetes mellitus: a cross-sectional survey in Chinese elderly adults

Guo¹,

Li²,

Fang³

et al. 2021

Ann Transl Med

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“…Numerous studies using either conventional observational 2 , 3 , 4 , 5 , 6 or more recent Mendelian Randomization methods 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 have investigated the relationship between dyslipidaemia and T2DM liability. However, the existing body of evidence has some important limitations.…”

Section: Introductionmentioning

confidence: 99%

Lipid traits and type 2 diabetes risk in African ancestry individuals: A Mendelian Randomization study

Soremekun¹,

Karhunen

et al. 2022

eBioMedicine

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“…For example, Mohamadi, et al showed that the increase in FBG, SBP, and BMI was associated with an increased likelihood of exhibiting T2DM [ 36 ]. Pan et al have reported that elevated LDL-C levels significantly increased the risk of T2DM [ 48 ]. Some reports have shown that hypertension was an independent risk factor for T2DM [ 49 , 50 ].…”

Section: Discussionmentioning

confidence: 99%

Deregulation of lncRNA HIST1H2AG-6 and AIM1-3 in peripheral blood mononuclear cells is associated with newly diagnosed type 2 diabetes

Jiang

Lou²,

Chen

et al. 2021

BMC Med Genomics

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Background Type 2 diabetes mellitus (T2DM) is mainly affected by genetic and environmental factors; however, the correlation of long noncoding RNAs (lncRNAs) with T2DM remains largely unknown. Methods Microarray analysis was performed to identify the differentially expressed lncRNAs and messenger RNAs (mRNAs) in patients with T2DM and healthy controls, and the expression of two candidate lncRNAs (lnc-HIST1H2AG-6 and lnc-AIM1-3) were further validated using quantitative real-time polymerase chain reaction (qRT-PCR). Spearman’s rank correlation coefficient was used to measure the degree of association between the two candidate lncRNAs and differentially expressed mRNAs. Furthermore, the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway and GO (Gene Ontology) enrichment analysis were used to reveal the biological functions of the two candidate lncRNAs. Additionally, multivariate logistic regression analysis and receiver operating characteristic (ROC) curve analysis were performed. Results The microarray analysis revealed that there were 55 lncRNAs and 36 mRNAs differentially expressed in patients with T2DM compared with healthy controls. Notably, lnc-HIST1H2AG-6 was significantly upregulated and lnc-AIM1-3 was significantly downregulated in patients with T2DM, which was validated in a large-scale qRT-PCR examination (90 controls and 100 patients with T2DM). Spearman’s rank correlation coefficient revealed that both lncRNAs were correlated with 36 differentially expressed mRNAs. Furthermore, functional enrichment (KEGG and GO) analysis demonstrated that the two lncRNA-related mRNAs might be involved in multiple biological functions, including cell programmed death, negative regulation of insulin receptor signal, and starch and sucrose metabolism. Multivariate logistic regression analysis revealed that lnc-HIST1H2AG-6 and lnc-AIM1-3 were significantly correlated with T2DM (OR = 5.791 and 0.071, respectively, both P = 0.000). Furthermore, the ROC curve showed that the expression of lnc-HIST1H2AG-6 and lnc-AIM1-3 might be used to differentiate patients with T2DM from healthy controls (area under the ROC curve = 0.664 and 0.769, respectively). Conclusion The profiles of lncRNA and mRNA were significantly changed in patients with T2DM. The expression levels of lnc-HIST1H2AG-6 and lnc-AIM1-3 genes were significantly correlated with some features of T2DM, which may be used to distinguish patients with T2DM from healthy controls and may serve as potential novel biomarkers for diagnosis in the future.

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LDL-C plays a causal role on T2DM: a Mendelian randomization analysis

Cited by 20 publications

References 51 publications

Gender differences of relationship between serum lipid indices and type 2 diabetes mellitus: a cross-sectional survey in Chinese elderly adults

Gender differences of relationship between serum lipid indices and type 2 diabetes mellitus: a cross-sectional survey in Chinese elderly adults

Lipid traits and type 2 diabetes risk in African ancestry individuals: A Mendelian Randomization study

Deregulation of lncRNA HIST1H2AG-6 and AIM1-3 in peripheral blood mononuclear cells is associated with newly diagnosed type 2 diabetes

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