Small dense low density lipoprotein predominance in patients with type 2 diabetes mellitus using Mendelian randomization

PLoS One. 2024 Feb 8;19(2):e0298070. doi: 10.1371/journal.pone.0298070. eCollection 2024.

Abstract

Background: Patients with T2DM often suffer from CVD-related complications, significantly impacting morbidity and mortality rates. The upsurge in CVD prevalence among them is partly linked to sd LDL particles. Understanding the mechanisms behind elevated sd LDL levels is critical for preventing and managing cardiovascular complications in diabetes.

Methods: MR was employed to identify instrumental variables and establish causality, exploring underlying mechanisms.

Results: Notably, T2DM itself, insulin resistance, and fasting glucose seemingly do not directly impact sd LDL levels. Instead, the presence of T2DM or insulin resistance, leading to reduced HDL cholesterol or elevated TG levels, directly contributes to subsequent sd LDL increases, indicating a comprehensive mediating effect. While LDL cholesterol levels correlate positively with sd LDL, they appear unaffected by T2DM or insulin resistance. Importantly, hypertension induced by T2DM or insulin resistance exhibits a positive effect on sd LDL reversal. Unlike T2DM or insulin resistance, blood glucose levels show no significant impact on all processes.

Conclusions: It is hoped that these insights might influence the treatment of patients with diabetes and the management of blood parameters in clinical practice. Examining the effect of T2DM or insulin resistance on sd LDL within HDL cholesterol and triglycerides pathways might provide valuable insights for targeted cardiovascular treatments. Additionally, the study's exploration of the potential positive effects of elevated blood pressure on sd LDL reversal may introduce novel considerations for blood pressure management in patients with diabetes.

MeSH terms

  • Cholesterol, HDL
  • Cholesterol, LDL
  • Diabetes Mellitus, Type 2*
  • Humans
  • Hypertension* / complications
  • Insulin Resistance* / physiology
  • Mendelian Randomization Analysis
  • Triglycerides

Substances

  • Cholesterol, HDL
  • Cholesterol, LDL
  • Triglycerides

Grants and funding

This research was funded by the Natural Science Foundation of Shandong Province (ZR2020MH361), China Postdoctoral Science Foundation (2021M692750), Special funding for Mount Tai Scholar Project. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.