Causal relationship between linoleic acid and type 2 diabetes and glycemic traits: a bidirectional Mendelian randomization study

Front Endocrinol (Lausanne). 2023 Nov 21:14:1277153. doi: 10.3389/fendo.2023.1277153. eCollection 2023.

Abstract

Objective: To investigate the causal relationships between linoleic acid and type 2 diabetes, and between linoleic acid and glycemic traits in European populations.

Methods: This study employed a two-sample Mendelian randomization approach to infer causality between linoleic acid and type 2 diabetes, as well as between linoleic acid and glycemic traits, leveraging genetic variations. Data were sourced from genome-wide association study summary datasets. Random-effects inverse-variance weighted, weighted median, and MR-Egger methods were used for the two-sample Mendelian randomization analyses. Results were presented as odds ratios with a 95% confidence interval. Multiple sensitivity analyses were conducted to assess result robustness.

Results: MR findings indicated a correlation between linoleic acid levels and the risk of type 2 diabetes, fasting blood glucose, and glycated hemoglobin (HbA1c), but not with fasting insulin. Specifically: type 2 diabetes (OR: 0.811, 95% CI: 0.688-0.956, P=0.013<0.05),fasting blood glucose (β_IVW): -0.056, 95% CI: (-0.091,-0.021), P=0.002< 0.0125), glycated hemoglobin (β_IVW: -0.032, 95% CI: (-0.048,-0.015), P=0.0002< 0.0125) and Fasting insulin (β_IVW: -0.024, 95% CI: (-0.056,-0.008), P=0.136 >0.05).Reverse MR analyses showed a correlation between type 2 diabetes and reduced levels of linoleic acid (β_IVW: -0.033, 95% CI: (-0.059,-0.006), P=0.014<0.05). Multiple sensitivity analyses also detected study heterogeneity but found no evidence of horizontal pleiotropy.

Conclusion: High levels linoleic acid can reduce the risk of type 2 diabetes, fasting blood glucose, and glycated hemoglobin, but has no significant relation with fasting insulin. Type 2 diabetes can lower linoleic acid levels; however, no significant causal relationship was observed between the three glycemic traits and reduced levels of linoleic acid.

Keywords: Mendelian randomization; causal relationship; glycemic traits; linoleic acid; type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Glucose
  • Diabetes Mellitus, Type 2* / epidemiology
  • Diabetes Mellitus, Type 2* / genetics
  • Genome-Wide Association Study
  • Glycated Hemoglobin
  • Humans
  • Insulin
  • Linoleic Acid*
  • Mendelian Randomization Analysis

Substances

  • Blood Glucose
  • Glycated Hemoglobin
  • Insulin
  • Linoleic Acid

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was funded by the National Natural Science Foundation Youth Project (82204876), the Shandong Province Natural Science Foundation (ZR2020MH347), and the Traditional Chinese Medicine Emergency Special Project for Novel Coronavirus Infection (2023ZYLCY J02-12).