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

Abstract

ObjectiveTo investigate the causal relationships between linoleic acid and type 2 diabetes, and between linoleic acid and glycemic traits in European populations.MethodsThis 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.ResultsMR 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.ConclusionHigh 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.

Association of dietary nutrient intake with type 2 diabetes: A Mendelian randomization study

“…[62] Studies by Hao Liang et al have suggested that higher linoleic acid levels might reduce the risk of T2D, yet our analysis using the FinnGen and DIAMANTE databases did not corroborate this finding. [63] Research by Benjamin De La Barrera and Despoina Manousaki indicated that vitamin D does not influence the risk of T2D in adolescents across different ethnicities, consistent with our study's results. [64] This MR study has the following advantages: Firstly, this research utilizes publicly available GWAS data for causal inference, studying dietary factors that may influence T2D onset using MR to mitigate confounding factors or reverse causation, common issues in observational studies.…”

“…[ 62 ] Studies by Hao Liang et al have suggested that higher linoleic acid levels might reduce the risk of T2D, yet our analysis using the FinnGen and DIAMANTE databases did not corroborate this finding. [ 63 ] Research by Benjamin De La Barrera and Despoina Manousaki indicated that vitamin D does not influence the risk of T2D in adolescents across different ethnicities, consistent with our study’s results. [ 64 ]…”

Lower plasma linoleic acids as a risk factor for gout: an integrated analysis of population-based cohort and genetic data

“…, diabetes). 37,38 In contrast to SFAs and MUFAs, essential LAs, the most abundant PUFAs, could not be synthesized de novo in humans. Circulating PUFA levels were more correlated with dietary intake and should be used more intensively to inform dietary guidelines.…”