Dataset Information

Metabolic profiling of smoking, associations with type 2 diabetes and interaction with genetic susceptibility.

ABSTRACT:

Background

Smokers are at increased risk of type 2 diabetes (T2D), but the underlying mechanisms are unclear. We investigated if the smoking-T2D association is mediated by alterations in the metabolome and assessed potential interaction with genetic susceptibility to diabetes or insulin resistance.

Methods

In UK Biobank (n = 93,722), cross-sectional analyses identified 208 metabolites associated with smoking, of which 131 were confirmed in Mendelian Randomization analyses, including glycoprotein acetyls, fatty acids, and lipids. Elastic net regression was applied to create a smoking-related metabolic signature. We estimated hazard ratios (HR) of incident T2D in relation to baseline smoking/metabolic signature and calculated the proportion of the smoking-T2D association mediated by the signature. Additive interaction between the signature and genetic risk scores for T2D (GRS-T2D) and insulin resistance (GRS-IR) on incidence of T2D was assessed as relative excess risk due to interaction (RERI).

Findings

The HR of T2D was 1·73 (95% confidence interval (CI) 1·54 - 1·94) for current versus never smoking, and 38·3% of the excess risk was mediated by the metabolic signature. The metabolic signature and its mediation role were replicated in TwinGene. The metabolic signature was associated with T2D (HR: 1·61, CI 1·46 - 1·77 for values above vs. below median), with evidence of interaction with GRS-T2D (RERI: 0·81, CI: 0·23 - 1·38) and GRS-IR (RERI 0·47, CI: 0·02 - 0·92).

Interpretation

The increased risk of T2D in smokers may be mediated through effects on the metabolome, and the influence of such metabolic alterations on diabetes risk may be amplified in individuals with genetic susceptibility to T2D or insulin resistance.

SUBMITTER: Wei Y

PROVIDER: S-EPMC11249521 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature

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Publications

Metabolic profiling of smoking, associations with type 2 diabetes and interaction with genetic susceptibility.

Wei Yuxia Y Hägg Sara S Mak Jonathan K L JKL Tuomi Tiinamaija T Zhan Yiqiang Y Carlsson Sofia S

European journal of epidemiology 20240331 6

<h4>Background</h4>Smokers are at increased risk of type 2 diabetes (T2D), but the underlying mechanisms are unclear. We investigated if the smoking-T2D association is mediated by alterations in the metabolome and assessed potential interaction with genetic susceptibility to diabetes or insulin resistance.<h4>Methods</h4>In UK Biobank (n = 93,722), cross-sectional analyses identified 208 metabolites associated with smoking, of which 131 were confirmed in Mendelian Randomization analyses, includi ...[more]

PMID: 38555549

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Dataset Information

Metabolic profiling of smoking, associations with type 2 diabetes and interaction with genetic susceptibility.

Background

Methods

Findings

Interpretation

Publications

Metabolic profiling of smoking, associations with type 2 diabetes and interaction with genetic susceptibility.

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