Fatty-acid patterns and odds of incident type 2 diabetes in South Asians: a causal mediation analysis within the CARRS cohort.

AIMS: We tested whether a serum fatty-acid (FA) pattern is associated with incident type 2 diabetes mellitus (T2DM) in South Asians, and whether the association is mediated by glycated haemoglobin (HbA1c), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C).

METHODS

In a nested case-control sample drawn from the CARRS cohort (N = 8,919), we included 391 incident T2DM cases and 395 controls who remained T2DM-free at follow-up. Serum FAs were quantified by nuclear magnetic resonance spectroscopy. Principal-component analysis summarised FA composition; PC1 (loaded on polyunsaturated and saturated FAs) was the primary exposure. Multivariable logistic regression estimated odds ratios (OR) per SD, adjusted for age, sex, education, smoking, and body-mass index. Counterfactual mediation through HbA1c, TG, and HDL-C was pooled across 20 imputations by Rubin's rules.

RESULTS

The FA pattern was associated with higher odds of incident T2DM (OR 1.26 per SD, 95% CI 1.07-1.48). HbA1c mediated 35.9% of the total effect (p = 0.017); triglycerides showed no indirect effect (p = 0.108). HDL-C acted as a suppressor, attenuating it by 18.0% (p = 0.002).

CONCLUSIONS

A polyunsaturated- and saturated-FA-loaded phenotype is associated with higher odds of incident T2DM in South Asians. The association operates through a glycaemic pathway and is partially offset by HDL-C. Replication is warranted.