Increased particle size of triacylglycerol-enriched remnant lipoproteins, but not their plasma concentration or lipid content, augments risk prediction of incident type 2 diabetes

Aims/hypothesis Type 2 diabetes prevention requires the accurate identification of those at high risk. Beyond the association of fasting serum triacylglycerols with diabetes, triacylglycerol-enriched remnant lipoproteins (TRLs) more accurately reflect pathophysiological changes that underlie progression to diabetes, such as hepatic insulin resistance, pancreatic steatosis and systemic inflammation. We hypothesised that TRL-related factors could improve risk prediction for incident diabetes. Methods We included individuals from the Brazilian Longitudinal Study of Adult Health cohort. We trained a logistic regression model for the risk of incident diabetes in 80% of the cohort using tenfold cross-validation, and tested the model in the remaining 20% of the cohort (test set). Variables included medical history and traits of the metabolic syndrome, followed by TRL-related measurements (plasma concentration, TRL particle diameter, cholesterol and triacylglycerol content). TRL features were measured using NMR spectroscopy. Discrimination was assessed using the area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC). Results Among 4463 at-risk individuals, there were 366 new cases of diabetes after a mean (±SD) of 3.7 (±0.63) years of follow-up. We derived an 18-variable model with a global AUROC of 0.846 (95% CI: 0.829, 0.869). Overall TRL-related markers were not associated with diabetes. However, TRL particle diameter increased the AUROC, particularly in individuals with HbA 1c