At baseline, 178 lipids were measured by mass spectrometry in 3,668 participants without diabetes from the Malmö Diet and Cancer Study. The population was randomly split into discovery (n = 1,868, including 257 incident cases) and replication (n = 1,800, including 249 incident cases) sets. We used orthogonal projections to latent structures discriminant analyses, extracted a predictive component for T2DM incidence (lipid-PC_DM), and assessed its association with T2DM incidence using Cox regression and lifestyle factors using general linear models.

A T2DM-predictive lipid-PC_DM derived from the discovery set was independently associated with T2DM incidence in the replication set, with hazard ratio (HR) among subjects in the fifth versus first quintile of lipid-PC_DM of 3.7 (95% CI 2.2–6.5). In comparison, the HR of T2DM among obese versus normal weight subjects was 1.8 (95% CI 1.2–2.6). Clinical lipids did not improve T2DM risk prediction, but adding the lipid-PC_DM to all conventional T2DM risk factors increased the area under the receiver operating characteristics curve by 3%. The lipid-PC_DM was also associated with a dietary risk score for T2DM incidence and lower level of physical activity.

A lifestyle-related lipidomic profile strongly predicts T2DM development beyond current risk factors. Further studies are warranted to test if lifestyle interventions modifying this lipidomic profile can prevent T2DM.