Miao G, Zhang Y, Huo Z, et al. - Occurrence of lipid dysregulation many years preceding type 2 diabetes (T2D) was found in this study, and findings demonstrate a significant association of novel molecular lipids (both baseline level and longitudinal change over time) with the risk of T2D beyond conventional risk factors.

• Among 1,958 participants of the Strong Heart Family Study, who were followed for up to 16 years, a total of 3,907 fasting plasma samples were repeatedly measured to detect plasma molecular lipids related to risk of T2D in American Indians.

• Elevated risk of T2D, at 5-year follow-up, was observed (odds ratio [OR] 1.50–2.85) in relation to higher baseline level of 33 lipid species (including triacylglycerols, diacylglycerols, phosphoethanolamines, and phosphocholines).

• At 16-year follow-up, 21 of these lipids were also related to risk of T2D.

• In prediabetes also, aberrant lipid profiles were evident (OR per SD rise in log2-transformed baseline lipids 1.30–2.19 for risk lipids and 0.70–0.78 for protective lipids).

• Significant association was found between longitudinal changes in 568 lipids and changes in continuous measures of T2D.

• In multivariate analysis, distinct lipidomic signatures discriminating high- from low-risk groups were revealed.