Lipidomic Signatures of Insulin Resistance Identified From Hyperinsulinemic-Euglycemic Clamp Studies in Asian Men

Insulin resistance (IR) is fundamental to the development of type 2 diabetes and usually precedes the disease by several years. Therefore, a better understanding of the molecular pathogenesis of IR may help better manage and prevent the metabolic syndrome. We used an integrated approach of anthropometric and biochemical measures in conjunction with serum lipidomics for metabolic phenotyping of multiethnic male participants with varied insulin sensitivity. By detailed characterization of the serum lipidomic profiles in the fasting state as well as temporal changes during the hyperinsulinemic-euglycemic clamp procedure (HIEC), we identified a systemic metabolic response to the HIEC represented by the marked changes in the acylcarnitine, nonesterified fatty acid, lysophospholipid, sphingosine-1-phosphate, and phosphatidylserine lipid classes. We demonstrate that a shared lipidomic signature between IR and liver fat shows gradual increase with increasing liver fat percentage. In summary, by stratifying the study participants according to the insulin sensitivity indices derived from the HIEC procedures, we identified a circulating lipidomic signature of IR and metabolic plasticity with a potential for prediction and management of metabolic health before the development of type 2 diabetes and other metabolic diseases.