Insulin resistance (IR) is constantly invoked as a contributor to numerous common diseases, e.g. diabetes, cardiovascular disease and Alzheimer’s disease; however, with the exception of a narrow segment of diabetes-related studies, IR is infrequently measured and rarely measured well. Our goal was to develop IR estimation models for the dynamic measure of insulin sensitivity (SI) and the basal measure of homeostatic model assessment of IR (HOMAIR) from metabolomics data combined with minimal clinical data, e.g. age, sex, BMI. Least Absolute Shrinkage and Selection Operator (LASSO) and Elastic Net regression were used to build estimation models using 1274 metabolites, prioritized by trait associations and collected in the Insulin Resistance Atherosclerosis Family Study (IRASFS). Three metabolite transformations were implemented (inverse normal transformation, standardization, and Box Cox transformation) to account for distributional differences and tested to optimize estimation. The analysis was performed in one Mexican American (MA) recruitment site (San Luis Valley, CO (SLV), N=450) and tested in another MA recruitment site (San Antonio, TX (SA), N=473). In addition, the two MA recruitment sites were combined and estimation models tested in the African American recruitment site (AA; Los Angeles, California, N=495) to assess generalizability. Estimated SI was correlated with empiric SI in the SA (r2=0.77) and AA (r2=0.74) testing datasets. Further, we tested estimated SI for association with BMI, low-density lipoprotein cholesterol and triglycerides with results consistent with those observed for empiric SI. The same framework was used to estimate HOMAIR, and yielded similar results. In summary, we have developed methods for estimating multiple measures of IR from a single blood sample. This approach will greatly expand our ability to provide meaningful insight into the role of IR in disease, supporting the potential for application to a wide-range of biomedical studies. Disclosure N.Allred: None. D.W.Bowden: None. F.Hsu: None. S.Chen: None. M.Ng: None. M.O.Goodarzi: Advisory Panel; Nestlé Health Science, Other Relationship; Nestlé Health Science. J.I.Rotter: None. L.E.Wagenknecht: None. M.Bancks: None. R.N.Bergman: Consultant; Lilly, ReCor Medical, Inc., Research Support; AstraZeneca. Funding National Institutes of Health (DK118062)
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