Proteins Altered by Surgical Weight Loss Highlight Biomarkers of Insulin Resistance in the Community
Arteriosclerosis, Thrombosis, and Vascular Biology, 2018
Shah R., Hwang S., Yeri A., Tanriverdi K., Pico A., Yao C., Murthy V., Ho J., Vitseva O., Demarco D., Shah S., Iafrati M., Levy D., Freedman J.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Metabolic Diseases | Patient Stratification | Plasma |  Olink Target 96 |
Abstract
Objective—
Mechanisms of early and late improvements in cardiovascular risk after bariatric surgery and applicability to larger, at-risk populations remain unclear. We aimed to identify proteins altered after bariatric surgery and their relations to metabolic syndrome and diabetes mellitus.
Approach and Results—
We identified 19 proteins altered in 32 nonfasting plasma samples from a study of patients undergoing bariatric surgery who were evaluated preoperatively (visit 1) versus both early (visit 2; ≈3 months) and late (visit 3; ≈12 months) postoperative follow-up using predefined protein panels (Olink). Using in silico methods and publicly available gene expression repositories, we found that genes encoding 8 out of 19 proteins had highest expression in liver relative to other assayed tissues, with the top biological and disease processes, including major obesity-related vascular diseases. Of 19 candidate proteins in the surgical cohort, 6 were previously measured in >3000 FHS (Framingham Heart Study) participants (IGFBP [insulin-like growth factor binding protein]-1, IGFBP-2, P-selectin, CD163, LDL (low-density lipoprotein)-receptor, and PAI [plasminogen activator inhibitor]-1). A higher concentration of IGFBP-2 at baseline was associated with a lower risk of incident metabolic syndrome (odds ratio per log-normal unit, 0.45; 95% CI, 0.32–0.64; P =7.7×10 -6 ) and diabetes mellitus (odds ratio, 0.63; 95% CI, 0.49–0.79; P =0.0001) after multivariable adjustment.
Conclusions—
Using a directed protein quantification platform (Olink), we identified known and novel proteins altered after surgical weight loss, including IGFBP-2. Future efforts in well-defined obesity intervention settings may further define and validate novel targets for the prevention of vascular disease in obesity.