A Decreasing Estimated Glucose Disposal Rate Is Associated with an Increase in Biomarkers of Inflammation

The estimated glucose disposal rate (eGDR) is a validated measure of insulin resistance. Also, it predicts Metabolic Syndrome (MetS), diabetic microvascular and macrovascular complications, atherosclerotic cardiovascular disease (ASCVD) and mortality. However, mechanistic insights examining the relationship between eGDR and the above sequela are scanty. Accordingly, we investigated the relationship between the eGDR and a detailed repertoire of biomarkers of inflammation, oxidative stress, and adipokine dysregulation in a cohort (n = 78) comprising nascent MetS without the confounding of type 2 diabetes mellitus(T2DM), ASCVD, smoking, chronic inflammation, and hypolipidemic drug therapy and matched controls using both tertiles of eGDR and correlations with relevant variables. Cardiometabolic features were significantly different across eGDR tertiles and correlated with eGDR. Receiver operating Characteristic (ROC) curve analysis revealed that eGDR was an excellent predictor of MetS with an area under the curve of 0.89. Also, CRP, IL-6, endotoxin, chemerin, leptin, retinol-binding protein-4 (RBP-4) and monocyte TLR-2 abundance and activity were significantly higher in tertile 1 versus tertile 3 of eGDR and all except RBP-4 correlated with eGDR. Biomarkers of oxidative stress were not significant over tertiles of eGDR. In conclusion, in patients without the confounding of T2DM, ASCVD, smoking, macro-inflammation and lipid therapy, the eGDR is an excellent predictor of MetS. It appears based on our findings that a pro-inflammatory state evidenced collectively by increases in hsCRP, endotoxin, chemerin, leptin, RBP-4, IL-6, TLR-2 abundance and activity, could be advanced as a mediating mechanism explaining the increased risk for diabetic complications and ASCVD.