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First Author: Joy Siting Trybula, PharmD, University of Pittsburgh School of Medicine, Class of 2017
Introduction: Worldwide obesity has nearly doubled since 1980 and prevalence of insulin resistance has increased concurrently. Obesity is associated with the dysregulation of adipokines, which are adipose tissue secreted hormones that influence metabolism. A novel adipokine, autotaxin (ATX), hydrolyzes lysophosphatidlycholine (LPC) to generate lysophosphatidic acid (LPA) – a lipid signaling molecule. In vitro studies implicate the ATX-LPA pathway in the development of insulin resistance, however the mechanism and relationship remains unknown. We hypothesize that there is a positive association between serum autotaxin and features of insulin resistance in humans.
Methods: The current study was completed using previously collected samples from the Re-Energize with Nutrition, Exercise, and Weight loss study (RENEW). The RENEW trial was designed to determine the efficacy of diet, exercise, and combination diet and exercise on weight loss in the obese. We assessed middle-aged, non-diabetic, overweight to obese female subjects for markers of insulin sensitivity, inflammation, and features of metabolic syndrome. Baseline serum ATX was measured by ELISA and data were analyzed using Spearman’s correlation test. Multivariate stepwise linear regression was used to determine predictive value of serum ATX.
Results: Serum ATX concentrations from 208 female subjects were evaluated. Median (IQR) age and BMI were 47.2 (40.6-51.9) years and 36.8 (27.3-43.2) kg/m2, respectively. As predicted, serum ATX concentration was higher in overweight to obese females (277.6 ng/mL) compared to normal weight females (211.4 ng/mL, p<0.0001). ATX correlated with insulin resistance in overweight to obese females (rho=0.3871, p<0.0001) and was independently associated with homeostatic model assessment of insulin resistance (HOMA-IR) (Multivariate OR [95%CI]) (0.002 [0.001-0.004], p=0.007).
Conclusion: Serum ATX is positively correlated with HOMA-IR and, more significantly, is an independent predictor of insulin resistance in our cohort. Serum ATX may be used as a therapeutic target or as a clinical diagnostic parameter for insulin resistance and diabetes.
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