Abstract 3595: Inverse Association of Adiponectin with Insulin Resistance is Attenuated with the Escalation of Insulin Resistance: a Possible Finding of Adiponectin Resistance

Introduction: Adiponectin has been known to play an important role in the glucose and lipid metabolism, and thereby may be considered as a potential treatment target for diabetes mellitus or atherosclerotic diseases. Recently, some basic studies showed that adiponectin might not function in an insulin-resistant condition, a concept called “adiponectin resistance.” However, this concept has not been confirmed in human. Therefore, we assessed the hypothesis that the well-known inverse association between adiponectin and insulin resistance is weakened in the insulin-resistant state. Methods: We studied 2,316 middle-aged Japanese men without a medical history of cancer, cardiovascular disease, diabetes, hypertension, or dyslipidemia to determine whether or not the association between serum adiponectin levels and the insulin resistance index (HOMA-IR) differed according to insulin resistant states. Results: Mean age and body mass index of study subjects were 48±7 and 23±3, respectively. A multiple linear regression analysis revealed that log-adiponectin was inversely associated with log-HOMA-IR independently of covariates (β= − 0.235, P <0.001). Subsequently, we re-analyzed after dividing study subjects according to the tertile of HOMA-IR. As shown in the Table , the inverse association between adiponectin and HOMA-IR was considerably weakened with the escalation of insulin resistance. Specifically, adiponectin was almost positively associated with HOMA-IR in insulin-resistant subjects (β= 0.114, P =0.059). Interestingly, statistically significant associations of adiponectin with triglyceride and HDL-C were uniformly observed in all tertiles. Conclusion: The inverse association of adiponectin with insulin resistance weakened with the escalation of insulin resistance, suggesting the existence of “adiponectin resistance” in insulin-resistant individuals. This adiponectin resistance may be restricted in glucose metabolism. Table. Coefficients of adiponectin in multiple linear regression analyses with independent variables