Plasma adiponectin as a marker of insulin receptor dysfunction: clinical utility in severe insulin resistance.

Abstract

Severe insulin resistance is associated with high morbidity. Identification of severely insulin-resistant patients who have genetic or acquired insulin receptor dysfunction may aid therapeutic decision making; however, onerous diagnostic tests allied to a low frequency of insulin receptor dysfunction often preclude formal diagnosis. Our previous observation of paradoxical hyperadiponectinemia in insulin receptoropathy provides a possible basis for a simpler and cheaper screening test. Receiver operating characteristics analysis was used to determine diagnostic thresholds for insulin receptoropathy in severe insulin resistance for adiponectin and for the insulin-regulated hepatic proteins sex hormone-binding globulin (SHBG) and IGF binding protein-1 (IGFBP-1). Adiponectin >7 mg/l in severe insulin resistance had a 97% positive predictive value for insulin receptoropathy and <5 mg/l a 97% negative predictive value. IGFBP-1 and SHBG had lesser, though still significant, utility. Use of these markers is likely to have significant value in accelerating the diagnosis of insulin receptoropathies.