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Plasma Adiponectin as a Marker of Insulin Receptor Dysfunction

Clinical utility in severe insulin resistance

¹ Institute of Metabolic Science, University of Cambridge, Addenbrooke's Hospital, Cambridge, U.K.
² Clinical Endocrinology Branch, Digestive and Kidney Diseases, National Institute of Diabetes, Bethesda, Maryland

Corresponding author: Dr. R. Semple, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, CB2 0QQ, U.K. E-mail: rks16{at}cam.ac.uk

OBJECTIVE—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.

RESEARCH DESIGN AND METHODS—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).

RESULTS—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.

CONCLUSIONS—Use of these markers is likely to have significant value in accelerating the diagnosis of insulin receptoropathies.

Abbreviations: IGFBP-1, IGF binding protein-1 • NPV, negative predictive value • PPV, positive predictive value • SHBG, sex hormone–binding globulin

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