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


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.
Semple
Robert K
RK
Institute of Metabolic Science, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK. rks16@cam.ac.uk
Cochran
Elaine K
EK
Soos
Maria A
MA
Burling
Keith A
KA
Savage
David B
DB
Gorden
Phillip
P
O'Rahilly
Stephen
S
D052242:Adiponectin / Q000097:blood*; D019943:Amino Acid Substitution; D015415:Biomarkers / Q000097:blood; D006801:Humans; D007328:Insulin / Q000172:deficiency / Q000627:therapeutic use; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D009154:Mutation; D009765:Obesity / Q000235:genetics; D011972:Receptor, Insulin / Q000172:deficiency* / Q000235:genetics
D052242:Adiponectin; D015415:Biomarkers; D007328:Insulin; D011972:Receptor, Insulin