Paradoxical elevation of high-molecular weight adiponectin in acquired extreme insulin resistance due to insulin receptor antibodies

Robert K. Semple, Nils H. Halberg, Keith Burling, Maria A. Soos, Todd Schraw, Jian'an Luan, Elaine K. Cochran, David B. Dunger, Nicholas J. Wareham, Philipp E. Scherer, Phillip Gorden, Stephen O'Rahilly

Research output: Contribution to journalArticle

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Abstract

Total plasma adiponectin and high-molecular weight (HMW) polymeric adiponectin are strongly positively correlated with insulin sensitivity. However, we have recently reported paradoxical hyperadiponectinemia in patients with severe insulin resistance due to genetically defective insulin receptors. This implies either that the insulin receptor has a critical physiological role in controlling adiponectin production and/or clearance or that constitutive insulin receptor dysfunction influences adiponectin levels through developmental effects. The aim of the current study was to distinguish between these possibilities using human model of reversible antibody-mediated insulin receptor dysfunction and to refine the previous observations by determining adiponectin complex distribution. Cross-sectional and longitudinal determination of fasting plasma adiponectin and adiponectin complex distribution was undertaken in patients with extreme insulin resistance due to insulin receptor mutations, anti-insulin receptor antibodies (type B insulin resistance), or an undefined cause. Despite extreme insulin resistance, patients with type insulin resistance (all women; mean age 42 years [range 12-54]) had dramatically elevated total plasma adiponectin compared with the general population (mean 43.0 mg/l [range 31.3-54.2] vs. 8.9 mg/l [1.5-28.5 for BMI <25 kg/m2]), which was accounted for largely by HMW polymers. Hyperadiponectinemia resolved in parallel with reduction of insulin receptor antibodies and clinical resolution of insulin resistance. Although the well-established inverse relationship between plasma insulin and adiponectin levels may, in part, reflect positive effects of adiponectin on insulin sensitivity, these data suggest that the magnitude of the effect of insulin action on adiponectin levels may have been underestimated.

Original languageEnglish (US)
Pages (from-to)1712-1717
Number of pages6
JournalDiabetes
Volume56
Issue number6
DOIs
StatePublished - Jun 2007

Fingerprint

Insulin Antibodies
Adiponectin
Insulin Receptor
Insulin Resistance
Molecular Weight
Insulin
Fasting
Polymers

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Semple, R. K., Halberg, N. H., Burling, K., Soos, M. A., Schraw, T., Luan, J., ... O'Rahilly, S. (2007). Paradoxical elevation of high-molecular weight adiponectin in acquired extreme insulin resistance due to insulin receptor antibodies. Diabetes, 56(6), 1712-1717. https://doi.org/10.2337/db06-1665

Paradoxical elevation of high-molecular weight adiponectin in acquired extreme insulin resistance due to insulin receptor antibodies. / Semple, Robert K.; Halberg, Nils H.; Burling, Keith; Soos, Maria A.; Schraw, Todd; Luan, Jian'an; Cochran, Elaine K.; Dunger, David B.; Wareham, Nicholas J.; Scherer, Philipp E.; Gorden, Phillip; O'Rahilly, Stephen.

In: Diabetes, Vol. 56, No. 6, 06.2007, p. 1712-1717.

Research output: Contribution to journalArticle

Semple, RK, Halberg, NH, Burling, K, Soos, MA, Schraw, T, Luan, J, Cochran, EK, Dunger, DB, Wareham, NJ, Scherer, PE, Gorden, P & O'Rahilly, S 2007, 'Paradoxical elevation of high-molecular weight adiponectin in acquired extreme insulin resistance due to insulin receptor antibodies', Diabetes, vol. 56, no. 6, pp. 1712-1717. https://doi.org/10.2337/db06-1665
Semple, Robert K. ; Halberg, Nils H. ; Burling, Keith ; Soos, Maria A. ; Schraw, Todd ; Luan, Jian'an ; Cochran, Elaine K. ; Dunger, David B. ; Wareham, Nicholas J. ; Scherer, Philipp E. ; Gorden, Phillip ; O'Rahilly, Stephen. / Paradoxical elevation of high-molecular weight adiponectin in acquired extreme insulin resistance due to insulin receptor antibodies. In: Diabetes. 2007 ; Vol. 56, No. 6. pp. 1712-1717.
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