Adiponectin

Introduction
White adipose tissue can elaborate a variety of molecules with paracrine and endocrine actions of proven or potential relevance to body weight and fuel metabolism. Most abundant of these secreted proteins is adiponectin, a multimeric hormone with homology to complement factor 1q that circulates in adults at levels that are inversely related to the total WAT mass. Circulating levels of adiponectin have been shown to correlate negatively with insulin sensitivity in a wide range of human populations and to be elevated on treatment with thiazolidinediones, and low adiponectin levels have been shown to identify those at future risk of type 2 diabetes and vascular disease.
Because of the stability and long half life of adiponectin it may be used as a marker of insulin resistance in situations where assay of insulin is impossible or difficult to interpret (e.g. in the non fasting state).

In severe insulin resistance adiponectin is generally very low. An exception is states of acquired or genetic loss of insulin receptor function, in which adiponectin is high. This can be used to direct subsequent investigations.

Clinical Indications
1. Diagnosis of Insulin Receptor Dysfunction in Severe Insulin Resistance.

Genetic defects of the insulin receptor, or antibodies directed against the insulin receptor, give rise to a minority of cases of severe insulin resistance. Identification of causative mutations in the insulin receptor gene permits pre-emptive screening of other family members, and also allows antenatal diagnosis where desired, while detection of anti-insulin receptor antibodies permits specific immunomodulatory treatments directed against the causative antibodies. However the insulin receptor gene is a large gene, and detection of insulin receptor antibodies is onerous, making screening of all severely insulin resistant patients impossible. Use of serum adiponectin to refine the pre-test probability of loss of insulin receptor function (an adiponectin level below 5 mg/l in the context of severe insulin resistance has a 97% negative predictive value for insulin receptor mutation or antibodies, while a level above 5mg/l has an 82% positive predictive value for insulin receptor dysfunction) permits directed screening with a high likelihood of a positive result, and should be part of the routine work up of patients with severe insulin resistance.

2. Use as a marker of insulin resistance and vascular risk
The long half life of adiponectin and its strong correlation with insulin sensitivity means that it is a useful marker of insulin resistance as well as vascular risk. This is likely to be increasingly exploited in routine clinical practice.

Method Information
2-site time resolved fluorescence immunoassay (DELFIA)

Patient Preparation
No special requirements

Sample Requirements
0.5mls of serum, EDTA or Lithium heparin anti-coagulated plasma

Sample Handling
Separate with 1 hour and freeze. Send frozen.

Interpretation
Appropriate Gender, Age and BMI related Reference range data will be provided

Reference Ranges

90TH CENTILE / (mg/L) MALE FEMALE
BMI <25 2.6-12.6 4.4-17.7
BMI 25-30 2.4-10.6 3.5-15.5
BMI 30-35 2.8-9.9 2.6-14.9

Quality Assessment
No EQA scheme available

Centres offering this assay

  • Cambridge Addenbrooke’s Hospital Endocrine Laboratory
  • References
    Lara-Castro C, Fu Y, Chung BH, Garvey WT. Adiponectin and the metabolic syndrome: mechanisms mediating risk for metabolic and cardiovascular disease. Curr Opin Lipidol. 2007 Jun;18(3):263-70.

    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. Paradoxical elevation of high-molecular weight adiponectin in acquired extreme
    insulin resistance due to insulin receptor antibodies. Diabetes. 2007 Jun;56(6):1712-7.

    Hemmila I, Dakubu S, Mukkala V-M, Siitari H & Lovgren T: Europium as a label in time-resolved immunofluoroimmunometric assay. Anal. Biochem. 137, 335-343 (1984)

    Suonpaa M, Merkela E, Stahlberg T & Hemmila I: Europium-labelled Streptavidin as a highly sensitive universal label. J. Immunol. Meth. 149, 247-253 (1992)

     

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