Total and High-Molecular Weight Adiponectin in Relation to Metabolic Variables at Baseline and in Response to an Exercise Treatment Program: Comparative Evaluation of Three Assays: Response to Bluher et al.

doi:10.2337/dc07-0398

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Total and High–Molecular Weight Adiponectin in Relation to Metabolic Variables at Baseline and in Response to an Exercise Treatment Program: Comparative Evaluation of Three Assays

Response to Blüher et al.

Maximilian von Eynatten, MD¹, Philipp M. Lepper, MD² and Per M. Humpert, MD³

¹ Department of Nephrology, Technical University Munich, Ismaningerstr, Munich, Germany
² Department of Intensive Care Medicine, University of Bern, Bern, Switzerland
³ Department of Medicine I and Clinical Chemistry, Heidelberg University, Im Neuenheimer Feld, Heidelberg, Germany

Address correspondence to Maximilian von Eynatten, Department of Nephrology, Technical University Munich, Ismaningerstr 22, 81675 Munich, Germany. E-mail: maximilian.eynatten{at}lrz.tum.de

Recently, increasing attention has been paid to the relationshipbetween multimeric forms of adiponectin and metabolic variablesto assess the metabolic significance of high–molecularweight (HMW) adiponectin. Blüher et al. (1) investigatedassociations between total adiponectin and HMW with insulinresistance and the metabolic syndrome. The study did not demonstratethe superiority of HMW over total adiponectin in assessing insulinsensitivity that was previously reported in larger groups (2,3).

We studied 328 Caucasian men and women (114 non–insulin-resistant,101 insulin-resistant, and 113 type 2 diabetic patients). Adiponectinconcentrations were detected using the enzyme-linked immunosorbentassay, described by Blüher et al. (ALPCO Diagnostics, Salem,NH). Total and HMW adiponectin showed significant negative correlationswith the metabolic syndrome (r = –0.31 and –0.45,respectively) and homeostasis model assessment of insulin resistance(r = –0.15 and –0.23, respectively). Receiver operatingcharacteristic curves were calculated to discriminate betweensubjects with (n = 144) and without (n = 184) the metabolicsyndrome, as defined by the International Diabetes Federationcriteria. The area under the curve for HMW adiponectin was significantlylarger than that for total adiponectin (HMW 0.763 [95% CI 0.711–0.814]vs. total 0.679 [0.621–0.737] adiponectin, P = 0.015).With respect to identification of insulin resistance (definedby homeostasis model assessment of insulin resistance >2.5,excluding patients treated with insulin), HMW adiponectin predictedthis condition better than total adiponectin. Again, the areaunder the curve for HMW adiponectin was significantly largerthan that for total adiponectin (HMW 0.832 [95% CI 0.771–0.892]vs. total 0.692 [0.612–0.791] adiponectin, P = 0.002).

The data presented here and in previous clinical studies (2,3)clearly show superiority of HMW adiponectin over total adiponectinin predicting the metabolic syndrome trait cluster. In addition,Lara-Castro et al. (2) found significant correlations of adiponectinparticle size, with insulin sensitivity detected in clamp studies.These clinical and experimental data are in contrast to thedata presented by Blüher et al. that do not show any associationsbetween HMW adiponectin and markers of the metabolic syndrome.Associations were previously reported in large independent cohorts,with HDL presenting particularly strong correlation coefficients(2,3). In our study, HMW adiponection accounted for 37.7% ofHDL variation. Hence, potential confounders, such as currentmedication (e.g., fibrates or thiazolidinediones known to affectadiponectin levels) or technical limitations may have influencedthe data reported by Blüher et al. Prospective clinicalstudies will be needed to clarify the role of HMW and totaladiponectin for the prediction of clinical end points associatedwith the metabolic syndrome.

References

Blüher M, Brennan AM, Kelesidis T, Kratzsch J, Fasshauer M, Kralisch S, Williams CJ, Mantzoros CS: Total and high-molecular weight adiponectin in relation to metabolic variables at baseline and in response to an exercise treatment program: comparative evaluation of three assays. Diabetes Care 30:280–285, 2007[Abstract/Free Full Text]
Lara-Castro C, Luo N, Wallace P, Klein RL, Garvey WT: Adiponectin multimeric complexes and the metabolic syndrome trait cluster. Diabetes 55:249–259, 2006[Abstract/Free Full Text]
Hara K, Horikoshi M, Yamauchi T, Yago H, Miyazaki O, Ebinuma H, Imai Y, Nagai R, Kadowaki T: Measurement of the high-molecular weight form of adiponectin in plasma is useful for the prediction of insulin resistance and metabolic syndrome. Diabetes Care 29:1357–1362, 2006[Abstract/Free Full Text]