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Elevated Levels of High-Molecular-Weight Adiponectin in Type 1 Diabetes

The Medical Research Laboratories (H.L., K.K.A., J.F., A.F.), Clinical Institute, Aarhus University Hospital, DK-8000 Aarhus, Denmark; Steno Diabetes Center (L.T., P.R.), Gentofte DK-2820 Copenhagen, Denmark; and Department of Endocrinology (H.-H.P.), Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, Denmark

Address all correspondence and requests for reprints to: Professor Allan Flyvbjerg, M.D., D.M.Sc., The Medical Research Laboratories, Clinical Institute, Aarhus University Hospital, Nørrebrogade 44, DK-8000 Aarhus C, Denmark. E-mail: allan.flyvbjerg{at}dadlnet.dk.

Background: Several studies have shown that type 1 diabetic patients have elevated total levels of the adipocyte-derived adipocytokine adiponectin. However, adiponectin circulates in three different subforms, and the high-molecular-weight (HMW) subform is believed to be the primary biologically active form. The effects of the medium-molecular-weight (MMW) subform and the low-molecular-weight (LMW) subform are still unresolved.

Purpose: The objective of the study was to investigate the distribution of the three molecular subforms of adiponectin in well-characterized groups of type 1 diabetics with varying degrees of nephropathy as well as in healthy control subjects.

Study Population: Two hundred seven individuals were included: 58 type 1 diabetics with normoalbuminuria, 46 with microalbuminuria, 46 with macroalbuminuria, and 57 matched controls.

Methods: The HMW, MMW, and LMW subforms were measured using a validated in-house time-resolved immunoflourometric assay after separation by fast protein liquid chromatography.

Results: The absolute concentrations of total adiponectin and all subforms were higher in type 1 diabetic patients than healthy controls. However, the relative HMW fraction was up-regulated in type 1 diabetes (P < 0.001), whereas the MMW (P < 0.001) and LMW fractions (P < 0.05) were down-regulated, compared with controls. Accordingly, the increase in concentration of total adiponectin was primarily caused by a major increase of the HMW subform. Levels of total adiponectin and the HMW subform (absolute and relative) were generally unaffected by nephropathy status defined by urinary albumin excretion rate.

Conclusion: Type 1 diabetes per se is associated with higher adiponectin levels than healthy subjects. This increase is mainly explained by an elevation in the HMW subform. The elevation is unaffected by gender and diabetic kidney disease.