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Hypoadiponectinemia Is Associated With Progression Toward Type 2 Diabetes and Genetic Variation in the ADIPOQ Gene Promoter

¹ Department of Endocrinopathies and Metabolic Diseases, Medical Faculty Carl-Gustav-Carus of the Technical University Dresden, Dresden, Germany
² Centre for Genome Research, North-West University, Pretoria, South Africa
³ Center for Clinical Studies, Center for Clinical Studies–Technical University Dresden, Dresden, Germany
⁴ Centre National de la Recherche Scientifique Unité Mixte de Recherche 8090 and EA 2694 University Hospital of Lille, Lille, France

Address correspondence and reprint requests to Dr. Peter E.H. Schwarz, Medical Faculty Carl-Gustav-Carus of the Technical University Dresden, Medical Clinic III, Building 46, Room 10, Fetscherstrasse 74, 01309, Dresden, Germany. E-mail: pschwarz{at}rcs.urz.tu-dresden.de

OBJECTIVE—Adiponectin encoded by the ADIPOQ gene modulates insulin sensitivity and glucose homeostasis. The aim of the current study was to investigate whether ADIPOQ gene variants in the promoter region predict adiponectin levels and type 2 diabetes progression.

RESEARCH DESIGN AND METHODS—A total of 550 subjects with increased risk of type 2 diabetes were investigated; they underwent a 75-g oral glucose tolerance test, repeated after 3 years. Adiponectin levels were analyzed, and two ADIPOQ promoter variant single nucleotide polymorphisms, –11391G>A and –11377C>G, were genotyped.

RESULTS—Tertiles of the adjusted adiponectin levels were associated with single nucleotide polymorphism –11391G>A and –11377C>G haplotypes (P < 0.0001). Carriers of the intermediate/high-level haplotype combination showed a bisected diabetes risk at the 3-year follow-up and were characterized by a "regression" of glucose tolerance. Evolution of disease status correlates with preexisting low adiponectin levels at inclusion rather than with variation in adiponectin levels.

CONCLUSIONS—We present data that gene variants in the ADIPOQ promoter region are associated with variations in adiponectin levels and thus with future type 2 diabetes and disease progression.

Abbreviations: IFG, impaired fasting glucose • IGT, impaired glucose tolerance • NGT, normal glucose tolerance • OGTT, oral glucose tolerance test • SNP, single nucleotide polymorphism

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