Hypoadiponectinemia is associated with progression toward type 2 diabetes and genetic variation in the ADIPOQ gene promoter.
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.


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.
Schwarz
Peter E H
PE
Department of Endocrinopathies and Metabolic Diseases, Medical Faculty Carl-Gustav-Carus of the Technical University Dresden, Medical Clinic III, Building 46, Room 10, Fetscherstrasse 74, 01309, Dresden, Germany. pschwarz@rcs.urz.tu-dresden.de
Towers
Gordon W
GW
Fischer
Sabine
S
Govindarajalu
Suresh
S
Schulze
Jan
J
Bornstein
Stephan R
SR
Hanefeld
Markolf
M
Vasseur
Francis
F
D052242:Adiponectin / Q000097:blood* / Q000235:genetics*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology* / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005951:Glucose Tolerance Test; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011446:Prospective Studies
D052242:Adiponectin