Serum aryl hydrocarbon receptor ligand activity is associated with insulin resistance and resulting type 2 diabetes.
OBJECTIVE
Dioxin or dioxin-like compounds are ligands of the aryl hydrocarbon receptor (AhR), which is a ligand-activated nuclear transcription factor. There are limited studies about the association of serum AhR ligand activities and T2DM. Our objective was to investigate the association of serum AhR ligand activities with T2DM and its related metabolic parameters.


METHODS
This case-control study involved 83 subjects with T2DM as well as age-, sex-, and body mass index (BMI)-matched subjects with impaired glucose tolerance (IGT, n = 130) and normal glucose tolerance (NGT, n = 83). Serum AhR ligand activities were measured using a cell-based AhR ligand assay and standardized as 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TCDDeq, pmol/l).


RESULTS
The T2DM group had the highest AhR ligand activities compared to the IGT and NGT groups [median (interquartile range), 68.1 (53.1, 81.5), 60.2 (45.8, 75.1), and 53.3 (46.1, 63.7) pmol/l, respectively; P = 0.003]. In the multivariate analysis, the log2-transformed TCDDeq levels were significantly associated with the risk of T2DM after adjusting for age, sex, and BMI (odds ratio 2.26, 95 % confidence interval 1.34-3.82; P = 0.002). In nondiabetic subjects, serum AhR ligand activities showed a positive correlation with fasting glucose and insulin concentrations and the homeostasis model assessment of insulin resistance, but showed a negative correlation with adiponectin concentrations.


CONCLUSIONS
Serum AhR ligand activities were higher in the T2DM group and were correlated with the parameters of insulin resistance. Further investigation is required to elucidate the causal relationship between AhR ligand activity and T2DM.
Department of Internal Medicine, Seoul National University Hospital, Seoul, 110-744, Korea.
Eun
E
Roh
Soo Heon
SH
Kwak
Hye Seung
HS
Jung
Young Min
YM
Cho
Youngmi Kim
YK
Pak
Kyong Soo
KS
Park
Seong Yeon
SY
Kim
Hong Kyu
HK
Lee
D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000209:etiology / Q000378:metabolism; D004147:Dioxins / Q000009:adverse effects* / Q000097:blood / Q000737:chemistry; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008024:Ligands; D008297:Male; D008875:Middle Aged; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism
D001786:Blood Glucose; D004147:Dioxins; D007328:Insulin; D008024:Ligands; D018336:Receptors, Aryl Hydrocarbon