| Part 1. Associations of Plasma Uric Acid with T2DMObjective: To explore the associations of plasma uric acid level and T2 DM.Methods: Participants taking oral glucose tolerance test for screening of T2 DM in endocrinology clinic were consecutively recruited to IGR, T2 DM and NGT group according to the diagnostic criteria recommended by World Health Organization(WHO) in 1999. Plasma uric acid concentrations were measured by Automatic biochemical analyzer(uricase-peroxidase method).Results:3685 subjects were recruited in the study, including 1322 T2 DM patients, 775 IGR patients and 1588 control subjects, with 59.91%, 63.10% and58.06% male subjects in each group. The median concentration of uric acid were4.69(3.91-5.72) mg/d L, 5.09(4.07-6.18) mg/d L and 5.22(4.26-6.27) mg/d L,respectively. Compared to the control group, participants with IGR and T2 DM had higher uric acid concentra- tions(P < 0.001).Plasma uric acid was divided into tertiles according to the distribution of plasma uric acid. Higher plasma uric acid concentration was associated with higher risk of developing IGR and T2 DM. After adjustment for age, sex, BMI, family history of diabetes and hypertension, the highest tertile of plasma uric acid comparing with the lowest tertile, had a increased risk of IGR and T2 DM with OR = 1.561(1.206-2.020)and OR = 1.236(0.995-1.535), respectively.Subgroup analysis according to sex of association of plasma uric acid withT2 DM suggests: after adjustment of above confunders, the association between serum uric acid level and risk T2 DM presents a trend of U shape. Namely, with the increasing of uric acid, the risk of developing T2 DM decreases.The adjusted ORs of the highest quantile compared with the lowest quantile of plasma uric acid concentration between 3.95-7.0 mg/d L for T2 DM and IGR & T2 DM in female were 2.614(1.805-3.787) and 2.842(2.022-3.993).Conclusion:Elevated plasma uric acid concentrations were associated with increased ORs for T2 DM and a U shaped association between plasma uric acid and risk of T2 DM was found in subgroup analysis of different sex. Difference existed in male and female subjects.The highest quantile compared with the lowest quantile of plasma uric acid concentration between 3.95-7.0 mg/d L could significantly increase the risk of T2 DM.Part Two. Associations of GCKR Polymorphism with T2DMObjective: To explore the associations of GCKR rs780094 and T2 DM.Methods: Subjects recruitment was described in part one. Polymorphism of locus rs780094 in gene GCKR was genotyped by Taq Man allelic discrimination real time PCR method.Results :Minor allele frequencies(C allele) in NGT, IGR and T2 DM groups were 48.7%, 49.0% and 51.3%, respectively. After adjustment for age, sex, BMI,family history of diabetes and hypertension, the ORs for subjects with T allele of delveloping IGR and T2 DM were 0.907(0.783-1.050) and 0.992(0.874-1.127)compared to the C allele. The adjusted ORs of IGR and T2 DM were0.828(0.618-1.109) and 0.983(0.766-1.261) for homozygous TT genotypes compared with CC genotypes. The adjusted ORs of IGR and T2 DM were 0.917(0.723-1.164)and 0.911(0.739-1.122) for CT+TT genotypes compared with CC genotypes.Nevertheless, the association between GCKR rs780094 polymorphism and risk of developing T2 DM and IGR did not reach the threshold of significance.Conclusion:T allele of GCKR rs780094 was associated with decreased ORs of IGR and T2 DM. The risk of IGR and T2 DM were decreased by 9.3% and 0.8% in subjects with T allele.Part Three. Interaction between Plasma Uric acid and GCKR polymorphism for T2DMObjective: To explore the interaction between plasma uric acid and GCKR rs780094 with T2 DM.Methods: As described in parts one and two.Results:In female subjects, strong interaction for plasma uric acid concentration and GCKR rs780094 variant in relation to T2 DM was observed(Pinteraction = 0.031). CC genotype of GCKR rs780094 enhanced the association between plasma uric acid and risk of T2DM; and elevated plasma uric acid also enhanced the destructive effects of CC genotype on T2 DM. No interaction was found for plasma uric acid(? 6.00 mg/d L)and polymorphism of GCKR rs780994 with T2 DM in male subjects(Pinteraction > 0.05).Conclusion:A strong interaction was observed for the GCKR rs780094 variant and plasma uric acid(3.95-7.00 mg/d L) in relation to T2 DM in female subjects. CC genotype of GCKR rs780094 enhanced the association between plasma uric acid and risk of T2DM; and elevated plasma uric acid also enhanced the destructive effects of CC genotype on T2 DM. No interaction was found for plasma uric acid(? 6.00 mg/d L)and polymorphism of GCKR rs780994 with T2 DM in male subjects(Pinteraction > 0.05). |
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