Associations Between Plasma Zinc, Zinc Transporter-8 Gene And Type 2 Diabetes

Part One Associations of Plasma Zinc with Impaired Glucose Regulation and Type 2 DiabetesObjective:To explore the associations of plasma zinc level with impaired glucose regulation (IGR) and type 2 diabetes (T2D).Methods:Participants were consecutively recruited from first-time patients attending the outpatient clinics. The definitions of IGR, T2D, and NGT met the respective diagnostic criteria recommended by the World Health Organization (WHO) in 1999. Plasma zinc concentrations were measured, using inductively coupled plasma mass spectrometry.Results:We recruited 1,796 participants:218 newly diagnosed IGR patients,785 newly diagnosed T2D patients, and 793controls. Compared to controls, the individuals with IGR and T2D had lower plasma zinc concentrations. Lower odds for New-IGR and T2D versus controls were associated with higher plasma zinc concentrations, with a likely dose-response trend. After adjustment for age, sex, BMI, family history of diabetes, and hypertension, the multivariable OR for T2D across 10 ?g/dl higher plasma zinc was 0.87 (95% CI:0.85-0.90). Meanwhile, when comparing the highest with the lowest tertile of plasma zinc, higher plasma zinc concentrations were associated with decreased odds of T2D (adjusted OR= 0.06; 95% CI:0.04-0.11). Similar results were obtained in IGR and IGR&T2D groups.Conclusion:Plasma zinc concentrations were inversely associated with ORs for IGR and T2D.Part Two Associations of Zinc Transporter-8 Gene with Impaired Glucose Regulation and Type 2 DiabetesObjective:To explore the associations of SLC30A8 rs 13266634 with IGR and T2D.Methods:Subjects recruitment was described in part one. The SLC30A8 polymorphism rs13266634 was genotyped using an allelic discrimination assay-by-design TaqMan method.Results:Minor allele frequencies (T allele) in NGT, IGR, and T2D groups were 47.80,42.20, and 41.97, respectively. Compared to the T allele, after adjustment for age, sex, BMI, family history of diabetes and hypertension, the C allele was associated with increased odds of T2D (OR=1.27; 95% CI:1.08-1.51). The adjusted OR of T2D was 1.53 (95% CI:1.11-2.09) for homozygous CC genotypes compared with TT. Similar associations were found in IGR and IGR&T2D groups.Conclusion:The C allele of SLC30A8 rs13266634 was associated with increased ORs of IGR and T2D.Part Three Interaction between Plasma Zinc and Zinc Transporter-8 Gene for Type 2 DiabetesObjective:To explore the interaction between plasma zinc and SLC30A8 rs 13266634 for T2D.Methods:As described in parts one and two.Results:The association between plasma zinc and T2D was weaker in CC genotype carriers and CT genotype carriers than in TT genotype carriers. The adjusted ORs and 95% CIs of T2D per each 10?g/dl increment of plasma zinc were 0.93 (0.90-0.97),0.83 (0.80-0.87), and 0.78 (0.72-0.85), respectively (P for interaction= 0.01). A similar interaction was found for IGR&T2D, but not for IGR alone. When the joint effects were examined, individuals with TT genotype and the highest tertile of plasma zinc concentration had a much lower risk of IGR&T2D (OR=0.008; 95% CI:0.001-0.061) than those with CC genotype in the lowest zinc tertile.Conclusion:A strong interaction was observed for the SLC30A8 rs 13266634 variant and plasma zinc concentrations in relation to T2D. The inverse association between increasing plasma zinc concentrations and T2D could significantly attenuate in the CT and CC genotype groups compared with in the TT genotype group.