Objective To investigate a potential relationship between Solute carrier family 30 （zinc transporter） member 8 （SLC3OAS） rs13266634 variant and efficacy of rosiglitazone or repaglinide in treating newly diagnosed Chinese type 2 diabetes patients. Methods A total of 209 diabetic patients without any antihyperglycemic history were recruited and treated with repaglinide or rosiglitazone randomly for 48 weeks （104 and 105 patients, respectively）. Anthropometric measurements and clinical laboratory tests were carried out before and after the treatment. An non-synonymous variant rs13266634 was genotyped by matrix-assisted laser desorption ionization-time of flight mass spectroscopy. Results Ninety-one patients in repaglinide group and ninety-three patients in rosiglitazone group completed the study. 6 value of homeostasis model assessment of beta cell function （HOMA-B） and 6 value of fasting proinsulin levels were statistically significant between three genotype groups （P=0.0149 and 0.0246, respectively） after rosiglitazone treatment. However, no genotype association was observed in the repaglinide or rosiglitazone group with other parameters. Conclusion The SLC3OA8 variant was associated with the efficacy of insulin sensitizer monotherapy on insulin secretion in patients with newly diagnosed type 2 diabetes mellitus in Shanghai, China.
Background KCNJ11, ABCC8, PPARG, and HNF4A have been found to be associated with type 2 diabetes in populations with different genetic backgrounds. The aim of this study was to test, in a Chinese Han population from Beijing, whether the genetic variants in these four genes were associated with genetic predisposition to type 2 diabetes. Methods We studied the association of four representative SNPs in KCNJ11, ABCC8, PPARG, and HNF4A by genotyping them using ABI SNaPshot Multiplex System in 400 unrelated type 2 diabetic patients and 400 unrelated normoglycaemic subjects. Results rs5219（E23K） in KCNJ11 was associated with genetic susceptibility to type 2 diabetes （OR=1.400 with 95% CI 1.117 1.755, P=0.004 under an additive model, 0R=1.652 with 95% CI 1.086 2.513, P=0.019 under a recessive model, and OR=1.521 with 95% Cl 1.089 2.123, P=0.014 under a dominant model） after adjusting for sex and body mass index （BMI）. We did not find evidence of association for ABCC8 rs1799854, PPARG rs1801282 （Pro12Ala） and HNF4A rs2144908. Genotype-phenotype correlation analysis revealed that rs1799854 in ABCC8 was associated with 2-hour postprandial insulin secretion （P=0.005） after adjusting for sex, age and BMI. Although no interactions between the four variants on the risk of type 2 diabetes were detected, the multiplicative interaction between PPARG Pro12Ala and HNF4A rs2144908 was found to be associated with 2-hour postprandial insulin （P=-0.004 under an additive model for rs2144908; and P=0.001 under a dominant model for rs2144908） after adjusting for age, sex and BMI, assuming a dominant model for PPARG Pro12Ala. Conclusions Our study replicated the association of rs5219 in KCNJ11 with type 2 diabetes in Chinese Han population in Beijing. And we also observed that ABCC8 as well as the interaction between PPARG and HNF4A may contribute to post-challenge insulin secretion.
WANG Fang HAN Xue-yao REN Qian ZHANG Xiu-ying HAN Ling-chuan LUO Ying-ying ZHOU Xiang-hai JI Li-nong
目的探讨蛋白酪氨酸磷酸酶抗体(IA-2A)对成人隐匿性自身免疫性糖尿病(LADA)的诊断价值。方法采用放射配体法检测2 027例初诊2型糖尿病(T2DM)患者的IA-2A和谷氨酸脱羧酶抗体(GAD-Ab),分析IA-2A在初诊T2DM患者中的分布及其与临床特征的关系。结果初诊T2DM患者中IA-2A阳性检出率低于GAD-Ab阳性检出率(2.2% vs 10.6%,P<0.01)。联合GAD-Ab和IA2A检测,可使LADA阳性检出率达11.5%。IA-2A在低体重、低C肽水平患者中阳性检出率高;随着起病年龄增大,IA-2A阳性检出率下降(P<0.05)。与T2DM组比较,单独IA-2A阳性患者使用胰岛素治疗的比例高(P<0.05)。高滴度IA-2A阳性LADA患者具有起病年龄小(P<0.01)、体重轻、高血压比例低、空腹C肽低、合并GAD-Ab阳性和使用胰岛素比例高(P<0.05)等特点。结论 IA-2A检测对LADA具有辅助诊断价值,与GAD-Ab联合检测可提高LADA诊断的敏感性。
