Jitapunkul S, Chalaprawat M, Bunnag S, Bhuvapanich S, Kangkaya V, Pasatrat S, Vajanamarhutue C
Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
J Med Assoc Thai. 1991 Feb;74(2):80-6.
Many investigators suggest that insulin resistance of the peripheral tissues is the primary defect that results in non-insulin dependent diabetes mellitus (NIDDM). It is also generally accepted that multifactorial controls, playing in concert for gene expression trigger this disease. Previous research reports indicated that uric acid metabolism plays a role in the pathogenesis of NIDDM. To investigate this hypothesis, we studied 53 NIDDM patients by using a double blind cross over control study, of allopurinol and placebo administration. We found a statistically significant elevation in the level of hemoglobin A1c (HbA1c) after the allopurinol intervention period of 12 weeks compared with the placebo period of the same duration (p less than 0.003). The elevation was also found in a subgroup with Body Mass Index (BMI) less than 25 kg/m2 (p less than 0.001) and BMI more than or equal to 25 kg/m2 (p less than 0.05). No statistically significant differences between fasting plasma glucose, glucose tolerance test, serum insulin, total cholesterol, triglycerides, high density lipoprotein cholesterol, creatinine, prior to and after use of allopurinol were noted except for serum uric acid (p less than 0.001). No relationship between changes in HbA1c and changes in uric acid, analysed by linear regression analysis and correlation was demonstrated (r = 0.15, p = 0.29). We conclude that the changing of hemoglobin A1c may be a direct effect of allopurinol or support the role of uric acid in the pathogenesis of NIDDM.
许多研究人员认为，外周组织的胰岛素抵抗是导致非胰岛素依赖型糖尿病（NIDDM）的主要缺陷。人们也普遍认为，多种因素共同作用于基因表达会引发这种疾病。先前的研究报告表明，尿酸代谢在NIDDM的发病机制中起作用。为了验证这一假设，我们采用双盲交叉对照研究，对53例NIDDM患者给予别嘌醇和安慰剂进行治疗。我们发现，与相同疗程的安慰剂期相比，别嘌醇干预12周后糖化血红蛋白（HbA1c）水平有统计学意义的升高（p<0.003）。在体重指数（BMI）小于25kg/m2的亚组（p<0.001）和BMI大于或等于25kg/m2的亚组（p<0.05）中也发现了这种升高。除血清尿酸外（p<0.001），别嘌醇使用前后空腹血糖、葡萄糖耐量试验、血清胰岛素、总胆固醇、甘油三酯、高密度脂蛋白胆固醇、肌酐之间均未发现统计学意义的差异。通过线性回归分析和相关性分析，未发现HbA1c变化与尿酸变化之间存在关联（r=0.15，p=0.29）。我们得出结论，HbA1c的变化可能是别嘌醇的直接作用，或支持尿酸在NIDDM发病机制中的作用。
