Response to Costa

I am very grateful to Costa et al. (1) for their letter in this issue of Diabetes Care, because their findings give me the opportunity to clarify several important points. Our recent paper (2) associated ACE gene insertion/deletion (I/D) polymorphism with metabolic syndrome (MS) in Chinese type 2 diabetic patients. Although Costa et al. showed a similar prevalence of MS in Brazilian type 2 diabetic patients, they did not find any association between ACE gene I/D polymorphism and MS. While we believe their findings are interesting, we do not believe that they can be used to support their claim that our findings came about by chance. The prevalence of MS in patients with type 2 diabetes among different ethnic populations could not be evaluated and compared until MS was defined by the World Health Organization in 1998 (3). According to Zimmet et al. (4), the incidence of type 2 diabetes is changing and ethnic differences exist in global distribution. Furthermore, while the incidence of type 2 diabetes may be similar among Chinese, Caucasian, and Brazilian populations, the prevalence of individual components of MS are quite different. While the prevalence of obesity, hypertension, and dyslipidemia (WHO criteria) are similar in our study and were comparable to those of the Botnia study in Finland and Sweden (5), the prevalence of “microalbumiura-nephropathy” differed. The prevalence of nephropathy was higher in Chinese than Caucasians in the Botnia group (41 vs. 17%). In fact, ethnic differences in macrovascular and microvascular morbidity and mortality have already been reported in one WHO MSVDD study (6), which showed that the prevalence of proteinuria-albuminuria renal failure was especially higher in Asian Chinese than in other populations studied. That same WHO Multinational Study of Vascular Disease in Diabetes (MSVDD) study also revealed that the major cause of death in Asian type 2 diabetic subjects was stroke, while the major cause of death in Western type 2 diabetic populations was ischemic coronary disease. Thus, based on our study and those of others, it is clear that ethnic differences exist in the phenotype presentation of MS, and from these differences it may be implied that the genetic mechanism of type 2 diabetes is also different. It is important to note that Costa et al. mention that the allele frequency of ACE gene I/D polymorphism varies according to the ethnic group.

ACE gene I/D polymorphism is associated with MS in our study mostly because we associated it with nephropathy. We have found ACE gene I/D polymorphism to be strongly associated with nephropathy in our patients when only 300 cases were studied. The more cases we collected, the stronger the statistical significance. Using correlation analysis for each component of MS, we found the correlation between ACE gene I/D polymorphism and dyslipidemia to be weak, but the association between ACE gene I/D polymorphism and MS to be strong. In fact, the association of ACE gene I/D polymorphism with individual components of MS and major cardiovascular diseases has been extensively reviewed (7), and our results are quite similar to those of others. Our only novel finding was that there was a strong association between the ACE gene I/D polymorphism and nephropathy in Chinese subjects with type 2 diabetes, thus contributing to those subjects with MS. Although the prevalence of the individual components of MS are not actually shown by Costa et al., we believe that if their prevalence of individual components of MS were revealed, the differences between Chinese and Brazilian subjects with regard to MS would be found. Costa et al. found no association between ACE gene I/D polymorphism with individual components of MS, and no association with MS at all. Thus, the major difference between our article and the article by Costa et al. may be the prevalence of nephropathy and the significance of association between the ACE gene I/D polymorphism and nephropathy. We conclude that ethnic and genetic differences do exist in the phenotype presentation of MS.