Barnett A H, Pyke D A
Clin Endocrinol Metab. 1986 Nov;15(4):715-26. doi: 10.1016/s0300-595x(86)80070-6.
Duration of disease is the major susceptibility factor for microangiopathy. Microangiopathy does not occur without the metabolic abnormality of diabetes and there is much circumstantial evidence to implicate poor diabetic control in its pathogenesis. The rate of development and severity of complications, however, are variable even in patients with apparently similar control and about 25% of diabetics will never develop clinical evidence of microangiopathy. Studies of identical twins suggest a genetic component in the pathogenesis of retinopathy in NIDDM, and less so in IDDM, but increased capillary basement membrane thickness does not occur in the non-diabetic identical co-twins of insulin dependent diabetics. There may also be genetic heterogeneity not only of diabetes, but also of its complications, although for a given type of diabetes the prevalence of microangiopathy is often very similar in different racial groups. Associations between several different HLA molecules (particularly DR4) and microangiopathy in IDDM have been reported but not consistently confirmed. Recently the finding of an increased frequency of the B3 allotype of the fourth component of complement C4B3 in subjects with retinopathy has suggested that there is an HLA linked association. Both complement and the immunoglobulins are concerned with humoral immunity and the report of an association between a phenotype of the IgG heavy chain markers on chromosome 14 and retinopathy is of particular interest. These associations appear to be additive but independent. These reports need confirmation but provide the best evidence we have for an immunogenetic component (HLA and non-HLA linked) of the aetiology of microangiopathy, at least in IDDM. The studies of identical twins, HLA and Gm associations provide good evidence that genetic factors are involved in susceptibility to microangiopathy, at least in some diabetics, although the most relevant genes may not have been identified. Searches for better genetic markers must continue in order to identify those patients at increased risk of developing microangiopathy.
疾病持续时间是微血管病变的主要易感因素。没有糖尿病的代谢异常就不会发生微血管病变，而且有很多间接证据表明糖尿病控制不佳与其发病机制有关。然而，即使在控制情况明显相似的患者中，并发症的发展速度和严重程度也各不相同，约25%的糖尿病患者永远不会出现微血管病变的临床证据。对同卵双胞胎的研究表明，非胰岛素依赖型糖尿病视网膜病变的发病机制中有遗传因素，而胰岛素依赖型糖尿病中遗传因素的作用较小，但胰岛素依赖型糖尿病患者的非糖尿病同卵双胞胎中并未出现毛细血管基底膜厚度增加的情况。不仅糖尿病可能存在遗传异质性，其并发症也可能存在遗传异质性，尽管对于某一特定类型的糖尿病，微血管病变的患病率在不同种族群体中通常非常相似。已有报道称胰岛素依赖型糖尿病中几种不同的HLA分子（尤其是DR4）与微血管病变有关，但尚未得到一致证实。最近发现视网膜病变患者中补体C4B3第四成分的B3同种异型频率增加，这表明存在HLA连锁关联。补体和免疫球蛋白都与体液免疫有关，14号染色体上IgG重链标记物表型与视网膜病变之间关联的报道尤其令人关注。这些关联似乎具有累加性但相互独立。这些报道需要得到证实，但它们为微血管病变病因中的免疫遗传成分（HLA连锁和非HLA连锁）提供了我们目前最好的证据，至少在胰岛素依赖型糖尿病中是这样。对同卵双胞胎、HLA和Gm关联的研究提供了充分证据，表明遗传因素参与了微血管病变的易感性，至少在一些糖尿病患者中是如此，尽管最相关的基因可能尚未确定。必须继续寻找更好的遗传标记，以便识别那些发生微血管病变风险增加的患者。
