Suzuki S
3rd Department of Internal Medicine, Tohoku University, School of Medicine, Sendai.
Rinsho Byori. 1995 May;43(5):463-7.
NIDDM is likely to have a major genetic component in view of the different prevalence between ethnic groups, the familial clustering, and the high concordance in monozygotic twins. Linkage analysis of extended pedigrees of patients with maturity-onset diabetes of the young (MODY) identified the glucokinase gene mutations. Specific phenotypes have also led to the discovery of the insulin gene mutations in patients with high insulin or proinsulin levels, to the insulin receptor mutations in patients with marked insulin resistance, and to the mutations in mitochondrial DNA associated with deafness and maternal inheritance. These four types of diabetogenic gene mutations account for only a minor proportion of NIDDM. Direct screening for mutations in candidate genes with single-strand conformation polymorphism or heteroduplex screening or with direct sequencing in the diabetic patients with the appropriate pathophysiological abnormality can be a successful strategy. Genetic diagnosis provides clear definite diagnosis and specific therapies, such as IGF-1 for the insulin receptor mutations and coenzyme Q10 for the mitochondrial gene mutations.
鉴于不同种族群体之间的患病率差异、家族聚集性以及同卵双胞胎的高一致性，非胰岛素依赖型糖尿病（NIDDM）可能具有主要的遗传成分。对年轻的成年发病型糖尿病（MODY）患者的扩展家系进行连锁分析，确定了葡萄糖激酶基因突变。特定的表型还导致在高胰岛素或胰岛素原水平的患者中发现胰岛素基因突变，在显著胰岛素抵抗的患者中发现胰岛素受体基因突变，以及在与耳聋和母系遗传相关的线粒体DNA中发现突变。这四种致糖尿病基因突变仅占NIDDM的一小部分。对于具有适当病理生理异常的糖尿病患者，采用单链构象多态性或异源双链筛查或直接测序对候选基因中的突变进行直接筛查可能是一种成功的策略。基因诊断可提供明确的诊断和特异性治疗，例如针对胰岛素受体突变的胰岛素样生长因子-1（IGF-1）和针对线粒体基因突变的辅酶Q10。
