Fajans S S, Bell G I, Bowden D W, Halter J B, Polonsky K S
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0354, USA.
Diabet Med. 1996 Sep;13(9 Suppl 6):S90-5.
MODY is a sub-type of NIDDM. It is characterized by an early age of onset and autosomal dominant mode of inheritance. These features, and the availability of large multigenerational pedigrees, make MODY useful for genetic studies of diabetes. In the large 5-generational RW pedigree, MODY is tightly linked to genetic markers on chromosome 20q. Affected subjects in this family show abnormalities of carbohydrate metabolism, varying from impaired glucose tolerance (IGT) to severe diabetes. Approximately 30% of diabetic subjects become insulin-requiring, and vascular complications occur. MODY is also linked to the glucokinase gene on chromosome 7p and many different mutations associated with MODY have been identified in this gene. MODY, due to mutations in the glucokinase gene, is a relatively mild form of diabetes with mild fasting hyperglycaemia and IGT in the majority. Clinical investigative studies indicate that the genetic or primary defect in MODY is characterized by deranged and deficient insulin secretion and not by insulin resistance. There are quantitative and qualitative differences in insulin secretory defects which differentiate subjects with MODY due to mutation in the gene on chromosome 20q from those with glucokinase mutations. These differences correlate with the severity of diabetes between these two genetic forms of MODY.
青少年发病的成年型糖尿病(MODY)是非胰岛素依赖型糖尿病(NIDDM)的一种亚型。其特点是发病年龄早,呈常染色体显性遗传模式。这些特征以及大型多代系谱的存在,使得MODY对糖尿病的遗传学研究很有用。在大型五代RW系谱中,MODY与20号染色体q臂上的遗传标记紧密连锁。这个家族中的患病个体表现出碳水化合物代谢异常,从糖耐量受损(IGT)到严重糖尿病不等。大约30%的糖尿病患者需要胰岛素治疗,并且会出现血管并发症。MODY还与7号染色体p臂上的葡萄糖激酶基因有关,并且在该基因中已经鉴定出许多与MODY相关的不同突变。由于葡萄糖激酶基因突变导致的MODY是一种相对较轻的糖尿病形式,大多数患者有轻度空腹高血糖和IGT。临床研究表明,MODY的遗传或原发性缺陷的特征是胰岛素分泌紊乱和不足,而非胰岛素抵抗。胰岛素分泌缺陷存在数量和质量上的差异,这将20号染色体q臂上基因突变导致的MODY患者与葡萄糖激酶基因突变导致的MODY患者区分开来。这些差异与这两种遗传形式的MODY之间糖尿病的严重程度相关。