Diabetes mellitus with mitochondrial gene mutations in Japan

Ann N Y Acad Sci. 2004 Apr;1011:185-92. doi: 10.1007/978-3-662-41088-2_19.


Diabetes mellitus due to the mitochondrial DNA 3243(A-G) mutation is reported to represent 0.5-1% of the general diabetic population in Japan. To further elucidate the clinical symptoms and course of diabetes mellitus with the 3243 mutation, we undertook a nationwide cross-sectional case-finding study and observational study of a genetically defined subject group. One hundred sixteen Japanese diabetic patients with the mutation were registered and analyzed. The patients had a higher maternal inheritance of diabetes or deafness, short stature, thin habitus, and early middle-aged onset of diabetes or deafness. Eighty-six percent of the patients required insulin therapy because of progressive insulin secretory defect. Although half of the patients had the phenotype of type 1 diabetes or slowly progressive type 1 diabetes, the patients lacked the presence of autoantibodies to glutamic acid decarboxylase. Diabetes in the mothers was characterized by early middle-aged onset, reduction in the insulin secretory capacity, early requirement of insulin therapy, and increases in the daily insulin dose. The heteroplasmic ratio of the 3243 mutation in leukocytes was low. The patients had mitochondria-related complications such as sensorineural deafness, cardiomyopathy, cardiac conductance disorders, encephalomyopathy, macular pattern dystrophy, and mental disorders. The patients also had advanced microvascular complications. Thus, this study has revealed that (1) diabetes mellitus with the 3243 mutation is a subtype of diabetes mellitus with mitochondria-related complications and (2) insulin secretory ability is more severely impaired in the patients whose mothers were also diabetic.

MeSH terms

  • Adult
  • Cross-Sectional Studies
  • DNA, Mitochondrial / genetics*
  • Diabetes Complications
  • Diabetes Mellitus / genetics*
  • Diabetes Mellitus / physiopathology*
  • Female
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Mitochondria / physiology*
  • Point Mutation*
  • RNA, Transfer, Amino Acyl / genetics


  • DNA, Mitochondrial
  • RNA, Transfer, Amino Acyl