title: Clinical features of diabetes mellitus with the mitochondrial DNA 3243 (A-G) mutation in Japanese: maternal inheritance and mitochondria-related complications.
abstract: Diabetes mellitus with the mitochondrial DNA 3243(A-G) mutation is reported to represent 0.5-2.8% of the general diabetic population. Since the characterization of diabetes with the mutation is still incomplete, we undertook a nation-wide case-finding study of genetically defined patients using questionnaires in Japan. One hundred and thirteen Japanese diabetic patients with the mutation were registered and analyzed. The patients had a high prevalence of maternal inheritance of diabetes and deafness, short and thin stature, and showed an early middle-aged onset of diabetes and deafness. Eighty-six percent of the patients required insulin therapy due to the progressive insulin secretory defect. Glucose intolerance of the mothers was associated with an early middle-aged onset of diabetes, reduction in the insulin secretory capacity, early requirement of insulin therapy, and increases in the daily insulin dose. The heteroplasmic concentrations of the 3243 mutation in leukocytes were low and declined with aging. The patients had advanced microvascular complications, and mitochondria-related complications such as cardiomyopathy, cardiac conductance disorders, neuromuscular symptoms, neuropsychiatric disturbance, and macular pattern dystrophy. 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 glucose intolerance.
authors.affiliation: Department of Molecular Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 1-1 Seiryou-machi, Aoba-ku, Sendai 980-8574, Japan. ssuzuki@int3.med.tohoku.ac.jp
authors.forename: Susumu
authors.initials: S
authors.lastname: Suzuki
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Oka
authors.forename: Takashi
authors.initials: T
authors.lastname: Kadowaki
authors.forename: Azuma
authors.initials: A
authors.lastname: Kanatsuka
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kuzuya
authors.forename: Masashi
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Tokio
authors.initials: T
authors.lastname: Sanke
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Seino
authors.forename: Kishio
authors.initials: K
authors.lastname: Nanjo
mesh_terms: D000328:Adult; D004272:DNA, Mitochondrial / Q000235:genetics*; D003638:Deafness / Q000453:epidemiology / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology* / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000453:epidemiology / Q000235:genetics; D003929:Diabetic Neuropathies / Q000453:epidemiology / Q000235:genetics; D003930:Diabetic Retinopathy / Q000453:epidemiology / Q000235:genetics; D005260:Female; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D017237:Mitochondrial Encephalomyopathies / Q000453:epidemiology / Q000235:genetics; D017354:Point Mutation; D015995:Prevalence; D012804:Sick Sinus Syndrome / Q000453:epidemiology / Q000235:genetics; D014927:Wolff-Parkinson-White Syndrome / Q000453:epidemiology / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial