[Diabetes mellitus--progress in diagnosis and treatment].
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Diabetes Mellitus↗
Biomedical subjects
Tokio Sanke
Publications and source records attributed to Tokio Sanke.
Clinical features of diabetes mellitus with the mitochondrial DNA 3243 (A-G) mutation in Japanese: maternal inheritance and mitochondria-related complications.
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.
Adult↗
Nonsense and missense mutations in the human hepatocyte nuclear factor-1 beta gene (TCF2) and their relation to type 2 diabetes in Japanese.
Mutations in transcription factors expressed in the pancreatic beta-cell are a major cause of maturity-onset diabetes of the young (MODY). They have also been found in patients diagnosed with type 1 and type 2 diabetes mellitus, which may highlight the difficulty in diagnosing these forms of diabetes or perhaps indicate a direct role in the development of multiple forms of diabetes. We have screened the hepatocyte nuclear factor-1 beta (HNF-1 beta/MODY5) gene for mutations in a group of 126 unrelated Japanese patients with type 2 diabetes and a family history of at least one first degree relative with diabetes. We identified one patient with a nonsense mutation (R276X) and another with a missense mutation (S465R). These mutations were present in the heterozygous state and were not found in 132 nondiabetic subjects (264 normal alleles). We identified a second patient with the S465R mutation on screening a second group of 272 randomly selected type 2 diabetic patients but not in another 122 nondiabetic subjects. Functional studies indicated that R276X-HNF-1 beta was inactive and S465R-HNF-1 beta exhibited a 22% reduction in activity compared with the wild-type protein. The S465R mutation may function in a dominant-negative manner. The subject with the R276X mutation had MODY5 misdiagnosed as common type 2 diabetes. He was diagnosed with diabetes at 13 yr of age and also had small kidneys with multiple bilateral renal cysts and decreased urinary concentrating ability. The two subjects with the S465R mutation had typical late-onset type 2 diabetes and no evidence of kidney disease. We have identified two novel mutations in human HNF-1 beta gene. The prevalence of MODY5 among our population of Japanese diabetes patients with a strong positive family of disease is 0.8%. The S465R mutation was found in 0.5% of our patients with common type 2 diabetes and thus may be a rare genetic risk factor contributing to the development of type 2 diabetes rather than MODY5.
Adolescent↗
[Mutation of amylin (IAPP) gene].
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Amyloid↗
[Minimal model].
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Diabetes Mellitus, Type 2↗
[Diagnostic use of gene polymorphism for type 2 diabetes].
Type 2 diabetes is thought be a multifactorial disease and both genetic and acquired factors contribute its pathogenesis. Elucidation of susceptibility genes for type 2 diabetes thus leads to primary prevention for the disease. Although main susceptibility genes for type 2 diabetes have not been found, I present our data using candidate gene approach. Our data include the amylin gene S20G and the Pax4 gene R121W mutations and also include the muscle glycogen synthase gene M416V polymorphism that correlates to insulin resistance as a thrifty gene.
Amyloid↗