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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As a result of advances in technology, genome searches have been carried out for susceptibility genes for type 1 diabetes in humans and in the NOD mouse. These have shown that, in the NOD mouse, diabetes susceptibility is under the control of at least ten separate chromosomal loci. In the human, in addition to HLA and INS, two new susceptibility genes have been localized, IDDM4 on chromosome 11q and IDDM5 on 6q, demonstrating the polygenic nature of type 1 diabetes and the role of HLA as the major locus. Candidate genes at these loci are the subject of current investigation. Genetic and immunological markers of disease may be of value in screening the general population for individuals at risk of developing type 1 diabetes. The predictive power of different screening strategies should be tested in order to work out the potential value to the general population of preventive therapies that are now undergoing clinical trials in high risk 'pre-diabetics'. Type 2 diabetes is genetically heterogeneous, and, since 1992, two distinct genetic subtypes have been identified. The first is defined by mutations in the GCK gene, which cause up to 60% of cases of MODY. The second, designated MIDD (maternally inherited diabetes and deafness), is defined by mutation in the mitochondrial gene for tRNA(Leu(UUR)). MIDD patients are less obese than is usual for typical type 2 diabetes, may present in early adult life or occasionally in childhood and may have been diagnosed as having autoimmune type 1 diabetes, type 2 diabetes or MODY. Typically, patients with MIDD require insulin earlier than do type 2 diabetics without mitochondrial mutations. Genetically complex diseases, such as diabetes, hypertension, cancer and coronary heart disease, are common in most populations. The approaches to the genetic analysis of diabetes outlined in this review are likely to be useful to the genetic analysis of many of these disorders. Progress in this area will have important implications for public health strategies in the next decade and beyond.
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PMID:Molecular genetics of diabetes mellitus. 757 35

Several studies have shown a consistent maternal effect in the transmission of Type 2 diabetes (NIDDM). The mitochondrial encephalomyopathies are a group of diseases characterized by maternal inheritance and a variety of mitochondrial DNA defects. Diabetes is a feature of some of these disorders and therefore the hypothesis arose that mitochondrial DNA mutations might play a role in patients with diabetes but no other features of neurological disease. Recent studies have confirmed that a specific point mutation in the gene encoding the mitochondrial tRNA for leucine segregates with diabetes and nerve deafness in families from the UK, Holland, France and Japan. Mitochondrial gene deletions have also been reported. Affected subjects present with progressive insulin deficiency and may fall into the broad classifications of either Type 1 (IDDM) or Type 2 diabetes (NIDDM). Future studies are aimed at searching for other mitochondrial gene defects in diabetes and attempting to explain the mechanism of hyperglycaemia by the development of phenotypic expression systems. Although an exciting development in the genetics of diabetes, currently described mitochondrial mutations do not fully explain the maternal effect in the transmission of Type 2 diabetes.
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PMID:Maternally inherited diabetes mellitus: the role of mitochondrial DNA defects. 774 54

A pedigree with maternally transmitted diabetes mellitus, deafness, and cardiomyopathy is described. A A-->G mutation at nucleotide pair 3243 in mitochondrial gene was detected by Apa I digestion of PCR amplified genomic DNA from 3 brothers and their mother. The proband, suffering from CHF, showed unique fine granular pattern of hyperechogenic cardiomyopathy as his brother and their mother did. Although he is recently treated with insulin, he was initially NIDDM treated by sulfonylurea. His urinary CPR excretion decreased gradually to as low as less than 10 micrograms/day in these 3 years. The insulin response to oral glucose was decreased in all other family members with the mutation. It is suggested that the defective insulin secretion exists in this family with the mutation and the progressive decrease in insulin secretion might resulted in IDDM in the proband.
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PMID:[A pedigree with maternally transmitted diabetes mellitus, deafness and cardiomyopathy]. 798 86

Four clinical forms of optic neuropathy can occur in diabetes: 1. Axial neuropathy is a classical optic neuropathy. 2. Anterior ischemic optic neuropathy is an acute optic disc ischaemia and the visual loss depends on the number of fibers destroyed. 3. Acute disc swelling occurs in young patients with a type 1 diabetes. It can be asymptomatic, but can also simulate optic disc new-vessels. It seems not to be a ciliary but rather an epipapillary and peripapillary capillaropathy. 4. Optic atrophy can constitute the final out come of forms one and too. In the child, the Wolfram ou DIDMOAD syndrome associates diabetes insipidus, diabetes mellitus, optic atrophy and deafness.
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PMID:[Optic neuropathy in diabetic subjects]. 805 17

Mutations in the mitochondrial gene were recently identified in a large pedigree of diabetes mellitus and deafness. As the mitochondrial gene is materially inherited, Japanese diabetic patients whose mothers were also diabetic were screened, using peripheral leucocytes, for an A to G transition at nucleotide pair 3243 of the mitochondrial gene, a tRNA(Leu(UUR)) mutation. This mutation was identified in four pedigrees from among 300 unrelated patients who were screened. Diabetes co-segregated with the mutation, except in one young subject, and was maternally inherited. The apparent onset of disease occurred between 11 and 68 years of age. Some of the affected members developed hearing impairment and congestive heart failure due to cardiomyopathy, though generally long after the onset of diabetes, and these patients had therefore not been diagnosed as having a specific form of diabetes. The duration of sulphonyl-urea treatment was not more than 8 years in these pedigrees and affected members were prone to progression to insulin-requiring diabetes. Thus, these patients were secondary sulphonylurea failures. Long-term follow-up revealed that the underlying disorder in affected members is a progressive impairment of insulin secretion. Some were initially diagnosed as having IDDM based on an apparent acute onset in youth and the clinical severity of their diabetes. Others were regarded as having MODY with an aggressive course. The mitochondrial gene mutation or diabetes is not transmitted to all offspring of the affected mothers.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mitochondrial diabetes mellitus: prevalence and clinical characterization of diabetes due to mitochondrial tRNA(Leu(UUR)) gene mutation in Japanese patients. 805 89

Two first cousins both suffering from insulin dependent diabetes mellitus since early childhood developed progressive optic atrophy from the age of 5 and 9 years respectively. They had similar ophthamological features which include optic atrophy with cupping, paracentral scotomata, and total achromatopsia. One patient also had stunted growth, delayed puberty and psychiatric disorder. Neither had diabetes insipidus and deafness. It is suggested that they may be a variant of DIDMOAD (Diabetes Insipidus, Juvenile Diabetes Mellitus, Optic Atrophy, Deafness).
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PMID:Progressive optic atrophy associated with juvenile diabetes mellitus: report of two cases among first cousins. 826 10

Wolfram's syndrome, also known as DIDMOAD syndrome, includes juvenile diabetes mellitus and optic atrophy variously associated with diabetes insipidus and deafness. We describe the neurological findings in 5 patients with Wolfram's syndrome. All patients had a neurological examination and were subjected electrophysiological and brain imaging including CT scan and, in one patient, MRI. There were two pairs of brothers and a sporadic case with paternal consanguinity suggesting recessive inheritance. Neurological abnormalities were found in four patients including dysarthria, seizures, anosmia, nystagmus, ataxia and changes in the electroencephalograms, electroretinograms and evoked potentials. In contrast with previous reports, four patients had abnormal brain CT scan with prominent atrophy of the brainstem. In the patient studied with NMR, severe brainstem and cerebellar atrophy was found. These neuroradiological findings are reminiscent of those described in olivopontocerebellar atrophy and are in agreement with previous pathological studies. We conclude that Wolfram's syndrome includes phenotypical manifestations of olivopontocerebellar atrophy. This reinforces the opinion that olivopontocerebellar atrophy is a nonspecific syndrome of varied causes.
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PMID:[Neurologic manifestations in Wolfram's syndrome]. 833 58

A family with maternally-transmitted deafness and diabetes mellitus is described. Although the proband clinically exhibited MELAS-like symptoms such as sudden-onset cerebellar ataxia and weakness of the proximal portion of the limbs in addition to deafness and diabetes mellitus, the other three members of the family had only deafness and diabetes mellitus and no neurological manifestations. The analysis of mitochondrial DNA of the two members revealed an A-->G mutation of tRNA(leu(UUR)), a mutation commonly seen in patients with MELAS. According to the clinical histories and endocrinological investigations, the type of the diabetes mellitus in this family was considered to be IDDM, which may be attributed to the dysfunction of mitochondrial of the pancreas islet cells, resulting from the mutation of the mitochondrial DNA.
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PMID:[A family with MELAS whose main manifestations are maternally-transmitted deafness and diabetes mellitus]. 840 88

An A to G mutation at nucleotide position 3243 of the mitochondrial genome has been shown to be associated with insulin-dependent diabetes mellitus (IDDM) and with noninsulin-dependent diabetes mellitus (NIDDM) with deafness. We investigated the prevalence of this mutation in Japanese patients with IDDM, NIDDM, and impaired glucose tolerance (IGT) and in nondiabetic control individuals and identified it in three of 300 patients with NIDDM or IGT (1.0%). None of these individuals had significant sensorineural hearing loss. None of the 94 IDDM or the 115 nondiabetic control subjects was positive for this mutation. Oral glucose tolerance test revealed that a 57-year-old male with this mutation was rather hyperinsulinemic in the fasting state. The insulin secretion in this patient decreased with age; he did not complain of any hearing disorder, although audiometry revealed a slight elevation of hearing threshold at high frequencies. In conclusion, we found that a mitochondrial gene mutation at np 3243 was present in about 1% of NIDDM patients including IGT, and the subtype of diabetes mellitus with this mutation may have a similar clinical profile to that found in patients with NIDDM commonly seen in outpatient clinics. Screening of 116 patients with type 1 diabetes mellitus and 149 patients with autoimmune thyroid diseases revealed that this mutation rarely exists in patients with autoimmune diseases.
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PMID:Involvement of mitochondrial gene abnormalities in the pathogenesis of diabetes mellitus. 868 45

Diabetes mellitus is a common disease with variations in its clinical expression and different modes of pathogenesis. The purpose of this review is to discuss a recently identified diabetic subtype. Based on the triad diabetes, maternal inheritance and impaired hearing in this subtype we have proposed the name Maternally Inherited Diabetes and Deafness (MIDD). This diabetic subtype associates in the vast majority of cases with a single mutation in mitochondrial DNA, at position 3243. The clinical presentation of MIDD which can be IDDM-like or NIDDM-like, its frequency of occurrence, possible pathogenic mechanisms and the contribution of other mitochondrial DNA mutations to the development of diabetes will be discussed.
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PMID:Maternally inherited diabetes and deafness: a diabetic subtype associated with a mutation in mitochondrial DNA. 910 98


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