Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 14-year-old boy presented with Type I diabetes mellitus and subsequently developed pancreatic exocrine insufficiency and systemic sclerosis (SSc). His diabetes had been diagnosed when he was about 5 years old, after the onset of ketoacidosis. Insulin treatment was provided from then until the time he was treated in our department. Exocrine pancreatic insufficiency, which occurred at age 9, was treated with pancreatic extracts. Cystic fibrosis was excluded after a chloride sweat test. The diagnosis of SSc was confirmed at age 14 on the basis of skin sclerosis, sclerodactyly and oesophageal and pulmonary involvement and then at age 18 by the occurrence of Raynaud's disease. Thus, this patient demonstrated a rare and previously unreported association of Type I diabetes mellitus and systemic scleroderma. Limited joint mobility and skin abnormalities are frequent in childhood diabetes mellitus but should not be misdiagnosed as systemic scleroderma.
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PMID:Case report: insulin-dependent diabetes mellitus in childhood associated with scleroderma. 869 7

We described a 60-year-old man with 5-year history of insulin dependent diabetes mellitus who developed continuous rigidity of truncal muscle and painless, rhythmic muscular spasm of trunk and proximal lower and upper extremities. The rigidity continued even in sleep. The painless muscle spasm was often precipitated by volitional movement and emotional stimuli. Intravenous administration of diazepam strongly attenuated the muscle spasm as well as truncal rigidity. Surface electromyography showed the continuous contraction of abdominal and paraspinal muscles. The rhythmic, clonic spasm of shoulder, triceps brachii, intercostal, abdominal, paraspinal and quadriceps femoris muscle induced by voluntary neck flexion was not compatible with typical stiff-man syndrome. Antibody against glutamic acid decarboxylase (GAD) was detected in the serum and cerebrospinal fluid of this patient. His condition was getting well with oral intake of sodium valproate. While painless, rhythmic spasm and persistent rigidity during sleep ruled out the patient from typical stiff-man syndrome, he was supposed to have the same pathophysiological mechanism as the anti-GAD autoantibody positive stiff-man syndrome.
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PMID:[A case of progressive continuous muscular rigidity and painless and rhythmic muscle spasm associated with autoantibody against glutamic acid decarboxylase]. 899 42

Results from a recent study suggested that polymorphisms within the HLA class II genes LMP2 and LMP7 were associated with the susceptibility for developing IDDM, and that this association could not be explained by linkage disequilibrium to HLA-DR or -DQ genes. We typed 285 IDDM patients and 337 HLA-DRB1-DQA1-DQB1 genotypically matched control subjects from an ethnically homogeneous population for both the G/T polymorphism in intron 6 of the LMP7 gene and the Arg-His polymorphism in the LMP2 gene. In addition, we typed IDDM families in which at least one parent was homozygous for a DRB1-DQA1-DQB1 haplotype and performed a transmission/disequilibrium test of these LMP polymorphisms. Our data suggest that none of these LMP2 or LMP7 polymorphisms are independently associated with IDDM susceptibility, in contrast to what has been previously reported by others. Further, our results suggest that one partial explanation for the previously reported independent association between IDDM and these LMP polymorphisms may have been that patients and control subjects were not matched for DRB1*04 subtypes. Our results emphasize the need for a complete matching for DRB1, DQA1, and DQB1 alleles between patients and control subjects when attempting to detect independent effects of other polymorphisms in the HLA complex on IDDM susceptibility or protection.
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PMID:No independent associations of LMP2 and LMP7 polymorphisms with susceptibility to develop IDDM. 900 Jul 9

A 6-yr-old boy presented with muscle weakness, lactic acidemia, and insulin-dependent diabetes mellitus (IDDM). Using PCR and restriction enzyme analysis, he was found to have the classical A3248G mitochondrial DNA (mtDNA) mutation frequently associated with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS). The mutation was confirmed by sequencing muscle mtDNA. The mutation in mtDNA from muscle, lymphoblasts, and blood was clearly demonstrable by standard methods using ethidium bromide staining. His mother also had IDDM, but no A3243G mutation could be detected in her blood or transformed lymphoblasts using the same PCR technique. When PCR was carried out in the presence of [32P]deoxycytidine triphosphate, subsequent autoradiography detected the presence of the mutation at low levels in mtDNA from the mother's lymphoblasts and blood. Study of the mother's muscle showed a mitochondrial myopathy, despite the fact that she was asymptomatic. We emphasize that the increased sensitivity of radiolabeled PCR may be necessary to detect small percentages of heteroplasmic A3243G mtDNA mutation in blood from diabetic subjects. Otherwise the incidence of mtDNA mutations in both IDDM and non-insulin dependent diabetes may be underestimated.
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PMID:Diabetes and mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS): radiolabeled polymerase chain reaction is necessary for accurate detection of low percentages of mutation. 928 4

One form of maturity-onset diabetes of the young, MODY3, is characterized by a severe insulin secretory defect, compared with MODY2, a glucokinase-deficient diabetes. It has recently been shown that mutations of the gene encoding the transcription factor hepatocyte nuclear factor (HNF)-1 alpha cause MODY3. Because of the rapid progress to overt diabetes and the high prevalence of required insulin treatment in patients with MODY3, we screened the HNF-1 alpha gene for mutations in Japanese subjects with IDDM. Ten exons and flanking introns of the HNF-1 alpha gene in these subjects were amplified by polymerase chain reaction and direct sequencing of the products. Mutations were identified in three (5.5%) of the 55 unrelated subjects with IDDM. A missense mutation of R272H (replacement of Arg by His in codon 272) in the DNA binding domain of HNF-1 alpha was found in a subject who developed IDDM 1 year after diagnosis of NIDDM at 8 years of age. A frameshift mutation of P291 fsinsC (insertion of a C in a polyC tract around codon 291 for Pro), which would generate a mutant truncated protein of 340 amino acids, was found in a subject who started insulin treatment when hyperglycemia and ketonuria were noticed at 13 years of age. A missense mutation of R583G (replacement of Arg by Gly in codon 583) in the transactivation domain of HNF-1 alpha was found in a subject with sudden-onset IDDM at 20 years of age. None of these mutations were present in 100 nondiabetic subjects (200 normal chromosomes). These results indicate that the HNF-1 alpha gene defects could lead to the development of not only early-onset NIDDM but also IDDM, implicating the importance of subclassification of HNF-1 alpha-deficient IDDM from a classical type of autoimmune-based IDDM in Japanese.
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PMID:Identification of mutations in the hepatocyte nuclear factor (HNF)-1 alpha gene in Japanese subjects with IDDM. 931 63

Susceptibility to the human autoimmune disease IDDM is strongly associated with those haplotypes of the major histocompatibility complex (MHC) carrying DQB1 alleles that do not encode aspartic acid at codon 57. Similarly, in a spontaneous animal model of this disease, the NOD mouse, the genes of the MHC play an important role in the development of diabetes. The DQB1 homolog in NOD mice, I-Ab(g7), encodes a histidine at codon 56 and a serine at codon 57, while all other known I-Ab alleles encode proline and aspartic acid, respectively, at these positions. We therefore mutated the NOD I-Ab allele to encode proline at position 56 and aspartic acid at position 57 and introduced this allele onto the NOD genetic background to study the effect of these substitutions on susceptibility to diabetes. No transgenic mice developed diabetes by 8 months of age, and transgenic mice had markedly reduced lymphocytic infiltration in the pancreas compared with nontransgenic littermates. Furthermore, splenocytes from transgenic mice failed to proliferate or secrete gamma-interferon in response to a panel of beta-cell autoantigens, although the mice did produce beta-cell specific antibodies. Interestingly, the proportion of IgG1 and IgE relative to IgG2a comprising these autoantibodies was much greater in transgenic mice compared with nontransgenic control mice. Finally, T-cells from transgenic mice inhibited the adoptive transfer of diabetes to irradiated recipients. This inhibition was partially reversed by treatment of the recipients with a combination of anti-interleukin (IL)-4 and anti-IL-10 monoclonal antibodies. Thus, a transgenic class II MHC allele encoding aspartic acid at B57 prevents diabetes, in part, by promoting the production of IL-4 and IL-10, which interfere with the effector phase of the diabetic process.
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PMID:Prevention of diabetes in NOD mice by a mutated I-Ab transgene. 975 94

We describe a patient with type I diabetes, clinical findings consistent with velocardiofacial syndrome, and a chromosome 22q11.2 deletion. A nine-year-old boy presented with a history of polyuria, polydipsia, weight loss, hyperglycemia, ketosis, serum insulin antibodies, and a low C-peptide level. He had distinctive facial features, learning disabilities, short stature, and a history of glottic web and clubfoot. Although a normal karyotype was obtained, fluorescence in situ hybridization (FISH) revealed a submicroscopic deletion in the DiGeorge/velocardiofacial syndrome critical region at 22q11.2. His maternal half-brother also carried a chromosome 22q11.2 deletion. His mother has similar facial features and hypoparathyroidism. Autoimmune problems associated with chromosome 22q11.2 deletions have been reported. We suggest that the defects in immune regulation due to T-cell deficiency in chromosome 22q11.2 deletion syndrome may predispose to autoimmune disorders, including type I diabetes mellitus.
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PMID:Type I diabetes mellitus in a patient with chromosome 22q11.2 deletion syndrome. 1134 31

Over the past 20 years, allo-transplantation of islet or whole pancreas for reaching and sustaining near-normoglycemia, as close as possible to the physiological model, have been undertaken. As previously known, even though islet transplantation is possible as a safe re-transplant, it is not well known whether re-transplantation of islets is suitable for patients who have lost the grafted islet function. We have performed a human islet allo-transplantation and re-transplantation on an IDDM patient for the first time in Asia and Korea. The recipient was a 32-year-old male and his insulin requirement was 75-85 U per day. After islet transplantation, the basal C-peptide increased from 0.6 to 2.1 ng/ml and insulin requirement decreased from 80 to 36 U per day, indicating that the grafted islets were functional. However, the grafted islets lost function 70 days after the transplantation. So, we performed re-transplantation of the islets. After the re-transplantation, the glucose profile became more stable and frequent episodes of severe hypoglycemia completely disappeared. His severe neuropathic pain improved dramatically and he could engage his ordinary daily life without any antineuropathic drugs. The success of this re-transplantation is one step closer to becoming a viable alternative for the millions of individuals who are suffering from diabetes.
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PMID:First human trial of pancreatic islet allo-transplantation in Korea--focus on re-transplantation. 1189 Oct 18

A 20-year-old Japanese man was admitted to our hospital because of thirst and weight loss. His fasting plasma glucose, glycated hemoglobin, and urinary C-peptide were 262 mg/dl, 13.6%, and 44.8 microg/day, respectively, and the autoimmune antibodies related to type 1 diabetes were negative. Chromosome analysis of his peripheral blood lymphocytes showed a mos45,XY,der(14;14)(q10;ql0)[129]/ 46,XY,+14, der(14;14)(q10;q10)[1] karyotype. His parents were karyotypically normal. Microsatellite marker analysis on chromosome 14 demonstrated mosaic maternal segmental isodisomy for 14q21-q24. Although the parents had normal glucose regulation, the patient who finally returned to impaired glucose tolerance and his mother both have a deficiency in early postprandial insulin secretion. Since obesity was mild (body mass index, 24.1 kg/m2) and he was relatively young for type 2 diabetes, we speculated that his isodisomy 14 may have been involved in the onset of diabetes mellitus in this patient.
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PMID:Maternal uniparental disomy for chromosome 14 with diabetes mellitus. 1232 99

Maturity-onset diabetes of the young (MODY) is a rare form of juvenile diabetes mellitus, defined by early onset, absence of ketosis, non-insulin-dependent diabetes and autosomal dominant inheritance. Advances in molecular genetic analysis have identified mutations accounting for different MODY subtypes, all of them associated with defects of insulin secretion. We present a case of a nine year-old boy, admitted to our outpatient clinic because of mild and intermittent osmotic symptoms (polyuria, polyphagia and polydipsia) and persistently high values of fasting blood glucose in the last year. He had a family history of diabetes in three consecutive generations compatible with autossomal dominant inheritance. His height was 138.5 cm (90th centile) and his weight was 33.5 Kg (90th centile). General examination was unremarkable, in a prepubertal boy. A standard oral glucose tolerance test was performed. The fasting blood glucose was 118 mg/dl with a two hour value of 160 mg/dl. ICA, IAA and GAD autoantibodies were undetectable. He started on diet therapy, keeping his fasting blood glucose measurements on the upper limits of normal and HbA1c in the normal range. He was diagnosed as having MODY 2 on a clinical basis, as it is not possible to perform molecular analysis of this pathology in Portugal. As MODY is recently thought to account for 2-5% of all cases of type 2 Diabetes Mellitus it is important to consider it as a possible diagnosis in children who present with incidental hyperglycaemia. Molecular genetic testing is very important as it enables us to make a firm diagnosis of MODY, to define a follow up plan and to reassure patients families, once the prognosis is significantly different among the different sub-types of MODY. We emphathize the need of creating national and international reference centres where such testing can be done.
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PMID:[Mature onset diabetes of the young (MODY)]. 1268 Feb 90


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