Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Among several glycated compounds (GC) which are based on Maillard reaction, glycated hemoglobin (HbA1c) and fructosamine (FRA) have been utilized widely as a markers of diabetes. Recently, glycated albumin (GA) has been pointed out as a new indicator. For the determination of GA, spectrophotometry combined with an affinity column method has been mainly used, however the procedure is complicated. Recently a two-column HPLC method (ion-exchange column and affinity column) has been developed by Shima. We have evaluated a GA analyzer GAA-2000 based on Shima's method. After a series of fundamental and performance evaluation studies, the GAA-2000 was found to be appropriate for our study. Reference values obtained from this equipment were 10.56-16.87%. Correlation coefficients based on GA using diabetic and diabetic nephropathy patient specimens (n = 87) were: FRA (r = 0.944) greater than HbA1c (r = 0.842) greater than Glucose (r = 0.510) Superoxide dismutase (SOD) and lipid peroxidase (LPO) with are produced in relation to active oxygen did not show a good correlation. Although we tried classify the patients according to juvenile (20-39), middle (40-64) and senile (greater than 65) the method of Asada et al., we could not find any distinct tendencies.
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PMID:[Relationship among glycated compounds, superoxide dismutase activities, and other related analytes in diabetic patients classified by ages]. 194 32

Autoantibodies against insulin, C-peptide, and glucagon were determined by radio-binding assay in 63 new-onset Type 1 (insulin-dependent) diabetic patients as well as in 70 controls. Plasma peptide binding was determined by means of 125I-labeled peptides and charcoal-dextran separation technique. Binding values exceeding the mean plus three standard deviations of the controls were considered as antibody-positive. Sixteen patients (25%) were positive for IAA, as 6 (10%) were positive for CAA and 2 (3%) for GAA. Of all control subjects, none were positive for either IAA or CAA, whereas 2 (2%) had GAA. The mean 125I-glucagon binding in the patients' group was, however, slightly enhanced and could be suppressed to normal values by excess unlabeled glucagon. The presence of IAA and/or CAA was significantly associated with more severe symptoms at diabetes manifestation. These results indicate that in new-onset Type 1 diabetics autoimmunity arises against all the insular peptides tested but is predominantly directed against those antigens secreted from the beta cells. Nevertheless, extremely low-binding GAA seem to be common in these patients. The determination of IAA/CAA might be useful in detecting a possible heterogeneity of Type 1 diabetes with regard to its clinical mode of manifestation.
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PMID:Autoantibodies against insulin (IAA), C-peptide (CAA), and glucagon (GAA) in new-onset type 1 diabetic patients. 218 37

An electrophoretic variant of the lactate dehydrogenase (LDH)-B(H) subunit was discovered in a patient with diabetes mellitus. His LDH activity in serum was slightly lower than normal and the LDH isozyme pattern showed an abnormal migration indicating an LDH-B subunit variant of the fast type. The LDH containing the variant subunit revealed a decreased heat stability. DNA analysis of the variant allele detected a base substitution, an A to G transition, at codon 6 (AAA-->GAA). The mutation resulted in the replacement of a lysine by a glutamic acid (K6E). The change may cause the heat instability and affect the net charge of the variant subunit, resulting in an electrophoretic LDH-B subunit variant of the fast type.
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PMID:Analysis of a genetic mutation in an electrophoretic variant of the human lactate dehydrogenase-B(H) subunit. 831 53

Friedreich ataxia (FA) is associated with the expansion of a GAA trinucleotide repeat in the first intron of the X25 gene. We found both alleles expanded in 67 FA patients from 48 Italian families. Five patients from three families were compound heterozygotes with expansion on one allele and an isoleucine-->phenylalanine change at position 154 on the other one. We found neither expansions nor point mutations in three patients. The length of FA alleles ranged from 201 to 1,186 repeat units, with no overlap with the normal range, and showed a negatively skewed distribution with a peak between 800 and 1,000 repeats. The FA repeat showed meiotic instability with a median variation of 150 repeats. The lengths of both larger and smaller alleles in each patient inversely correlated with age at onset of the disorder. Smaller alleles showed the best correlation, accounting for approximately 50% of the variation of age at onset. Mean allele length was significantly higher in patients with diabetes and in those with cardiomyopathy.
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PMID:The relationship between trinucleotide (GAA) repeat length and clinical features in Friedreich ataxia. 875 56

The DQB1*0602 allele confers dominant protection from Type I diabetes even among islet cell antibody positive (ICA+) first degree relatives of affected individuals. Lack of progression to diabetes in these subjects, despite ICA positivity, could be explained by a loss of tolerance limited to fewer islet autoantigens than in ICA+ relatives progressing to the disease. To test this hypothesis we have determined autoantibodies by radioassay to three islet autoantigens, glutamic acid decarboxylase (GAD), insulin and the novel neuroendocrine antigen ICA512/IA-2 in 84 HLA-typed ICA+ first degree relatives of patients with Type I diabetes. Among the eleven relatives expressing the 0602 allele (0602+) only two were positive for more than one antibody as determined by radioassay. In contrast, 55/73 ICA+ relatives lacking this allele (non-0602) expressed more than one autoantibody (P < 0.01). The prevalence of antibodies to GAD (GAA) was not significantly different in ICA+ relatives with and without the 0602 allele (7/11 in 0602+ versus 60/73 in non-0602). In contrast, anti-insulin antibodies (IAA) were present in only 2/11 0602+ ICA+ relatives versus 47/70 in non-0602 ICA+ relatives (P < 0.01). Similarly, only one individual carrying the 0602 allele was positive for ICA512 autoantibodies versus 33/70 in the non-0602 group (P < 0.01). These data indicate that even among ICA+ relatives the 0602 allele is associated with a limited immune response to islet antigens and amongst 0602+ relatives this response is mostly directed against GAD.
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PMID:Limited loss of tolerance to islet autoantigens in ICA+ first degree relatives of patients with type I diabetes expressing the HLA dqb1*0602 allele. 881 81

Friedreich's ataxia is the most common hereditary ataxia and is frequently associated with disturbances of glucose metabolism. This autosomal recessive disease is caused by the decreased expression of a mitochondrial protein, frataxin, encoded by the X25 gene. Homozygous expansion of a GAA repeat in the first intron of X25 inhibits frataxin expression and is associated with clinical disease. We evaluated whether heterozygous expansions of the triplet repeat in the frataxin gene X25 may be associated with NIDDM in two genetically distinct populations--one in Germany (n = 358) and the other in the U.S. (n = 292)--using a polymerase chain reaction-based assay. Intermediate expansions (10-36 repeats), which are longer than normal but not sufficient for the appearance of the ataxia phenotype, were found in 24.7 and 27.3% of these two NIDDM cohorts compared with 7.6 and 6.3% of the matched control subjects (both P < 0.001). The odds ratios were 3.36 (95% CI 1.72-6.55) for the German group and 4.01 (2.08-7.74) for the U.S. group. Therefore, we conclude that the X25/frataxin GAA repeat polymorphism is associated with NIDDM in a frequency higher than any other mutation heretofore described. Further studies are needed to elucidate the possible role of frataxin in the pathogenesis of NIDDM.
Diabetes 1998 May
PMID:An association between NIDDM and a GAA trinucleotide repeat polymorphism in the X25/frataxin (Friedreich's ataxia) gene. 958 63

The 11 beta-hydroxysteroid dehydrogenase type II enzyme (11 beta HSD2) inactivates glucocorticoids in the kidney and thus prevents glucocorticoids from occupying the non-selective mineralocorticoid receptor in epithelial tissues. Mutations in the HSD11B2 gene have been found to cause the syndrome of apparent mineralocorticoid excess, a rare autosomal recessive disease characterized by severe hypertension. Thus, this locus could also be an ideal candidate involved in the etiology of primary hypertension. We identified a polymorphism in exon 3 characterized by a GAG to GAA transition at codon 178, with the loss of an Alu I restriction site and analysed it in an association study using end-stage renal disease patients, diabetic or essential hypertensive patients and control subjects. Two-hundred and eighty nine subjects and patients were analysed; the genotype was determined by amplification of genomic DNA and subsequent digestion with Alu I restriction enzyme. The prevalence of the Alu I allele was 8.6% in healthy control subjects (n = 116). This prevalence was lower (chi 2 P = 0.035 vs. controls) than the 18.0% in a group of renal transplant patients (n = 61). The corresponding values for patients with diabetes mellitus (n = 25), hypertension (n = 41) and patients on dialysis (n = 46) were 4.0%, 4.8% and 4.3%, respectively. There was no correlation between blood pressure and the marker in non-ESRD subjects. These data indicate the presence of a polymorphic marker in exon 3 of the HSD11B2 gene; this marker is associated with end-stage renal disease but not with essential hypertension in humans.
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PMID:A new polymorphic restriction site in the human 11 beta-hydroxysteroid dehydrogenase type 2 gene. 958 99

Mutations of mitochondrial DNA (mtDNA) are associated with a wide spectrum of disorders encompassing the myopathies, encephalopathies and cardiomyopathies, in addition to organ specific presentations such as diabetes mellitus and deafness. The pathogenesis of mtDNA mutations is not fully understood although it is assumed that their final common pathway involves impaired oxidative phosphorylation. The identification of a specific respiratory chain defect (complex I deficiency) in Parkinson's disease (PD) 10 years ago focused attention on the aetiological and pathogenetic roles that mitochondria may play in neurodegenerative diseases. There is evidence now emerging that mtDNA abnormalities may determine the complex I defect in a proportion of PD patients and it may prove possible to use biochemical analysis of platelet and cybrid complex I function to identify those that lie within this group. Respiratory chain defects of a different pattern have been identified in Huntington's disease (HD) (complex II/III deficiency) and Friedreich's ataxia (FA) complex I-III deficiency). In both these disorders, the mitochondrial abnormality is secondary to the primary nuclear mutation:CAG repeat in the huntingtin gene in HD, and GAA repeat in the frataxin gene in FA. Nevertheless, it appears that the mitochondrion may be the target of the biochemical defects that are the consequence of these mutations. There is a close and reciprocal relationship between respiratory chain dysfunction and free radical generation, and there is evidence for oxidative stress and damage in PD, HD and FA, which together with the mitochondrial defect may result in cell damage. Impaired oxidative phosphorylation and free radical generation may independently adversely affect the maintenance of mitochondrial transmembrane potential (Deltapsim). A fall in Deltapsim is an early event (preceding nuclear fragmentation) in the apoptotic pathway. It is possible therefore that mitochondrial dysfunction in the neurodegenerative disorders may result in a fall in the apoptotic threshold of neurones which, in some, may be sufficient to induce cell death whilst, in others, additional factors may be required. In any event, mitochondria present an important target for future strategies for 'neuroprotection' to prevent or retard neurodegeneration.
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PMID:Mitochondrial dysfunction in neurodegenerative disorders. 971 16

A variable expansion of a GAA repeat is present in the first intron of the frataxin gene, also termed FRDA1 or X25. Long repeat lengths (>66 repeats) are present in patients with Friedreich's ataxia, while an intermediate expansion (10-66 repeats) has recently been reported to be highly associated with type 2 diabetes. Using a polymerase chain reaction-based assay, we found that 32.4% (95%CI 29.9-34.9) of 636 Danish Caucasian type 2 diabetic patients were carriers of an intermediate expansion, whereas the frequency was 30.4% (26.4-34.4) among 224 matched glucose-tolerant control subjects (P = 0.6). In the control subjects, the values of serum insulin and C-peptide responses during an oral glucose tolerance test were similar between the 69 carriers and 155 noncarriers. Furthermore, we investigated a possible relationship between expansions of the FRDA1 gene and glucose-induced beta-cell function in 338 young Caucasians (33.7% [30.1-37.3] carriers) and in 215 glucose-tolerant subjects (31.0% [26.6-35.4] carriers) with a type 2 diabetic parent. In neither population did the carriers differ from noncarriers according to values of fasting plasma glucose, serum insulin, or C-peptide, acute serum insulin, or C-peptide responses after intravenous glucose. In conclusion, intermediate expansion of the frataxin trinucleotide repeat is not associated with type 2 diabetes or altered glucose-induced insulin secretion in Danish Caucasians.
Diabetes 1999 Apr
PMID:Intermediate expansions of a GAA repeat in the frataxin gene are not associated with type 2 diabetes or altered glucose-induced beta-cell function in Danish Caucasians. 1010 12

Friedreich's ataxia is associated with GAA trinucleotide repeat expansions in the frataxin gene. In the general population, these trinucleotide expansions are variable in length, and three types of expansions are seen: short, intermediate, and long repeats. Friedreich's ataxia patients are generally homozygous for the long repeats and exhibit diabetes as pronounced comorbidity. Ristow et al. recently reported an association between the intermediate-length normal allele in the frataxin gene and type 2 diabetes. We have investigated in 94 subjects with impaired glucose tolerance (IGT) as to whether the length of the GAA trinucleotide repeat polymorphism in the frataxin gene associates with parameters reflecting beta-cell function. A hyperglycemic clamp at 10 mmol/l glucose for 3 h was used to quantitate beta-cell characteristics. Carriers of one or two intermediate repeat alleles (n = 32) had a 50% higher median first- phase insulin response to glucose than the noncarriers. Furthermore, they needed less time to reach peak insulin. An analysis of the distribution of the various repeat lengths in elderly type 2 diabetic (n = 179) and control subjects (n = 183), with the same age and ethnic background, did not provide evidence for an association of the intermediate-length repeat allele with type 2 diabetes in Dutch Caucasians.
Diabetes 1999 Apr
PMID:Altered beta-cell characteristics in impaired glucose tolerant carriers of a GAA trinucleotide repeat polymorphism in the frataxin gene. 1010 15


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