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Biomedical subjects

Y Uchigata

Publications and source records attributed to Y Uchigata.

At least 19 recordsLinked to original sources
PubMed2005

Clinical and immunogenetic characteristics of fulminant type 1 diabetes associated with pregnancy.

OBJECTIVE: The objective of this study was to characterize the clinical and immunogenetic features of Japanese pregnancy-associated fulminant type 1 diabetes (PF). A group of patients with PF was compared with a group of patients of child-bearing age with fulminant type 1 diabetes that was not associated with pregnancy (NPF) in a nationwide survey conducted from 2000-2004. PATIENTS: The clinical characteristics of the 22 patients in the PF group were compared with those of the 48 patients in the NPF group. Human leukocyte antigen (HLA) class II DR and DQ genotyping of 17 PF and 20 NPF patients was performed. RESULTS: Arterial pH was significantly lower (P = 0.0366), and amylase values tended to increase in PF patients compared with NPF patients (P = 0.0515). In 22 PF patients, 18 developed disease during pregnancy (26.3 wk; range, 7-38), whereas four cases occurred immediately after delivery (10.5 d; range, 7-14 d). Twelve cases that developed during pregnancy resulted in stillbirth (67%), and five of the six fetal cases that survived were delivered by cesarean section. The haplotype frequency of HLA DRB1*0901-DQB1*0303 in PF was significantly higher than those in NPF (P = 0.0244) and controls (P = 0.0001), whereas that of DRB1*0405-DQB1*0401 in NPF was significantly higher than those in PF (P = 0.0162) and controls (P < 0.0001). CONCLUSIONS: The clinical symptoms of PF patients were more severe than those of NPF patients, and the prognosis of their fetuses was extremely poor. The type 1 diabetes-susceptible HLA class II haplotype is distinct in PF and NPF patients, suggesting that different HLA haplotypes underlie the presentation of PF or NPF.

Adolescent↗
PubMed2005

Different contribution of class II HLA in fulminant and typical autoimmune type 1 diabetes mellitus.

AIMS/HYPOTHESIS: Fulminant type 1 diabetes, which is characterised by a markedly acute onset of diabetes and an absence of islet-related autoantibodies, accounts for 20% of type 1 diabetes in Japan. We aimed to clarify the contribution of the HLA subtype to fulminant type 1 diabetes in Japanese. METHODS: We determined the serological subtypes of HLA-A, -DR and -DQ in 115 patients with fulminant type 1 diabetes, 98 patients with typical type 1A diabetes and 190 normal control subjects. RESULTS: The frequency of HLA-DR4, but not DR9, was significantly higher in fulminant type 1 diabetes, while those of HLA-DR1, DR2, DR5 and DR8 were significantly lower than those in controls. In contrast, DR9 but not DR4 was more frequent and DR2 was extremely rare in typical type 1A diabetes. Haplotype analysis revealed that DR4-DQ4 was significantly more frequent, and both DR2-DQ1 and DR8-DQ1 were less frequent in fulminant diabetes. In type 1A diabetes, DR2-DQ1 was extremely rare while DR9-DQ3 was significantly more frequent. In the combination analysis, the homozygotes of DR4-DQ4 in fulminant type 1 diabetes and DR9-DQ3 in typical type 1A diabetes indicated high odds ratios (13.3 and 13.3, respectively). CONCLUSIONS/INTERPRETATION: Our results suggest that class II HLA contributes to the development of fulminant type 1 diabetes. Susceptibility and resistance of the HLA subtype to type 1 diabetes are distinct between fulminant and typical autoimmune type 1 diabetes.

Adolescent↗
PubMed2004

Autoantibodies to REG, a beta-cell regeneration factor, in diabetic patients.

BACKGROUND: Regenerating gene (Reg) product, Reg, acts as an autocrine/paracrine growth factor for beta-cell regeneration. The presence of autoimmunity against REG may affect the operative of the regenerative mechanisms in beta cells of Type 1 and Type 2 diabetes patients. We screened sera from Type 1 and Type 2 diabetes subjects for anti-REG autoantibodies, searched for correlations in the general characteristics of the subjects with the presence of anti-REG autoimmunity, and tested the attenuation of REG-induced beta-cell proliferation by the autoanitibodies. MATERIAL AND METHODS: We examined the occurrence of anti-REG autoantibodies in patients' sera (265 Type 1, 368 Type 2 diabetes patients, and 75 unrelated control subjects) by Western blot analysis, and evaluated inhibitory effects of the sera on REG-stimulated beta-cell proliferation by a 5'-Bromo-2'-deoxyuridine (BrdU) incorporation assay in vitro. RESULTS: Anti-REG autoantibodies were found in 24.9% of Type 1, 14.9% of Type 2 and 2.7% of control subjects (P = 0.0004). There were significant differences between the autoantibody positive and negative groups in the duration of disease in the Type 1 subjects (P = 0.0035), and the age of onset in the Type 2 subjects (P = 0.0274). The patient sera containing anti-REG autoantibodies significantly attenuated the BrdU incorporation by REG (35.6 +/- 4.06% of the control), whereas the nondiabetic sera without anti-REG autoantibodies scarcely reduced the incorporation (88.8 +/- 5.10%). CONCLUSION: Anti-REG autoantibodies, which retard beta-cell proliferation in vitro, are found in some diabetic patients. Thus, autoimmunity to REG may be associated with the development/acceleration of diabetes in at least some patients.

Adolescent↗
PubMed2004

Development and progression of diabetic retinopathy in patients with Type 1 diabetes who are positive for GAD autoantibody.

AIMS: To investigate the relationship between autoantibodies to glutamic acid decarboxylase (GAD) and proliferative diabetic retinopathy (PDR) to assess the role of autoimmunity in retinopathy. METHODS: Patients with Type 1 diabetes for more than 10 years who had been diagnosed under age 30 (13-28 years) were studied. They were classified into three groups. The PDR group consisted of 22 patients, the pre-PDR group was 26 patients, while the non-DR group was 32 patients who had Type 1 diabetes without retinopathy. Blood was collected to measure autoantibodies to GAD, and the relationship between PDR and GAD positivity was investigated in a cross-sectional study. RESULTS: The highest positivity rate of GAD autoantibodies was 50.0% in the non-DR group, followed by the pre-PDR group (30.8%) and the PDR group (18.2%). CONCLUSIONS: Production or existence of GAD autoantibodies may contribute to the prevention of retinopathy.

Adolescent↗
PubMed2001

Association between IA-2 autoantibody epitope specificities and age of onset in Japanese patients with autoimmune diabetes.

The IA-2 is a major autoantigen of type 1 diabetes belonging to the protein tyrosine phosphatase family. We report on the humoral autoimmunity to an alternatively-spliced variant of IA-2 (IA-2 variant) and autoimmune-mediated diabetes age of onset association with IA-2 autoantibody epitope specificities, in 144 recent-onset patients with type 1 diabetes and 54 GAD autoantibody-positive patients with type 2 diabetes. The cytoplasmic domain of IA-2 (IA-2ic) detected a somewhat greater proportion of patients expressing autoantibodies than IA-2 variant (56%vs. 52% of patients with type 1 diabetes and 17%vs. 9% of GAD autoantibody-positive patients with type 2 diabetes). Conversely, only 1% of IA-2 variant autoantibody-positive patients failed to react to IA-2ic construct. Among 80 patients with type 1 diabetes who were positive for autoantibodies to IA-2ic, 8% recognized the juxtamembrane region (JM, representing amino acids 601-629) only, 64% bound the protein tyrosine phosphatase (PTP)-like domain of IA-2 only, and 29% bound both JM and PTP epitopes. Autoantibodies to the PTP-like domain were prevalent in children and adolescents with type 1 diabetes. The age of disease onset in patients with IA-2JM autoantibodies only, was significantly higher than those in patients reacted with the PTP-like domain of IA-2 (P< 0.02). Among GAD autoantibody-positive patients with type 2 diabetes reacted with IA-2ic, 44% bound the JM region only, and 33% bound epitopes in the PTP-like domain only; 22% had autoantibodies to both regions. The frequency of GAD autoantibody-positive patients with type 2 diabetes positive for autoantibodies to the JM region only, was significantly higher than that in patients with type 1 diabetes (P< 0.01). IA-2PTP autoantibodies were significantly associated with HLA-DR4, while the additional reactivity to IA-2JM was associated with HLA-DR9 allele. These results suggest that autoantibody recognition of IA-2 epitopes in autoimmune diabetes is associated with age of disease onset, which may reflect the intensity of the beta-cell destruction process.

Adolescent↗
PubMed2001

The Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT): initial aims and impact of the family history of type 1 diabetes mellitus in Japanese children.

The Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT) was established in July 1994 with the chief aim to improve the quality of therapy for type 1 diabetes in children, an entity far less common in Japan than in Europe. We proposed four initial research topics: (i) to determine the current status of medical care and glycemic control in Japanese children with type 1 diabetes mellitus; (ii) to standardize the measurement of hemoglobin A1c; (iii) to establish a registry of a large cohort of patients in order to enable prospective studies to improve the quality of therapy for children with type 1 diabetes in Japan; and (iv) to enable participants of the JSGIT to hold a workshop twice annually. We registered a total of 736 patients from 45 hospitals throughout Japan. Intervention via insulin treatment was instituted after 2 yr for those patients whose hemoglobin A1c level was more than 8.1%. The proportion of patients receiving multiple insulin injections increased after intervention; however, average hemoglobin A1c in females remained significantly higher than in males. We identified two forms of diabetes in Japanese children: a rapidly progressive form and a more slowly progressive form. There was a significantly higher prevalence of a family history of diabetes in first-degree relatives in the slowly progressive form. These preliminary findings are the result of the first collaborative study of childhood diabetes in Japan.

Journal Article↗
PubMed2001

Hypoglycaemia due to insulin autoimmune syndrome: report of two cases with characterisation of HLA alleles and insulin autoantibodies.

OBJECTIVE: Insulin autoimmune syndrome (IAS) has been reported mainly in Japan and so far only 27 IAS cases have been described from outside Asia. We describe two unrelated Portuguese patients with IAS and characterise their insulin autoantibodies and HLA alleles. PATIENTS: Patient 1, a 24-year-old white female suffered an episode of unconsciousness in the late postprandial state and blood glucose was found to be 33 mg/dl with serum insulin levels of >3980 microIU/ml (normal range 0-30 microIU/ml). She was receiving monthly injections of penicillin G for the prophylaxis of recurrent tonsillitis. Patient 2, was a 19-year-old white female, with episodes of sweating, hand tremor, weakness and hunger occurring in the postprandial state and blood glucose levels during the attacks of 28-56 mg/dl. Very high insulin levels (602-708 microIU/ml) were present. METHODS AND RESULTS: Anti-insulin antibodies, determined by a semi-quantitative method, were strongly positive in both patients (91.7% in patient 1 and 88.6% in patient 2; normal range < or =7%). Sephadex G-100 chromatography of the sera showed most of insulin immunoreactivity present in the void volume which was retained by an affinity column with anti-human-immunoglobulin G antibodies (87% and 95% from patients 1 and 2 respectively). Scatchard plot analysis and molecular typing of the DRB1 gene revealed a polyclonal antibody and DRB1*0406 in patient 1, and a monoclonal antibody and DRB1*0403 in patient 2. CONCLUSIONS: These two Portuguese patients with IAS had different HLA-DR4 subtypes and insulin autoantibodies: DRB1*0406 and a polyclonal antibody in a patient treated with penicillin, and DRB1*0403 and a monoclonal antibody in a patient with "idiopathic" IAS.

Adult↗
PubMed2001

[Inhaled insulin (pulmonary administered insulin)].

The first report according to Inhaled insulin came out in 1924. Recent clinical trials of inhaled insulin made a real story to insulin-treated diabetic patients. Among some companies, insulin preparation of Pfizer company group consists of dry insulin dispersed by aerosol into particles sufficiently fine to drift into the distal twigs of the respiratory tree. Skylar et al in 2001 reported a randomized proof-of-concept study of inhaled insulin in type 1 diabetes mellitus. The result showed the same efficacy to the same time injections of regular insulin. Other reports showed the efficacy of inhaled insulin comparable to that of lispro insulin and the same action to not only type 1 but also type 2 diabetic patients.

Administration, Inhalation↗
PubMed2000

Marriage rate and number of children among young adults with insulin-dependent diabetes mellitus in Japan.

The main purpose of our study was to identify the social circumstances and lifestyle of IDDM patients in Japan. The present study focused on the marriage status of both men and women with IDDM as well as the number of children of women with IDDM. A questionnaire was sent to hospitals across the country. Doctors handed it or mailed it to IDDM patients aged 18 years or older. Unsigned answer sheets were returned directly by the patients. Data on the marriage rate and number of children were obtained, and possible factors affecting these indices were assessed. One thousand and thirteen patients (354 men and 659 women) answered the questionnaire. Both men and women with IDDM were less likely to be married in comparison with age-matched Japanese. The number of children of married IDDM women in various age groups was also lower in comparison with the general Japanese female population. Several factors other than diabetes complications including job discrimination, high medical costs, and psychological pressures, were thought to be responsible for these results.

Adult↗
PubMed2000

Worldwide differences in the incidence of insulin autoimmune syndrome (Hirata disease) with respect to the evolution of HLA-DR4 alleles.

The relationship between the geographic distribution of susceptibility genes to insulin autoimmune syndrome (IAS) and the incidence of insulin autoimmune syndrome was investigated in order to examine the distribution of the genetic background to susceptibility to certain diseases. The HLA-DR4 allele, DRB1*0406, is associated with increased susceptibility to IAS among Japanese, while the DRB1*0403 and DRB1*0407 alleles are not (the odds ratio of which are 1.6 and 1.1, respectively). The worldwide geographic distribution of the three DR*04 alleles showed that the distribution of DRB1*0403 encompassed that of DRB1*0406 and DRB1*0407. Taken together with the findings that Glu at position 74 in the DRB1 molecule is shared by the three DRB1*04 alleles, there are only a few differences between the DRB1 molecule-nucleotide sequences of DRB1*0403, DRB1*0406 and DRB1*0407, and that all the three DRB1*04 alleles are carried by the same class II haplotype, DQA1*0301/DQB1*0302, it may be considered that DRB1*0403 is the ancestral allele of DRB1*0406 and DRB1*0407. Therefore, populations with a higher prevalence of DRB1*0406 have a higher risk of developing IAS. The extremely low prevalence of IAS among Caucasians can be explained by the low prevalence of DRB1*0406 in this population. This is a good example of the association between the predisposition to risk of development of certain diseases and the evolution of susceptibility genes.

Alleles↗
PubMed2000

Higher incidence of diabetic nephropathy in type 2 than in type 1 diabetes in early-onset diabetes in Japan.

BACKGROUND: Whether the type of diabetes, race, and year and age of diagnosis affect the incidence of diabetic vascular complications is unknown. That both type 1 and type 2 diabetes occur in the young Japanese population prompted us to investigate whether the type of diabetes and the year of diagnosis are related to the incidence of nephropathy. METHODS: Of the 17,256 diabetic patients who visited the outpatient clinic at our diabetes center between 1965 and 1990, 1578 (9.1%) had early-onset diabetes (diagnosed before the age of 30); of these, 620 (39%) had type 1, and 958 (61%) had type 2 diabetes. The incidence of nephropathy was analyzed in the patients according to postpubertal duration and year of diagnosis. RESULTS: The cumulative incidence of nephropathy after 30 years of postpubertal diabetes was significantly higher (P < 0.0001) in type 2 diabetic patients (44.4%, 95% CI, 37.0 to 51.8%) than in type 1 diabetic patients (20.2%, 95% CI, 14.9 to 25.8%). The incidence of nephropathy among type 1 diabetic patients has declined during the past two decades, whereas it has not among type 2 diabetic patients. The rate ratio for type 2 diabetic patients diagnosed between 1980 and 1984 relative to type 1 diabetic patients diagnosed in the same period was 2.74 (95% CI, 1. 17 to 6.41). CONCLUSIONS: The incidence of nephropathy has declined in Japanese patients with type 1 but not in those with type 2 diabetes. In young Japanese patients, because of the higher incidence of nephropathy in type 2 diabetes and the higher prevalence of type 2 than type 1 diabetes, type 2 diabetes is likely the major cause of diabetic nephropathy.

Adolescent↗
PubMed2000

Antibody-mediated insulin resistance treated by cessation of insulin administration.

A 45-year-old Japanese man was referred to our hospital because of hyperglycemia despite the administration of as much as 120 U/day of human insulin. He had no history of injecting animal insulin. Free insulin was below 5 microU/ml, but a high titer of total insulin (about 3,000 microU/ml) was observed, suggesting the presence of antibodies against human insulin. Scatchard analysis showed an increased insulin binding capacity in the plasma characterized by a higher affinity for insulin. He was successfully treated by cessation of insulin administration. A Scatchard analysis series showed that a reduction in the insulin binding capacity of antibodies paralleled the improvement in glycemic control.

Blood Glucose↗
PubMed1999

Autoantibodies to multiple islet autoantigens in patients with abrupt onset type 1 diabetes and diabetes diagnosed with urinary glucose screening.

It has been reported that there is a heterogeneity in the clinical course of Japanese patients with type 1 diabetes. To elucidate the associations of expression of autoantibodies to multiple islet antigens with age of onset and mode of diagnosis of diabetes in Japanese patients with type 1 diabetes, autoantibodies against the protein tyrosine phosphatase-like molecules ICA512 (IA-2) and phogrin (IA-2beta) (ICA512/phogrin-A), GAD (GADA), insulin (IAA), and islet cell cytoplasm (ICA) were determined in sera from 73 Japanese patients with type 1 diabetes obtained within 14 days of diagnosis. Patients were divided into groups based on the age of onset (</=10 years, n=24 and >10 years, n=49) or the mode of onset (abrupt onset, n=59 and urinary screening identified, n=14). Of 73 new-onset patients with type 1 diabetes, 43 (59%) and 32 (44%) had ICA512A and phogrin-A levels exceeding the 99th percentile of 184 normal control subjects, respectively. Forty-five patients (62%) were positive for either ICA512A or phogrin-A. The frequencies for other autoantibodies were 71% for GADA, 48% for IAA, and 62% for ICA. The frequency of ICA512/phogrin-A was significantly higher in patients with an age of onset less than 10 years (83%) than in patients aged >10 years (51%, P<0.01). The positivity of ICA512/phogrin-A was less in patients whose diabetes was diagnosed by the urine glucose screening test (21%, P<0.001) than in abrupt onset patients (71%). Combined analysis (>/=1 antibody) of GADA, IAA, and ICA512/phogrin-A detected 88% of abrupt onset and 93% of screening-positive patients vs. 70% and 29%, respectively, for ICA (P<0.0005). These results indicate that the expression of ICA512/phogrin-A and cytoplasmic ICA is less in patients identified by urinary glucose testing but indicate that with combined autoantibody testing 90% of patients can be identified independent of the mode of diagnosis.

Adolescent↗
PubMed1999

Differences between bulimia nervosa and binge-eating disorder in females with type 1 diabetes: the important role of insulin omission.

This study explored the differences between bulimia nervosa ("BN," n=22) and binge-eating disorder ("BED," n=11) in type 1 diabetic females and the factors most predictive of poor glycemic control in patients suffering from these disorders. These two groups and a control group without eating disorders (n=32) were compared across a number of demographic, psychological, and medical variables. BN manifested significantly more severe disturbances related to eating disorders, depression, anxiety, a higher rate of co-occurring mental disorders, and poorer psychosocial functioning compared with BED. BN also showed poorer glycemic control. Multivariate analysis indicated that higher serum glycosylated hemoglobin (HbA1c) levels were most associated with the presence of severe insulin omission in type 1 diabetic females with binge eating. Clinicians may be able to determine the psychological/medical severity of illness in these patients by identifying the presence of compensatory behaviors to prevent weight gain such as severe insulin omission, as described in the DSM-IV.

Adolescent↗
PubMed1999

Genetic polymorphism of renin-angiotensin system is not associated with diabetic vascular complications in Japanese subjects with long-term insulin dependent diabetes mellitus.

In a hospital cohort study, we examined whether or not ACE (Angiotensin-I converting enzyme) and AGT (Angiotensinogen) gene polymorphisms were associated with the development of nephropathy in long-term Japanese insulin-dependent diabetes mellitus (IDDM) patients with or without proliferative retinopathy, and whether or not the polymorphisms were associated with an arteriosclerotic family history in first degree relatives of the patients. A total of 201 patients with IDDM for more than 10 years and 159 patients with IDDM for more than 15 years were randomly selected in our hospital. All patients received uniform diabetes management and were divided into three groups, no nephropathy, incipient nephropathy and clinical nephropathy groups. There were no differences in clinical characteristics excluding urinary albumin to creatinine ratio and systolic blood pressure between the three groups. ACE I/D polymorphism was related to plasma ACE activity, but there were no associations between ACE I/D polymorphism and the development of diabetic nephropathy, nor was renal deterioration observed in patients with proliferative retinopathy even in those with a history of diabetes for more than 15 years. The AGT polymorphism did not have an additive effect on the association between ACE polymorphism and the development of diabetic nephropathy in patients with or without retinopathy. Development of diabetic nephropathy in the patients with or without proliferative retinopathy did not result in ACE or AGT polymorphisms. On the other hand, the ACE DD genotype was associated with a family history of ischemic heart disease in first degree relatives (X2 score = 9.04, P < 0.05). ACE and AGT gene polymorphisms may not play a role in the protective or accelerative effect against the development of diabetic nephropathy in the patients with or without proliferative retinopathy, but ACE gene polymorphism might be related to an arteriosclerotic family history in Japanese IDDM patients.

Adult↗
PubMed1998

Association of distal chromosome 2q with IDDM in Japanese subjects.

An insulin-dependent diabetes mellitus (IDDM)-susceptibility gene (IDDM13) has recently been mapped to a region of distal chromosome 2q, which is syntenic to the region of mouse chromosome 1 containing a murine susceptibility gene for IDDM, Idd5. To determine the contribution of this region to IDDM disease susceptibility further and to narrow the region for positional cloning of susceptibility genes, we have studied the association of distal chromosome 2q with IDDM in the genetically distinct Japanese population. A 137 mobility unit (mu) allele at D2S137 locus was significantly associated with IDDM (odds ratio 1.92, p = 0.0016). Other markers, D2S301 and D2S143, located in the same region were not associated with IDDM, indicating that IDDM13 is in linkage disequilibrium with D2S137, but not with D2S301 or D2S143. The association of D2S137 with IDDM was observed in patients lacking one of two high risk HLA alleles, DQBI*0303 and DQBI*0401, but not in patients with either of these alleles. The frequency of high risk HLA alleles was significantly lower in patients with the susceptible allele at D2S137, suggesting that IDDMI3 contributes to IDDM susceptibility in subjects without high risk genotypes at IDDM1. Demonstration of allelic association of D2S137 with IDDM localizes IDDM13 in the close vicinity (<2 centiMorgans) of D2S137, greatly facilitating fine structure mapping and positional cloning of IDDM13.

Adolescent↗