PubMed Health⌕ Search

Biomedical subjects

Y Uchigata

Publications and source records attributed to Y Uchigata.

At least 37 records · Page 2Linked to original sources
PubMed1998

An IDDM patient who complained of chest oppression with ischemic changes on ECG in insulin-induced hypoglycemia.

A 34-year-old female IDDM patient complained of chest oppression in hypoglycemic episodes and electrocardiograms revealed reversible ischemic changes occurring concomitantly with hypoglycemia. The ECG changes improved and the chest oppression disappeared following increasing blood glucose level by glucose intake. Master's double load test and treadmill load test were positive for ischemic changes. Radioisotopic myocardial scintigraphy by thallium and BMIPP did not show any filling defects and coronary angiography revealed no remarked stenosis in the coronary arteries. She had no mitochondrial tRNA(Leu) (A-->G) gene mutation at nucleotide position 3243, but both the patient and her mother had a G-to-A transition within the replication origin of the light strand at nucleotide position 5744 of the mitochondrial gene. As the patient's maternal family had no history of ischemic heart disease, it is not clear whether mitochondrial gene mutation at nucleotide position 5744 reflects the occurrence of cardiac ischemia. Some disorders of microcirculation in capillary vessels in cardiac muscles may occur in such patients.

Adult↗
PubMed1998

Onset age-dependent variations of three islet specific autoantibodies in Japanese IDDM patients.

The age related incidence rate of insulin-dependent diabetes mellitus shows a bimodal distribution, not only in Caucasians but also in Japanese. To evaluate the onset age-related autoimmune profile at presentation in insulin-dependent diabetes mellitus (IDDM), glutamic acid decarboxylase (GAD) autoantibody, islet cell antibody (ICA), and insulin autoantibody (IAA) were measured in 137 newly diagnosed Japanese IDDM patients with onset ages between 0-29 years. The prevalence of GAD autoantibody was significantly increased from the lowest (32%) in the 0-5 years onset age group to 75% in the 13-19 years onset age group (P < 0.05), whereas the IAA prevalence significantly decreased from the peak (48%) in the 6-12 years onset age group to 10% in the 20-29 years onset age group (P < 0.05). The ICA prevalence was increased from the lowest (32%) in the 0-5 years onset age group to the highest (53%) in the 20-29 years onset age group similar to that for the GAD autoantibody. Such results demonstrate that there was age-related autoimmune characteristics at presentation of IDDM in Japanese as well as in Caucasians.

Adolescent↗
PubMed1998

Ischemic change on electrocardiogram induced by hypoglycemia in a diabetic patient.

A 34-year-old female patient who presented to our hospital had been treated with insulin for diabetes since she was 25 year old. For the previous year she had experienced chest pain on exertion and during hypoglycemia. During both chest pain and exercise tests, ST depression and flattening of the T wave were recognized in leads II, III, aVF, and V2-V6 on the electrocardiogram, and thus ischemic heart disease was suspected. Cardiac catheterization was performed, but no organic stenosis or spasms were found. Hypoglycemia (41 mg/dl) was induced by intravenous injection of rapid insulin (total 18 U, 0.4 U/kg). However, no coronary change was seen, although she felt chest pain and the same ischemic electrocardiographic changes occurred. We hypothesized the causes of the ischemic change to be both the effects of insulin on the cardiovascular system and the physiologic stress induced by the existence of microvascular abnormality. Special care should therefore be taken with diabetic patients being treated with insulin or hypoglycemic agents.

Adult↗
PubMed1998

High incidence of diabetic nephropathy in early-onset Japanese NIDDM patients. Risk analysis.

OBJECTIVE: Because early-onset Japanese NIDDM patients (diagnosed before age 30 years) can develop diabetic end-stage renal failure (ESRF) in their thirties, this study was performed to elucidate the incidence and determinants for the development of diabetic nephropathy. RESEARCH DESIGN AND METHODS: The incidence of diabetic nephropathy and its relationship to baseline characteristics and long-term metabolic control were determined in 426 early-onset Japanese NIDDM patients who were followed for a mean of 6.8 years. RESULTS: Of these 426 patients, 41 developed diabetic nephropathy manifested by persistent proteinuria (incidence rate [95%CI]/1,000 person-years; 14.1 [10.4-19.1]). Among patients whose mean HbA1c (measured by a high-performance chromatography method that is standardized and comparable to the one used in the Diabetes Control and Complications Trial study) was around 7% or less, few developed nephropathy. The incidence of nephropathy increased with increasing mean HbA1c level in a dose-dependent manner (chi 2 trend = 49.9, P < 0.0001). Diastolic blood pressure and duration of diabetes at entry had significant predictive effects independent of metabolic control. CONCLUSIONS: The incidence rate of diabetic nephropathy in early-onset Japanese NIDDM patients is potentially high, similar to or higher than that in Pima Indian NIDDM or Caucasian IDDM patients of comparable age. Diabetic nephropathy in NIDDM patients aged in their thirties or forties is likely to be an early feature that leads to ESRF, and this would contribute to the marked increase in the number of new patients with diabetic ESRF in Japan. NIDDM is a serious disease if near-normal glycemia is not achieved.

Adult↗
PubMed1997

Insulin gene region contributes to genetic susceptibility to, but may not to low incidence of, insulin-dependent diabetes mellitus in Japanese.

In the Caucasian population, it has been demonstrated that the insulin gene (INS) region contains the insulin-dependent diabetes mellitus locus (IDDM2). In the Japanese population, however, there has been no report demonstrating the contribution of IDDM2 to the pathogenesis of IDDM. We conducted an association study of IDDM in a large number of Japanese subjects with multiple polymorphisms in INS region. We found a significant association of the INS region with IDDM. Alleles positively associated with IDDM in INS region were the same as those positively-associated with IDDM in Caucasian population, although positively-associated alleles are very common (allele frequencies > 0.9) in the Japanese general population. These data suggest that IDDM2 is involved in the genetic susceptibility to IDDM in Japanese. The high frequencies of disease-associated alleles in the general population suggest that IDDM2 locus is not responsible for the low incidence of IDDM in Japanese.

DNA, Satellite↗
PubMed1997

Existence of early-onset NIDDM Japanese demonstrating severe diabetic complications.

OBJECTIVE: To identify the clinical characteristics of early-onset NIDDM patients with severe diabetic complications. RESEARCH DESIGN AND METHODS: The clinical cases of a large number of diabetic patients who visited a diabetes center within the period 1970-1990 were reviewed. Of a total of 16,842 diabetic patients, 1,065 (6.3%) had early-onset NIDDM (diabetes diagnosed before 30 years of age). These 1,065 patients were divided into two groups, those who developed proliferative retinopathy before the age of 35 (n = 135) and those who did not (n = 930). Development of proliferative retinopathy, nephropathy, renal failure, blindness, and atherosclerotic vascular disease were compared between the two groups. RESULTS: The subgroup of 135 patients was characterized by poor glycemic control, often requiring insulin therapy and a higher familial prevalence of diabetes, and contained a greater proportion of women than the subgroup of 930 patients. Of the 135 patients, 99 (67%) developed proliferative retinopathy before the first visit. The 135 patients developed severe progressive complications in contrast to the 930 patients. A total of 81 patients (60%) developed diabetic nephropathy at a mean age of 31 years, 31 (23%) developed renal failure requiring dialysis at a mean age of 35 years, 32 (24%) became blind at a mean age of 32 years, and 14 (10%) developed atherosclerotic vascular disease at a mean age of 36 years. CONCLUSIONS: Some Japanese early-onset NIDDM patients develop severe diabetic complications in their youth. Most of them had no symptoms nor regular treatment regarding diabetes until they were noticed to have developed severe diabetic complications. Although the relevant prevalence and the pathogenetic mechanism underlying the rapid onset of the complications remain to be determined, prolonged inadequate treatment of and familial predisposition to diabetes may be contributing factors. Careful diabetes care in the twenties, not only for IDDM but also for NIDDM patients, is warranted.

Adult↗
PubMed1996

Recurrent hypoglycaemia caused by the insulin autoimmune syndrome: the first Dutch case.

The insulin autoimmune syndrome is extremely rare outside of Japan. We describe a 45-year-old Caucasian woman who presented with fasting hypoglycaemia and weight gain. The presence of fasting insulin concentrations in excess of 1000 mU/l, very low C-peptide concentrations during hypoglycaemic attacks and high titres of insulin autoantibodies led to the diagnosis. Treatments aimed at decreasing endogenous insulin secretion by either dietary intervention alone or in combination with acarbose, octreotide or diazoxide had only limited success, while a 2-week course of immunosuppression with prednisone was without any antihypoglycaemic effect.

Autoantibodies↗
PubMed1995

A new mitochondrial DNA mutation associated with non-insulin-dependent diabetes mellitus.

Mitochondria play an important role in glucose-induced insulin secretion in pancreatic beta cells. We therefore examined whether patients with NIDDM exhibit genetic variability in mitochondrial DNA (mtDNA), a candidate gene for NIDDM. We sequenced mtDNA in the region encoding tRNALeu and the adjacent region in several diabetic patients with clinical features suggesting mitochondrial DNA mutations. We found a new point mutation at position 3316 that leads to an amino acid change in the ND-1 protein. The frequency of the mutation was screened with PCR-RFLP in 295 NIDDM patients and 406 controls. We found ten NIDDM patients (3.4%) harbored the mutation. Although 4 control subjects had the mutation, the frequency was significantly higher in the NIDDM patients than in the control subjects (p = 0.02). These results suggest that the 3316 mutation is associated with NIDDM.

Base Sequence↗
PubMed1995

Mutation in the mitochondrial tRNA(leu) at position 3243 and spontaneous abortions in Japanese women attending a clinic for diabetic pregnancies.

Mitochondrial DNA is exclusively maternally inherited. We recently found the prevalence of diabetic patients with an A to G transition at position 3243 of leucine tRNA (3243 base pair (bp) mutation) to be nearly 1% in randomly selected Japanese subjects. Here, we report the higher prevalence of diabetic patients with the 3243 bp mutation in a specific Japanese population of women attending a diabetic pregnancy clinic. Of 102 patients with non-insulin-dependent diabetes mellitus 6 (5.9%) were positive for the mutation, 1 (8.3%) of 12 patients with gestational diabetes and 2 (5.9%) out of 34 borderline diabetic patients. In contrast, none of 64 patients (0%) with insulin-dependent diabetes mellitus had the 3243 bp mutation. Moreover, there was a difference in the prevalence of spontaneous abortions between patients with and without this mutation (27.3 vs 12.4%). Among nine probands with the mutation, four had a history of one spontaneous abortion (p = 0.0518) and two had a history of two abortions (p = 0.0479). Two probands had a spontaneous abortion even while under strict diabetic metabolic control. The 3243 bp mutation thus may cause spontaneous abortion during pregnancy.

Abortion, Spontaneous↗
PubMed1995

Metabolic regulation and microangiopathy in a cohort of Japanese IDDM-patients.

In Caucasian patients with insulin-dependent diabetes mellitus (IDDM) proliferative diabetic retinopathy (PDR) and persistent proteinuria (PP) are associated, and major risk factors for development of microangiopathy have been identified. The aim of the present study was to evaluate whether these risk factors are also relevant and whether an association exists between the microangiopathic complications in Japanese IDDM-patients. A clinic-based cohort of 324 Japanese IDDM-patients was followed (a mean follow-up of 7 years). Annual examination for development of PDR and PP was performed. Fifty-eight patients developed PDR and 24 developed PP. Development of PDR was associated to high HbA1c-levels, i.e., the 4th quartile (RR 7.9, P < 0.0001), background retinopathy at admission (RR 9.9, P < 0.0001), high age at diabetes onset (RR 2.9, P < 0.0001) and female gender (RR 1.7, P < 0.05). Development of PP was associated to high HbA1c-levels (RR 2.8, P < 0.001) and background background retinopathy at admission (RR 7.9, P < 0.0001). The risk of developing PP was 9 times higher in patients developing PDR than in patients not developing PDR (P < 0.0001). The effect of metabolic control in our cohort was similar to that found in the DCCT and SDIS studies. In conclusion, development of PP is closely associated with PDR, also in Japanese IDDM-patients. The effect of metabolic control is the same as in Caucasian patients. Development of malignant angiopathy in IDDM-patients is not confined to Caucasian IDDM-patients, and the incidence rates are comparable to those found in Caucasian IDDM.

Adolescent↗
PubMed1995

Differential immunogenetic determinants of polyclonal insulin autoimmune syndrome (Hirata's disease) and monoclonal insulin autoimmune syndrome.

The insulin autoimmune syndrome (IAS), or Hirata's disease, is characterized by the combination of fasting hypoglycemia, high concentration of total serum immunoreactive insulin, and presence of autoantibodies to native human insulin in serum. Autoantibody production is classified as monoclonal or polyclonal, with the majority of IAS cases classified as polyclonal. Previously, we observed a striking association between the human leukocyte antigen (HLA) class II alleles DRB1*0406/DQA1* 0301/DQB1*0302 and Japanese IAS patients with polyclonal insulin autoantibodies (IAAs) and T-cell recognition of human insulin in the context of DRB1*0406 molecules. Because of such a strong HLA association in IAS, we performed intra- and interethnic studies on IAS-associated DRB1 alleles and searched for the critical amino acid residue(s) for IAS pathogenesis. Glutamate at position 74 in the HLA-DR4 beta 1-chain was presumed to be essential to the production of polyclonal IAA in IAS, whereas alanine at the same position of the HLA-DR beta 1-chain might be important in the production of monoclonal IAA.

Adult↗