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Biomedical subjects

T Y Tai

Publications and source records attributed to T Y Tai.

At least 37 records · Page 2Linked to original sources

Quantitative sensory testing and risk factors of diabetic sensory neuropathy.

The goal of this study was to identify risk factors for diabetic peripheral sensory neuropathy in type 2 diabetes mellitus in a Chinese population. Peripheral sensory neuropathy was detected by quantitative sensory testing (5.07/10 g monofilament, neurometer and 128-Hz Riedel Seiffert graduated tuning fork). Those who had two or more abnormal quantitative sensory testings were defined as having diabetic sensory neuropathy. Of the 558 non-insulin dependent diabetes mellitits subjects, 62 (11.1%) had peripheral neuropathy. In 59 (10.6%) detection was by monofilament testing, 45 (8.1%) by graduated tuning fork, and 189 (33.9%) by neurometer. In a multivariate logistic regression model, age and insulin therapy were significantly associated with peripheral neuropathy. Age, serum triglyceride, height, and fasting plasma glucose were independently associated with large fiber neuropathy. Our results confirm the previously identified multiple risk factors of diabetic neuropathy. Different quantitative sensory testings detect different nerve fiber defects. The weak correlation between these tests indicates the need to use more than one test in screening for diabetic neuropathy.

Aged↗

Assessment of the function and effect of diabetes education programs in Taiwan.

A multi-center prospective study was conducted to assess the function and impact of diabetic education programs on diabetic control. A total of 208 subjects with type 2 diabetes were recruited. Diabetes self-care, assessed by questionnaire, was evaluated before, and 4 months after attending a diabetes education course. A total of 121 subjects who received advanced diabetes education courses were designated as the experimental group. A second group of 87 cases receiving a basic course served as controls. In addition to basic knowledge, the advanced education programs included dietary control, blood glucose monitoring, management of hypoglycemia, medication compliance, foot care and exercise. Diabetes self-care techniques were significantly improved in the experimental group. The overall score for diabetes self-care techniques improved in both groups at the 4th month over baseline values. The change was significant with the controls' (P < 0.001). Multiple regression analysis confirmed the intensity of diabetic education was the only significant variable correlated with the decrease of fasting blood glucose and systolic blood pressure. In conclusion, integrated and intensive diabetes education program in diabetes education centers provides an effective method for improving diabetes self-care techniques and metabolic outcome.

Aged↗

Screening for the Gly40Ser mutation in the glucagon receptor gene among patients with type 2 diabetes or essential hypertension in Taiwan.

As a major counterregulatory hormone of insulin, glucagon plays an important role in regulating glucose homeostasis through its binding to the glucagon receptor. Recently a missense mutation in the glucagon-receptor gene (Gly40Ser) was found to be associated with type 2 diabetes in France and Sardinia, with a frequency as high as 4.6% and 8.3%, respectively. This mutation was also found to be associated with essential hypertension in the white population with a frequency of 5.4%. To investigate the role of this mutation in the pathogenesis of type 2 diabetes and essential hypertension in Taiwanese population, we screened 121 normal controls, 213 unrelated subjects with type 2 diabetes, and 107 unrelated subjects with essential hypertension by use of polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP). None of the Taiwanese subjects recruited in the study had this receptor mutation. Our results demonstrate a strong genetic heterogeneity among the ethnic group and suggest that the Gly40Ser mutation of the glucagon receptor gene plays little role, if any, in the pathogenesis of type 2 diabetes and essential hypertension in the Taiwanese population.

Amino Acid Substitution↗

A case-control study on risk factors for Type 1 diabetes in Taipei City.

To search for non-genetic risk factors for Type 1 diabetes among Chinese, a total of 117 Type 1 diabetes patients identified from the Taipei Type 1 Diabetes Registry and 193 frequency-matched controls with normal glucose tolerance were recruited. The controls were selected from classmates or colleagues of cases with similar distributions of age, sex, and parental and individual educational levels. Information on Type 1 diabetes risk factors was obtained through standardized interviews according to a structured questionnaire administered by two trained nurses. In the univariate analyses, the order of pregnancy of the study subject, the number of spontaneous and induced abortions reported by the mother before giving birth to the study subjects, the duration of breast-feeding and monthly family income were significantly associated with Type 1 diabetes in a dose-response manner. There was a U-shaped relationship with Type 1 diabetes for birth weight and paternal age at the conception of the study subjects. After further adjustment for multiple risk factors through logistic regression analysis, the biological gradient for pregnancy order, duration of breast-feeding, and the U-shaped relationship for paternal age remained statistically significant.

Abortion, Induced↗

Role of an outpatient clinic in screening chronic complications of diabetes: a model for diabetes managed care.

The purpose of this study was to evaluate the need for an outpatient clinic for screening chronic complications of diabetes mellitus and to explore the major risk factors for such complications. A total of 558 patients (293 men and 265 women, aged 61.4 +/- 10.0 yr) with non-insulin-dependent diabetes mellitus were recruited. All examinations were performed in all patients except for those with previously known complications. A nonmydriatic fundus camera was used to detect retinopathy. Microalbuminuria was detected with a semiquantitative method. A monofilament, semiquantitative tuning fork and neurometer were used to detect peripheral neuropathy. The relationships of demographic and metabolic factors with diabetic complications were analyzed. Among the 558 patients, 443 (79.3%) were found to have at least one chronic complication. Less than half (41.5%) of patients had been identified as having a complication(s) before screening. The rates of undiagnosed complications ranged from 46.7% to 83.4% for each complication. The duration of diabetes, hemoglobin A1c (HbA1c), and systolic blood pressure (BP) were strongly associated with microvascular complications (p = 0.009, 0.018 and 0.037, respectively). The microvascular complication rates reached a plateau when HbA1c reached 8.0% at least among patients with a systolic BP of less than 130 mmHg. Our findings indicate that undiagnosed complications (average, 58.5%) can be found with routine screening, increasing the chances for prompt attention and early intervention. The duration of diabetes, HbA1c, and systolic BP were strongly associated with microvascular complications. Diabetes care can be improved by the implementation of a screening clinic in daily practice. Identification of the specific risk factors in a defined population in specific clinical settings will allow early modification of interventions for optimal diabetes care.

Adult↗

Insertion/deletion polymorphism of the angiotensin I-converting enzyme gene in patients with hypertension, non-insulin-dependent diabetes mellitus, and coronary heart disease in Taiwan.

An insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene has been identified that determines most of the plasma ACE activity genetically. Association of the D allele with insulin sensitivity and of the D/D genotype with coronary heart disease (CHD) has been reported in various ethnic populations. To study the role of this genetic polymorphism in patients with hypertension, non-insulin-dependent diabetes mellitus (NIDDM), and NIDDM with CHD in a Taiwanese population, we used a polymerase chain reaction (PCR)-based genotyping technique with an insertion-specific primer for confirmation of the I allele. One hundred ninety-seven unrelated normal controls, 67 subjects with hypertension, 107 subjects with NIDDM, and 70 subjects with NIDDM and CHD were recruited for this study; all were Han Chinese. Subjects without a history of diabetes were studied by a standard 75-g oral glucose tolerance test. Hypertension was diagnosed according to the Fifth Joint National Committee criteria, and CHD was confirmed by a history of acute myocardial infarction and coronary angiographic intervention. The frequency of the I allele of the ACE gene in the normal population was 64.2%, which was higher than reported in white populations. The prevalence of the I allele of the ACE gene was not significantly increased in subjects with hypertension (73.1%), NIDDM (62.1%), and NIDDM with CHD (65%) compared with healthy controls. The I allele of the ACE gene did not correlate with demographic and metabolic variables. I/D polymorphism of the ACE gene is not a marker for hypertension, NIDDM, or CHD in this Taiwanese population.

Age of Onset↗

Anti-GAD65 autoantibody in Taiwanese patients with insulin-dependent diabetes mellitus: effect of HLA on anti-GAD65 positivity and clinical characteristics.

OBJECTIVE: Anti-GAD65 antibody has been studied widely in patients with insulin-dependent diabetes mellitus (IDDM) in many different populations. However, the prevalence of GAD65 autoantibody has not been assessed in Taiwanese patients with IDDM. We therefore characterized GAD65 antibody and investigated the effect of HLA-DR phenotypes on GAD65 autoimmunity and other clinical characteristics in Taiwanese subjects with IDDM. SUBJECTS AND MEASUREMENTS: Two hundred and twenty-five patients (male 102, female 123) with IDDM were recruited. The diagnostic criteria for IDDM were age of onset before 30 years, presence of diabetic ketoacidosis, and insulin-dependency within 3 years of onset. We employed a radioligand method to detect GAD65 antibody. HLA-DR typing was performed by the PCR-SSO techniques. Plasma C-peptide and anti-thyroid microsomal antibody were also measured. RESULTS: The prevalence of GAD65 antibody according to duration of disease were 50/91 (54.9%), 37/95 (38.9%), 8/24 (33%), and 3/15 (20%) among the groups of duration < or = 5, 6-10, 11-15, and > 15 years, respectively (p = 0.0011). There were no significant differences between GAD(+) and GAD(-) patients in age of onset (11.5 +/- 6.5 and 11.6 +/- 13.4 years, respectively), gender distribution (male:female 39:59 and 58:69, respectively) and percentage with residual beta cell function (38.8% and 29.1%, respectively). Multiple regression analysis revealed that duration of IDDM correlated inversely with residual beta cell function. Earlier onset of IDDM correlated with a loss of beta cell function and a HLA-DR phenotype containing DR3/4, DR3/3 or DR3/9. CONCLUSIONS: Prevalence of GAD65 autoantibody among Taiwanese subjects with IDDM was negatively correlated with duration of disease. Different determinants in the HLA-DR locus contributed to the clinical onset of IDDM but not to GAD autoimmunity.

Adolescent↗

Lipid profile and peripheral vascular disease in arseniasis-hyperendemic villages in Taiwan.

To examine whether lipid abnormalities contributed to the endemic peripheral vascular disease (PVD) in villages where arseniasis was hyperendemic in Taiwan, the authors studied 533 adults with Doppler ultrasound and lipid profiles including total cholesterol, triglyceride, high- and low-density lipoprotein cholesterol, apolipoprotein AI, and apolipoprotein B. Among them, 63 had PVD based on an ankle-brachial index < 0.90. Long-term arsenic exposure indices including cumulative arsenic exposure in mg/L-years, duration of drinking artesian well water in years, and duration of living in arseniasis-hyperendemic villages in years were calculated from detailed history obtained through standardized interviews based on a structured questionnaire and arsenic concentration in well water. Possible confounders including age, sex, body mass index, cigarette smoking, and disease status of diabetes mellitus and hypertension were considered in the analyses. None of the lipid profiles differed significantly between the presence and absence of PVD. The odds ratios for PVD did not differ among different quintiles of lipid profiles with the lowest quintile as the referent. However, a significant dose-response relation was found for the long-term arsenic exposure indices. The multivariate-adjusted odds ratios for cumulative arsenic exposure of 0.1 approximately 19.9 and > or = 20 mg/L-years were 2.77 and 4.68, respectively, compared with the unexposed. These results suggest that the PVD in arseniasis-hyperendemic villages is correlated with ingested inorganic arsenic and not with the lipid profiles.

Adult↗

Induction and suppression of renal and hepatic cytochrome P450-dependent monooxygenases by acute and chronic streptozotocin diabetes in hamsters.

The acute and chronic effects of streptozotocin diabetes on kidney and liver microsomal monooxygenases were studied using hamsters 2 days and 6 weeks following treatment with the diabetogen, respectively. Acute diabetes increased aniline hydroxylation and N-nitrosodimethylamine demethylation, decreased pentoxyresorufin O-dealkylation, without affecting benzo(a)pyrene hydroxylation and 7-ethoxycoumarin O-deethylation in kidney and liver microsomes. The effects of chronic diabetes on the microsomal monooxygenases were similar to the effects of acute diabetes, except that the chronic diabetic condition markedly decreased benzo(a)pyrene and 7-ethoxycoumarin oxidations in kidney microsomes. Total cytochrome P450 content and NADPH-cytochrome P450 reductase activity in kidney and liver microsomes of the diabetic hamsters were similar to the controls. Gel electrophoresis of microsomes from control and streptozoptocin treated hamster tissues revealed that diabetes enhanced the intensity of protein band(s) in the P450 molecular weight region. Immunoblotting of microsomal proteins showed that acute and chronic streptozotocin diabetes induced proteins immunorelated to P450s 2E1 and 1A in kidney and liver. In marked contrast, the acute and chronic diabetic conditions decreased the level of a P450 2B-immunorelated protein(s) in kidney and liver. The present study demonstrates that acute and chronic streptozotocin diabetes has the ability to induce P450 2E1 and 1A and suppress P450 2B in hamster kidney and liver and that the hamster monooxygenase responds to diabetes differently from the rat enzyme.

Acute Disease↗

Dose-response relationship between peripheral vascular disease and ingested inorganic arsenic among residents in blackfoot disease endemic villages in Taiwan.

The purpose of this study was to examine the correlation between previous arsenic exposure and peripheral vascular disease after stopping consumption of high-arsenic artesian well water for more than two decades in blackfoot disease endemic villages in Taiwan. A total of 582 adults (263 men and 319 women, aged 52.6 +/- 10.6 years) living in these villages underwent Doppler ultrasound measurement of systolic pressures on bilateral ankle (posterior tibial and dorsal pedal) and brachial arteries and estimation for long-term arsenic exposure. The diagnosis of peripheral vascular disease was based on an ankle-brachial index (the ratio between ankle and brachial systolic pressures) <0.90 on either side. Three indices of arsenic exposure were estimated: (1) duration of living in blackfoot disease endemic villages; (2) duration of artesian well water consumption; and (3) cumulative arsenic exposure in mg/l-years based on the detailed history of residential addresses and artesian well water consumption and the arsenic concentration in artesian well water. Multiple logistic regression analysis was used to assess the association between peripheral vascular disease and arsenic exposure. A dose-response relation was observed between the prevalence of peripheral vascular disease and the long-term arsenic exposure. The odds ratios (95% confidence intervals) after adjustment for age, sex, body mass index, cigarette smoking, serum cholesterol and triglyceride levels, diabetes mellitus and hypertension were 2.77 (0.84-9.14), and 4.28 (1.26-14.54) for those who had cumulative arsenic exposure of 0.1-19.9 and > or = 20.0 mg/l-years, respectively, compared with those who were not exposed. This study suggests a close relation between long-term arsenic exposure and peripheral vascular disease in blackfoot disease endemic villages in Taiwan after stopping consumption of artesian well water.

Adult↗

HLA DRB1/DQA1/DQB1 haplotype determines thyroid autoimmunity in patients with insulin-dependent diabetes mellitus.

OBJECTIVE: Thyroid autoimmunity is frequently associated with insulin-dependent diabetes mellitus (IDDM). The genetic factors which contribute to thyroid autoimmunity and IDDM have been described but vary between different races. We have therefore investigated the effect of class II HLA genes at both loci and the HLA haplotypes on the presence of autoimmunity in patients with IDDM in Taiwan. SUBJECTS AND MEASUREMENTS: Eighty-three patients with IDDM and 105 unrelated normal controls were recruited for the measurement of thyroid autoantibodies and for genotyping of HLA DRB1, DQA1 and DQB1 by polymerase chain reaction-based DNA typing techniques. RESULTS: Among 83 patients with IDDM, 23 (27.7%) were positive for antithyroid autoantibodies. Compared to those without thyroid autoimmunity, there was a female preponderance for IDDM with thyroid autoimmunity (female: male, 3:20 vs 29:31). Among the DR specificities, DR6 was associated with a weak protective effect against thyroid autoimmunity in IDDM patients. Upon detailed analysis of class II HLA haplotypes, the DRB1*0301/ DQA1*0501/DQB1*0201 haplotype was found to be associated with an increased risk of IDDM regardless of thyroid autoimmunity, while DRB1*0405/DQA1*0301/ DQB1*0401 was significantly increased only in the IDDM patients with thyroid autoimmunity. IDDM individuals with the HLA DRB1*0405/DQA1*0301/DQB1*0302 haplotype were not at risk of thyroid autoimmunity. CONCLUSIONS: Our data indicated that there was a generalized genetic factor within or associated with the DRB1*0301/DQA1*0501/DQB1*0201 haplotype, and a more restricted effect with the DRB1*0405/DQA1*0301/DQB1*0401 haplotype which led to thyroid autoimmunity in patients with insulin-dependent diabetes mellitus.

Adolescent↗

Signal transduction pathways for interleukin 4 and insulin in human hepatoma cells.

IRS-1 has been found to relay the signals from the receptors for insulin, insulin-like growth factor-1, growth hormone, and many cytokines for the downstream effects in the various cell types tested. For interleukin 4 signaling, most studies were performed on hematopoietic cells and cell lines transfected with rat liver IRS-1 cDNA. In a liver cell lineage, IRS-1 expression has been found to be increased in hepatoma cells and hepatocytes in regenerating liver. To elucidate the possible function and the signal transduction pathway for interleukin 4, in comparison with insulin, in liver cells, we used the Hep 3B hepatoma cell line as a model system. Following insulin and interleukin 4 stimulation, rapid tyrosyl phosphorylation of IRS-1 occurred. Interleukin 4, but not insulin, stimulated the tyrosine phosphorylation of JAK1 and, to a lesser extent, JAK2. In contrast to the other cell types, the association of IRS-1 and Grb2 through the SH2 of Grb2 was demonstrated after IL-4 and insulin stimulation of the Hep3B hepatoma cells. Both insulin and interleukin 4 stimulated tyrosine phosphorylation and the enzyme activity of Erk1 kinase. Our results indicate that interleukin 4 and insulin might modulate hepatic cell growth and differentiation through many different or common pathways for the activation of JAK kinases and the usage of IRS-1 as a docking protein. The binding of IRS-1 with Grb2 after IL-4 as well as insulin stimulation may lead to MAP kinase activation, probably through the Grb2/sos/p21ras pathway.

Adaptor Proteins, Signal Transducing↗

Mitochondrial gene mutations in patients with insulin-dependent diabetes mellitus in Taiwan.

We studied the prevalence of mitochondrial gene mutations in subjects with insulin-dependent diabetes mellitus (IDDM) in a Chinese population living in Taiwan. Eighty-four subjects with insulin-dependent diabetes mellitus and 105 unrelated normal controls were recruited in the present study. Both an A-to-G mutation at position 3243 and a mutation at position 8,344 of the mitochondrial DNA were screened by polymerase chain reaction-restriction fragment length polymorphism methods and confirmed by direct DNA sequence analysis. The insulin secretory response was assessed by the C-peptide response to glucagon administration. Among 84 IDDM patients, two (2.4%) subjects were found to carry the 3,243 nucleotide pair (np) mutation. There was no np 8,344 mutation in this series. Of the two subjects carrying a mitochondrial gene mutation, case 1 manifested initially as gestational diabetes mellitus. Manifestation of case 2 was consistent with MELAS, a syndrome of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes. The pancreatic beta cell reserve was reduced, as the glucagon-stimulated C-peptide response was very low in these two cases. HLA genotyping studies revealed that case 2 carried DRB1*0301-DQA1*0501-DQB*0201/ DRB1*0405-DQA1*0301-DQB1*0302, which was the most susceptible genotype to IDDM in our population. Anti-GAD65 antibody was also positive in this patient. In addition to the nuclear genes, a defective mitochondrial gene might contribute to some of the clinical cases with IDDM.

Adult↗

A rapid method to study heat shock protein 70-2 gene polymorphism in insulin-dependent diabetes mellitus.

To examine the role of DNA loci within the human leukocyte antigen (HLA) region and insulin-dependent diabetes mellitus (IDDM), we studied fine mapping of HSP70-2 gene. Polymerase chain reaction (PCR)-based genotyping was then developed and applied to type HSP70-2 in 59 patients with IDDM and 83 unrelated controls recruited from the inhabitants of northern Taiwan. Southern blot analysis revealed a diallelic PstI polymorphism of the HSP 70-2 gene, i.e., 9.6- and 8.5-kb alleles. The polymorphic site was mapped in the intragenic PstI sequences (nucleotides 1051-1056) of the HSP70-2 gene. PCR-based restriction fragment length polymorphism studies revealed that the frequency of the 8.5-kb allele was increased in IDDM (56.8%, vs. 40.4% in controls; p < 0.009), with a relative risk of 1.93 (95% confidence interval = 1.20-3.11). The genotypic frequencies of 9.6/9.6, 9.6/8.5, and 8.5/8.5 were 17.0, 52.5, and 30.5% for IDDM were different from those of controls (36.1, 47.0, and 16.9%, respectively; the homozygous 9.6/ 9.6 genotype was significantly decreased in the IDDM group, p < 0.02). In conclusion, we provide a simple, rapid, and nonradioactive method for HSP70-2 genotyping. Our data confirmed that the 8.5-kb allele of HSP70-2 was associated with IDDM susceptibility in the Taiwanese population.

Adult↗

High frequency of two mutations in codon 778 in exon 8 of the ATP7B gene in Taiwanese families with Wilson disease.

The gene for Wilson disease (WD) has been cloned as a P type copper transporter gene (ATP7B). To elucidate the possible genetic mechanism for the diversity of clinical manifestations, we characterised 22 Taiwanese families with WD by microsatellite haplotyping of close DNA markers D13S314-D13S301-D13S316. We also screened for mutations of codon 778 in the transmembrane region. There were at least 15 haplotypes within eight broad subgroups observed among 44 WD chromosomes. Among the 22 unrelated patients, we found that six patients (27%) carried a codon 778 mutation. Nucleotide sequence analysis showed there were two different mutations: the previously reported Arg778Leu mutation in four patients and Arg778Gln, a new mutation, in two patients. The two different mutations of the same codon occurred in two distinct microsatellite haplotypes.

Codon↗