Biomedical subjects

T Y Tai

Publications and source records attributed to T Y Tai.

At least 19 recordsLinked to original sources

PubMed2004

An alarmingly high prevalence of diabetic nephropathy in Asian type 2 diabetic patients: the MicroAlbuminuria Prevalence (MAP) Study.

AIM/HYPOTHESIS: Microalbuminuria represents the earliest clinical evidence of diabetic nephropathy and is a marker of increased cardiovascular morbidity and mortality. Its early detection allows the implementation of individualised and aggressive intervention programmes to reduce cardiovascular risk factors. There is limited information on the prevalence of microalbuminuria among hypertensive type 2 diabetic patients in Asia. METHODS: This cross-sectional epidemiological study aimed to assess the prevalence of microalbuminuria and macroalbuminuria among consecutively screened hypertensive type 2 diabetic adult patients in 103 centres in 10 Asian countries or regions. Predictive factors for microalbuminuria and macroalbuminuria were characterised using a stepwise logistic regression model. RESULTS: A total of 6,801 patients were enrolled and 5,549 patients constituted the per-protocol population (patients with bacteriuria and haematuria were excluded). The prevalence of microalbuminuria was 39.8% (39.2-40.5; 95% CI) and the prevalence of macroalbuminuria was 18.8% (18.2-19.3; 95% CI). Only 11.6% of the patients had systolic and diastolic blood pressure below the 130/80 mm Hg target. In the multivariate analyses, the predictive factors for the presence of microalbuminuria were age, BMI, systolic blood pressure and ethnic origin. The highlighted predictive factors for the presence of macroalbuminuria were age, sex, ethnic origin, BMI, duration of diabetes, presence of diabetic complications, intake of diuretics, intake of calcium channel blockers, diastolic and systolic blood pressure. CONCLUSIONS/INTERPRETATION: The high prevalence (58.6%) of micro or macroalbuminuria observed in these patients is alarming and indicates an impending pandemic of diabetic cardiovascular and renal diseases in Asia with its potential economic consequences.

Albuminuria↗

PubMed2002

The status of diabetes control in Asia--a cross-sectional survey of 24 317 patients with diabetes mellitus in 1998.

AIMS: To establish the status of diabetes control in Asia, the Diabcare-Asia 198 study collected data from 230 diabetes centres in Bangladesh, People's Republic of China, India, Indonesia, Malaysia, Philippines, Singapore, South Korea, Sri Lanka, Taiwan, Thailand and Vietnam from March to December 1998. METHODS: Data were obtained either by patient interview during the enrolment visit or by reviewing medical records for the most recent laboratory assessment and clinical examinations. Blood samples were also collected during patients'. visits for central assessments of HbA1c (normal range 4.7-6.4%). RESULTS: The mean of centrally measured HbA1c was 8.6 +/- 2.0% for 18 211 patients (82% of the analysis population). Of the patients with central HbA1c measurements, the majority (55%) had values exceeding 8%, indicative of poor glycaemic control. The prevalence of retinopathy, microalbuminuria and neuropathy was also higher in the group of patients with higher HbA1c. Based on the findings from central HbA1c measurements and reported local HbA1c assessments, it also appears that more patients with poor glycaemic control did not have access to glycated haemoglobin measurements. Mean HbA1c of thediabetic populations in Bangladesh, Indonesia, Korea, Malaysia and Taiwan were significantly lower (all P = 0.0001, except P = 0.0007 for Malaysia), while that of China, India, Philippines and Vietnam was significantly higher (all P = 0.0001) than the grand mean. CONCLUSIONS: In our study population of the Asian diabetes patients treated at diabetes centres, more than half were not well controlled. The prevalence of diabetic microvascular complications was higher in the group of patients with higher HbA1c. Further therapeutic actions to improve glycaemic control are required to prevent chronic diabetic complications.

Adolescent↗

PubMed2002

The Diabcare-Asia 1998 study--outcomes on control and complications in type 1 and type 2 diabetic patients.

UNLABELLED: The aim of this study was to describe the glycaemic and metabolic control and diabetes-related complications in type 1 and type 2 Asian patients. METHODS: Data of diabetes patients from 230 diabetes centres in 12 Asian regions were collected on a retrospective-prospective basis through review of medical records, interview and laboratory assessments. Analysis of glycated haemoglobin (HbA1c) was carried out in central laboratories appointed by Bio-Rad. The data collection case record forms were scanned electronically. RESULTS: 22177 patients with valid data made up the analysis population. Among patents with type 1 and type 2 diabetes, there was a higher proportion of women than men (53% vs. 47% for type 1 patients and 56% vs. 44% for type 2 diabetes). Hypertension (61%) and overweight (40% with BMI > or = 25 kg/m2 were common in type 2 patients. Dyslipidaemia was also present in at least half of both types of patients. Control of glycaemia (mean HbA,1c and fasting blood glucose [FBG]) was poor in type 1 (9.9 +/- 2.5%; 10.2 +/- 5.2 mmol/l) and type 2 patients (8.5 +/- 2.0%; 8.9 +/- 3.4 mmol/l). Glycaemia in the majority of both types of patients fell short of those stipulated by various guidelines. In type 2 patients, glycaemia deteriorated (HbA1c > 7.5%, FBG > or = 7.0 mmol/l) with duration of diabetes > 7 years. Both types of diabetes appear to share a similar high prevalence of complications of cataract, retinopathy and neuropathy, although the prevalence of cataract (27%) and neuropathy (35%) was higher in type 2 diabetes. Screening for microalbuminuria was not common. CONCLUSIONS: The Inadequate metabolic and hypertension control, especially in type 2 patients, needs to be addressed.

Adult↗

PubMed2001

Exogenous peptides presented by transporter associated with antigen processing (TAP)-deficient and TAP-competent cells: intracellular loading and kinetics of presentation.

This study investigates the differential capacity of TAP-deficient T2 cells, TAP-competent EBV cells, and immature and mature dendritic cells to present peptides to preformed CTL lines. It demonstrates that presentation of exogenous peptides involves peptide uptake and loading onto newly synthesized MHC class I molecules. This mechanism was best demonstrated for low affinity peptides in the presence of irrelevant peptides competing for HLA binding sites. Under these circumstances, inhibition of protein synthesis with cycloheximide or vesicular trafficking with brefeldin A significantly reduced the presentation of low affinity peptides. This was not restored by adding exogenous beta(2)-microglobulin to stabilize the MHC complex on the cell surface. In contrast, presentation of high affinity peptides was not sensitive to cycloheximide or brefeldin A, which suggests that different mechanisms may operate for presentation of high and low affinity peptides by TAP-competent cells. High affinity peptides can apparently compete with peptides in preloaded MHC class I molecules at the cell surface, whereas low affinity peptides require empty MHC molecules within cells. Accordingly, very high concentrations of exogenous low affinity peptides in conjunction with active MHC class I metabolism were required to allow successful presentation against a background of competing intracellular high affinity peptides in TAP-competent cells. These findings have implications for the design of peptide and protein-based vaccines.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2001

Molecular scanning of the human sorbin and SH3-domain-containing-1 (SORBS1) gene: positive association of the T228A polymorphism with obesity and type 2 diabetes.

In the mouse, the SH3P12 or the c-Cbl-associated protein (CAP) has been shown as an important signaling molecule in insulin-stimulated glucose uptake. The human homolog for the sorbin and SH3-domain-containing-1 gene, termed SORBS1, might play a role in human disorders with insulin resistance. To explore the genetic role of SORBS1 in human obesity and type 2 diabetes, we investigated the nucleotide polymorphisms in the SORBS1 gene with molecular scanning. After scanning for a total of 13,136 bp in each of 40 chromosomes, we have identified 14 single nucleotide polymorphisms (SNPs) in the human SORBS1 gene. Among them, two SNPs affected amino acid coding (R74W and T228A), four occurred within exons but did not affect amino acid coding, and the remaining eight occurred within introns, which were located outside of the consensus region of the splicing mechanism. Further studies in 202 non-obese, 113 obese and 455 subjects with type 2 diabetes revealed that the A-allele of the T228A polymorphism in exon 7 exerted a protective role for both obesity [relative risk 0.466; 95% confidence interval (95% CI) 0.265-0.821] and diabetes (relative risk 0.668; 95% CI 0.472-0.945). Neither allele of the R74W polymorphism was associated with either obesity or diabetes. In conclusion, our results suggest that the A228 allele of the T228A polymorphism of the SORBS1 gene is a protective factor for both obesity and diabetes, and also imply that the SORBS1 gene plays an important role in the pathogenesis of human disorders with insulin resistance.

Amino Acid Sequence↗

PubMed2001

Cloning, mapping, and characterization of the human sorbin and SH3 domain containing 1 (SORBS1) gene: a protein associated with c-Abl during insulin signaling in the hepatoma cell line Hep3B.

SH3P12/CAP/ponsin, a gene product with a sorbin homology domain and three consecutive SH3 domains in the carboxy-terminus, has been isolated from murine adipocytes and identified as an important adaptor during insulin signaling. Here we describe the cloning, mapping, and expression of the human homologue, termed SORBS1 (sorbin and SH3 domain containing 1). Multiple transcripts of this gene with different mRNA isoforms were observed among different tissues. Here we report 13 alternatively spliced exons, which were ascertained from the full-length cDNA cloned in adipose, liver, and skeletal muscle tissues. Among the major isoforms, the shortest, 2223-bp, open reading frame (ORF) encodes a protein with a predicted molecular weight of 81.5 kDa, while the longest, 3879-bp, ORF encodes a protein of about 142.2 kDa. This gene was mapped to human chromosome 10q23.3-q24.1, which is a candidate region for insulin resistance found in Pima Indians. In human hepatoma Hep3B cells, SORBS1 was partly dissociated from the insulin receptor complex and bound to c-Abl protein upon insulin stimulation. This interaction with c-Abl was through the third SH3 domain and a possible conformational change of SORBS1 induced by insulin. Our data suggest that c-Abl oncoprotein via SORBS1 might play a role in the insulin signaling pathway.

Amino Acid Sequence↗

PubMed2001

Degeneration of nociceptive nerve terminals in human peripheral neuropathy.

Patients with peripheral neuropathy have symptoms involving small-diameter nociceptive nerves and elevated thermal thresholds. Nociceptive nerves terminate in the epidermis of the skin and are readily demonstrated with the neuronal marker, protein gene product 9.5 (PGP 9.5). To investigate the pathological characteristics of elevated thermal thresholds, we performed PGP 9.5 immunocytochemistry on 3 mm punch skin biopsies (the forearm and the leg) from 55 normal subjects and 35 neuropathic patients. Skin innervation was evaluated by quantifying epidermal nerve densities. Epidermal nerve densities were reduced in neuropathic patients compared to normal subjects. Epidermal nerve densities were variably correlated with thermal thresholds. The proportion of neuropathic patients with reduced epidermal nerve densities was larger than the proportion of neuropathic patients with elevated thermal thresholds. These results indicated that degeneration of epidermal nerve terminals preceded the elevation of thermal thresholds. Skin biopsy together with immunocytochemical demonstration of epidermal innervation offers a new approach to evaluate small-fiber sensory neuropathy.

Adult↗

PubMed2001

Sibling-based association study of the PPARgamma2 Pro12Ala polymorphism and metabolic variables in Chinese and Japanese hypertension families: a SAPPHIRe study. Stanford Asian-Pacific Program in Hypertension and Insulin Resistance.

The peroxisome proliferator activated receptor (PPAR) gamma2 is a transcription factor that has been shown to be involved in adipocyte differentiation, adipogenesis, and insulin sensitivity. To address the role of PPARgamma2 in glucose homeostasis and insulin sensitivity, among many other objectives, we conducted a sibling-controlled association study in a multicenter program - the Stanford Asian-Pacific Program in Hypertension and Insulin Resistance (SAPPHIRe). Approximately 2525 subjects in 734 Chinese and Japanese families have been recruited from six field centers for SAPPHIRe. In total, 1702 subjects including parents and siblings from 449 families have been genotyped for PPARgamma2, of which 328 families were Chinese and 121 Japanese. Only 88 subjects of the 1525 siblings screened for the P12A polymorphism were found to be carriers of the A variant, the most common variant of the PPARgamma2 gene. A variant frequencies of the siblings were 4.27% in Chinese and 2.72% in Japanese. A sibling-controlled association study was performed through genetically discordant sibships (i.e., P/P genotype vs. P/A + A/A genotypes). Specifically, we examined whether there were differences in metabolic variables between the discordant siblings within families. In total, 88 subjects carrying either 1 or 2 A alleles had at least one sibling who was discordant for the P12A polymorphism, yielding a total of 180 individuals from 47 families for analyses, among which 92 siblings were homozygous for wild-type P allele. Siblings with the A variant tended to have lower levels of fasting plasma glucose (OG-10), and lower glucose levels at 60 min following oral glucose loading after adjusting for age, gender, and body mass index. Using a mixed model treating family as a random effect, we found that P12A polymorphism of the PPARgamma2 gene contributes significantly to the variance in fasting plasma glucose, glucose level at 60 min, and insulin-resistance homeostasis model assessment. Our results suggest that within families siblings with the A variant in the PPARgamma2 gene may be more likely to have better glucose tolerance and insulin sensitivity independent of obesity in Chinese and Japanese populations.

Adult↗

PubMed2001

Direct costs-of-illness of patients with diabetes mellitus in Taiwan.

The purpose of the present study was to examine the characteristics of healthcare costs for diabetic patients in Taiwan. The study analyzed claim data from the Bureau of National Health Insurance for the period from July 1997 to June 1998. There were 536159 documented diabetic patients who were treated within the universal healthcare system in Taiwan during this study period. The annual number of visits of these diabetic patients was 6.2% of the total outpatient visits of all patients due to all causes during the one-year study period. Diabetes-related problems were the causes of 25.2% of outpatient visits among diabetic patients, while 74.8% of visits were for causes unrelated to diabetes. The distribution of treatment for the diabetic patients was by oral hypoglycemic agents 88.3%, insulin only 6.9%, and a combination of insulin and oral agents 4.8%. Diabetic patients accounted for 4,724,711 hospital inpatient days during the study period, which was 22.1% of the total inpatient days in Taiwan. Of the inpatient admissions, 13.9% were for diabetes as the principal cause, 23.4% were for diabetes-related disease, and 62.7% were for causes unrelated to diabetes. The direct costs of healthcare for the documented diabetic patients was 11.5% of the total costs of healthcare in Taiwan, and was 4.3 times higher than the average costs of care for non-diabetic individuals.

Ambulatory Care↗

PubMed2001

The current state of diabetes management in Taiwan.

The aim of this study was to provide an overview of diabetes management and complication status in Taiwan. A cohort of 2446 patients (from 25 diabetic centers) with more than 12 months of diabetes management participated and data were collected by interviews and reviewing the medical records. Overall, 97% were diagnosed as type 2 diabetes, with a mean age (+/-S.D.) of 61.6+/-11.3 years, duration of diabetes of 10.3+/-7.3 years and age at onset of diabetes of 51.5+/-11.8 years. Mean BMI was 25.1+/-3.6 kg/m(2) and about 50% had BMI>25 kg/m(2). Majority (75%) were treated with oral hypoglycemic agents (OHAs), 14% with insulin and 10% with combination of insulin and OHA. Mean HbA(1c) was 8.1+/-1.6% and 59% had HbA(1c) >7.4% (1% above the upper limit of normal range, 4.7-6.4%). Mean FBG was 9.0+/-3.3 mmol/l and 59% had FBG>7.8 mmol/l. Of all the patients who had screening for complications, cataract (38%), neuropathy (30%), proteinuria (17%) and stroke (6%) were the most frequently reported eye, feet, kidney and late complications. We conclude that the majority of patients involved in this study had unsatisfactory glycaemic control which may lead to diabetes complications.

Adolescent↗

PubMed2001

Platelet collagen receptor alpha2beta1 integrin and glycoprotein IIIa Pl(A1/A2) polymorphisms are not associated with nephropathy in type 2 diabetes.

Platelet glycoprotein receptors play a role in the pathogenesis of chronic diabetic complications. Genetic polymorphisms of the alpha2beta1 integrin and glycoprotein IIIa (GPIIIa) have been associated with myocardial infarction, stroke, and diabetic retinopathy. To identify risk factors for their development in a cohort of patients with type 2 diabetes, we evaluated clinical variables and genetic polymorphisms in the alpha2beta1 integrin and GPIIIa genes. Two hundred thirty-four subjects with type 2 diabetes (126 patients with and 108 patients without diabetic nephropathy), as well as 217 nondiabetic healthy subjects, were recruited for this study. Clinical factors for investigation included sex, age at diagnosis, duration of diabetes, body mass index (BMI), and fasting plasma glucose, hemoglobin A(1c) (HbA(1c)), total cholesterol, and triglyceride levels. Genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism analyses. No difference in the Bgl II polymorphism of the alpha2beta1 integrin gene was found between patients with type 2 diabetes with or without nephropathy (11 [8.7%], 47 [37.3%], and 68 patients [54.0%] versus 10 [9.3%], 32 [29.6%], and 66 patients [61.1%] for Bgl II+/+, Bgl II+/-, and Bgl II-/-, respectively; P = 0.271). Multiple logistic regression analyses showed that duration of diabetes, BMI, hypertension, and poor glycemic control were four independent predictors for the development of diabetic nephropathy. No contribution of the Bgl II+ allele of the alpha2beta1 integrin was found for the risk for nephropathy (odds ratio, 1.258; 95% confidence interval, 0.655 to 2.418; P = 0.490). The Pl(A2) allele genotype was not found among our studied subjects. In conclusion, age, duration of diabetes, BMI, and HbA(1c) level are strong predictors for nephropathy in patients with type 2 diabetes. However, the Bgl II polymorphism of the alpha2beta1 integrin gene and the Apa I polymorphism of the platelet GPIIIa gene do not have a major role in the development of diabetic nephropathy in our population.

Blood Platelets↗

PubMed2001

Weight reduction increases plasma levels of an adipose-derived anti-inflammatory protein, adiponectin.

Adiponectin, an adipose tissue-specific plasma protein, was recently revealed to have anti-inflammatory effects on the cellular components of vascular wall. Its plasma levels were significantly lower in men than in women and lower in human subjects with obesity, type 2 diabetes mellitus, or coronary artery disease. Therefore, it may provide a biological link between obesity and obesity-related disorders such as atherosclerosis, against which it may confer protection. In this study, we observed the changes of plasma adiponectin levels with body weight reduction among 22 obese patients who received gastric partition surgery. A 46% increase of mean plasma adiponectin level was accompanied by a 21% reduction in mean body mass index. The change in plasma adiponectin levels was significantly correlated with the changes in body mass index (r = -0.5, P = 0.01), waist (r = -0.4, P = 0.04) and hip (r = -0.6, P = 0.0007) circumferences, and steady state plasma glucose levels (r = -0.5, P = 0.04). In multivariate linear regression models, the increase in adiponectin as a dependent variable was significantly related to the decrease in hip circumference (beta = -0.16, P = 0.028), after adjusting body mass index and waist circumference. The change in steady state plasma glucose levels as a dependent variable was related to the increase of adiponectin with a marginal significance (beta = -0.92, P = 0.053), after adjusting body mass index and waist and hip circumferences. In conclusion, body weight reduction increased the plasma levels of a protective adipocytokine, adiponectin. In addition, the increase in plasma adiponectin despite the reduction of the only tissue of its own synthesis suggests that the expression of adiponectin is under feedback inhibition in obesity.

Adiponectin↗

PubMed2001

Rosiglitazone (BRL 49653) enhances insulin secretory response via phosphatidylinositol 3-kinase pathway.

To elucidate the direct effect of rosiglitazone (RSG), a new thiazolidinedione antihyperglycemic agent, on pancreatic insulin secretion, an in situ investigation by rat pancreatic perfusion was performed. At a basal glucose concentration of 6 mmol/l, RSG (0.045-4.5 micromol/l) stimulated insulin release in a dose-dependent manner. In addition, 4.5 micromol/l RSG potentiated the glucose (10 mmol/l)-induced insulin secretion. Both the first and second phases of glucose-induced insulin secretion were significantly enhanced by RSG, by 80.7 and 52.4%, respectively. The effects of RSG on insulin secretion were inhibited by a phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002. In contrast, the glucose-stimulated insulin secretion was not affected by LY294002. The potentiation effect of RSG on glucose-stimulated insulin secretion, in both the first and second phases, was significantly blocked by LY294002. These results suggest that RSG has a direct potentiation effect on insulin secretion in the presence of 10 mmol/l glucose, mediated through PI3K activity. The inability of LY294002 to inhibit glucose-induced insulin secretion suggests that different pathways are responsible for glucose and RSG signaling.

Animals↗

PubMed2000

Epidemiologic study of type 2 diabetes in Taiwan.

Diabetes mellitus (DM) in adults is a global health problem, although its prevalence varies widely between different populations and the rate has generally increased worldwide. In Taiwan, the mortality rate from DM has almost doubled over the past 10 years. The prevalence of DM in Taiwan was established between 1985 and 1996 and the rates were between 4.9 and 9.2%. The prevalence of impaired glucose tolerance (IGT) was 15.5% (men 15% and women 15.9%). The prevalence of DM and IGT increased significantly with age for both genders. The significant factors associated with newly diagnosed DM were age, BMI, family history of DM, systolic blood pressure (hypertension), physical activity and serum triglyceride levels. The prevalence of large vessel disease (LVD) in DM and non-diabetic subjects were 20.0 and 12.9%, respectively. Among diabetics, 15.8% had ischemic heart disease (IHD), 1.7% leg vessel disease (leg VD), and 2.5% stroke. In non-diabetics, the prevalence of the aforementioned macroangiopathies were 11.5, 0.2 and 1.2%, respectively. The diabetics had a significantly higher prevalence of macrovascular disease than non-diabetic subjects. The most significantly associated with the LVD was serum cholesterol levels. Serum cholesterol and HbA1(c) were significantly associated with the development of IHD. Cigarette smoking and female gender were significantly associated with the leg VD. The prevalence of diabetic retinopathy (DR) was 35.0%. (background DR 30%, preproliferative DR 2.8% and proliferative DR 2.2%, respectively.) The prevalence of DR for previously and newly diagnosed diabetics were 45.2 and 28.3% (men 42.8 vs. 33.3% and women 47.5 vs. 24.8%), respectively. From multiple logistic regression analysis, duration of DM was the most important risk factor related to DR. Diabetic subjects treated with insulin had a higher risk of developing retinopathy than those treated with dietary control. The prevalence of nephropathy and neuropathy were 12.9 and 23.5%, respectively. For those patients with and those without nephropathy and neuropathy, the duration of DM, percentage of insulin treatment, percentage of hypertension, and fasting plasma glucose were significantly different. Diabetic duration, hypertension, insulin treatment and glycemic control consistently correlated with nephropathy and neuropathy. In conclusion, the prevalence of DM in Taiwan was between 4.9 and 9.2%, and the prevalence of IGT was 15.5%. The possible risk factors of newly diagnosed diabetes were age, family history of DM, BMI, SBP (hypertension), physical activity and triglyceride levels. Diabetes in Chinese subjects share many characteristics similar to other Asian populations. The burden imposed by the chronic complications of diabetes is massive. In Taiwan, the mortality rates from DM have increased greatly over the past 10 years. Reduction of the modificable risk factors such as BMI, hypertenion and dyslipidemia, and increase of physical activity and good glycemic control through public health efforts may help to reduce the risk of DM and its chronic complications.

Adult↗

PubMed2000

The incidence of type 2 diabetes mellitus in Taiwan.

Currently, diabetes mellitus is the fifth leading cause of death in Taiwan. The trends of diabetes mortality is increasing steadily. Epidemiologic studies also showed increasing prevalence of diabetes mellitus over the past few decades. The incidence of diabetes mellitus in Taiwan has only been studied in recent 10 years. The areas that have been included as study areas for diabetes incidence are Kin-Chen (Kinmen), Chu-Dung, Pu-Tzu, Pu-Li and Pu-Tai. The reported incidence rates ranged from 1.0 to 4.0% per year for people with varying degrees of baseline plasma glucose levels not reaching the diagnosis of diabetes mellitus according to the criteria of the World Health Organization. Age, baseline glucose level, and obesity are important predictors for the development of diabetes mellitus. In the Pu-Tai study, which was aimed at following a group of people who had been living in the hyperendemic villages of blackfoot disease and had been exposed to arsenic from drinking artesian well water, the incidence of diabetes mellitus was calculated to be 27.4 per 1000 person years. The incidence of diabetes mellitus in these arseniasis-hyperendemic villages correlated with age, body mass index and cumulative arsenic exposure.

Adult↗

PubMed2000

Vitamin D receptor gene polymorphisms influence susceptibility to type 1 diabetes mellitus in the Taiwanese population.

OBJECTIVE: Vitamin D and its receptor have been suggested to play a role in the pathogenesis of type 1 diabetes mellitus. We have therefore studied the influence of vitamin D receptor (VDR) gene polymorphisms on susceptibility to type 1 diabetes, and rates of glutamic acid decarboxylase (GAD65) autoantibody and islet cell autoantibody (ICA512) positivity. SUBJECTS: AND MEASUREMENTS One hundred and fifty-seven type 1 diabetic patients and 248 unrelated normal controls were recruited for this study. Genomic DNA was extracted from peripheral blood leucocytes. All type 1 diabetic patients and controls were genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP), for three restriction sites in the VDR gene, BsmI, ApaI and TaqI. The chi2 test was used to compare the frequency of the VDR gene polymorphisms in patients and normal controls. The association of VDR gene polymorphisms in type 1 diabetes with the presence of GAD65 and ICA512 autoantibodies were also examined using the chi2 test. RESULTS: The allele frequency of the BsmI and ApaI polymorphisms, but not TaqI polymorphism, differed between patients and controls (BsmI P = 0.015; ApaI P = 0.018; TaqI P = 0.266). However, after correction for the three different polymorphisms tested, only the BsmI was significant (pc = 0.045). CONCLUSIONS: Vitamin D receptor gene polymorphisms were associated with type 1 diabetes in a Taiwanese population. However, functional studies are needed to establish the role of the vitamin D receptor in the pathogenesis of type 1 diabetes mellitus.

Adolescent↗

PubMed2000

Peroxisome proliferator-activated receptor gamma 2 Pro12Ala gene variant is strongly associated with larger body mass in the Taiwanese.

The peroxisome proliferator-activated receptor gamma 2 (PPARgamma2) has been studied extensively because of its putative role in adipocyte differentiation and insulin sensitivity. The association of the Pro12Ala and Pro115Gln PPARgamma2 gene variants with type 2 diabetes mellitus, the body mass index (BMI), and other diabetes-related phenotypes was examined in the Taiwanese population. Genotypes were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Allele frequencies were compared between 280 subjects with type 2 diabetes mellitus and 310 subjects without diabetes using the chi-square test. Continuous phenotype analysis was performed by multiple logistic regression adjusting for age and BMI where appropriate. There was no significant association between the Pro12Ala gene variant and type 2 diabetes; the frequency of the Ala12 allele was 0.03 in type 2 diabetics and 0.04 in nondiabetics (P = .40). The Gln115 allele was not detected in any of the cases or controls. In multiple linear regression analysis of all cases and controls combined adjusted for age, sex, and diabetic status, carriers of the Ala12 allele had a mean BMI of 25.9+/-0.5 kg/m2 (mean +/- SE), compared with 24.2+/-0.1 kg/m2 in Pro12 homozygotes (P < .001). In addition, carriers of the Ala12 allele have a 2.9 times (95% confidence interval [CI], 1.5 to 5.5) higher odds of having a BMI of at least 25 kg/m2. These results suggest that in the Taiwanese, the Pro12Ala PPARgamma2 gene variant may contribute to fat accumulation and a higher BMI independent of type 2 diabetes. These results need to be confirmed in future studies, as a linkage disequilibrium of this variant with other mutations cannot be ruled out.

Adult↗

PubMed2000

Long-term arsenic exposure and incidence of non-insulin-dependent diabetes mellitus: a cohort study in arseniasis-hyperendemic villages in Taiwan.

Diabetes prevalence in arseniasis-hyperendemic villages in Taiwan has been reported to be significantly higher than in the general population. The aim of this cohort study was to further evaluate the association between ingested inorganic arsenic and the incidence of non-insulin-dependent diabetes mellitus in these villages. A total of 446 nondiabetic residents in these villages were followed biannually by oral glucose tolerance test. Diabetes is defined as a fasting plasma glucose level > or = 7.8 mmol/L and/or a 2-hr post-load glucose level > or = 11.1 mmol/L. During the follow-up period of 1499.5 person-years, 41 cases developed diabetes, showing an overall incidence of 27.4/1,000 person-years. The incidence of diabetes correlated with age, body mass index, and cumulative arsenic exposure. The multivariate-adjusted relative risks were 1.6, 2.3, and 2.1 for age > or = 55 versus < 55 years, a body mass index ¿Greater/Equal to] 25 versus < 25 kg/m(2), and a cumulative arsenic exposure > or = 17 versus < 17 mg/L-years, respectively. The incidence density ratios (95% confidence intervals) between the hyperendemic villages and the two nonendemic control townships were 3.6 (3.5-3.6), 2.3 (1.1-4.9), 4.3 (2.4-7.7), and 5.5 (2.2-13.5), respectively, for the age groups of 35-44, 45-54, 55-64, and 65-74 years. The findings are consistent with our previous cross-sectional observation that ingested inorganic arsenic is diabetogenic in human beings.

Adult↗