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Biomedical subjects

L M Chuang

Publications and source records attributed to L M Chuang.

At least 37 records · Page 2Linked to original sources
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

Beta cell function declines with age in glucose tolerant Caucasians.

OBJECTIVE: As type 2 diabetes results from an imbalance between insulin sensitivity and beta cell function, either or both may worsen with age. However, existing data are controversial on the effect of ageing on both insulin sensitivity and beta cell function. SUBJECTS AND DESIGN: We enrolled 149 healthy, glucose tolerant and normotensive Caucasians (age 35 +/- 1 years, body mass index 26.07 +/- 0.44 kg/m2, waist-hip ratio 0.842 +/- 0.009 cm/cm, mean +/- standard error). A cross-sectional study was designed to examine the impact of age on insulin sensitivity and beta cell function. Their beta cell function (percentage B [%B]) and insulin sensitivity (percentage S [%S]) were estimated using the homeostasis model assessment. RESULTS: Simple regression analysis revealed that %B declined with age (P = 0.008) while no relation was found between %S and age (P = 0.769). A stepwise regression analysis revealed that body mass index and diastolic blood pressure explained 14.7% of variation in %S, while age, waist-hip ratio, gender, and systolic blood pressure had no influence on %S. Age, body mass index and diastolic blood pressure together accounted for 21.7% of variation in %B, with age being an independent variable. CONCLUSIONS: In the present study, we showed that beta cell function declined with age at a rate of about 1% per year. In contrast, insulin sensitivity was not affected by ageing. Our observations suggest that the age-related decline in glucose tolerance is primarily related to the loss of beta-cell function.

Adult↗
PubMed2000

Insulin sensitivity is inversely correlated with plasma intact parathyroid hormone level.

Abnormal glucose metabolism and a high prevalence of diabetes have been reported in patients with primary and secondary hyperparathyroidism. We hypothesize that plasma intact parathyroid hormone (iPTH) level is a determinant of either insulin sensitivity or beta-cell function. The study included 52 normotensive, healthy subjects with glucose tolerance. Insulin sensitivity and beta-cell function were assessed using a hyperglycemic clamp. Fasting plasma iPTH was determined. The relationships between its level and insulin sensitivity index and beta-cell function were examined. Insulin sensitivity index was inversely correlated with plasma iPTH level (r2 = .104, P = .020). The first phase insulin response was positively correlated with plasma iPTH level (r2 = .098, P = .023), but no correlation existed with the second phase insulin response. After adjusting for age, gender, ethnicity, and waist-to-hip ratio, plasma iPTH level was an independent determinant of insulin sensitivity index (P = .019). However, no independent relationship between plasma iPTH level and beta-cell function (the first phase and second phase insulin response) was found. In normotensive, glucose-tolerant, and healthy subjects, plasma iPTH level accounts for 10.4% of the variation in insulin sensitivity index. For each pg/mL increment in plasma iPTH level, there is a decrease of 0.247 micromol/L/m2/min/pmol/L in insulin sensitivity index. Although the molecular basis of this relationship is not clear, our results indicate that plasma iPTH level is inversely correlated with insulin sensitivity index.

Adult↗
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

The I27L amino acid polymorphism of hepatic nuclear factor-1alpha is associated with insulin resistance.

Mutations of the hepatic nuclear factor-1alpha (HNF-1alpha) gene have been found in patients with maturity-onset diabetes of the young. We examined the relation between the I27L polymorphism of HNF-1alpha and insulin sensitivity and beta-cell function assessed by a hyperglycemic clamp. This study included 52 healthy glucose-tolerant and normotensive subjects (age, 19-40 yr; body mass index, 17.58-35.61 kg/m2; waist/hip ratio, 0.65-1.03). We identified 19 LL subjects, 24 IL, and 9 II subjects. No difference was noted in the demographic features among the three genotypes. The LL group had the highest postchallenge insulin levels at 30 and 90 min (P = 0.038 and P = 0.015, respectively) and also the highest insulin area under curve (P = 0.009) among the three genotypes. The LL group was more insulin resistant than the IL and II groups (P = 0.042 for insulin sensitivity index). After adjusting for age, gender, obesity, and ethnicity, the I27L polymorphism was an independent determinant of the insulin sensitivity index (P = 0.001). However, it had no impact on either the first or second phase insulin response. Therefore, we conclude that the I27L polymorphism is associated with insulin resistance, but not beta-cell function. The mechanism of this association is unclear, but HNF-1alpha may play a role in regulating hepatic glucose metabolism.

Adult↗
PubMed2000

Insulin sensitivity differs among ethnic groups with a compensatory response in beta-cell function.

OBJECTIVE: A drastic difference is evident in the prevalence of type 2 diabetes among ethnic groups. We examined the role of beta-cell function and insulin sensitivity in this disparity among 4 ethnic groups. RESEARCH DESIGN AND METHODS: beta-Cell function and insulin sensitivity were assessed in 77 healthy glucose-tolerant subjects using a hyperglycemic clamp (18 Asian-Americans, 9 African-Americans, 34 Caucasians, and 16 Mexican-Americans). RESULTS: A wide range of variation was evident in clinical features of the studied subjects. Insulin sensitivity index and the second-phase insulin response differed among the 4 groups (P = 0.0023 and P = 0.0082, respectively), whereas the first-phase insulin response was marginally different (P = 0.1090). Stepwise regression analysis revealed that ethnicity was an independent determinant for the insulin sensitivity index (P = 0.0014) after adjusting for sex, age, diastolic blood pressure, waist-to-hip ratio, and BMI. Also, a compensatory response of beta-cell function was observed among the ethnic groups. CONCLUSIONS: In this study, we observed a drastic difference in insulin sensitivity among the different ethnic groups and observed that their beta-cell function compensates for the prevailing insulin sensitivity. The difference in the prevalence of abnormal glucose tolerance in different ethnic groups could be a result of differences in insulin sensitivity

Adult↗
PubMed2000

Serum leptin and leptin receptor isoforms in omental adipose tissue of nondiabetic women undergoing gynecologic surgery for benign disease.

BACKGROUND AND PURPOSE: Leptin is important in the regulation of fat mass and body weight. Adipose tissue not only secretes leptin but also serves as a site of action for leptin. This study was designed to examine the relationships among tissue expression of leptin receptors, serum leptin, and body mass index. METHODS: Omental adipose tissue and fasting blood samples were obtained from 57 nondiabetic women who underwent surgery for either myoma of the uterus or ovarian cyst. Tissue RNA was extracted using Trizol reagent and serum leptin concentrations were determined with commercial kits. The leptin receptor isoforms in tissues were quantified using real-time Taqman technology. RESULTS: Three leptin receptor isoforms, Ob-Rb, HuB219.1, and HuB219.3, were found in human omental adipose tissue. The amounts of HuB219.1 and HuB219.3 mRNA relative to that of Ob-Rb were 1314.2 and 16.7, respectively. Higher body mass index was significantly correlated with an increase in serum leptin concentration and a decrease in leptin receptor HuB219.1 isoform in omental fat, even after adjustment for age and menopausal status. There was no direct association between serum leptin concentration and tissue HuB219.1 mRNA level. CONCLUSIONS: HuB219.1 is the major isoform of leptin receptor expressed in human omental adipose tissue. Our findings suggest that the shorter leptin receptor isoforms in human omental adipose tissue might play an important role in body weight control. Further studies on the inter-relationship between leptin concentrations and multiple leptin receptor isoforms are needed to elucidate the exact mechanism of obesity.

Adipose Tissue↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1998

Autoimmune IDDM in a sporadic MELAS patient with mitochondrial tRNA(Leu(UUR)) mutation.

We report a 28-year-old young male with MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) presenting with two previous episodes of stroke-like manifestation, lactic acidosis and mitochondrial cardiomyopathy. He was also affected with insulin-dependent diabetes mellitus (IDDM), as diagnosed by the experience of diabetic ketoacidosis (DKA), and dependence on insulin therapy. On admission, the serum lactate level was found to be increased to 5.4 mmol/l, and plasma glucose level to 7.9 mmol/l with haemoglobin A1c 8.4%, while he was using insulin 26-30 units per day. Physical examination revealed a short stature male of height of 150 cm and weight of 49 kg. Mild mental retardation with bilateral sensorineural hearing impairment was observed. After glucagon stimulation, C-peptide levels rose from 0.46 nmol/l to 0.53 nmol/l, indicative of impaired insulin secretion. Anti-glutamate decarboxylase (anti-GAD) antibody was positive. In addition, human leucocyte associated antigen (HLA) typing showed DR3 and DR4, suggesting the strong contribution of autoimmunity to the pathogenesis of IDDM in this patient. Moreover, the result of a treadmill exercise test was positive due to inferior wall myocardial ischaemia. Cardiac catheterization and endomyocardial biopsy disclosed a normal coronary angiogram and confirmed the diagnosis of mitochondrial cardiomyopathy. Molecular genetic analysis of his family revealed a sporadic occurrence of mitochondrial DNA (mtDNA) mutation at base pair (bp) 3243. The degree of heteroplasmy of mtDNA mutation from a total of 19 passages of skin-derived fibroblasts from this patient showed a slightly downward trend. This extremely rare case of sporadic MELAS syndrome with autoimmune IDDM harbouring mtDNA mutation highlights the possible pathogenetic role of mtDNA mutations in autoimmune disease.

Adult↗
PubMed1998

Autoantibodies to thyroid peroxidase in patients with type 1 diabetes in Taiwan.

OBJECTIVE: Type 1 diabetes mellitus is frequently associated with autoimmune thyroid disease (ATD). Genetic susceptibility to autoantibody formation in association with ATD and type 1 diabetes mellitus has been described with varying frequencies, but there is still debate about the situation in the Chinese population. We have, therefore, investigated the prevalence of anti-thyroid peroxidase (anti-TPO) in type 1 diabetic patients, and compared the effect of anti-glutamate decarboxylase (anti-GAD) on the thyroid autoimmunity in patients with type 1 diabetes mellitus in Taiwan. SUBJECTS AND METHODS: Two hundred and forty-three subjects with type 1 diabetes mellitus and seventy unrelated normal controls were recruited for the detection of anti-TPO. Two hundred and seventeen sera from two hundred and forty-three type 1 diabetic patients were tested for anti-GAD. RIA and immunoprecipitation were used for anti-TPO and anti-GAD detection respectively. RESULTS: The intra-assay and interassay coefficients of variation of anti-TPO detected by the RIA method ranged from 5.5% to 11.1%. Among 243 type 1 diabetic patients, 53 (21.8%) were positive for anti-TPO. Compared with those without thyroid autoimmunity, there was a female preponderance for the type 1 diabetic patients with thyroid autoimmunity (female:male, 99:91 vs 37:16 respectively). Among the type 1 diabetic patients with thyroid autoimmunity, anti-TPO tended to occur in those of older age or with long-standing disease. The frequency of anti-GAD was 45.6%, (99 of 217), without gender preponderance (males:females, 18.0% vs 27.61%). Compared with those with negative anti-GAD, no significant difference of anti-TPO positivity for the type 1 diabetic patients with positive anti-GAD was found. CONCLUSION: Our data indicated that the RIA method for anti-TPO detection is sensitive and precise for routine clinical use. The presence of anti-TPO in 21.8% of our type 1 diabetic patients confirmed the strong association of ATD and type 1 diabetes mellitus without ethnic differences. The absence of correlation between anti-TPO and anti-GAD in our type 1 diabetic patients suggested genetic heterogeneity in the role of autoimmunity of type 1 diabetes mellitus and ATD among races.

Adolescent↗
PubMed1998

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↗
PubMed1998

Germline RET proto-oncogene mutations in two Taiwanese families with multiple endocrine neoplasia type 2A.

To elucidate the germline RET proto-oncogene mutations in Taiwanese families with multiple endocrine neoplasia type 2A (MEN 2A), we extracted DNA from peripheral blood leukocytes of 28 members of two families with MEN 2A. Oligonucleotide primers for exons 10 and 11 were used to analyze the nucleotide sequence of codons 609, 611, 618, and 620 of exon 10, and codon 634 of exon 11 of the RET proto-oncogene. Two fragments of genomic DNA were amplified by polymerase chain reaction (PCR). The amplified PCR products were separated and purified from primers and free nucleotides in agarose gels, and the expected 187-bp and 234-bp bands were cut from the gels and sequenced. Thirteen family members in the two MEN 2A kindreds had mutations in codon 634 of exon 11. In kindred 1 (15 members available for this study), a heterozygous codon 634 mutation in nine members and a homozygous codon 634 mutation in one member led to the substitution of Phe (TTC) for Cys (TGC). Three members of kindred 2 (13 members available for this study) had a heterozygous base pair change in codon 634, which led to the substitution of Arg (CGC) for Cys (TGC). In this study, we found two mutation events occurring in two MEN 2A kindreds and also discovered a homozygous point mutation in one woman that led to heterozygous mutations in all of her children.

Drosophila Proteins↗
PubMed1997

Novel pathway of insulin signaling involving Stat1alpha in Hep3B cells.

STAT proteins are important transcription factors that regulate cell growth and differentiation. To elucidate the molecular mechanisms of insulin actions, we have studied how insulin activates STAT proteins in Hep3B cells. Insulin rapidly phosphorylated Stat1alpha at tyrosine residues and increased its specific binding activities to a GAS/ISRE consensus oligonucleotide. IL-4 also phosphorylated Stat1alpha and increased DNA binding activities to the same Stat1alpha responsive element. There was no increase in tyrosine phosphorylation of JAK family of kinases following insulin stimulation. In contrast, IL-4 stimulated tyrosine phosphorylation of JAK1, JAK2 and tyk2 in this cell line. These data indicate that insulin receptor signaling can activate the transcriptional regulatory function of STAT protein, and that insulin actions on Stat1alpha are mediated through signaling pathways independent of JAK family of kinases.

Animals↗
PubMed1997

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↗