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Biomedical subjects

A C Thai

Publications and source records attributed to A C Thai.

At least 19 recordsLinked to original sources
PubMed2005

Development of ipsilateral adrenocortical carcinoma sixteen years after resection of an adrenal tumour causing Cushing's syndrome.

INTRODUCTION: At times, it may be difficult to differentiate early stage, low-grade adrenocortical carcinoma from benign adrenal adenoma. CLINICAL PICTURE: A 53-year-old lady underwent right adrenalectomy for a 4-cm adrenocortical tumour causing Cushing's syndrome. Histology revealed an adrenocortical adenoma. Sixteen years later, she presented with a 14-cm adrenal tumour, again on the right side. TREATMENT: She underwent surgical removal of the tumour. Histology confirmed adrenocortical carcinoma. OUTCOME: She died of metastatic disease 17 months later. CONCLUSIONS: This case highlights the importance of long-term, systematic follow-up of patients treated for benign adrenal adenomas, especially if the tumour size exceeds 4 cm.

Adrenal Cortex Neoplasms↗
PubMed2004

Absence of ion channels CACN1AS and SCN4A mutations in thyrotoxic hypokalemic periodic paralysis.

Muscle weakness in patients with thyrotoxicosis during hypokalemic episodes (thyrotoxic periodic paralysis [TPP]) occurs sporadically and mostly in males. It is treated by infusion or oral supplementation with potassium and with resolution of the thyrotoxicosis state. The clinical features of TPP resemble familial hypokalemic periodic paralysis (hypoKPP), which has been linked to two mutations in the gene encoding the skeletal muscle calcium channel alpha-1 subunit (CACN1AS; Arg528His and Arg1239His) and to the sodium channel alpha-subunit (SCN4A; Arg672His). We screened for the mutations (CACN1AS by polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP]; SCN4A by single-strand conformation polymorphism analysis) described in hypoKPP in 20 unrelated patients with documented episodes of TPP (mean age, 40.0 +/- 12.3 years 19 males). Forty-eight patients with hyperthyroidism resulting from Graves' disease (48.5 +/- 12.3 years; 13 males), 1 patient with idiopathic hypoKPP (a 32-year-old male) and 32 healthy subjects (41.0 +/- 19.1 years; 16 males) were included. We found none of the TPP patients carry CACN1AS and SCN4A mutations. The hyperthyroid patients and control subjects were also negative for the mutations. The patient with idiopathic hypoKPP was genotyped to have the Arg528His mutation. These results suggest that despite close similarities between TPP and hypoKPP, a likely genetic basis for TPP does not involve the same gene mutations associated with hypoKPP.

Adult↗
PubMed2004

Metabolic, immunological and clinical characteristics in newly diagnosed Asian diabetes patients aged 12-40 years.

AIM: To describe the clinical, biochemical and immunological characteristics of young-onset diabetes in Asia. METHODS: Clinical, biochemical and immunological variables were assessed in 919 newly diagnosed (duration less than 12 months) young onset Asian diabetic patients aged between 12 and 40 years. The subjects constituted 57% Chinese, 29% Indians and 14% Malays, recruited from diabetes centres in China, Hong Kong, India, Malaysia and Singapore. RESULTS: The mean age (+/- sd) was 31.6 +/- 7.2 years, with the majority (66%) in the 31-40 years age group. Mean body mass index (BMI) (+/- sd) was 25.3 +/- 5.0 kg/m2 with 47% exceeding the suggested Asian cut-off point for obesity (BMI > or = 25). Ethnic difference in clinical characteristics included BMI, blood pressure, mode of treatment and degree of insulin resistance. Most patients had a clinical presentation of Type 2 diabetes. About 10% had a classical combination of ketotic presentation, presence of autoimmune-markers and documented insulin deficiency indicative of Type 1 diabetes. Forty-eight percent were receiving oral hypoglycaemic agents (OHAs) while 31% were on diet only, 18% were receiving insulin and 2% were on a combination of insulin and OHA. CONCLUSION: Young onset diabetes patients in Asia represent a heterogeneous group in terms of their clinical and biochemical characteristics and classical Type 1 diabetes is relatively uncommon. The 5-year follow up study will determine the progress of these patients and help to clarify the natural history.

Administration, Oral↗
PubMed2002

IgG1 subclass dominates autoimmune response to tyrosine phosphatase-like molecule IA-2 in Chinese type 1 diabetes patients.

BACKGROUND AND AIMS: Islet autoantibodies are known markers for type 1 diabetes with an immune-mediated basis; their isotype or subclass profiles may also provide clues to changes in immune response during disease or after intervention. For ICAs and GADab, the IgG1 subclass consistently dominates in recent-onset disease. The aims of our study were to determine the isotype patterns for IA-2ab in Asian Chinese patients with autoimmune diabetes. MATERIALS AND METHODS: From an initial screening of over 400 diabetes patients, 40 subjects (mean age 22.2 +/- 15.8 years) with IA-2ab were enrolled for this study. IA-2ab was detected by radioimmunoassay of [35S]-labelled recombinant human IA-2 ic(605 - 979). Of them, 31 (median age 15 years, range 2 - 57 years; 16 children) had clinical type 1 diabetes (that is, they required insulin at onset or within 1 year) with the majority having been recently diagnosed (< 1 year). The other 9 patients had clinical type 2 diabetes phenotype. RESULTS: IA-2ab IgG subclasses determined with monospecific secondary antibodies showed that both type 1 diabetic adults and children had similarly non-restricted isotype patterns with a strong presence of IgG1-IA-2ab. The rank order was IgG1 > 3 > 2 > 4; 15 subjects had detectable IgG4-IA-2ab. Clonality of immune response determined with kappa/lambda chain-specific antibodies also showed a non-restricted pattern. Patients aged 38.2 +/- 15.2 years with type 2 diabetes had broad patterns of isotypes - IgG1/3 was detected more frequently (n = 8) than IgG2/4 (n = 5). Of three patients on insulin treatment, one was also positive for GADab. The remaining 6 patients were on oral hypoglycaemic treatment. IA-2ab in type 2 diabetes showed a low titre compared to type 1 diabetes. CONCLUSIONS: Isotype responses to IA-2 had a strong IgG1 presence, similar to ICAs and GADab. With IgG3 subclass representation, a predominant Th1 milieu in the systemic environment is likely. There is no suggestion of differences in immune response to IA-2 between adults and children with type 1 diabetes.

Adolescent↗
PubMed2002

Tyrosine phosphatase-like protein (IA-2) and glutamic acid decarboxylase (GAD65) autoantibodies: a study of Chinese patients with diabetes mellitus.

Type 1 diabetes in most Asian populations may not have a salient autoimmune basis when assessed with single determinations of the major markers, islet cell antibodies (ICAs) and glutamic acid decarboxylase antibodies (GAD65ab). With the inclusion of antibodies to tyrosine phosphatase-like protein IA-2 (IA-2ab) as an additional major marker, we re-examined autoimmune diabetes in a group of Chinese patients. We studied 272 subjects at various stages of disease with blood samples procured for biochemical analysis. ICAs were measured by immunofluorescence, GAD65ab and IA-2ab by radioimmunoassay. Sixty-seven patients fulfilled clinical diagnosis of type 1 diabetes and the remaining 205 patients were type 2. Prevalence of single autoantibody type in recent-onset type 1 diabetes ( < 1 year duration; n = 47) showed 10.6% with ICAs, 44.7% GAD65ab and 36.2% IA-2ab. GAD65ab account for more than two-thirds of the markers found in type 1 diabetes. Combined analysis further showed that 51.1% had at least one antibody type, 31.9% with two or more antibodies and 8.5% with all three antibodies. Islet autoimmunity presence in childhood-onset type 1 diabetes improved with the addition of IA-2ab, though less impact was seen in the adult-onset. Similarly, combined analysis for type 2 patients with recent diabetes showed a modest increase to 13% with islet autoimmunity compared to 8% when assessed by GAD65ab alone. Combining IA-2ab and GAD65ab assays results detected slightly more immune-mediated diabetes, compared to using a single GAD65ab determination. Non-autoimmune causes need to be considered in the pathogenesis of type 1 diabetes in Chinese, particularly in adults.

Adult↗
PubMed2001

Prevalence of ICA and GAD antibodies at initial presentation of type 1 diabetes mellitus in Singapore children.

OBJECTIVE: To determine the prevalence of islet cell antibodies (ICA) and antibodies to glutamic acid decarboxylase (GAD) in Asian children with diabetes mellitus (DM) at the time of diagnosis. PATIENTS AND METHODS: 41 children were studied at their initial presentation from 1993 to 2000. RESULTS: Mean age of onset (+/- SD) of DM was 7.6 (+/- 4.2) years. One or both of the two autoantibodies, ICA and anti-GAD, were present in 17 of the 41 children (41.5%) at the time of diagnosis. Comparing the group of children with autoantibodies and the group without detectable autoantibodies, there were no significant differences in body mass index (15.4 vs. 16.3 kg/m2), age of onset (7.4 vs. 7.8 years), random C-peptide levels (203 vs. 311 pmol/l), HbA1c levels (13.2 vs. 12.7%), and frequency of diabetic ketoacidosis at presentation (53.3 vs. 55%). CONCLUSION: Prevalence of antibodies at presentation of DM in Singapore (41.5%) is lower than in Caucasian populations (60-90%). Other autoantibodies yet to be identified may be contributory. Alternatively, non-immune mediated mechanisms may be responsible for a significant proportion of type 1 DM in Singapore children.

Asian People↗
PubMed2001

A window on the current status of diabetes mellitus in Singapore--the Diabcare-Singapore 1998 study.

The Diabcare-Singapore project was carried out in 22 clinics (general hospitals, GH and primary healthcare centres, PHC) to provide an overview of diabetes management and metabolic control status. Data from 1697 diabetic patients were collected on paper forms and analysed centrally. Type 2 diabetes mellitus patients constituted 91.4% and type I patients constituted 8.1% of population. The proportion of type I patients was greater in GH (18.1%) vs PHC (3.4%). The mean age (+/- SD) was 58.1 +/- 14.4 years and mean duration of diabetes was 10.1 +/- 7.5 years. Mean body mass index (BMI) was 25.1 +/- 4.4 kg/m2 and more than half (53%) of patients were overweight (BMI >25 kg/m2). Mean HbA1c and FBG levels were 8.0 (1.9% and 9.1 +/- 3.1 mmol/l. A total of 51% of patients had HbA1c (1% above the Upper Limits of Normal (ULN). Fasting blood glucose (FBG) was >7.8 mmol/l in 61% of patients. The majority (70%) had satisfactory levels of fasting lipids (triglycerides, total cholesterol and HDL-cholesterol). Only 19.7% practised home blood glucose self-monitoring, while 99% reported receiving some diabetes education. Sixteen percent of patients had abnormal levels of protein (>500 mg/24 h) in the urine, 3% had elevated serum creatinine levels and 36% had microalbuminuria. Retinopathy (12%), cataract (16%) and neuropathy (12%) were commonly reported diabetic complications. The data revealed suboptimal glycaemic control in about half of patients studied.

Adolescent↗
PubMed2001

The status of diabetes mellitus in primary care institution and restructured hospitals in Singapore.

The Diabcare-Asia Singapore 1998 project was carried out using data from 22 centres collected on paper forms to provide an overview of diabetes management and metabolic control status in 1697 diabetic patients from both primary health care clinic (PHC) (67%) and restructured hospital (RH) (33%) settings. PHC patients were on average older than RH patients (61.3 +/- 11.2 years vs 51.5 +/- 17.7 years), and had a shorter duration of diagnosed diabetes (9.2 +/- 6.8 years vs 12.0 +/- 8.5 years). The mean body mass index (BMI) for PHC patients was 25.5 +/- 4.4 kg/m2 vs 24.5 +/- 4.2 kg/m2 for RH patients. Proportionately more PHC than RH patients were overweight (BMI >25 kg/m2) (49% vs 42%). Patients with type I diabetes constituted 3.5% of PHC vs 18.1% of the RH cohort. HbA1c information was available for 92.5% of RH vs 69% of PHC patients. HbA1c measurements were <1% above ULN in 50% of PHC vs 37% of RH patients, while FBG was >7.8 mmol/l in >61% of all patients. Proteinuria (>500 mg/24 hrs) was reported in 13% of PHC vs 26% of RH patients tested. Microalbuminuria (20-300 mg/l) was noted in 36% of 171 RH patients tested. Oral hypoglycaemic agents were used as sole therapy in 83.5% of PHC vs 43% of RH patients. Eye, feet, renal and severe late complications were more commonly reported by RH than PHC patients. There is a variation in the patient profiles and care between PHC and RH patients.

Diabetes Complications↗
PubMed2000

Evaluation of a rapid screening test for microalbuminuria with a spot measurement of urine albumin-creatinine ratio.

INTRODUCTION: Microalbuminuria has been established as a marker of incipient diabetic nephropathy, and a regular screening programme has been advocated in patients with diabetes mellitus. We investigated if urine albumin levels normalised by creatinine give results comparable to the urinary albumin excretion rate (UAER) with a timed 24-h urine for detecting microalbuminuria. MATERIALS AND METHODS: Morning urine specimens and 24-h collections were obtained from 65 diabetic patients. Albumin and creatinine levels in the spot urine specimens were measured in a single rapid (7 min) assay format using the Bayer DCA2000+ desktop system. Results of albumin/creatinine ratio and urine albumin concentration were then compared to the reference laboratory method of measuring UAER with the timed 24-h urine sample. RESULTS: The determination of the albumin/creatinine ratio gave good performance characteristics for diagnosis of microalbuminuria (defined as > 30 mg/g creatinine) with sensitivity of 71.4% and specificity of 98.0%. With urine albumin concentration alone, sensitivity was 64.3% and specificity was 96.1%. Receiver operating characteristic (ROC) curves, however, suggest similar diagnostic usefulness for screening microalbuminuria with albumin levels expressed in concentration units or as a ratio of creatinine compared to the reference method. Analysis also indicated that lowering the established cut-off values in general, improves diagnostic performance. CONCLUSIONS: Measurement of microalbuminuria with a spot morning specimen using the DCA2000+ desktop system that simultaneously measures albumin and creatinine levels, provides a rapid and reliable method for incipient diabetic nephropathy in clinical practice.

Adult↗
PubMed1999

Systemic levels of cytokines and GAD-specific autoantibodies isotypes in Chinese IDDM patients.

It is not clear if a Th1/Th2 imbalance in Type 1 diabetes (insulin-dependent diabetes mellitus, IDDM) would lead to a particular antigen-specific IgG subclass dominant as had been shown in the mouse model. In new-onset Type 1 diabetics, an autoantibody response to glutamate decarboxylase (GADab) is frequently observed but the GADab subclass repertoire is not well-established. We determined the systemic levels of representative Th1 and Th2 cytokines and the GADab IgG subclass distribution in 41 Chinese IDDM patients of whom 26 were recently diagnosed (< or = 1 year) and 32 had GADab, to ascertain a likely association of antigen-specific antibody isotype and the Th1/Th2 dichotomy. With high-sensitivity ELISA systems that measure sub-picogram cytokine concentrations, 26 of the 41 patients (63.4%) had at least one of the pro-inflammatory Th1 cytokines (TNF-alpha, IFN-gamma and IL-12) detected. Fewer patients (4/41) had the anti-inflammatory Th2 cytokine IL-4 detected. For IL-10, all subjects had measurable quantities but only three diabetics had levels above the upper limit for healthy subjects (n = 20). Grouped according to the profile of detectable cytokines, there were 24 Th1, 2 Th2 and 2 Th0 patterns. GAD-specific IgG1 antibody was more frequently expressed; 22 of 32 GADab[+] patients. The rank order for the GADab subclasses was IgG1 > 4 > 3 > 2; IgG2 was found in 11 GADab[+] patients. Recent-onset diabetics have a similar ranking of the GAD-specific IgG subclasses. In human Type 1 diabetes, a predominance of GAD-specific IgG1 antibody response is observed together with a dominant Th1 cytokine pattern.

Adolescent↗
PubMed1999

HLA microsatellite associations with insulin-dependent diabetes mellitus in Singaporean Chinese.

Singaporean Chinese with insulin-dependent diabetes mellitus (IDDM) have previously been shown to be associated with the DRB1*0301 haplotype and the joint occurrence of DRB1*0301/*0901 and DRB1*0301/*04. The present study extended previous HLA associations by investigating the HLA region using four microsatellites (TNFa, D6S273, TAP1, DQCARII). Seventy-five IDDM patients and 80 healthy controls were studied. TNFa*3 (RR = 2.26), TNFa*12 (RR = 3.30), TAP1*9 (RR = 2.55) showed increased frequencies while TNFa*11 (RR = 0.29), TAP1*4 (RR = 0.50) showed decreased frequencies in patients compared to controls. Linkage analysis suggested that the positive associations of TNFa*3 and TAP1*9 were secondary to that of DRB1*0301. However, TNFa*12 appeared to provide additional risks to IDDM besides the DRB1*0301 haplotype, whereas TNFa*11 and TAP1*4 conferred an independent protective effect against IDDM. Our findings reinforce the notion that susceptibility to and protection against IDDM may include TNF region. In the present study, TNFa*12 seemed to be the primary association in the DRB1*0405 haplotype and may play an independent role in the pathogenesis of IDDM through TNF-alpha function.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Testosterone and leptin in a group of Chinese with and without diabetes.

AIM: Leptin levels in the overweight and differences between men and women may be confounded by sex hormones in obesity-related type 2 diabetes. We carried out a study of leptin and testosterone and the effect of diabetes on this relationship in 71 Chinese subjects (51 with type 2 diabetes and 20 healthy non-diabetics) of whom 32 were overweight (body mass index (b.m.i.) > 25.0 kg/m2). METHODS AND RESULTS: Leptin levels were similar in the diabetic (median 7.4, interquartile range 4.2-10.6 ng ml-1) and non-diabetic (11.3 (6.0-16.3) ng ml-1) subjects. Testosterone and free testosterone in diabetics and non-diabetics were similar for both gender. Regardless of diabetes status, testosterone and its free form tend to increase in overweight women and decrease in men. Leptin correlated with testosterone in women with diabetes (Pearson correlation coefficient r = 0.495, p = 0.037) but not in diabetic men. Sixty-eight per cent of leptin variance was affected by b.m.i, insulin, sex (female) and diabetes status in a regression model that excluded testosterone (total and free). However, testosterone and insulin were predictors of leptin changes in the non-diabetic subjects. In diabetes, b.m.i., sex (female) and insulin remained as predictors of leptin changes. CONCLUSIONS: These results suggest that apart from body adiposity, testosterone also influences leptin levels and that diabetes has a significant effect on this association.

Adult↗
PubMed1998

The use of semi-quantitative urine test-strip (Micral Test) for microalbuminuria screening in patients with diabetes mellitus.

BACKGROUND: Microalbuminuria is an early marker of prognostic significance in diabetic renal disease. However, testing for microalbuminuria in a timed sample of urine using the double antibody radioimmunoassay (RIA) method is cumbersome and requires special laboratory facilities. Recently, a test strip for microalbuminuria, the Micral Test was available and we evaluated the performance of this test strip as a screening method for detection of microalbuminuria. METHODS: One hundred consecutive diabetic patients who were tested to be dipstick-negative (Albustix) for proteinuria were enrolled for the study. Micral Tests were performed on a paired first morning and random urine specimen from the same patient and the results compared with a timed 24-hour urine measurement of urine albumin excretion using the RIA method. RESULTS: Eighteen specimens were tested positive by the RIA method with a urinary albumin range of 32-177 mg/24 hours. With the Micral Test, the following sensitivity, specificity, positive and negative predictive values were obtained: 66.7%. 97.6%, 85.7% and 93.0% for the first morning urine specimens, and 77.8%, 91.5%, 66.7% and 94.9% for the random urine specimens. CONCLUSIONS: These results suggest that Micral Test with either the first morning or random urine specimen offers a simple, reliable, rapid and convenient method for screening of microalbuminuria in the diabetic patient.

Adult↗
PubMed1998

A case of accelerated development of proliferative diabetic retinopathy in a woman with type 2 diabetes mellitus after pregnancy.

Whilst it is recognised that diabetic retinopathy is a consequence of prolonged elevation of blood glucose levels, recent studies suggest rapid normalisation of blood sugar as a causal factor in accelerating its development. In this case report, a non-insulin dependent diabetic with poor blood glucose control but no retinopathy in early pregnancy had normalisation of glucose control by the third trimester. However, glucose control deteriorated rapidly postnatally, and she had a sudden blurring of vision three months after delivery of her baby, at which time severe proliferative diabetic retinopathy was diagnosed. The reason for the unusually rapid development of proliferative retinopathy was uncertain, but appeared to have a temporal association with the deterioration of her glycaemic control postnatal after a period of strict diabetes control in the perinatal period.

Adult↗
PubMed1998

The incidence of IDDM in Singapore children.

OBJECTIVE: To determine the incidence of insulin dependent diabetes mellitus (IDDM) in children 0-12 years of age in Singapore, which has a population of 2.9 million. METHODS: The primary source was a 2-year phone and mail survey of doctors in the government and government restructured hospitals and the private sector. The secondary source was the membership records of the Diabetes Society of Singapore. RESULTS: Using the capture-recapture method, ascertainment was assessed to be 92.2% complete. The age standardised incidence rate was 2.46 per 100,000 children 0-12 years old, for the period 1992-1994 (95% confidence interval: 2.16-2.75). The data seemed to indicate a rising incidence of IDDM in this population, being 1.4/100,000 in 1992, 2.4/100,000 in 1993 and 3.8/100,000 in 1994. The male: female ratio is 1:1.85. There was seasonal variation with fewer cases from July to October and more from November to May. Five percent of patients had a first degree relative with IDDM. Malays appeared to have a lower incidence (1.23/100,000) compared to the Chinese (2.25/100,000) and the Indians (5.78/100,000). CONCLUSIONS: The incidence of IDDM in Singapore children is similar to that reported for Hong Kong and Japan, but higher than that for Shanghai. The female preponderance is similar to that seen in other Asian population. The data suggests a rising incidence of IDDM in Singapore and differences in incidence between the Malays, Chinese and Indians, but further observations are needed.

Child↗
PubMed1997

Anti-GAD antibodies in Chinese patients with youth and adult-onset IDDM and NIDDM.

An autoimmune basis for the pathogenesis of insulin-dependent diabetes mellitus (IDDM) is supported by the frequent presence of autoantibodies - islet cell antibodies (ICAs) and GAD antibodies (GADab). However, in Chinese patients with clinical IDDM, a low prevalence of ICAs was observed. In non-insulin-dependent diabetic (NIDDM) patients, it has been suggested that the presence of GADab may identify a subset of latent autoimmune diabetes in adults (LADA). We determined the frequency of GADab in a large group of 134 IDDM and 168 NIDDM Chinese patients, and assessed the relation with ICAs status. Results showed that 39.6% IDDM and 16.1% NIDDM patients had GADab, and 20.1% and 4.8%, respectively had detectable ICAs. Frequency of GADab positivity was not influenced by whether the patients had youth or adult-onset IDDM or NIDDM, or by duration of diabetes. NIDDM patients seropositive for GADab shared similar clinical characteristics and fasting C-peptide levels with those who were GADab negative. Presence of GADab therefore did not serve to identify a subgroup of patients with latent or slow-onset IDDM. Half (53%) of our IDDM patients had neither GADab nor ICAs. The reason for this observation is unclear. One theory is that other autoantigens yet to be identified may be contributory. Alternatively, in the Chinese, autoimmunity may not be the major factor in the pathogenesis of IDDM.

Adolescent↗
PubMed1996

High prevalence of dyslipidaemia despite adequate glycaemic control in patients with diabetes.

Forty-seven patients with newly diagnosed diabetes were followed up for 1 year with lipid parameters (total cholesterol, low-density lipoprotein [LDL] cholesterol, high-density lipoprotein [HDL] cholesterol and triglycerides) and glycated haemoglobin measured at diagnosis and 6-monthly intervals. The prevalence of these lipid parameters exceeding the risk level for coronary heart disease at diagnosis ranged from 34% to 64%, the commonest dyslipidaemic pattern being hypercholesterolaemia (43%), followed by mixed hyperlipidaemia (17%) and hypertriglyceridaemia (17%). There was no improvement in the lipids profile over a 1-year period despite achieving good glycaemic control in both the insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) patients. Twenty-four (51%) patients will need lipid lowering treatment because of persistent dyslipidaemia despite adequate non-pharmacologic measures. We suggest that an active strategy of early detection and drug treatment for dyslipidaemia is needed for patients with diabetes mellitus.

Adolescent↗