Objective. We wished to examine the effects of ambient glycaemia on hypothalamic somatostatinergi... more Objective. We wished to examine the effects of ambient glycaemia on hypothalamic somatostatinergic tone in insulin-dependent diabetes mellitus. Design. After 6-hour periods of either euglycaemia (5 mmol/l) or hyperglycaemia (15 mmol/l), exercise-induced GH secretion was measured. Patients. Seven insulin dependent diabetics with no evidence of complications were recruited. Results. There was no significant difference between basal GH levels during euglycaemia and hyperglycaemia (5.50 vs 5.53 mU/l). Nor was there a significant difference when mean ? GH levels (33.9 vs 27.4 mU/l) or mean area under GH curve (2331 vs 4038 mU min/l) during euglycaemia or hyperglycaemia were compared. Conclusions. We find no evidence therefore to support short-term effects of ambient glucose concentration on GH responsiveness, and by inference no direct effect of short-term changes in glycaemic control on hypothalamic release of somatostatin in the aetiology of GH hypersecretion in insulin-dependent diabetes mellitus.
Diabetes Research and Clinical Practice, Dec 31, 1994
The reported glucose and immunoreactive insulin (IRI) responses to oral and intravenous glucose i... more The reported glucose and immunoreactive insulin (IRI) responses to oral and intravenous glucose in subjects with Type 2 diabetes have not always been consistent. This may have resulted from variations in the method of glucose administration, the ethnic backgrounds of subjects, the diagnostic criteria applied, the duration of the disease or IRI assay methods. The use of a mixed meal rather than glucose has been shown to provide a more physiological stimulus to the pancreatic beta-cell due to both glucose and non-glucose secretagogues. We have analysed the metabolic and hormonal responses of 188 newly diagnosed Caucasian subjects with Type 2 diabetes and 38 non-diabetic subjects to a 500 kcal mixed meal. The diabetic subjects were stratified according to fasting plasma glucose (FPG) (< 9, 9-12, 12-15 and > or = 15 mmol/l) and body mass index (BMI) (< 26.5, 26.5-30 and > or = 30 kg/m2). Increasing FPG was associated with higher peak glucose concentrations and increasing failure to achieve basal glucose levels by 4 h. Median fasting IRI concentrations were similar to those of normal subjects, but all diabetic subjects had reduced early-phase insulin secretion. Diabetic subjects with FPG < 9 mmol/l showed augmented IRI area under the curve (AUC) at 2 and 4 h, whereas those with FPG > 9 mmol/l had progressive falls in IRI AUC to below that of the normal subjects (P < 0.0001 for the trend). Peak IRI concentrations declined progressively with increasing FPG. Despite equivalent glucose exposure simple trends of increasing AUC, IRI with increasing BMI were statistically significant (P < 0.001, P < 0.02, P < 0.001 and P < 0.01, respectively for each FPG group). Both fasting and AUC non-esterified fatty acid concentrations increased significantly with FPG regardless of BMI (P < 0.001 for the trends). These results using a more physiological mixed meal challenge in a large number of recently diagnosed Type 2 diabetic subjects demonstrate a marked and increasing loss of beta-cell secretory function with increasing fasting hyperglycaemia aggravated by insulin resistance with increasing obesity.
Evidence-Based Complementary and Alternative Medicine, 2016
Purpose.Type 2 diabetes consists of progressive hyperglycemia and insulin resistance, which could... more Purpose.Type 2 diabetes consists of progressive hyperglycemia and insulin resistance, which could result from glucose toxicity, inflammatory cytokines, and oxidative stress. In the present study we investigated the effect of Gelam honey and quercetin on the oxidative stress-induced inflammatory pathways and the proinflammatory cytokines.Methods.HIT-T15 cells were cultured and preincubated with the extract of Gelam honey (20, 40, 60, and 80 μg/mL), as well as quercetin (20, 40, 60, and 80 μM), prior to stimulation by 20 and 50 mM glucose.Results.HIT-T15 cells cultured under hyperglycemic condition showed a significant increase in the inflammatory pathways by phosphorylating JNK, IKK-β, and IRS-1 at Ser307 (p<0.05). There was a significant decrease in the phosphorylation of Akt at Ser473 (p<0.05). Pretreatment with Gelam honey and quercetin reduced the expression of phosphorylated JNK, IKK-β, and IRS-1, thereby significantly reducing the expression of proinflammatory cytokines l...
We examined the prevalence of diabetes among inpatients in our hospital, the relationship of the ... more We examined the prevalence of diabetes among inpatients in our hospital, the relationship of the diagnoses on admission to diabetes, and the frequency of testing for HbA1c as a marker of long-term glycaemic control, proteinuria, and hypercholesterolaemia. In addition, patients with raised laboratory plasma glucose without a known history of diabetes mellitus, were studied to see if there had been
Several lines of evidence from studies of both twins and offspring of people with type 2 diabetes... more Several lines of evidence from studies of both twins and offspring of people with type 2 diabetes have shown the importance of genetics in its pathogenesis. Impaired glucose tolerance (IGT) may reflect these genetic changes during the prediabetic stage. Thus, we performed a comprehensive analysis of the gene expression profiles of the peripheral blood mononuclear cells among offspring of one
Background. Oxidative stress induced by reactive oxygen and nitrogen species is critically involv... more Background. Oxidative stress induced by reactive oxygen and nitrogen species is critically involved in the impairment ofβ-cell function during the development of diabetes.Methods. HIT-T15 cells were cultured in 5% CO2and then preincubated with Gelam honey extracts (20, 40, 60, and 80 µg/mL) as well as quercetin (20, 40, 60, and 80 µM), prior to stimulation by 20 and 50 mM of glucose. Cell lysate was collected to determine the effect of honey extracts and quercetin on the stress activated NF-κB, MAPK pathways, and the Akt (ser473) activated insulin signaling pathway.Results. HIT-T15 cells cultured under hyperglycemic conditions demonstrated insulin resistance with a significant increase in the levels of MAPK, NF-κB, and IRS-1 serine phosphorylation (ser307); however, Akt expression and insulin contents are significantly decreased. Pretreatment with quercetin and Gelam honey extract improved insulin resistance and insulin content by reducing the expression of MAPK, NF-κB, and IRS-1 se...
Background: People with pre-diabetes are at high risk of developing type 2 diabetes and cardiovas... more Background: People with pre-diabetes are at high risk of developing type 2 diabetes and cardiovascular diseases. Measurements of health-related quality of life (HRQOL) among pre-diabetics enable the health care providers to understand their overall health status and planning of interventions to prevent type 2 diabetes. Therefore we aimed to determine the HRQOL and physical activity level; and its association with Body Mass Index (BMI) among pre-diabetics. Methods: This was a cross sectional study carried out in two primary care clinics in a semi-urban locality of Ampangan, Negeri Sembilan, Malaysia. Data was collected through self-administered questionnaires assessing the demographic characteristics, medical history, lifestyle and physical activity. The Short Form 36-items health survey was used to measure HRQOL among the pre-diabetics. Data entry and analysis were performed using the SPSS version 19. Results: A total of 268 eligible pre-diabetics participated in this study. The prevalence of normal weight, overweight and obesity were 7.1%, 21.6% and 71.3% respectively. Their mean (SD) age was 52.5 (8.3) years and 64.2% were females. Among the obese pre-diabetics, 42.2% had both IFG and IGT, 47.0% had isolated IFG and 10.8% had isolated IGT, 36.2% had combination of hypertension, dyslipidemia and musculoskeletal diseases. More than 53.4% of the obese pre-diabetics had family history of diabetes, 15.7% were smokers and 60.8% were physically inactive with mean PA of < 600 MET-minutes/week. After adjusted for co-variants, Physical Component Summary (PCS) was significantly associated with BMI categories [F (2,262) = 11.73, p < 0.001] where pre-diabetics with normal weight and overweight had significantly higher PCS than those obese; normal vs obese [M diff = 9.84, p = 0.006, 95% CI diff = 2.28, 17.40] and between overweight vs obese [M diff = 8.14, p < 0.001, 95% CI diff = 3.46, 12.80]. Conclusion: Pre-diabetics who were of normal weight reported higher HRQOL compared to those overweight and obese. These results suggest a potentially greater risk of poor HRQOL among pre-diabetics who were overweight and obese especially with regard to the physical health component. Promoting recommended amount of physical activity and weight control are particularly important interventions for pre-diabetics at the primary care level.
A simple and rapid real-time reverse transcription-PCR (RT-PCR) technique using SYBR green fluore... more A simple and rapid real-time reverse transcription-PCR (RT-PCR) technique using SYBR green fluorescence was developed to quantify Zonula Occludens-1 (ZO-1) mRNA expression in histamine-treated cultured bovine retinal microvessel endothelial cells. There was no dif-ference between the quantity of ZO-1 mRNA expression in histamine-treated (10-7M to 10-9 M) and untreated bovine retinal endothelial cells at high magnesium levels. Immunohisto-chemistry staining and
a b s t r a c t Aim: To report the national prevalence of metabolic syndrome (MetS) and its risk ... more a b s t r a c t Aim: To report the national prevalence of metabolic syndrome (MetS) and its risk factors among adult Malaysians (>18 years old) based on World Health Organization (WHO), the National Cholesterol Education Program Expert Panel III (ATP III), International Diabetes Federation (IDF) and the 'Harmonized' criteria.
Introduction: Insulin resistance in latent autoimmune diabetes in adults (LADA) patients is contr... more Introduction: Insulin resistance in latent autoimmune diabetes in adults (LADA) patients is controversial. The aim of this study was to evaluate insulin resistance and its related factors (metabolic syndrome parameters) among subjects with LADA and glutamic acid decarboxylase antibodies (GADA) negative diabetes, as well as the impact of these factors on insulin resistance. Materials and Methods: GADA levels were investigated in 1140 diabetic patients aged between 30 and 70 years. Insulin resistance and metabolic syndrome parameters were assessed in LADA and GAD-negative diabetic patients by general linear model. In addition, the impact of metabolic syndrome factors on insulin resistance was assessed in LADA and glutamic acid decarboxylase (GAD)-negative diabetic patients. Results: LADA was diagnosed in 33 subjects from 1140 Malaysian diabetic patients (prevalence = 2.9%). The results showed that LADA patients had higher insulin resistance and high density lipoprotein cholesterol (HDLc) (P = 0.003 and 0.00017 respectively) and lower body mass index (BMI) (P = 0.007) compared to GAD-negative diabetic patients. The HDLc was associated with decreased insulin resistance in LADA patients (P=0.041), whereas HbA1c, triacylglycerides (TG) and waist were associated with increased insulin resistance in GAD-negative diabetic patients (P=3.6x10(-12), 1.01x10(-5) and 0.004 respectively). HbA1c was highly associated with decreasing beta-cell function in both LADA (P = 0.009) and GAD-negative diabetic subjects (P=2.2x10(-28)). Conclusion: Insulin resistance is significantly higher in LADA than GAD-negative diabetic Malaysian subjects.
Background: Several studies have shown the association of solute carrier family 30 (zinc transpor... more Background: Several studies have shown the association of solute carrier family 30 (zinc transporter) member 8 (SLC30A8) rs13266634 with type 2 diabetes (T2D). However, the association of alternative variants and haplotypes of SLC30A8 with T2D have not been studied in different populations. The aim of this study is to assess the association of the alternative SLC30A8 variants, rs7002176 and rs1995222 as well as the most common variant, rs13266634 and haplotypes with glutamic acid decarboxylase antibodies (GADA) negative diabetes in Malaysian subjects. Methods: Single nucleotide polymorphisms (SNPs) of SLC30A8; rs7002176, rs1995222 and rs13266634 were genotyped in 1140 T2D and 973 non-diabetic control subjects. Of these, 33 GADA positive diabetic subjects and 353 metabolic syndrome (MetS) subjects were excluded from subsequent analysis. Results: The recessive genetic model controlled for age, race, gender and BMI shows that the alternative SLC30A8 variant, rs1995222 is associated with GADA negative diabetes (OR = 1.29, P = 0.02) in Malaysian subjects. The most common variant, rs13266634 is also associated with GADA negative diabetes (OR = 1.45, P = 0.001). This association is more pronounced among Malaysian Indians (OR = 1.93, P = 0.001). Moreover, the CG haplotype and CG-CG diplotype have been equally associated with increased diabetic risk (OR = 1.67, P = 8.6 x 10(-5)). Conclusions: SLC30A8 SNPs and haplotypes are associated with GADA negative diabetes in Malaysian subjects, and this association is markedly higher among Malaysian Indian subjects.
We report the presence of adenosine receptors at molecular level and study their role in the infl... more We report the presence of adenosine receptors at molecular level and study their role in the inflammatory pathway under hyperglycemic condition. Human Muller cells were cultured in low (5 mM) and high (25 mM) glucose with 10% FBS and 1% P/S. Cells were starved in 0% FBS for 18 h and then treated with various agonists CCPA, CGS 21680, NECA and IB-MECA for 6, 12 and 24 h. The adenosine receptors were identified by immunocytochemistry. ELISA was used to measure the levels of TNF-alpha, IL-1 beta and ICAM 1. Four types of adenosine receptors (A(1), A(2A), A(2B) and A(3)) were identified in human Muller cells. TNF-alpha content increased after agonist A(1) and A(3) treatment, but decreased after agonist A(2A) and An treatment. There was no significant effect on ICAM-1 and IL-1 beta. Stimulation of human Muller cells with adenosine A(2A) agonist (CGS 21680) and adenosine A(2B) agonist (NECA) reduces the level of TNF-alpha when exposed to high glucose, whereas A(1) adenosine agonist (CCPA) and A(3) adenosine agonist (IB-MECA) both positively and negatively regulate the TNF-alpha in hyperglycemia. However, none of these agonists has any significant role in affecting ICAM-1 and IL-1 beta.
Introduction: Metabolic syndrome (MetS) had been known as clustering of risk factors for cardiov... more Introduction: Metabolic syndrome (MetS) had been known as clustering of risk factors for cardiovascular disease and diabetes. Over the years, clinical criteria had been revised to highlight importance of various risk factors in defining MetS. Studies had reported different clustering of factors based on different population characteristics.
Objective: Our study aimed to identify the clustering factors among our Malaysian population based on sexes and 4 major ethnic groups namely Malay, Chinese, Indian and other minor ethnic
Methods: A national cross sectional study was done covering both Peninsular and East Malaysia. Subjects’ sociodemographic, body mass index (BMI), waist, hip and neck circumference, blood pressure,
fasting triglycerides (TG) and HDL-cholesterol and glucose, urine microalbumin and serum insulin were taken. Principal component factor analysis with Varimax rotation was done to identify the clustering based on sex and ethnic groups.
Results: One thousand two hundred and sixty eight male and 2355 female subjects were recruited. Majority of subjects were Malays (63.0%) followed by Chinese (13.3%), Indian (7.4%) and other ethnic
groups (13.8%) which followed the population composition in Malaysia. Four factors were identified for both men and women. The factors were anthropometry, glycemia, blood pressure and dyslipidemia given the cumulative percent of variance of 69.4 and 65.9 respectively. There are 4 factors identified for Malay,
Chinese and Aborigines but 5 factors for Indian ethnic groups given cumulative percent of variance explained ranged from 65.1 to 77.7.
Discussion and Conclusion: BMI, neck circumference, blood pressure, Fasting TG and HDL had a high factor loading in both sexes suggesting that for field screening, diagnostic criteria would be adequate criteria. These factors also showed a similar pattern of loading by different ethnic groups. In conclusion,in Malaysian population, at least one measurement from each components namely anthropometric, blood pressure, glycemia and dyslipidemia is adequate to diagnose MetS.
Background: The association of Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) comm... more Background: The association of Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) common variants (rs4402960 and rs1470579) with type 2 diabetes (T2D) has been performed in different populations. The aim of this study was to evaluate the association of alternative variants of IGF2BP2; rs6777038, rs16860234 and rs7651090 with glutamic acid decarboxylase antibodies (GADA) negative diabetes in Malaysian Subjects. Methods/Principal Findings: IGF2BP2; rs6777038, rs16860234 and rs7651090 single nucleotide polymorphisms (SNPs) were genotyped in 1107 GADA negative diabetic patients and 620 control subjects of Asian from Malaysia. The additive genetic model adjusted for age, race, gender and BMI showed that alternative variants; rs6777038, rs16860234 and rs7651090 of IGF2BP2 associated with GADA negative diabetes (OR = 1.21; 1.36; 1.35, P = 0.03; 0.0004; 0.0002, respectively). In addition, the CCG haplotype and diplotype CCG-TCG increased the risk of diabetes (OR = 1.51, P = 0.01; OR = 2.36, P = 0.009, respectively). Conclusions/Significance: IGF2BP2 alternative variants were associated with GADA negative diabetes. The IGF2BP2 haplotypes and diplotypes increased the risk of diabetes in Malaysian subject.
INTERNATIONAL JOURNAL OF ENDOCRINOLOGY AND METABOLISM (IJEM), 2004
Soluble vascular cell adhesion molecule-1 (sVCAM-1) and intercellular adhesion molecule-1 (sICAM-... more Soluble vascular cell adhesion molecule-1 (sVCAM-1) and intercellular adhesion molecule-1 (sICAM-1) have been shown to be elevated in patients with Graves’ disease and may play significant roles in the pathogenesis of the disease. The objective of this study was to measure the levels of sVCAM-1, sICAM-1, IL-6 and thyroid receptor stimulating antibodies (TRAb) in a cohort of hyperthyroid patients and determine their associations to thyroid hormones status, before and after 3 months therapy with carbimazole.
Materials and Methods: Patients were given fixed daily dose of 20 mg carbimazole for 3 months and blood samples were collected at baseline and end of the study. Thirty eight patients were recruited from the Endocrine Clinic, Hospital University Kebangsaan Malaysia, con-sisting of 26 females and 12 males, age ranging from 16 to 65 years. Blood samples collected be-fore and at end of study were analyzed for TSH, Free T3, Free T4, thyroid receptor stimulating anti-bodies (TRAb), sVCAM-1, sICAM-1 and IL-6.
Results: TRAb level of ?10 U/L was taken to be negative, while TRAb level of >10 U/L was considered as positive. Twenty-six patients (68%) were TRAb positive (TRAb+) and 12 patients (30%) were TRAb negative (TRAb-). Median TRAb in TRAb+ patients was 23 U/L at baseline, declining to 16.7 U/L (p<0.001) in the third 3 month. Serum sVCAM-1 levels were signifi-cantly elevated in TRAb+ patients compared to TRAb- (860 versus 499 ng/mL, p<0.001). The level decreased significantly to 537 ng/mL with treat-ment but remained higher than in TRAb- patients (p=0.003). Irrespective of TRAb status, all but one patient had elevated serum sICAM-1 levels that remained unaffected by carbimazole therapy. In contrast, IL-6 levels of hyperthyroid patients were within the reference range of 1.4-14.1 pg/mL. Baseline and post-treatment sVCAM-1, and not TRAb levels, were significantly corre-lated to thyroid hormones. Conclusion: Compared to other inflammatory markers, sVCAM-1 showed significant correlation to thyroid stimulating antibodies and was most sensitive to changes in thyroid status. The significance of these findings in relation to Graves’ disease warrants further investigation.
Southeast Asian Journal of Tropical Medicine and Public Health, 2005
The concentration of plasma sialic acid was estimated using the modified chemical method and the ... more The concentration of plasma sialic acid was estimated using the modified chemical method and the more sensitive enzymatic method in 20 subjects with impaired glucose tolerance and 20 control subjects. The mean sialic acid concentration values of the control subjects and subjects with impaired glucose tolerance using the enzymatic method were 1.747 ± 0.047 and 2.583 ± 0.070 mmole/l and 1.753 ± 0.067 and 2.591 ± 1.02 mmole/l for the chemical method. The intra-assay coefficient of variation for the control subjects and for the subjects with impaired glucose tolerance were 1.963% and 1.583%, respectively, for the enzymatic assay and 2.728% and 2.431%, respectively, for the chemical assay. The inter-assay coefficient of variation for the control subjects and for the subjects with impaired glucose tolerance were 2.686% and 2.723% for the enzymatic assay, and 3.819% and 3.95% for the chemical assay. Since the values do not differ significantly, the chemical assay is a cost effective method that can be used in large epidemiological studies.
Levels of sialic acid and Vascular Cell Adhesion Molecule-1 (VCAM-1) in the first degree relative... more Levels of sialic acid and Vascular Cell Adhesion Molecule-1 (VCAM-1) in the first degree relatives of type 2 diabetes mellitus patients and their possible role as an early marker of the prediabetic stage were studied in 74 controls and 150 first degree relatives. The total sialic acid concentration was significantly higher (p<0.05) in the first degree relatives compared to the control subjects. Amongst the offsprings, the total sialic acid concentration was significantly higher in the offspring with Normal Glucose Tolerance (NGT) than those with Impaired Glucose Tolerance (IGT). However the level of VCAM-1 did not differ amongst the controls and the first degree relatives. The total cholesterol and triglycerides were significantly higher (p<0.05) in the offspring with IGT when compared to the control subjects and the offspring with NGT. The above data suggests that desialylation of the vascular endothelium is an early event that precedes the expression of IGT or any lipid changes in asymptomatic offspring of one type 2 diabetic parent.
Aim of this study was to investigate the relationship between sialic acid component and C-reactiv... more Aim of this study was to investigate the relationship between sialic acid component and C-reactive protein and lipids in the plasma of 80 healthy subjects. Levels of sialic acid, C-Reactive Protein (CRP) and plasma lipids were measured in a normal population consisting of 80 subjects. The possible correlation between sialic acid and CRP was also studied. The total sialic acid concentration was 2.61±0.61 mM L-1, CRP (2.52±2.32 mmole L-1), total cholesterol (5.504±1.28 mM L-1), triglycerides (1.31±0.87 mM L-1), low density lipoprotein (3.51±1.11 mM L-1) and high density lipoprotein (1.40±0.37 mM L-1). There was a positive correlation between sialic acid and CRP (r = 0.283, p<0.05). However, there was no correlation between CRP and the plasma lipids.
Objective. We wished to examine the effects of ambient glycaemia on hypothalamic somatostatinergi... more Objective. We wished to examine the effects of ambient glycaemia on hypothalamic somatostatinergic tone in insulin-dependent diabetes mellitus. Design. After 6-hour periods of either euglycaemia (5 mmol/l) or hyperglycaemia (15 mmol/l), exercise-induced GH secretion was measured. Patients. Seven insulin dependent diabetics with no evidence of complications were recruited. Results. There was no significant difference between basal GH levels during euglycaemia and hyperglycaemia (5.50 vs 5.53 mU/l). Nor was there a significant difference when mean ? GH levels (33.9 vs 27.4 mU/l) or mean area under GH curve (2331 vs 4038 mU min/l) during euglycaemia or hyperglycaemia were compared. Conclusions. We find no evidence therefore to support short-term effects of ambient glucose concentration on GH responsiveness, and by inference no direct effect of short-term changes in glycaemic control on hypothalamic release of somatostatin in the aetiology of GH hypersecretion in insulin-dependent diabetes mellitus.
Diabetes Research and Clinical Practice, Dec 31, 1994
The reported glucose and immunoreactive insulin (IRI) responses to oral and intravenous glucose i... more The reported glucose and immunoreactive insulin (IRI) responses to oral and intravenous glucose in subjects with Type 2 diabetes have not always been consistent. This may have resulted from variations in the method of glucose administration, the ethnic backgrounds of subjects, the diagnostic criteria applied, the duration of the disease or IRI assay methods. The use of a mixed meal rather than glucose has been shown to provide a more physiological stimulus to the pancreatic beta-cell due to both glucose and non-glucose secretagogues. We have analysed the metabolic and hormonal responses of 188 newly diagnosed Caucasian subjects with Type 2 diabetes and 38 non-diabetic subjects to a 500 kcal mixed meal. The diabetic subjects were stratified according to fasting plasma glucose (FPG) (&lt; 9, 9-12, 12-15 and &gt; or = 15 mmol/l) and body mass index (BMI) (&lt; 26.5, 26.5-30 and &gt; or = 30 kg/m2). Increasing FPG was associated with higher peak glucose concentrations and increasing failure to achieve basal glucose levels by 4 h. Median fasting IRI concentrations were similar to those of normal subjects, but all diabetic subjects had reduced early-phase insulin secretion. Diabetic subjects with FPG &lt; 9 mmol/l showed augmented IRI area under the curve (AUC) at 2 and 4 h, whereas those with FPG &gt; 9 mmol/l had progressive falls in IRI AUC to below that of the normal subjects (P &lt; 0.0001 for the trend). Peak IRI concentrations declined progressively with increasing FPG. Despite equivalent glucose exposure simple trends of increasing AUC, IRI with increasing BMI were statistically significant (P &lt; 0.001, P &lt; 0.02, P &lt; 0.001 and P &lt; 0.01, respectively for each FPG group). Both fasting and AUC non-esterified fatty acid concentrations increased significantly with FPG regardless of BMI (P &lt; 0.001 for the trends). These results using a more physiological mixed meal challenge in a large number of recently diagnosed Type 2 diabetic subjects demonstrate a marked and increasing loss of beta-cell secretory function with increasing fasting hyperglycaemia aggravated by insulin resistance with increasing obesity.
Evidence-Based Complementary and Alternative Medicine, 2016
Purpose.Type 2 diabetes consists of progressive hyperglycemia and insulin resistance, which could... more Purpose.Type 2 diabetes consists of progressive hyperglycemia and insulin resistance, which could result from glucose toxicity, inflammatory cytokines, and oxidative stress. In the present study we investigated the effect of Gelam honey and quercetin on the oxidative stress-induced inflammatory pathways and the proinflammatory cytokines.Methods.HIT-T15 cells were cultured and preincubated with the extract of Gelam honey (20, 40, 60, and 80 μg/mL), as well as quercetin (20, 40, 60, and 80 μM), prior to stimulation by 20 and 50 mM glucose.Results.HIT-T15 cells cultured under hyperglycemic condition showed a significant increase in the inflammatory pathways by phosphorylating JNK, IKK-β, and IRS-1 at Ser307 (p<0.05). There was a significant decrease in the phosphorylation of Akt at Ser473 (p<0.05). Pretreatment with Gelam honey and quercetin reduced the expression of phosphorylated JNK, IKK-β, and IRS-1, thereby significantly reducing the expression of proinflammatory cytokines l...
We examined the prevalence of diabetes among inpatients in our hospital, the relationship of the ... more We examined the prevalence of diabetes among inpatients in our hospital, the relationship of the diagnoses on admission to diabetes, and the frequency of testing for HbA1c as a marker of long-term glycaemic control, proteinuria, and hypercholesterolaemia. In addition, patients with raised laboratory plasma glucose without a known history of diabetes mellitus, were studied to see if there had been
Several lines of evidence from studies of both twins and offspring of people with type 2 diabetes... more Several lines of evidence from studies of both twins and offspring of people with type 2 diabetes have shown the importance of genetics in its pathogenesis. Impaired glucose tolerance (IGT) may reflect these genetic changes during the prediabetic stage. Thus, we performed a comprehensive analysis of the gene expression profiles of the peripheral blood mononuclear cells among offspring of one
Background. Oxidative stress induced by reactive oxygen and nitrogen species is critically involv... more Background. Oxidative stress induced by reactive oxygen and nitrogen species is critically involved in the impairment ofβ-cell function during the development of diabetes.Methods. HIT-T15 cells were cultured in 5% CO2and then preincubated with Gelam honey extracts (20, 40, 60, and 80 µg/mL) as well as quercetin (20, 40, 60, and 80 µM), prior to stimulation by 20 and 50 mM of glucose. Cell lysate was collected to determine the effect of honey extracts and quercetin on the stress activated NF-κB, MAPK pathways, and the Akt (ser473) activated insulin signaling pathway.Results. HIT-T15 cells cultured under hyperglycemic conditions demonstrated insulin resistance with a significant increase in the levels of MAPK, NF-κB, and IRS-1 serine phosphorylation (ser307); however, Akt expression and insulin contents are significantly decreased. Pretreatment with quercetin and Gelam honey extract improved insulin resistance and insulin content by reducing the expression of MAPK, NF-κB, and IRS-1 se...
Background: People with pre-diabetes are at high risk of developing type 2 diabetes and cardiovas... more Background: People with pre-diabetes are at high risk of developing type 2 diabetes and cardiovascular diseases. Measurements of health-related quality of life (HRQOL) among pre-diabetics enable the health care providers to understand their overall health status and planning of interventions to prevent type 2 diabetes. Therefore we aimed to determine the HRQOL and physical activity level; and its association with Body Mass Index (BMI) among pre-diabetics. Methods: This was a cross sectional study carried out in two primary care clinics in a semi-urban locality of Ampangan, Negeri Sembilan, Malaysia. Data was collected through self-administered questionnaires assessing the demographic characteristics, medical history, lifestyle and physical activity. The Short Form 36-items health survey was used to measure HRQOL among the pre-diabetics. Data entry and analysis were performed using the SPSS version 19. Results: A total of 268 eligible pre-diabetics participated in this study. The prevalence of normal weight, overweight and obesity were 7.1%, 21.6% and 71.3% respectively. Their mean (SD) age was 52.5 (8.3) years and 64.2% were females. Among the obese pre-diabetics, 42.2% had both IFG and IGT, 47.0% had isolated IFG and 10.8% had isolated IGT, 36.2% had combination of hypertension, dyslipidemia and musculoskeletal diseases. More than 53.4% of the obese pre-diabetics had family history of diabetes, 15.7% were smokers and 60.8% were physically inactive with mean PA of < 600 MET-minutes/week. After adjusted for co-variants, Physical Component Summary (PCS) was significantly associated with BMI categories [F (2,262) = 11.73, p < 0.001] where pre-diabetics with normal weight and overweight had significantly higher PCS than those obese; normal vs obese [M diff = 9.84, p = 0.006, 95% CI diff = 2.28, 17.40] and between overweight vs obese [M diff = 8.14, p < 0.001, 95% CI diff = 3.46, 12.80]. Conclusion: Pre-diabetics who were of normal weight reported higher HRQOL compared to those overweight and obese. These results suggest a potentially greater risk of poor HRQOL among pre-diabetics who were overweight and obese especially with regard to the physical health component. Promoting recommended amount of physical activity and weight control are particularly important interventions for pre-diabetics at the primary care level.
A simple and rapid real-time reverse transcription-PCR (RT-PCR) technique using SYBR green fluore... more A simple and rapid real-time reverse transcription-PCR (RT-PCR) technique using SYBR green fluorescence was developed to quantify Zonula Occludens-1 (ZO-1) mRNA expression in histamine-treated cultured bovine retinal microvessel endothelial cells. There was no dif-ference between the quantity of ZO-1 mRNA expression in histamine-treated (10-7M to 10-9 M) and untreated bovine retinal endothelial cells at high magnesium levels. Immunohisto-chemistry staining and
a b s t r a c t Aim: To report the national prevalence of metabolic syndrome (MetS) and its risk ... more a b s t r a c t Aim: To report the national prevalence of metabolic syndrome (MetS) and its risk factors among adult Malaysians (>18 years old) based on World Health Organization (WHO), the National Cholesterol Education Program Expert Panel III (ATP III), International Diabetes Federation (IDF) and the 'Harmonized' criteria.
Introduction: Insulin resistance in latent autoimmune diabetes in adults (LADA) patients is contr... more Introduction: Insulin resistance in latent autoimmune diabetes in adults (LADA) patients is controversial. The aim of this study was to evaluate insulin resistance and its related factors (metabolic syndrome parameters) among subjects with LADA and glutamic acid decarboxylase antibodies (GADA) negative diabetes, as well as the impact of these factors on insulin resistance. Materials and Methods: GADA levels were investigated in 1140 diabetic patients aged between 30 and 70 years. Insulin resistance and metabolic syndrome parameters were assessed in LADA and GAD-negative diabetic patients by general linear model. In addition, the impact of metabolic syndrome factors on insulin resistance was assessed in LADA and glutamic acid decarboxylase (GAD)-negative diabetic patients. Results: LADA was diagnosed in 33 subjects from 1140 Malaysian diabetic patients (prevalence = 2.9%). The results showed that LADA patients had higher insulin resistance and high density lipoprotein cholesterol (HDLc) (P = 0.003 and 0.00017 respectively) and lower body mass index (BMI) (P = 0.007) compared to GAD-negative diabetic patients. The HDLc was associated with decreased insulin resistance in LADA patients (P=0.041), whereas HbA1c, triacylglycerides (TG) and waist were associated with increased insulin resistance in GAD-negative diabetic patients (P=3.6x10(-12), 1.01x10(-5) and 0.004 respectively). HbA1c was highly associated with decreasing beta-cell function in both LADA (P = 0.009) and GAD-negative diabetic subjects (P=2.2x10(-28)). Conclusion: Insulin resistance is significantly higher in LADA than GAD-negative diabetic Malaysian subjects.
Background: Several studies have shown the association of solute carrier family 30 (zinc transpor... more Background: Several studies have shown the association of solute carrier family 30 (zinc transporter) member 8 (SLC30A8) rs13266634 with type 2 diabetes (T2D). However, the association of alternative variants and haplotypes of SLC30A8 with T2D have not been studied in different populations. The aim of this study is to assess the association of the alternative SLC30A8 variants, rs7002176 and rs1995222 as well as the most common variant, rs13266634 and haplotypes with glutamic acid decarboxylase antibodies (GADA) negative diabetes in Malaysian subjects. Methods: Single nucleotide polymorphisms (SNPs) of SLC30A8; rs7002176, rs1995222 and rs13266634 were genotyped in 1140 T2D and 973 non-diabetic control subjects. Of these, 33 GADA positive diabetic subjects and 353 metabolic syndrome (MetS) subjects were excluded from subsequent analysis. Results: The recessive genetic model controlled for age, race, gender and BMI shows that the alternative SLC30A8 variant, rs1995222 is associated with GADA negative diabetes (OR = 1.29, P = 0.02) in Malaysian subjects. The most common variant, rs13266634 is also associated with GADA negative diabetes (OR = 1.45, P = 0.001). This association is more pronounced among Malaysian Indians (OR = 1.93, P = 0.001). Moreover, the CG haplotype and CG-CG diplotype have been equally associated with increased diabetic risk (OR = 1.67, P = 8.6 x 10(-5)). Conclusions: SLC30A8 SNPs and haplotypes are associated with GADA negative diabetes in Malaysian subjects, and this association is markedly higher among Malaysian Indian subjects.
We report the presence of adenosine receptors at molecular level and study their role in the infl... more We report the presence of adenosine receptors at molecular level and study their role in the inflammatory pathway under hyperglycemic condition. Human Muller cells were cultured in low (5 mM) and high (25 mM) glucose with 10% FBS and 1% P/S. Cells were starved in 0% FBS for 18 h and then treated with various agonists CCPA, CGS 21680, NECA and IB-MECA for 6, 12 and 24 h. The adenosine receptors were identified by immunocytochemistry. ELISA was used to measure the levels of TNF-alpha, IL-1 beta and ICAM 1. Four types of adenosine receptors (A(1), A(2A), A(2B) and A(3)) were identified in human Muller cells. TNF-alpha content increased after agonist A(1) and A(3) treatment, but decreased after agonist A(2A) and An treatment. There was no significant effect on ICAM-1 and IL-1 beta. Stimulation of human Muller cells with adenosine A(2A) agonist (CGS 21680) and adenosine A(2B) agonist (NECA) reduces the level of TNF-alpha when exposed to high glucose, whereas A(1) adenosine agonist (CCPA) and A(3) adenosine agonist (IB-MECA) both positively and negatively regulate the TNF-alpha in hyperglycemia. However, none of these agonists has any significant role in affecting ICAM-1 and IL-1 beta.
Introduction: Metabolic syndrome (MetS) had been known as clustering of risk factors for cardiov... more Introduction: Metabolic syndrome (MetS) had been known as clustering of risk factors for cardiovascular disease and diabetes. Over the years, clinical criteria had been revised to highlight importance of various risk factors in defining MetS. Studies had reported different clustering of factors based on different population characteristics.
Objective: Our study aimed to identify the clustering factors among our Malaysian population based on sexes and 4 major ethnic groups namely Malay, Chinese, Indian and other minor ethnic
Methods: A national cross sectional study was done covering both Peninsular and East Malaysia. Subjects’ sociodemographic, body mass index (BMI), waist, hip and neck circumference, blood pressure,
fasting triglycerides (TG) and HDL-cholesterol and glucose, urine microalbumin and serum insulin were taken. Principal component factor analysis with Varimax rotation was done to identify the clustering based on sex and ethnic groups.
Results: One thousand two hundred and sixty eight male and 2355 female subjects were recruited. Majority of subjects were Malays (63.0%) followed by Chinese (13.3%), Indian (7.4%) and other ethnic
groups (13.8%) which followed the population composition in Malaysia. Four factors were identified for both men and women. The factors were anthropometry, glycemia, blood pressure and dyslipidemia given the cumulative percent of variance of 69.4 and 65.9 respectively. There are 4 factors identified for Malay,
Chinese and Aborigines but 5 factors for Indian ethnic groups given cumulative percent of variance explained ranged from 65.1 to 77.7.
Discussion and Conclusion: BMI, neck circumference, blood pressure, Fasting TG and HDL had a high factor loading in both sexes suggesting that for field screening, diagnostic criteria would be adequate criteria. These factors also showed a similar pattern of loading by different ethnic groups. In conclusion,in Malaysian population, at least one measurement from each components namely anthropometric, blood pressure, glycemia and dyslipidemia is adequate to diagnose MetS.
Background: The association of Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) comm... more Background: The association of Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) common variants (rs4402960 and rs1470579) with type 2 diabetes (T2D) has been performed in different populations. The aim of this study was to evaluate the association of alternative variants of IGF2BP2; rs6777038, rs16860234 and rs7651090 with glutamic acid decarboxylase antibodies (GADA) negative diabetes in Malaysian Subjects. Methods/Principal Findings: IGF2BP2; rs6777038, rs16860234 and rs7651090 single nucleotide polymorphisms (SNPs) were genotyped in 1107 GADA negative diabetic patients and 620 control subjects of Asian from Malaysia. The additive genetic model adjusted for age, race, gender and BMI showed that alternative variants; rs6777038, rs16860234 and rs7651090 of IGF2BP2 associated with GADA negative diabetes (OR = 1.21; 1.36; 1.35, P = 0.03; 0.0004; 0.0002, respectively). In addition, the CCG haplotype and diplotype CCG-TCG increased the risk of diabetes (OR = 1.51, P = 0.01; OR = 2.36, P = 0.009, respectively). Conclusions/Significance: IGF2BP2 alternative variants were associated with GADA negative diabetes. The IGF2BP2 haplotypes and diplotypes increased the risk of diabetes in Malaysian subject.
INTERNATIONAL JOURNAL OF ENDOCRINOLOGY AND METABOLISM (IJEM), 2004
Soluble vascular cell adhesion molecule-1 (sVCAM-1) and intercellular adhesion molecule-1 (sICAM-... more Soluble vascular cell adhesion molecule-1 (sVCAM-1) and intercellular adhesion molecule-1 (sICAM-1) have been shown to be elevated in patients with Graves’ disease and may play significant roles in the pathogenesis of the disease. The objective of this study was to measure the levels of sVCAM-1, sICAM-1, IL-6 and thyroid receptor stimulating antibodies (TRAb) in a cohort of hyperthyroid patients and determine their associations to thyroid hormones status, before and after 3 months therapy with carbimazole.
Materials and Methods: Patients were given fixed daily dose of 20 mg carbimazole for 3 months and blood samples were collected at baseline and end of the study. Thirty eight patients were recruited from the Endocrine Clinic, Hospital University Kebangsaan Malaysia, con-sisting of 26 females and 12 males, age ranging from 16 to 65 years. Blood samples collected be-fore and at end of study were analyzed for TSH, Free T3, Free T4, thyroid receptor stimulating anti-bodies (TRAb), sVCAM-1, sICAM-1 and IL-6.
Results: TRAb level of ?10 U/L was taken to be negative, while TRAb level of >10 U/L was considered as positive. Twenty-six patients (68%) were TRAb positive (TRAb+) and 12 patients (30%) were TRAb negative (TRAb-). Median TRAb in TRAb+ patients was 23 U/L at baseline, declining to 16.7 U/L (p<0.001) in the third 3 month. Serum sVCAM-1 levels were signifi-cantly elevated in TRAb+ patients compared to TRAb- (860 versus 499 ng/mL, p<0.001). The level decreased significantly to 537 ng/mL with treat-ment but remained higher than in TRAb- patients (p=0.003). Irrespective of TRAb status, all but one patient had elevated serum sICAM-1 levels that remained unaffected by carbimazole therapy. In contrast, IL-6 levels of hyperthyroid patients were within the reference range of 1.4-14.1 pg/mL. Baseline and post-treatment sVCAM-1, and not TRAb levels, were significantly corre-lated to thyroid hormones. Conclusion: Compared to other inflammatory markers, sVCAM-1 showed significant correlation to thyroid stimulating antibodies and was most sensitive to changes in thyroid status. The significance of these findings in relation to Graves’ disease warrants further investigation.
Southeast Asian Journal of Tropical Medicine and Public Health, 2005
The concentration of plasma sialic acid was estimated using the modified chemical method and the ... more The concentration of plasma sialic acid was estimated using the modified chemical method and the more sensitive enzymatic method in 20 subjects with impaired glucose tolerance and 20 control subjects. The mean sialic acid concentration values of the control subjects and subjects with impaired glucose tolerance using the enzymatic method were 1.747 ± 0.047 and 2.583 ± 0.070 mmole/l and 1.753 ± 0.067 and 2.591 ± 1.02 mmole/l for the chemical method. The intra-assay coefficient of variation for the control subjects and for the subjects with impaired glucose tolerance were 1.963% and 1.583%, respectively, for the enzymatic assay and 2.728% and 2.431%, respectively, for the chemical assay. The inter-assay coefficient of variation for the control subjects and for the subjects with impaired glucose tolerance were 2.686% and 2.723% for the enzymatic assay, and 3.819% and 3.95% for the chemical assay. Since the values do not differ significantly, the chemical assay is a cost effective method that can be used in large epidemiological studies.
Levels of sialic acid and Vascular Cell Adhesion Molecule-1 (VCAM-1) in the first degree relative... more Levels of sialic acid and Vascular Cell Adhesion Molecule-1 (VCAM-1) in the first degree relatives of type 2 diabetes mellitus patients and their possible role as an early marker of the prediabetic stage were studied in 74 controls and 150 first degree relatives. The total sialic acid concentration was significantly higher (p<0.05) in the first degree relatives compared to the control subjects. Amongst the offsprings, the total sialic acid concentration was significantly higher in the offspring with Normal Glucose Tolerance (NGT) than those with Impaired Glucose Tolerance (IGT). However the level of VCAM-1 did not differ amongst the controls and the first degree relatives. The total cholesterol and triglycerides were significantly higher (p<0.05) in the offspring with IGT when compared to the control subjects and the offspring with NGT. The above data suggests that desialylation of the vascular endothelium is an early event that precedes the expression of IGT or any lipid changes in asymptomatic offspring of one type 2 diabetic parent.
Aim of this study was to investigate the relationship between sialic acid component and C-reactiv... more Aim of this study was to investigate the relationship between sialic acid component and C-reactive protein and lipids in the plasma of 80 healthy subjects. Levels of sialic acid, C-Reactive Protein (CRP) and plasma lipids were measured in a normal population consisting of 80 subjects. The possible correlation between sialic acid and CRP was also studied. The total sialic acid concentration was 2.61±0.61 mM L-1, CRP (2.52±2.32 mmole L-1), total cholesterol (5.504±1.28 mM L-1), triglycerides (1.31±0.87 mM L-1), low density lipoprotein (3.51±1.11 mM L-1) and high density lipoprotein (1.40±0.37 mM L-1). There was a positive correlation between sialic acid and CRP (r = 0.283, p<0.05). However, there was no correlation between CRP and the plasma lipids.
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Papers by Ikram Ismail
Objective: Our study aimed to identify the clustering factors among our Malaysian population based on sexes and 4 major ethnic groups namely Malay, Chinese, Indian and other minor ethnic
Methods: A national cross sectional study was done covering both Peninsular and East Malaysia. Subjects’ sociodemographic, body mass index (BMI), waist, hip and neck circumference, blood pressure,
fasting triglycerides (TG) and HDL-cholesterol and glucose, urine microalbumin and serum insulin were taken. Principal component factor analysis with Varimax rotation was done to identify the clustering based on sex and ethnic groups.
Results: One thousand two hundred and sixty eight male and 2355 female subjects were recruited. Majority of subjects were Malays (63.0%) followed by Chinese (13.3%), Indian (7.4%) and other ethnic
groups (13.8%) which followed the population composition in Malaysia. Four factors were identified for both men and women. The factors were anthropometry, glycemia, blood pressure and dyslipidemia given the cumulative percent of variance of 69.4 and 65.9 respectively. There are 4 factors identified for Malay,
Chinese and Aborigines but 5 factors for Indian ethnic groups given cumulative percent of variance explained ranged from 65.1 to 77.7.
Discussion and Conclusion: BMI, neck circumference, blood pressure, Fasting TG and HDL had a high factor loading in both sexes suggesting that for field screening, diagnostic criteria would be adequate criteria. These factors also showed a similar pattern of loading by different ethnic groups. In conclusion,in Malaysian population, at least one measurement from each components namely anthropometric, blood pressure, glycemia and dyslipidemia is adequate to diagnose MetS.
Materials and Methods: Patients were given fixed daily dose of 20 mg carbimazole for 3 months and blood samples were collected at baseline and end of the study. Thirty eight patients were recruited from the Endocrine Clinic, Hospital University Kebangsaan Malaysia, con-sisting of 26 females and 12 males, age ranging from 16 to 65 years. Blood samples collected be-fore and at end of study were analyzed for TSH, Free T3, Free T4, thyroid receptor stimulating anti-bodies (TRAb), sVCAM-1, sICAM-1 and IL-6.
Results: TRAb level of ?10 U/L was taken to be negative, while TRAb level of >10 U/L was considered as positive. Twenty-six patients (68%) were TRAb positive (TRAb+) and 12 patients (30%) were TRAb negative (TRAb-). Median TRAb in TRAb+ patients was 23 U/L at baseline, declining to 16.7 U/L (p<0.001) in the third 3 month. Serum sVCAM-1 levels were signifi-cantly elevated in TRAb+ patients compared to TRAb- (860 versus 499 ng/mL, p<0.001). The level decreased significantly to 537 ng/mL with treat-ment but remained higher than in TRAb- patients (p=0.003). Irrespective of TRAb status, all but one patient had elevated serum sICAM-1 levels that remained unaffected by carbimazole therapy. In contrast, IL-6 levels of hyperthyroid patients were within the reference range of 1.4-14.1 pg/mL. Baseline and post-treatment sVCAM-1, and not TRAb levels, were significantly corre-lated to thyroid hormones. Conclusion: Compared to other inflammatory markers, sVCAM-1 showed significant correlation to thyroid stimulating antibodies and was most sensitive to changes in thyroid status. The significance of these findings in relation to Graves’ disease warrants further investigation.
Objective: Our study aimed to identify the clustering factors among our Malaysian population based on sexes and 4 major ethnic groups namely Malay, Chinese, Indian and other minor ethnic
Methods: A national cross sectional study was done covering both Peninsular and East Malaysia. Subjects’ sociodemographic, body mass index (BMI), waist, hip and neck circumference, blood pressure,
fasting triglycerides (TG) and HDL-cholesterol and glucose, urine microalbumin and serum insulin were taken. Principal component factor analysis with Varimax rotation was done to identify the clustering based on sex and ethnic groups.
Results: One thousand two hundred and sixty eight male and 2355 female subjects were recruited. Majority of subjects were Malays (63.0%) followed by Chinese (13.3%), Indian (7.4%) and other ethnic
groups (13.8%) which followed the population composition in Malaysia. Four factors were identified for both men and women. The factors were anthropometry, glycemia, blood pressure and dyslipidemia given the cumulative percent of variance of 69.4 and 65.9 respectively. There are 4 factors identified for Malay,
Chinese and Aborigines but 5 factors for Indian ethnic groups given cumulative percent of variance explained ranged from 65.1 to 77.7.
Discussion and Conclusion: BMI, neck circumference, blood pressure, Fasting TG and HDL had a high factor loading in both sexes suggesting that for field screening, diagnostic criteria would be adequate criteria. These factors also showed a similar pattern of loading by different ethnic groups. In conclusion,in Malaysian population, at least one measurement from each components namely anthropometric, blood pressure, glycemia and dyslipidemia is adequate to diagnose MetS.
Materials and Methods: Patients were given fixed daily dose of 20 mg carbimazole for 3 months and blood samples were collected at baseline and end of the study. Thirty eight patients were recruited from the Endocrine Clinic, Hospital University Kebangsaan Malaysia, con-sisting of 26 females and 12 males, age ranging from 16 to 65 years. Blood samples collected be-fore and at end of study were analyzed for TSH, Free T3, Free T4, thyroid receptor stimulating anti-bodies (TRAb), sVCAM-1, sICAM-1 and IL-6.
Results: TRAb level of ?10 U/L was taken to be negative, while TRAb level of >10 U/L was considered as positive. Twenty-six patients (68%) were TRAb positive (TRAb+) and 12 patients (30%) were TRAb negative (TRAb-). Median TRAb in TRAb+ patients was 23 U/L at baseline, declining to 16.7 U/L (p<0.001) in the third 3 month. Serum sVCAM-1 levels were signifi-cantly elevated in TRAb+ patients compared to TRAb- (860 versus 499 ng/mL, p<0.001). The level decreased significantly to 537 ng/mL with treat-ment but remained higher than in TRAb- patients (p=0.003). Irrespective of TRAb status, all but one patient had elevated serum sICAM-1 levels that remained unaffected by carbimazole therapy. In contrast, IL-6 levels of hyperthyroid patients were within the reference range of 1.4-14.1 pg/mL. Baseline and post-treatment sVCAM-1, and not TRAb levels, were significantly corre-lated to thyroid hormones. Conclusion: Compared to other inflammatory markers, sVCAM-1 showed significant correlation to thyroid stimulating antibodies and was most sensitive to changes in thyroid status. The significance of these findings in relation to Graves’ disease warrants further investigation.