Displaying publications 1 - 20 of 24 in total

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  1. C Thambiah S, Lai LC
    Pract Lab Med, 2021 Aug;26:e00248.
    PMID: 34368411 DOI: 10.1016/j.plabm.2021.e00248
    Diabetes mellitus (DM) is an escalating pandemic and an established cardiovascular risk factor. An important aspect of the interaction between DM and atherosclerotic cardiovascular disease (ASCVD) is diabetic dyslipidaemia, an atherogenic dyslipidaemia encompassing quantitative [hypertriglyceridaemia (hyperTG) and decreased high density lipoprotein cholesterol (HDL)] and qualitative [increased small dense low density lipoprotein cholesterol (sdLDL) particles, large very low density lipoprotein cholesterol (VLDL) subfraction (VLDL1) and dysfunctional HDL] modifications in lipoproteins. Much of the pathophysiology linking DM and dyslipidaemia has been elucidated. This paper aims to review the pathophysiology and management of diabetic dyslipidaemia with respect to ASCVD. Briefly, the influence of diabetic kidney disease on lipid profile and lipid changes causing type 2 diabetes mellitus are highlighted. Biomarkers of diabetic dyslipidaemia, including novel markers and clinical trials that have demonstrated that non-lipid and lipid lowering therapies can lower cardiovascular risk in diabetics are discussed. The stands of various international guidelines on lipid management in DM are emphasised. It is important to understand the underlying mechanisms of diabetic dyslipidaemia in order to develop new therapeutic strategies against dyslipidaemia and diabetes. The various international guidelines on lipid management can be used to tailor a holistic approach specific to each patient with diabetic dyslipidaemia.
  2. Thambiah, Subashini Chellapah, Zalinah Ahmad, Zarida Hambali, Malina Osman, Munia Mohd Zain, Fuziah Md Zain, et al.
    MyJurnal
    A clinical descriptive study was done to determine the sociodemographic, laboratory and clinical characteristics of patients with congenital adrenal hyperplasia (CAH) referred to Hospital Putrajaya, a tertiary endocrine centre in Malaysia. Electronic laboratory data of 51 CAH patients were obtained. The demographics and clinical details of the study population were acquired from a questionnaire completed by parents of participants. There were 25 males (49%) and 26 females (51%), of which, 58.8% were Malays. Median age of participants was 4 years whilst median age at diagnosis of CAH was two years. Parental consanguinity was documented in three patients (5.9%). Patients originated from Johor (19.6%), Selangor (19.6%), Negeri Sembilan (17.6%) and Kedah (13.7%). Majority of patients were diagnosed after one week of life (80.4%) although more females were diagnosed under the age of one week compared to males (p=0.041). Most females presented with ambiguous genitalia (42.3%) [p=0.001] whereas 72% of males presented with salt wasting (p=0.003). No significant associations between race and all other variables, though interestingly three Malay patients presented with ambiguous genitalia and hypertension. Equal gender distribution noted as expected in an autosomal recessive condition, although not in keeping with other Asian countries. Early diagnosis in females attributed to obvious genital ambiguity at birth. Varied clinical presentation, although in minority, necessitates genetic studies for prompt diagnosis and treatment. Considering that majority of patients presented with salt wasting and the age at diagnosis was delayed, the introduction of a neonatal screening programme is essential in Malaysia.
  3. Thambiah, Subashini, Nor Shaibah Ramley, Nur Syazwani Ghazali, Ng, Ooi Chuan, Intan Nureslyna Samsudin, Siti Yazmin Zahari Sham
    MyJurnal
    Introduction: The prevalence of diabetes mellitus (DM) in Malaysia is drastically increasing. Subjects with DM are
    more likely to have deranged liver function tests (LFT). This study aimed to determine the prevalence of abnormal liver enzymes [(alanine aminotransferase (ALT) and alkaline phosphatase (ALP)] and its associated factors among type
    2 DM (T2DM) subjects visiting a referral diabetic clinic in a tertiary government hospital. Methods: This retrospective, cross-sectional study included electronic data of 300 T2DM subjects ≥18 years old in the outpatient specialist
    clinic from January 2011 to December 2014. Statistical analysis was performed using SPSS version 22. Results: The
    study population at large included Malays, of age >60 years with comparable gender percentage. Most subjects had
    long-standing DM, poor glycaemic control and were on treatment. The prevalence of abnormal ALT and ALP was
    27.3% and 13%; with 90.2% and 97.4% having mild ALT and ALP elevations, respectively. Significant associations
    noted for age, body mass index (BMI) and duration of T2DM for ALT whereas for ALP, anti-diabetic medication was
    significant between groups of normal and abnormal levels. Deranged liver enzymes were associated significantly
    with dyslipidaemia. Conclusion: Our study on the crude prevalence of raised liver enzymes may help identify T2DM
    patients at increased risk of non-alcoholic fatty liver disease (NAFLD). Modification of metabolic risk factors, such
    as weight loss, control of dyslipidaemia rather than just tighter glycaemic control should be emphasised to reduce
    morbidity and mortality. Liver enzymes remain a simple and non- invasive marker of liver pathology in daily medical
    practice.
  4. Thambiah SC, Yeap SS
    Clin Biochem Rev, 2020 Feb;41(1):29-40.
    PMID: 32158060 DOI: 10.33176/AACB-19-00034
    Osteoporosis (OP) is a condition where there is low bone density and microarchitectural deterioration which can predispose to fragility fractures. There is a wealth of literature on OP from the developed countries, but less so from Asia. This review will explore the field of OP research in South-East Asia with regard to the epidemiology, the diagnosis of OP and the role of laboratory tests in the management of OP, with emphasis on 25-dihydroxyvitamin D and bone turnover markers.
  5. Intan Nureslyna Samsudin, Thambiah, Subashini C., Wan Mohamad Asyraf Wan Mohammed Ayub, Cheng, Ng Wan, Zanariah Hussein, Nurain Mohd Noor, et al.
    MyJurnal
    The glycosylated haemoglobin (HbA1c) test is the most widely accepted laboratory test for evaluating long term glycaemic control. Patient’s understanding of HbA1c can lead to better glycaemic control. This study is aimed to determine the awareness and level of understanding of HbA1c among type 2 DM patients and its association with glycaemic control. A cross-sectional descriptive study among Type 2 DM patients undergoing routine follow up in an endocrine clinic of a tertiary centre in Malaysia. Patients were invited to answer a validated questionnaire which assessed their awareness and understanding of HbA1c. Their last HbA1c results were retrieved from the laboratory information system. A total of 92 participants were recruited. Fifty-six (60.9%) were aware of the term HbA1c. Fifty percent were categorised as having good HbA1c understanding, with age, monthly income and level of education being the factors associated with understanding. No significant association was noted between HbA1c understanding and glycaemic control, although more patients with good HbA1c understanding had achieved the target glycaemic control compared to those with poor understanding. The level of HbA1c awareness and understanding was acceptable. Factors associated with understanding were age, income and level of education. Continuing efforts however, must be made to improve patients understanding of their disease and clinical disease biomarkers.
  6. Lai YY, Samsudin IN, Mohamed Mokhtar N, C Thambiah S
    Clin Chem, 2020 05 01;66(5):652-657.
    PMID: 32353132 DOI: 10.1093/clinchem/hvaa017
  7. Arifin A, Thambiah SC, Abdullah H, Samsudin IN
    Clin Chem, 2021 06 01;67(6):823-826.
    PMID: 34059896 DOI: 10.1093/clinchem/hvab031
  8. Riyahi N, Tohit ERM, Thambiah SC, Ibrahim Z
    Asia Pac J Clin Nutr, 2017 12 10;27(1):182-188.
    PMID: 29222897 DOI: 10.6133/apjcn.032017.01
    BACKGROUND AND OBJECTIVES: Recent studies have reported that obesity is associated with platelet activation and systemic inflammation. Malaysia has the highest prevalence of obesity, hence, this research is performed to evaluate the development of low-grade inflammation and platelet activation, measured using soluble CD40 ligand (sCD40L) and soluble P-selectin (sP-sel), and to determine their association with obesity. In addition, we assessed the mean platelet volume (MPV) and platelet count (PLT), which are novel parameters consistently associated with obesity.

    METHODS AND STUDY DESIGN: A cross-sectional study was conducted on 112 healthy men and women from 3 main ethnic group (Malay, Chinese, and Indian) who were aged 18-60 years. The participants were categorized into normal body mass index (BMI), overweight and obese groups according to WHO criteria for BMI in Asian populations (18.5 kg/m2

  9. Meor Anuar Shuhaili MFR, Samsudin IN, Stanslas J, Hasan S, Thambiah SC
    Int J Endocrinol Metab, 2017 Apr;15(2):e43319.
    PMID: 28848611 DOI: 10.5812/ijem.43319
    CONTEXT: The present review aimed at reviewing the effects of different statins on lipid profile, particularly in Asians.

    EVIDENCE ACQUISITION: PubMed searches were conducted using the keywords 'statin, effect, and lipid profile' from database inception through March 2016. In this review, 718 articles were retrieved from the primary search. After reviewing the titles, abstracts, and full texts, we found that 59 studies met our inclusion criteria. These also included subsequent reference searches of retrieved articles.

    RESULTS: CURVES study compared the effect on lipid profile between atorvastatin and other statins. This study demonstrated that low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG) were reduced more with atorvastatin compared to simvastatin, pravastatin, lovastatin, and fluvastatin. However, simvastatin provided a greater elevation of high-density lipoprotein cholesterol (HDL-C) compared to atorvastatin. The STELLAR trial was based on dose-to-dose comparisons between atorvastatin and rosuvastatin efficacy in reducing LDL-C. Te present study also revealed that as the doses of rosuvastatin, simvastatin, and pravastatin increased, HDL-C also increased, with rosuvastatin having the greatest effect. However, HDL-C levels decreased as the dose of atorvastatin increased. The DISCOVERY study involving the Asian population revealed that the percentage of patients achieving the European goals for LDL-C and TC at 12 weeks was higher in rosuvastatin group compared to atorvastatin group.

    CONCLUSIONS: The effects of statins on lipid profile are dose dependent. Most studies showed that rosuvastatin has the best effect on lipid profile. Prescribing lower doses of statins in Asians seems necessary.

  10. Azmi JA, C Thambiah S, Lee YL, Zahari Sham SY, Abdul Hamid H, Samsudin IN
    J Paediatr Child Health, 2023 Jan;59(1):185-187.
    PMID: 36222293 DOI: 10.1111/jpc.16243
  11. Lai YY, Lim CH, Nazli MS, Samsudin IN, Thambiah SC
    Clin Chem, 2023 Nov 02;69(11):1220-1225.
    PMID: 37932109 DOI: 10.1093/clinchem/hvad158
  12. Vasikaran S, Thambiah SC, Tan RZ, Loh TP, APFCB Harmonization of Reference Interval Working Group
    Ann Lab Med, 2024 Mar 01;44(2):126-134.
    PMID: 37869778 DOI: 10.3343/alm.2023.0214
    Bone-turnover marker (BTM) measurements in the blood or urine reflect the bone-remodeling rate and may be useful for studying and clinically managing metabolic bone diseases. Substantial evidence supporting the diagnostic use of BTMs has accumulated in recent years, together with the publication of several guidelines. Most clinical trials and observational and reference-interval studies have been performed in the Northern Hemisphere and have mainly involved Caucasian populations. This review focuses on the available data for populations from the Asia-Pacific region and offers guidance for using BTMs as diagnostic biomarkers in these populations. The procollagen I N-terminal propeptide and β-isomerized C-terminal telopeptide of type-I collagen (measured in plasma) are reference BTMs used for investigating osteoporosis in clinical settings. Premenopausal reference intervals (established for use with Asia-Pacific populations) and reference change values and treatment targets (used to monitor osteoporosis treatment) help guide the management of osteoporosis. Measuring BTMs that are not affected by renal failure, such as the bone-specific isoenzyme alkaline phosphatase and tartrate-resistant acid phosphatase 5b, may be advantageous for patients with advanced chronic kidney disease. Further studies of the use of BTMs in individuals with metabolic bone disease, coupled with the harmonization of commercial assays to provide equivalent results, will further enhance their clinical applications.
  13. Mobarak A, C Thambiah S, Masiman AD, Samsudin IN, Lai YY
    Pract Lab Med, 2024 May;40:e00395.
    PMID: 38707259 DOI: 10.1016/j.plabm.2024.e00395
    Acquired methemoglobinemia, predominantly due to oxidizing medications occurs when heme iron in hemoglobin is oxidized from ferrous to ferric ion and binds oxygen irreversibly leading to functional anemia, cyanosis, and tissue hypoxia. We report a case of a 60-year-old man with multiple comorbidities who was diagnosed with coronavirus disease 2019 (COVID-19) and developed methemoglobinemia after consumption of prescribed supplements. He presented with dyspnea and cyanosis. An oxygen saturation gap with characteristic chocolate-brown arterial blood indicated methemoglobinemia. Outsourced methemoglobin (MetHb) was increased at 9.0%. Despite aggressive intervention, he succumbed to his illness. In this case, we discuss the pathophysiology of why some individuals, especially the elderly with COVID-19 are more susceptible to develop methemoglobinemia after possibly being exposed to oxidizing agents. Laboratory methods for assessing oxygen saturation, including pulse oximetry, arterial blood gas and co-oximetry are examined in relation to this case. The importance of considering a diagnosis of methemoglobinemia based on clinical and biochemical findings although MetHb assay or co-oximetry are not readily available is also emphasized.
  14. Thambiah SC, George E, Samsudin IN, Hong LH, Chuo LL, Ramli N, et al.
    Natl Med J India, 2016 May-Jun;29(3):136-140.
    PMID: 27808061
    BACKGROUND: The principal cause of iron overload in patients with haematological malignancies is recurrent red cell transfusions for anaemia. The serum ferritin level reflects the iron burden in the body, in the absence of inflammation or liver disease. In Malaysia, data are lacking on the association between pre-transplant serum ferritin levels and outcome after allogeneic haemopoietic stem cell transplant.

    METHODS: We did a cross-sectional study using retrospective data of 106 post-allogeneic haemopoietic stem cell transplant patients (HLA-matched sibling) with haematological malignancies at Hospital Ampang to determine the relationship between pre-transplant serum ferritin levels and post-transplant outcome, post-transplant complications and survival time. Patients were divided into two groups according to the iron status: serum ferritin level >1000 μg/L (iron overload) and <1000 μg/L.

    RESULTS: The median age for patients was 30.5 (18-58) years. The median pre-transplantation serum ferritin level and the prevalence of pre-transplantation iron overload were 2423 (408.2-7664) μg/L and 87.5%, respectively. No significant association was found between iron status and demographic factors, type of haematological malignancy and post-transplant complications. Although insignificant, patients with iron overload had a shorter survival time (36 months) compared to those with no iron overload (40 months). There was also no significant association between the iron status and post-transplant outcome. Significant post-transplant complications associated with post-transplant outcome were the need for total parenteral nutrition (TPN) (p=0.014) and chronic graft-versus-host disease (GVHD) (p=0.008). Similarly, significant associations were found between age group (p=0.003), TPN (p=0.035) and chronic GVHD (p=0.012) with survival time using Kaplan-Meir analysis. However, after Cox regression, only age group was found to be significantly associated with survival time (p=0.014).

    CONCLUSION: Serum ferritin is an acute phase reactant and its levels increase in the presence of tissue necrosis and inflammation. Both these events occur in haematological malignancies. Although serum ferritin level is a non-invasive, relatively cost-effective, widely available and practical indicator of iron status, it is not specific to iron overload. Therefore, a true association between the serum ferritin level and iron burden is problematic in patients with haematological malignancies.
  15. Salleh MFB, Lai YY, Mohamed Mokhtar NB, Thambiah SC, Samsudin IN
    Clin Pediatr (Phila), 2024 Aug 23.
    PMID: 39180240 DOI: 10.1177/00099228241271944
  16. Thambiah SC, Wong TH, Das Gupta E, Radhakrishnan AK, Gun SC, Chembalingam G, et al.
    Malays J Pathol, 2018 Dec;40(3):287-294.
    PMID: 30580359
    INTRODUCTION: Low 25-hydroxyvitamin D [25(OH)D] levels have not been consistently associated with bone mineral density (BMD). It has been suggested that calculation of the free/bioavailable 25(OH)D may correlate better with BMD. We examined this hypothesis in a cohort of Malaysian women.

    MATERIALS AND METHODS: A cross-sectional study of 77 patients with rheumatoid arthritis (RA) and 29 controls was performed. Serum 25(OH)D was measured using the Roche Cobas E170 immunoassay. Serum vitamin D binding protein (VDBP) was measured using a monoclonal enzyme-linked immunosorbent assay (ELISA). Free/bioavailable 25(OH)D were calculated using both the modified Vermuelen and Bikle formulae.

    RESULTS: Since there were no significant differences between RA patients and controls for VDBP and 25(OH)D, the dataset was analysed as a whole. Calculated free 25(OH)D by Vermeulen was strongly correlated with Bikle (r = 1.00, p < 0.001). A significant positive correlation was noted between measured total 25(OH)D with free/bioavailable 25(OH)D (r = 0.607, r = 0.637, respectively, p < 0.001). Median free/bioavailable 25(OH)D values were significantly higher in Chinese compared with Malays and Indians, consistent with their median total 25(OH)D. Similar to total 25(OH)D, the free/bioavailable 25(OH)D did not correlate with BMD.

    CONCLUSION: In this first study of a multiethnic female Malaysian population, free/bioavailable 25(OH)D were found to reflect total 25(OH)D, and was not superior to total 25(OH)D in its correlation with BMD. Should they need to be calculated, the Bikle formula is easier to use but only calculates free 25(OH)D. The Vermuelen formula calculates both free/bioavailable 25(OH)D but is more complex to use.
  17. Yeap SS, Thambiah SC, Suppiah S, Md-Said S, Appannah G, Samsudin IN, et al.
    PLoS One, 2021;16(7):e0255069.
    PMID: 34293028 DOI: 10.1371/journal.pone.0255069
    OBJECTIVE: This study aimed to determine the prevalence of vertebral fractures (VF) in a selected urban population in Malaysia and to explore possible variables associated with VF in the study population.

    METHODS: A cross-sectional study involving community-living, healthy subjects aged between 45-90 years from the state of Selangor, Malaysia, were invited to attend a bone health check-up. Subjects with diseases known to affect bone metabolism or were on treatment for osteoporosis (OP) were excluded. Bone mineral density (BMD) was measured using dual energy X-ray absorptiometry (DXA). Lateral and antero-posterior view lumbar spine x-rays were performed and VF was determined by the semi-quantitative Genant method.

    RESULTS: A total of 386 subjects were studied. Asymptomatic morphometric VF were found in 44 (11.4%) subjects. T12 was the most common vertebrae to be fractured. The prevalence of VF was significantly higher in menopausal women (12.4%) compared to non-menopausal women, in those above the age of 60 (18.5%), in those of Chinese ethnicity (16.5%), in those with a low body fat percentage (17.1%) and among those with OP (27.0%). The mean (standard deviation) 25-hydroxyvitamin D [25(OH)D] levels were significantly higher in those with VF compared to those without VF, 67.64 (23.50) and 57.47 (21.71) nmol/L, respectively. However, after multiple regression analysis, age over 60 years and OP on DXA BMD measurement were the only significant associated factors for VF.

    CONCLUSION: Overall, 11.4% of a selected Malaysian urban population had asymptomatic morphometric VF. Age over 60 years and OP on DXA BMD measurement, but not 25(OH)D levels, were associated with VF.

  18. C Thambiah S, Meor Anuar Shuhaili MFR, Chew BH, Samsudin IN, Abdul Rahman H, Stanslas J, et al.
    Biomarkers, 2019 Nov;24(7):659-665.
    PMID: 31342800 DOI: 10.1080/1354750X.2019.1648554
    Introduction: Statin, the first-line treatment for dyslipidaemia, may have suboptimal adherence due to its associated muscle adverse events. These data, however, remain limited. Aim: To determine the association of serum creatine kinase (CK) and SLCO1B1 rs4363657 polymorphism with statin-associated muscle adverse events (SAMAE) among dyslipidaemia participants.
    Methods: This was a prospective cohort study at government health clinics involving newly diagnosed adults with dyslipidaemia. SAMAE were recorded based on the patient's complaint after a month on statin. CK was taken at baseline and follow-up. Genetic profiling was performed for SLCO1B1 rs4363657 polymorphism.
    Results: Among 118 participants, majority were Malay (72%) males (61%) with a mean age of 49 ± 12.2 years old and prescribed lovastatin (61.9). There was a significant association between statin types (lovastatin and simvastatin) and SAMAE (p = 0.0327); no significant association noted between CK and SAMAE (p = 0.5637). The SLCO1B1 rs4363657 polymorphism was significantly associated SAMAE (p 
  19. Ratnasingam J, Niyaz M, Mariyappan S, Ong T, Chan SP, Hew FL, et al.
    Arch Osteoporos, 2024 Mar 20;19(1):18.
    PMID: 38503995 DOI: 10.1007/s11657-024-01371-w
    Fracture risk stratification is crucial in countries with limited access to bone density measurement. 24.8% women were in the high-risk category while 30.4% were in the low-risk category. In the intermediate risk group, after recalculation of fracture risk with bone density, 38.3% required treatment. In more than half, treatment decisions can be made without bone density.

    PURPOSE: We aimed to examine the role of age-dependent intervention thresholds (ITs) applied to the Fracture Risk Assessment (FRAX) tool in therapeutic decision making for osteoporosis in the Malaysian population.

    METHODS: Data were collated from 1380 treatment-naïve postmenopausal women aged 40-85 years who underwent bone mineral density (BMD) measurements for clinical reasons. Age-dependent ITs, for both major osteoporotic fracture (MOF) and hip fracture (HF), were calculated considering a woman with a BMI of 25 kg/m2, aged between 40 and 85years, with a prior fragility fracture, sans other clinical risk factors. Those with fracture probabilities equal to or above upper assessment thresholds (UATs) were considered to have high fracture risk. Those below the lower assessment thresholds (LATs) were considered to have low fracture risk.

    RESULTS: The ITs of MOF and HF ranged from 0.7 to 18% and 0.2 to 8%, between 40 and 85years. The LATs of MOF ranged from 0.3 to 11%, while those of HF ranged from 0.1 to 5.2%. The UATs of MOF and HF were 0.8 to 21.6% and 0.2 to 9.6%, respectively. In this study, 24.8% women were in the high-risk category while 30.4% were in the low-risk category. Of the 44.8% (n=618) in the intermediate risk group, after recalculation of fracture risk with BMD input, 38.3% (237/618) were above the ITs while the rest (n=381, 61.7%) were below the ITs. Judged by the Youden Index, 11.5% MOF probability which was associated with a sensitivity of 0.62 and specificity of 0.83 and 4.0% HF probability associated with a sensitivity of 0.63 and a specificity 0.82 were found to be the most appropriate fixed ITs in this analysis.

    CONCLUSION: Less than half of the study population (44.8%) required BMD for osteoporosis management when age-specific assessment thresholds were applied. Therefore, in more than half, therapeutic decisions can be made without BMD based on these assessment thresholds.

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