Displaying publications 1 - 20 of 46 in total

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  1. Lai P, Nagammai T, Vethakkan S
    Malays Fam Physician, 2013;8(2):47-52.
    PMID: 25606283 MyJurnal
    Bisphosphonates are pyrophosphate analogues, with a strong affinity for bones. They inhibit bone resorption and are currently the first choice of treatment for osteoporosis. Bisphosphonates should be taken in a specific manner and for at least one year to be effective in the maintenance and improvement of bone mineral density (BMD), as well as for protection against fractures. We report a case of a postmenospausal osteoporotic woman who lost BMD despite being on bisphosphonate therapy for eight years, highlighting issues that a primary care doctor needs to address before deciding on the next best option.
  2. Sthaneshwar P, Vethakkan SR, Wong CW
    Med J Malaysia, 2014 Aug;69(4):175-7.
    PMID: 25500845 MyJurnal
    INTRODUCTION: Glycohemoglobin (HbA1c) most accurately reflects the previous two to three months of glycaemic control. HbA1c should be measured regularly in all patients with diabetes, and values should be maintained below 7% to prevent the risk of chronic complications. Apart from the genetic variants of haemoglobins many other conditions also known to affect HbA1c measurements. In this study we evaluated the conditions that cause low HbA1c results.

    METHODS AND MATERIALS: The data was collected retrospectively HbA1c was measured in our laboratory by Biorad Variant II turbo 2.0. The method is based on chromatographic separation of HbA1c on a cation exchange cartridge. This method has been certified by National Glycohemoglobin Standardization Programme (NGSP). 58437 requests were received in a period of one year (January to December 2011). Medical records were reviewed to identify the conditions that might be associated with these low values.

    RESULTS: Among 58437 samples analysed, 53 patients had HbA1c levels < 4.0%. Fourteen patients had haemoglobinopathy. In 34 patients without Hb variants had conditions such as chronic liver disease, chronic kidney disease, haemolytic anaemia, pregnancy, and anaemia of chronic disease. Five non-pregnant individuals who were screened for diabetes mellitus had HbA1c levels < 4%.

    CONCLUSION: Our study underscores the importance of that both laboratories and the physicians should be aware of the factors that can influence the HbA1c results. The haematological status should be taken into consideration for proper interpretation of HbA1c results.
  3. Tong WT, Vethakkan SR, Ng CJ
    BMJ Open, 2015 Jan 29;5(1):e006407.
    PMID: 25633285 DOI: 10.1136/bmjopen-2014-006407
    OBJECTIVE: To explore factors influencing poor glycaemic control in people with type 2 diabetes using insulin.
    RESEARCH DESIGN: A qualitative method comprising in-depth individual interviews. A semistructured interview guide was used. The interviews were audiorecorded, transcribed verbatim and analysed using a thematic approach.
    PARTICIPANTS: Seventeen people with type 2 diabetes using insulin with glycated haemoglobin (HbA1c) ≥9% for >1 year.
    SETTING: The Primary Care Clinic and Diabetes Clinic in the University of Malaya Medical Centre (UMMC), Malaysia.
    RESULTS: Data analysis uncovered four themes: lifestyle challenges in adhering to medical recommendations; psychosocial and emotional hurdles; treatment-related factors; lack of knowledge about and self-efficacy in diabetes self-care.
    CONCLUSIONS: Factors that explain the poor glycaemic control in people with type 2 diabetes using insulin were identified. Healthcare providers could use these findings to address patients' concerns during consultations and help to improve glycaemic control.
    Study site: Primary Care Clinic and Diabetes Clinic, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
  4. Zaman Huri H, Permalu V, Vethakkan SR
    PLoS One, 2014;9(9):e106505.
    PMID: 25181406 DOI: 10.1371/journal.pone.0106505
    Sliding-scale and basal-bolus insulin regimens are two options available for the treatment of severe or acute hyperglycemia in type 2 diabetes mellitus patients. Although its use is not recommended, sliding-scale insulin therapy is still being used widely. The aims of the study were to compare the glycemic control achieved by using sliding-scale or basal-bolus regimens for the management of severe or acute hyperglycemia in patients with type 2 diabetes and to analyze factors associated with the types of insulin therapy used in the management of severe or acute hyperglycemia. This retrospective study was conducted using the medical records of patients with acute or severe hyperglycemia admitted to a hospital in Malaysia from January 2008 to December 2012. A total of 202 patients and 247 admissions were included. Patients treated with the basal-bolus insulin regimen attained lower fasting blood glucose (10.8 ± 2.3 versus 11.6 ± 3.5 mmol/L; p = 0.028) and mean glucose levels throughout severe/acute hyperglycemia (12.3 ± 1.9 versus 12.8 ± 2.2; p = 0.021) compared with sliding-scale insulin regimens. Diabetic ketoacidosis (p = 0.043), cardiovascular diseases (p = 0.005), acute exacerbation of bronchial asthma (p = 0.010), and the use of corticosteroids (p = 0.037) and loop diuretics (p = 0.016) were significantly associated with the type of insulin regimen used. In conclusion, type 2 diabetes patients with severe and acute hyperglycemia achieved better glycemic control with the basal-bolus regimen than with sliding-scale insulin, and factors associated with the insulin regimen used could be identified.
  5. Jamaluddin JL, Huri HZ, Vethakkan SR
    Pharmacogenomics, 2016 06;17(8):867-81.
    PMID: 27249660 DOI: 10.2217/pgs-2016-0010
    AIM: To determine the clinical and genetic predictors of the dipeptidyl peptidase-4 (DPP-4) inhibitor treatment response in Type 2 diabetes mellitus (T2DM) patients.

    PATIENTS & METHODS: DPP4, WFS1 and KCNJ11 gene polymorphisms were genotyped in a cohort study of 662 T2DM patients treated with DPP-4 inhibitors sitagliptin, vildagliptin or linagliptin. Genotyping was performed by Applied Biosystems TaqMan SNP genotyping assay.

    RESULTS: Patients with triglyceride levels less than 1.7 mmol/l (odds ratio [OR]: 2.2.; 95% CI: 1.031-4.723), diastolic blood pressure (DBP) less than 90 mmHg (OR: 1.7; 95% CI: 1.009-2.892) and KCNJ11 rs2285676 (genotype CC) (OR: 2.0; 95% CI: 1.025-3.767) were more likely to response to DPP-4 inhibitor treatment compared with other patients, as measured by HbA1c levels.

    CONCLUSION: Triglycerides, DBP and KCNJ11 rs2285676 are predictors of the DPP-4 inhibitor treatment response in T2DM patients.

  6. Zaman Huri H, Selamat N, Vethakkan SR
    Int J Endocrinol, 2014;2014:367564.
    PMID: 25258626 DOI: 10.1155/2014/367564
    Dipeptidyl-4 (DPP-4) inhibitors are oral antidiabetic agents recently introduced to Malaysia. Thus, limited data is available on their utilization patterns and factors associated with their use. This study aims to analyse the utilization patterns of DPP-4 inhibitors, factors that influenced the choice of agent, and the rationale for treatment with DPP-4 inhibitors in patients with type 2 diabetes mellitus. This retrospective study was conducted to address the utilization pattern of DPP-4 inhibitors and factors that influence choice in type 2 diabetes mellitus patients. 299 subjects taking either sitagliptin or vildagliptin from September 2008 to September 2012 were included in the study. Sitagliptin was more frequently prescribed than vildagliptin. Of the patients prescribed DPP-4 inhibitors, 95% received combinations of these and other agents, whereas only 5% were prescribed DPP-4 inhibitors as monotherapy. Factors affecting the utilization of DPP-4 inhibitors included age (P = 0.049) and concomitant use of beta blockers (P = 0.045) and aspirin (P = 0.008). Early identification of factors associated with DPP-4 inhibitors is essential to enhance quality use of the drugs.
  7. Jamaluddin JL, Huri HZ, Vethakkan SR, Mustafa N
    Pharmacogenomics, 2014 Feb;15(2):235-49.
    PMID: 24444412 DOI: 10.2217/pgs.13.234
    In the adult pancreas, the expression of the genes PAX4, KCNQ1, TCF7L2, KCNJ11, ABCC8, MTNR1B and WFS1 are mainly restricted to β cells to maintain glucose homeostasis. We have identified these genes as the main regulators of incretin-mediated actions, and therefore they may potentially influence the response of DPP-4 inhibitors. This review represents the first detailed exploration of pancreatic β-cell genes and their variant mechanisms, which could potentially affect the response of DPP-4 inhibitors in Type 2 diabetes. We have focused on the signaling pathways of these genes to understand their roles in gastrointestinal incretin-mediated effects; and finally, we sought to associate gene mechanisms with their Type 2 diabetes risk variants to predict the responses of DPP-4 inhibitors for this disease.
  8. Arumugam T, Razali SN, Vethakkan SR, Rozalli FI, Shahrizaila N
    Eur J Neurol, 2016 Feb;23(2):354-60.
    PMID: 26498575 DOI: 10.1111/ene.12836
    In the current study, the aim was to characterize the nerve ultrasound cross-sectional areas (CSAs) of type 2 diabetic patients with diabetic sensorimotor polyneuropathy (DSP) of different severities.
  9. Loganadan NK, Huri HZ, Vethakkan SR, Hussein Z
    Pharmacogenomics J, 2016 06;16(3):209-19.
    PMID: 26810132 DOI: 10.1038/tpj.2015.95
    The clinical response to sulphonylurea, an oral antidiabetic agent often used in combination with metformin to control blood glucose in type 2 diabetes (T2DM) patients, has been widely associated with a number of gene polymorphisms, particularly those involved in insulin release. We have reviewed the genetic markers of CYP2C9, ABCC8, KCNJ11, TCF7L2 (transcription factor 7-like 2), IRS-1 (insulin receptor substrate-1), CDKAL1, CDKN2A/2B, KCNQ1 and NOS1AP (nitric oxide synthase 1 adaptor protein) genes that predict treatment outcomes of sulphonylurea therapy. A convincing pattern for poor sulphonylurea response was observed in Caucasian T2DM patients with rs7903146 and rs1801278 polymorphisms of the TCF7L2 and IRS-1 genes, respectively. However, limitations in evaluating the available studies including dissimilarities in study design, definitions of clinical end points, sample sizes and types and doses of sulphonylureas used as well as ethnic variability make the clinical applications challenging. Future studies need to address these limitations to develop personalized sulphonylurea medicine for T2DM management.
  10. Loganathan R, Tarmizi AHA, Vethakkan SR, Teng KT
    J Oleo Sci, 2020 Oct 07;69(10):1163-1179.
    PMID: 32908089 DOI: 10.5650/jos.ess20036
    Sixty-four bottles of red palm olein and palm olein (constituted as control) samples were stored at permutations of common home setting variables which are: temperature (room temperature (24°C) or 8°C), light (kept in dark or exposure under light) and oxygen (opened or sealed caps). The effects of temperature, oxygen and light on the stability of red palm olein and palm olein were studied over 4 months of storage at simulated domestic conditions. The degree of auto- and photo-oxidations was evaluated by monitoring the following quality parameters: acidity, peroxide and p-anisidine values, fatty acids composition, carotenes and vitamin E. It is noted from the study that opened bottles of red palm olein was found to be stable for 4 months in comparison to its counterpart (palm olein) evidenced from their primary oxidative constituents (peroxides) and hydrolytic behavior (free fatty acids). Opened bottles are better off when stored at 8°C and protected from light for a longer shelf-life. Sealed bottles of palm olein showed better storage stability in the dark at 8°C; whereas sealed bottles of red palm olein was found to be stable at both temperatures studied without the influence of light. After 4 months of varying storage conditions, the fatty acid composition, vitamin E and carotenes of both oils remained unchanged. The phytonutrients in red palm olein rendered better storage stability when compared to palm olein.
  11. Loganadan NK, Huri HZ, Vethakkan SR, Hussein Z
    Pharmacogenomics, 2020 06;21(9):587-600.
    PMID: 32468916 DOI: 10.2217/pgs-2019-0171
    Background: Due to several limitations in the study designs of sulfonylurea pharmacogenomics studies, we investigated the clinical and genetic predictors of secondary sulfonylurea failure in Type 2 diabetes patients. Materials & methods: Patients receiving the maximum sulfonylurea and metformin doses for >1 year were enrolled. Secondary sulfonylurea failure was defined as HbA1c >7.0% (>53 mmol/mol) after a 12-month follow-up. Results: By multivariate analysis, increased insulin resistance (HOMA2-IR), baseline HbA1c >7.0%, residing in eastern Peninsular Malaysia, and the CC genotype of rs757110 ABCC8 gene polymorphism were independent predictors of secondary sulfonylurea failure (p 
  12. Loganathan R, Tarmizi AHA, Vethakkan SR, Teng KT
    J Oleo Sci, 2020 Mar 01;69(3):167-183.
    PMID: 32051355 DOI: 10.5650/jos.ess19209
    Red palm olein is known to be high in carotenes and vitamin E (tocols) and possess various nutritional benefits. This study evaluates the effect of prolonged heating using three common cooking techniques i.e. deep-fat fryer, microwave oven and conventional oven, on the profiles of carotenes and tocols as well as the physico-chemical changes occurring in red palm olein when compared to conventional palm olein. Physico-chemical changes in all oils were gauged based on their peroxide, p-anisidine and total oxidation values, acidity, and fatty acid composition. Both red palm olein and palm olein were thermally stable based on their lower rate of hydrolytic and oxidative degradations as well as higher tocols retention, which allow the oils to undergo heating up to 3 hours using deep-fat fryer and conventional oven. Nevertheless, red palm olein seemed not suitable for prolonged heating processes considering lower retention of carotenes. Microwave heating also influenced the stability of phytonutrients.
  13. Loganathan R, Tarmizi AHA, Vethakkan SR, Teng KT
    J Oleo Sci, 2020 Jul 02;69(7):671-676.
    PMID: 32522941 DOI: 10.5650/jos.ess19253
    The study was designed to evaluate the nutritive value, thermal stability and consumer acceptance of cupcakes baked with red palm olein compared to palm olein. Thermal stability was evaluated for acidity, peroxide, p-anisidine and total oxidation value (cumulative between peroxide and p-anisidine values), as well as fatty acid composition. The concentrations of phytonutrients including tocopherols and tocotrienols, alpha- and beta-carotene after baking were also determined. Acceptance of the cupcakes was assessed using a structured hedonic scale of five points by 29 panelists. As compared to initial test oil (red palm olein), acidity (red palm olein, 0.07±0.01% vs cupcakes containing red palm olein, 0.09±0.01%; P=0.0232), peroxide value (red palm olein, 0.33±0.05 meq O2 kg-1 vs cupcakes containing red palm olein 0.73±0.06 meq O2 kg-1; P=0.0011) and total oxidation value (red palm olein, 2.24±0.13 unit vs cupcakes containing red palm olein, 3.09±0.17 unit; P=0.0012) were found to be higher in cupcakes containing red palm olein, which is within the acceptable rancidity range (peroxide value < 7.5 meq O2 kg-1) for snack food category. No changes were found on oxidative parameters (acidity, peroxide, p-anisidine values and total oxidation value) in cupcakes containing palm olein. Cupcakes made with red palm olein retained nearly 100% of alpha- and beta-carotenes upon baking. Tocopherol homologues were stable in both comparisons, with 95% retention as compared to tocotrienol homologues (~85%). Cupcakes made from red palm olein received higher score (mean=3.29) in sensory evaluation as compared to cupcakes containing palm olein (mean=3.07). The study, therefore, encourages the inclusion of red palm olein in the formulation of bakery products.
  14. Loganadan NK, Huri HZ, Vethakkan SR, Hussein Z
    Pharmacogenomics, 2021 11;22(16):1057-1068.
    PMID: 34665019 DOI: 10.2217/pgs-2021-0059
    Aim: This study investigated the incidence of sulfonylurea-induced hypoglycemia and its predictors in Type 2 diabetes (T2D) patients. Patients & methods: In this prospective, observational study, T2D patients on maximal sulfonylurea-metformin therapy >1 year were enrolled. Hypoglycemia was defined as having symptoms or a blood glucose level <3.9 mmol/l. Results: Of the 401 patients, 120 (29.9%) developed sulfonylurea-induced hypoglycemia during the 12-month follow-up. The ABCC8 rs757110, KCNJ11 rs5219, CDKAL1 rs7756992 and KCNQ1 rs2237892 gene polymorphisms were not associated with sulfonylurea-induced hypoglycemia (p > 0.05). Prior history of hypoglycemia admission (odds ratio = 16.44; 95% CI: 1.74-154.33, p = 0.014) independently predicted its risk. Conclusion: Sulfonylurea-treated T2D patients who experienced severe hypoglycemia are at increased risk of future hypoglycemia episodes.
  15. Borhan MK, Vethakkan SR, Sarvanandan T, Paramasivam SS
    JCEM Case Rep, 2023 Nov;1(6):luad134.
    PMID: 37954835 DOI: 10.1210/jcemcr/luad134
    Lactation ketoacidosis is a rare yet severe metabolic emergency that has been reported in breastfeeding mothers. Reduced carbohydrate intake during breastfeeding has been reported as a common trigger for ketoacidosis. We report the case of a 31-year-old mother without diabetes who presented with life-threatening lactation ketoacidosis after following a ketogenic diet while exclusively breastfeeding her newborn baby. She was managed in the intensive care unit with dextrose and insulin infusion to reverse ketoacidosis. With prompt treatment, the patient's ketoacidosis resolved within 24 hours, and she was discharged well 3 days later. We further discuss the underlying increased metabolic demand in lactating women that puts them at risk of ketoacidosis, underlining the importance of early recognition of lactation ketoacidosis and nutritional education for lactating women.
  16. Mohan Dallumal R, Chua SS, Wu DB, Vethakkan SR
    Int J Endocrinol, 2015;2015:950571.
    PMID: 26089904 DOI: 10.1155/2015/950571
    Aim. The present study was conducted to determine the glycaemic effects of sitagliptin in type 2 diabetes patients. Methods. Data was collected from patient medical records of a major teaching hospital in Malaysia, from 2009 to 2012. Glycated hemoglobin (HbA1c) values prior to and up to 12 months after the initiation of sitagliptin were analysed. The change in HbA1c values was accounted for based on a generalized linear model generated using the Generalized Estimating Equations (GEE) method. Results and Discussion. Of the 457 patients, 53.6% were elderly and 81.4% were overweight. The mean HbA1c (standard deviation) before initiation of sitagliptin was 8.5 (1.4)%. This dropped to 7.7 (1.4)%, 3 to 6 months after initiation of sitagliptin, with a mean difference of 0.8% (95% confidence interval (CI): 0.7-1.0; P < 0.001). However, this value increased to 8.0 (1.7)% after 7 to 12 months on sitagliptin (P = 0.002) with a mean difference from baseline of 0.6% (95% CI: 0.4-0.7; P < 0.001). Conclusion. In routine clinical practice, sitagliptin produces a significant reduction in mean HbA1c (0.8%) within the first 6 months of use which corresponds to efficacy data obtained in controlled clinical trials. However, this reduction was lesser, 7 to 12 month later.
  17. Ratnasingam J, Karim N, Paramasivam SS, Ibrahim L, Lim LL, Tan AT, et al.
    Pituitary, 2015 Aug;18(4):448-55.
    PMID: 25134488 DOI: 10.1007/s11102-014-0593-6
    PURPOSE: Radiation fields for nasopharyngeal cancer (NPC) include the base of skull, which places the hypothalamus and pituitary at risk of damage. We aimed to establish the prevalence, pattern and severity of hypothalamic pituitary (HP) dysfunction amongst NPC survivors.

    METHODS: We studied 50 patients (31 males) with mean age 57 ± 12.2 years who had treatment for NPC between 3 and 21 years (median 8 years) without pre-existing HP disorder from other causes. All patients had a baseline cortisol, fT4, TSH, LH, FSH, oestradiol/testosterone, prolactin and renal function. All patients underwent dynamic testing with insulin tolerance test to assess the somatotroph and corticotroph axes. Baseline blood measurements were used to assess thyrotroph, gonadotroph and lactotroph function.

    RESULTS: Hypopituitarism was present in 82% of patients, 30% single axis, 28% two axes, 18% three axes and 6% four axes deficiencies. Somatotroph deficiency was most common (78%) while corticotroph, gonadotroph and thyrotroph deficiencies were noted in 40% (4 complete/16 partial), 22 and 4% of the patients respectively. Hyperprolactinaemia was present in 30% of patients. The development of HP dysfunction was significantly associated with the time elapsed from irradiation, OR 2.5 (1.2, 5.3), p = 0.02, for every 2 years post treatment. The use of concurrent chemo-irradiation (CCRT) compared to those who had radiotherapy alone was also significantly associated with HP dysfunction, OR 14.5 (2.4, 87.7), p < 0.01.

    CONCLUSION: Despite low awareness and detection rates, HP dysfunction post-NPC irradiation is common. Use of CCRT may augment time related pituitary damage. As these endocrinopathies result in significant morbidity and mortality we recommend periodic assessment of pituitary function amongst NPC survivors.

  18. Chan WK, Tan AT, Vethakkan SR, Tah PC, Vijayananthan A, Goh KL
    Clin Res Hepatol Gastroenterol, 2014 Jun;38(3):284-91.
    PMID: 24736032 DOI: 10.1016/j.clinre.2014.02.009
    BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and cardiovascular diseases are both common among patients with diabetes mellitus.
    OBJECTIVE: The aim of this study is to determine if ultrasonography-diagnosed NAFLD is associated with prevalent ischemic heart disease (IHD) among patients with diabetes mellitus.
    METHODS: This is a cross-sectional study on consecutive patients seen at the Diabetic Clinic, University of Malaya Medical Centre. The medical record for each patient was reviewed for documented IHD. Patients without documented IHD but had symptoms and/or electrocardiographic changes suggestive of IHD were referred for cardiac evaluation.
    RESULTS: Data for 399 patients were analyzed. Mean age was 62.8±10.5 years with 43.1% male. NAFLD and IHD were present in 49.6 and 26.6%, respectively. The prevalence of IHD among patients with and without NAFLD was 24.7 and 28.4%, respectively (P=0.414). The prevalence of IHD was highest among the Indians (34.1%) followed by the Malays (29.2%) and the Chinese (20.1%). No association was found between NAFLD and IHD when analyzed according to ethnicity. On multivariate analysis, independent factors associated with IHD were older age, lower levels of physical activity, greater waist circumference and higher serum glycated hemoglobin level.
    CONCLUSIONS: Ultrasonography-diagnosed NAFLD was not associated with prevalent IHD among patients with diabetes mellitus in a multiracial Asian hospital clinic population.

    Study site: Diabetic clinc, University Malaya Medical Centre (UMMC)
  19. Ratnasingam J, Tan AT, Vethakkan SR, Paramasivam SS, Ibrahim L, Lim LL, et al.
    J Clin Endocrinol Metab, 2013 Mar;98(3):869-70.
    PMID: 23337722 DOI: 10.1210/jc.2012-3839
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