Displaying publications 21 - 40 of 46 in total

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  1. Chang LF, Vethakkan SR, Nesaretnam K, Sanders TA, Teng KT
    J Clin Lipidol, 2016 09 17;10(6):1431-1441.e1.
    PMID: 27919361 DOI: 10.1016/j.jacl.2016.09.006
    BACKGROUND: Current dietary guidelines recommend the replacement of saturated fatty acids (SAFAs) with carbohydrates or monounsaturated fatty acids (MUFAs) based on evidence on lipid profile alone, the chronic effects of the mentioned replacements on insulin secretion and insulin sensitivity are however unclear.

    OBJECTIVE: To assess the chronic effects of the substitution of refined carbohydrate or MUFA for SAFA on insulin secretion and insulin sensitivity in centrally obese subjects.

    METHODS: Using a crossover design, randomized controlled trial in abdominally overweight men and women, we compared the effects of substitution of 7% energy as carbohydrate or MUFA for SAFA for a period of 6 weeks each. Fasting and postprandial blood samples in response to corresponding SAFA, carbohydrate, or MUFA-enriched meal-challenges were collected after 6 weeks on each diet treatment for the assessment of outcomes.

    RESULTS: As expected, postprandial nonesterified fatty acid suppression and elevation of C-peptide, insulin and glucose secretion were the greatest with high-carbohydrate (CARB) meal. Interestingly, CARB meal attenuated postprandial insulin secretion corrected for glucose response; however, the insulin sensitivity and disposition index were not affected. SAFA and MUFA had similar effects on all markers except for fasting glucose-dependent insulinotropic peptide concentrations, which increased after MUFA but not SAFA when compared with CARB.

    CONCLUSION: In conclusion, a 6-week lower-fat/higher-carbohydrate (increased by 7% refined carbohydrate) diet may have greater adverse effect on insulin secretion corrected for glucose compared with isocaloric higher-fat diets. In contrast, exchanging MUFA for SAFA at 7% energy had no appreciable adverse impact on insulin secretion.

  2. Lim LL, Brnabic AJ, Chan SP, Ibrahim L, Paramasivam SS, Ratnasingam J, et al.
    J Diabetes Investig, 2017 Jul;8(4):453-461.
    PMID: 27863088 DOI: 10.1111/jdi.12596
    AIMS/INTRODUCTION: Studies on the relative contributions of fasting and postprandial hyperglycemia (FH and PPH) to glycated hemoglobin (HbA1c ) in patients with type 2 diabetes have yielded inconsistent results. We aimed to assess the relationship by using continuous glucose monitoring in a multi-ethnic cohort.

    MATERIALS AND METHODS: A total of 100 adults with type 2 diabetes were assessed with 6-day continuous glucose monitoring and HbA1c . Area under the curve (AUC) ≥5.6 mmol/L was defined as AUCTOTAL . AUC equal to or greater than each preprandial glucose for 4-h duration was defined as AUCPPH . The total PPH (AUCTPPH ) was the sum of the various AUCPPH. The postprandial contribution to overall hyperglycemia was calculated as (AUCTPPH / AUCTOTAL ) × 100%.

    RESULTS: The present study comprised of Malay, Indian, and Chinese type 2 diabetes patients at 34, 34 and 28% respectively. Overall, the mean PPH significantly decreased as HbA1c advanced (mixed model repeated measures adjusted, beta-estimate = -3.0, P = 0.009). Age (P = 0.010) and hypoglycemia (P = 0.006) predicted the contribution difference. In oral antidiabetic drug-treated patients (n = 58), FH contribution increased from 54% (HbA1c 6-6.9%) to 67% (HbA1c ≥10%). FH predominance was significant in poorly-controlled groups (P = 0.028 at HbA1c 9-9.9%; P = 0.015 at HbA1c ≥10%). Among insulin users (n = 42), FH predominated when HbA1c was ≥10% before adjustment for hypoglycemia (P = 0.047), whereas PPH was numerically greater when HbA1c was <8%.

    CONCLUSIONS: FH and PPH contributions were equal in well-controlled Malaysian type 2 diabetes patients in real-world practice. FH predominated when HbA1c was ≥9 and ≥10% in oral antidiabetic drug- and insulin-treated patients, respectively. A unique observation was the greater PPH contribution when HbA1c was <8% despite the use of basal and mealtime insulin in this multi-ethnic cohort, which required further validation.

  3. Lai LL, Wan Yusoff WNI, Vethakkan SR, Nik Mustapha NR, Mahadeva S, Chan WK
    J Gastroenterol Hepatol, 2019 Aug;34(8):1396-1403.
    PMID: 30551263 DOI: 10.1111/jgh.14577
    BACKGROUND AND AIM: The recommendation in regard to screening for non-alcoholic fatty liver disease (NAFLD) among type 2 diabetes mellitus (T2DM) patients differs in major guidelines. The aim of this paper was to study the prevalence of NALFD and advanced fibrosis among T2DM patients.

    METHODS: This is a cross-sectional study of consecutive adult T2DM patients attending the Diabetes Clinic of a university hospital. Significant hepatic steatosis and advanced fibrosis was diagnosed based on transient elastography if the controlled attenuation parameter was ≥ 263 dB/m, and the liver stiffness measurement was ≥ 9.6 kPa using the M probe or ≥ 9.3 kPa using the XL probe, respectively. Patients with liver stiffness measurement ≥ 8 kPa were referred to the Gastroenterology and Hepatology Clinic for further assessment, including liver biopsy.

    RESULTS: The data of 557 patients were analyzed (mean age 61.4 ± 10.8 years, male 40.6%). The prevalence of NAFLD and advanced fibrosis based on transient elastography was 72.4% and 21.0%, respectively. On multivariate analysis, independent factors associated with NAFLD were central obesity (OR 4.856, 95% confidence interval [CI] 2.749-8.577, P = 0.006), serum triglyceride (OR 1.585, 95% CI 1.056-2.381, P = 0.026), and alanine aminotransferase levels (OR 1.047, 95% CI 1.025-1.070, P 

  4. Tan EZ, Lai LL, Vethakkan SR, Nik Mustapha NR, Mahadeva S, Chan WK
    J Gastroenterol Hepatol, 2021 Mar;36(3):751-757.
    PMID: 32583444 DOI: 10.1111/jgh.15160
    BACKGROUND: The effect of modest alcohol intake on prevalence of significant hepatic steatosis and severity of liver disease in patients with type 2 diabetes mellitus (T2DM) is unclear.

    METHODS: This is a cross-sectional study on T2DM patients. Modest alcohol intake was defined as alcohol intake ≤ 21 units/week in men and ≤ 14 units/week in women. Significant hepatic steatosis was diagnosed on the basis of controlled attenuation parameter > 263 dB/m, while advanced fibrosis was diagnosed on the basis of liver stiffness measurement ≥ 9.6 kPa using M probe or ≥ 9.3 kPa using XL probe. Patients with liver stiffness measurement ≥ 8.0 kPa were offered liver biopsy.

    RESULTS: Five hundred fifty-seven patients underwent transient elastography, and 71 patients underwent liver biopsy. The prevalence of modest drinking was 16.5%. Modest drinking was equally prevalent among ethnic Indians and Chinese at 22.9% and 23.3%, respectively, but uncommon among ethnic Malays at 1.7%. Modest drinkers were more likely to be male, smoked, and had significantly lower glycated hemoglobin, total cholesterol, low-density lipoprotein cholesterol, alkaline phosphatase, and platelet count. There was no significant difference in the prevalence of significant hepatic steatosis or advanced fibrosis based on transient elastography and steatohepatitis or advanced fibrosis between modest drinkers and nondrinkers. The prevalence of significant hepatic steatosis was higher among ethnic Malays and Indians compared with ethnic Chinese, but the Chinese did not have a lower prevalence of more severe liver disease.

    CONCLUSION: Modest alcohol intake is not associated with higher prevalence of significant hepatic steatosis or more severe liver disease among patients with T2DM.

  5. Chuah KH, Lai LL, Vethakkan SR, Nik Mustapha NR, Mahadeva S, Chan WK
    J Gastroenterol Hepatol, 2020 Aug;35(8):1404-1411.
    PMID: 31907981 DOI: 10.1111/jgh.14978
    BACKGROUND AND AIM: Repeating liver stiffness measurement (LSM) was recently reported to improve accuracy to diagnose fibrosis stage in patients with non-alcoholic fatty liver disease (NAFLD). There are to date no other studies confirming this finding. This aims to evaluate the accuracy of repeating LSM for the diagnosis of fibrosis stage in NAFLD patients.

    METHODS: Retrospective analysis of prospectively collected data on adult NAFLD patients who had two FibroScan examination within 6 months prior to liver biopsy. F3-F4 fibrosis was excluded using LSM cut-off of 7.9 kPa.

    RESULTS: A total of 136 patients were recruited. Eighty-five percent (115/136) of patients had high baseline LSM (≥ 7.9 kPa). Among them, 25% (29/115) had low repeat LSM (

  6. Chan WK, Tan AT, Vethakkan SR, Tah PC, Vijayananthan A, Goh KL
    J Gastroenterol Hepatol, 2013 Aug;28(8):1375-83.
    PMID: 23517307 DOI: 10.1111/jgh.12204
    BACKGROUND AND AIM:
    There is currently no published study comparing prevalence of non-alcoholic fatty liver disease (NAFLD) and associated factors among diabetics of different ethnicity in the Asia-Pacific region.

    METHODS:
    Cross-sectional study of consecutive patients in the Diabetic Clinic in University of Malaya Medical Centre. The Global Physical Activity Questionnaire and a semiquantitative food-frequency questionnaire were used to assess physical activity and dietary intake, respectively. Diagnosis of NAFLD was ultrasound-based and following exclusion of significant alcohol intake.

    RESULTS:
    Data for 399 patients were analyzed (mean age 62.3 ± 10.5 years, 43.1% men). The racial distribution was Chinese 43.6%, Indian 33.1%, Malay 22.3%, and others 1.0%. The prevalence of NAFLD was 49.6%. On univariate analysis, factors associated with NAFLD were age < 65 years, race, obesity, central obesity, glycated hemoglobin ≥ 7.0%, and elevated serum alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase levels. Patients with low physical activity were more likely to have NAFLD (odds ratio [OR] = 1.67, 95% confidence interval [CI] = 1.06-2.63, P = 0.020). The prevalence of NAFLD was highest among Malays (60.7%), followed by Indians (51.5%), and lowest among Chinese (42.0%) consistent with higher prevalence of central obesity and higher percentage calorie intake from fat in the former groups of patients. On multivariate analysis, independent factors associated with NAFLD were central obesity (OR = 2.20, 95% CI = 1.29-3.75, P = 0.004) and elevated serum ALT level (OR = 1.98, 95% CI = 1.21-3.25, P = 0.007).

    CONCLUSIONS:
    NAFLD was seen in half of a cohort of diabetic patients and was independently associated with central obesity and elevated serum ALT level. Prevalence of NAFLD was different and paralleled the difference in prevalence of central obesity and in percentage calorie intake from fat among the different ethnic groups.

    © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

    KEYWORDS:
    diabetes mellitus; dietary intake; epidemiology; ethnicity; non-alcoholic fatty liver disease; physical activity
    Study site: Diabetic clinic, University Malaya Medical Centre (UMMC)
  7. Lim LL, Kitan N, Paramasivam SS, Ratnasingam J, Ibrahim L, Chan SP, et al.
    J Med Case Rep, 2015;9:277.
    PMID: 26619967 DOI: 10.1186/s13256-015-0757-7
    Determining the etiology of Cushing's syndrome is very challenging to endocrinologists, with most of the difficulty arising from subtype differentiation of adrenocorticotropic hormone-dependent Cushing's syndrome. We present the pitfalls of evaluating a rare cause of adrenocorticotropic hormone-independent Cushing's syndrome in the transition period between adolescence and adulthood.
  8. Chan WK, Chuah KH, Rajaram RB, Lim LL, Ratnasingam J, Vethakkan SR
    J Obes Metab Syndr, 2023 Sep 30;32(3):197-213.
    PMID: 37700494 DOI: 10.7570/jomes23052
    Metabolic dysfunction-associated steatotic liver disease (MASLD) is the latest term for steatotic liver disease associated with metabolic syndrome. MASLD is the most common cause of chronic liver disease and is the leading cause of liver-related morbidity and mortality. It is important that all stakeholders be involved in tackling the public health threat of obesity and obesity-related diseases, including MASLD. A simple and clear assessment and referral pathway using non-invasive tests is essential to ensure that patients with severe MASLD are identified and referred to specialist care, while patients with less severe disease remain in primary care, where they are best managed. While lifestyle intervention is the cornerstone of the management of patients with MASLD, cardiovascular disease risk must be properly assessed and managed because cardiovascular disease is the leading cause of mortality. No pharmacological agent has been approved for the treatment of MASLD, but novel anti-hyperglycemic drugs appear to have benefit. Medications used for the treatment of diabetes and other metabolic conditions may need to be adjusted as liver disease progresses to cirrhosis, especially decompensated cirrhosis. Based on non-invasive tests, the concepts of compensated advanced chronic liver disease and clinically significant portal hypertension provide a practical approach to stratifying patients according to the risk of liver-related complications and can help manage such patients. Finally, prevention and management of sarcopenia should be considered in the management of patients with MASLD.
  9. 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.
  10. 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.
  11. 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.
  12. Long Bidin MB, Khan AM, Tan FHS, Aziz NA, Ali NM, Kamaruddin NA, et al.
    J ASEAN Fed Endocr Soc, 2023;38(1):75-80.
    PMID: 37252416 DOI: 10.15605/jafes.038.01.06
    OBJECTIVE: This study aims to report the demographic features of patients with acromegaly, the disease burden, and the corresponding treatment patterns and outcomes in Malaysia.

    METHODOLOGY: This is a retrospective study that included patients from the Malaysian Acromegaly registry who were diagnosed with acromegaly from 1970 onwards. Data collected included patient demographics, clinical manifestations of acromegaly, biochemical results and imaging findings. Information regarding treatment modalities and their outcomes was also obtained.

    RESULTS: Registry data was collected from 2013 to 2016 and included 140 patients with acromegaly from 12 participating hospitals. Median disease duration was 5.5 years (range 1.0 - 41.0 years). Most patients had macroadenoma (67%), while 15% were diagnosed with microadenoma. Hypertension (49.3%), diabetes (37.1%) and hypopituitarism (27.9%) were the most common co-morbidities for patients with acromegaly. Majority of patients had surgical intervention as primary treatment (65.9%) while 20.7% were treated medically, mainly with dopamine agonists (18.5%). Most patients had inadequate disease control after first-line treatment regardless of treatment modality (79.4%).

    CONCLUSION: This registry study provides epidemiological data on patients with acromegaly in Malaysia and serves as an initial step for further population-based studies.

  13. 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.
  14. Loh HH, Lim LL, Yee A, Loh HS, Vethakkan SR
    Minerva Endocrinol., 2019 Jun;44(2):221-231.
    PMID: 28294593 DOI: 10.23736/S0391-1977.17.02584-6
    INTRODUCTION: We conducted a meta-analysis to assess the effects of vitamin D replacement on biochemical and skeletal parameters in subjects with mild primary hyperparathyroidism (PHPT) and coexistent vitamin D deficiency.

    EVIDENCE ACQUISITION: A systematic search of all English-language medical literature published from 1980 till May 2016 using PubMed, Embase and Ovid was performed. Nine observational studies were evaluated after fulfilling the inclusion and exclusion criteria.

    EVIDENCE SYNTHESIS: A total of 547 patients were examined. All studies used vitamin D2/D3 or calcifediol (25-hydroxyvitamin D3), There was significant improvement of serum 25(OH)D with unchanged serum iPTH level after vitamin D replacement, with pooled d+: 3.10 (95% CI 2.25 to 3.95), P<0.01 and pooled d+: 0.82 (95% CI -0.35 to 1.98), P=0.16 respectively. There was neither worsening of the pre-existing hypercalcemia (pooled d+: -0.27 [95% CI -1.09 to 0.64, P=0.56]) nor hypercalciuria (pooled d+: 3.64 [95% CI -0.55 to 7.83, P=0.09]). Two studies assessed in this meta-analysis reported unchanged bone density with vitamin D replacement.

    CONCLUSIONS: Vitamin D replacement in subjects with mild PHPT and coexistent vitamin D deficiency improved serum 25(OH)D level without worsening of pre-existing hypercalcemia or hypercalciuria. Well-designed multicenter randomized controlled trials examining pre- and postoperative outcomes of vitamin D therapy in patients with different severities of PHPT and vitamin D inadequacy are warranted to elucidate the most appropriate vitamin D treatment protocol and determine the long-term safety concerns.

  15. Goh LY, Shahrom EE, Ganesan CC, Vethakkan SR, Goh KJ
    Neurology Asia, 2017;22(4):325-331.
    MyJurnal
    Objective: To determine prevalence and factors associated with neuropathic pain symptoms in a multiethnic cohort of Malaysian adult diabetic patients.
    Methods: This was aprospective cross-sectional observational study of hospital-based diabetic outpatients in Malaysia. Subjects were interviewed for their demographic data and medical history. The painDETECT questionnaire was used to screen for neuropathic pain symptoms and pain intensity was assessed using the numeric pain rating scale (NPRS). Neuropathy symptoms and signs were assessed using the Neuropathy Symptom Score (NSS) and Neuropathy Disability Score (NDS).
    Results:Of 242 patients,140 (58%) were women, with a mean age of 61 + 11.4 years (range 21 to 81). Ninety nine(40.9%) were Malay, 64 (26.4%) Chinese, 76 (31.4%) Indian and three (1.2%) were Eurasian. Mean duration of diabetes was 15.9+ 9.8 years (range 1 to 53) and 232 (95.9%) patients had Type II diabetes. Peripheral neuropathy,based on NSS and NDS criteria, was found in 83 (34.3%). Thirteen (5.4%) patients were found to likely have neuropathic pain symptoms and this was independently associated with peripheral neuropathy ((OR) = 3.40, 95% confidence interval (CI): 1.04, 11.14) and Indian ethnicity (OR = 5.44, 95% CI: 1.50,
    19.57)). Patients with neuropathic pain had higher average pain intensity scores.
    Conclusions: The prevalence of neuropathic pain symptoms in a Malaysian DM patient cohort was low and was associated with the severity of neuropathy symptoms and Indian ethnicity. The causes for ethnic differences are unknown and could be due socio-cultural or physiological differences in neuropathic pain perception.
    Study site: Diabetic clinic, University of Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
  16. 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.
  17. 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.

  18. 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 
  19. 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.
  20. 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.

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