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  1. Hassanein MM, Huri HZ, Baig K, Abduelkarem AR
    Nutrients, 2023 Jan 29;15(3).
    PMID: 36771392 DOI: 10.3390/nu15030685
    Hormonal fluctuations, excessive clothing covering, sunscreen use, changes in body fat composition, a vitamin D-deficient diet, and a sedentary lifestyle can all predispose postmenopausal women to vitamin D deficiency. An effective supplementation plan requires a thorough understanding of underlying factors to achieve the desired therapeutic concentrations. The objective of this study was to conduct a systematic review of the predictors that affect vitamin D status in postmenopausal women. From inception to October 2022, we searched MEDLINE, Embase, Web of Science, Scopus, and clinical trial registries. Randomized clinical trials of postmenopausal women taking supplements of vitamin D with serum 25-hydroxyvitamin D (25(OH)D) measurement as the trial outcome were included. Two independent reviewers screened selected studies for full-text review. The final assessment covered 19 trials within 13 nations with participants aged 51 to 78. Vitamin D supplementation from dietary and pharmaceutical sources significantly increased serum 25(OH)D to optimal levels. Lower baseline serum 25(OH)D, lighter skin color, longer treatment duration, and prolonged skin exposure were all associated with a better response to vitamin D supplementation in postmenopausal women.
  2. Kasim NB, Huri HZ, Vethakkan SR, Ibrahim L, Abdullah BM
    Biomark Med, 2016 Apr;10(4):403-15.
    PMID: 26999420 DOI: 10.2217/bmm-2015-0037
    Generally, obese and overweight individuals display higher free fatty acid levels, which stimulate insulin resistance. The combination of overweight or obesity with insulin resistance can trigger Type 2 diabetes mellitus (T2DM) and are primary contributing factors to the development of uncontrolled T2DM. Genetic polymorphisms also play an important role as they can impact a population's susceptibility to becoming overweight or obese and developing related chronic complications, such as uncontrolled T2DM. This review specifically examines the genetic polymorphisms associated with overweight and obesity in patients with uncontrolled T2DM. Particularly, gene polymorphisms in ADIPOQ (rs1501299 and rs17300539), LepR (rs1137101 and rs1045895), IRS2 (rs1805092), GRB14 (rs10195252 and rs3923113) and PPARG (rs1801282) have been associated with overweight and obesity in uncontrolled T2DM.
  3. Huri HZ, Ling DY, Ahmad WA
    Drug Des Devel Ther, 2015;9:4735-49.
    PMID: 26316711 DOI: 10.2147/DDDT.S87294
    PURPOSE: Cardiovascular disease (CVD) is a macrovascular complication in patients with type 2 diabetes mellitus (T2DM). To date, glycemic control profiles of antidiabetic drugs in cardiovascular (CV) complications have not been clearly elucidated. Therefore, this study was conducted retrospectively to assess the association of antidiabetic drugs and glycemic control with CV profiles in T2DM patients. The association of concurrent medications and comorbidities with glycemic control was also investigated.

    METHODS: A total of 220 T2DM patients from the University of Malaya Medical Centre, Malaysia, who had at least one CV complication and who had been taking at least one antidiabetic drug for at least 3 months, were included. The associations of antidiabetics, cardiovascular diseases, laboratory parameters, concurrent medications, comorbidities, demographics, and clinical characteristics with glycemic control were investigated.

    RESULTS: Sulfonylureas in combination (P=0.002) and sulfonylurea monotherapy (P<0.001) were found to be associated with good glycemic control, whereas insulin in combination (P=0.051), and combination biguanides and insulin therapy (P=0.012) were found to be associated with poor glycemic control. Stroke (P=0.044) was the only type of CVD that seemed to be significantly associated with good glycemic control. Other factors such as benign prostatic hyperplasia (P=0.026), elderly patients (P=0.018), low-density lipoprotein cholesterol levels (P=0.021), and fasting plasma glucose (P<0.001) were found to be significantly correlated with good glycemic control.

    CONCLUSION: Individualized treatment in T2DM patients with CVDs can be supported through a better understanding of the association between glycemic control and CV profiles in T2DM patients.

  4. Abbaspour Babaei M, Kamalidehghan B, Saleem M, Huri HZ, Ahmadipour F
    Drug Des Devel Ther, 2016;10:2443-59.
    PMID: 27536065 DOI: 10.2147/DDDT.S89114
    c-Kit, a receptor tyrosine kinase, is involved in intracellular signaling, and the mutated form of c-Kit plays a crucial role in occurrence of some cancers. The function of c-Kit has led to the concept that inhibiting c-Kit kinase activity can be a target for cancer therapy. The promising results of inhibition of c-Kit for treatment of cancers have been observed in some cancers such as gastrointestinal stromal tumor, acute myeloid leukemia, melanoma, and other tumors, and these results have encouraged attempts toward improvement of using c-Kit as a capable target for cancer therapy. This paper presents the findings of previous studies regarding c-Kit as a receptor tyrosine kinase and an oncogene, as well as its gene targets and signaling pathways in normal and cancer cells. The c-Kit gene location, protein structure, and the role of c-Kit in normal cell have been discussed. Comprehending the molecular mechanism underlying c-Kit-mediated tumorogenesis is consequently essential and may lead to the identification of future novel drug targets. The potential mechanisms by which c-Kit induces cellular transformation have been described. This study aims to elucidate the function of c-Kit for future cancer therapy. In addition, it has c-Kit inhibitor drug properties and their functions have been listed in tables and demonstrated in schematic pictures. This review also has collected previous studies that targeted c-Kit as a novel strategy for cancer therapy. This paper further emphasizes the advantages of this approach, as well as the limitations that must be addressed in the future. Finally, although c-Kit is an attractive target for cancer therapy, based on the outcomes of treatment of patients with c-Kit inhibitors, it is unlikely that Kit inhibitors alone can lead to cure. It seems that c-Kit mutations alone are not sufficient for tumorogenesis, but do play a crucial role in cancer occurrence.
  5. Hassanein MM, Huri HZ, Baig K, Abduelkarem AR, Al-Momani M
    Int J Gynaecol Obstet, 2024 Feb;164(2):613-623.
    PMID: 37702968 DOI: 10.1002/ijgo.15106
    OBJECTIVES: To develop and validate an electronic, patient-reported outcomes measure (PROM) specific for genitourinary syndrome of menopause (GSM) patients. The PROM aimed to accurately assess the burden of GSM symptoms, their impact on health-related and sexual quality of life, and the acceptability of vaginal treatments.

    METHODS: The study encompassed a comprehensive three-stage approach to the development and validation of the PROM. Initially, during the preliminary design stage, the necessity for a new PROM was recognized, an expert panel was formed, and semi-structured qualitative interviews were carried out with GSM patients. In the second stage, the study used the five-step pre-validation methodology established by Prior et al. to generate and refine the PROM items. The third and final stage encompassed the determination of scale and item content validity indexes to ensure validity. Additionally, the reliability of each construct was evaluated using Cronbach's α.

    RESULTS: The resulting PROM was named GSM-SVTAQ (GSM-symptoms and vaginal treatments acceptability questionnaire). It demonstrated excellent validity in assessing symptoms burden, health-related and sexual quality of life, and vaginal treatment acceptability, with high content validity indices and strong internal consistency. The scale content validity indices and Cronbach's α coefficients for the three domains were (0.926, 0.939), (0.875, 0.947), and (0.824, 0.855), respectively.

    CONCLUSION: The GSM-SVTAQ stands as the first GSM-specific, valid, and reliable PROM capable of comprehensively measuring the three components of GSM and the acceptability of vaginal treatments. Its implementation has the potential to significantly enhance patient care and outcomes in GSM management.

  6. Hassanein MM, Huri HZ, Abduelkarem AR, Baig K
    Nutrients, 2023 Aug 30;15(17).
    PMID: 37686835 DOI: 10.3390/nu15173804
    Recent years have witnessed the emergence of growing evidence concerning vitamin D's potential role in women's health, specifically in postmenopausal women. This evidence also includes its connection to various genitourinary disorders and symptoms. Numerous clinical studies have observed improvements in vulvovaginal symptoms linked to the genitourinary syndrome of menopause (GSM) with vitamin D supplementation. These studies have reported positive effects on various aspects, such as vaginal pH, dryness, sexual functioning, reduced libido, and decreased urinary tract infections. Many mechanisms underlying these pharmacological effects have since been proposed. Vitamin D receptors (VDRs) have been identified as a major contributor to its effects. It is now well known that VDRs are expressed in the superficial layers of the urogenital organs. Additionally, vitamin D plays a crucial role in supporting immune function and modulating the body's defense mechanisms. However, the characterization of these effects requires more investigation. Reviewing existing evidence regarding vitamin D's impact on postmenopausal women's vaginal, sexual, and urological health is the purpose of this article. As research in this area continues, there is a potential for vitamin D to support women's urogenital and sexual health during the menopausal transition and postmenopausal periods.
  7. Abdullah BM, Zubairi SI, Huri HZ, Hairunisa N, Yousif E, Basu RC
    PLoS One, 2016;11(3):e0151603.
    PMID: 27008312 DOI: 10.1371/journal.pone.0151603
    Presently, plant oils which contain high percentage of linoleic acid 1 are perceived to be a viable alternative to mineral oil for biolubricant applications due to their biodegradability and technical properties. In order to get biodegradable lubricant, triester derivatives compounds (1-5) were synthesized and characterized. The processes involved were monoepoxidation of linoleic acid 2, oxirane ring opening 3, esterification 4 and acylation 5. The structures of the products were confirmed by FTIR, 1H and 13C-NMR and LC-MS. The results that showed lowest temperature properties were obtained for triester 5, with a pour point value (PP) of -73°C, highest onset temperature (260°C) and lowest volatility at 0.30%. Viscosity index (VI) increased for the ester's synthetic compounds (2, 3, 4, 5), while the PP decreased. This behavior is the result of the increase of the chain length of the branching agents. Triester based linoleic acid has improved properties such as low-temperature and tribological properties. These results will make it feasible for plant oil to be used for biolubricants, fuels in chain saws, transmission oil and brake fluid.
  8. Elnaem MH, Kamarudin NH, Syed NK, Huri HZ, Dehele IS, Cheema E
    PMID: 34501893 DOI: 10.3390/ijerph18179306
    The perspectives of hypertensive patients on the state of hypertension control during the ongoing pandemic restrictions have not been extensively studied in Malaysia. Therefore, this study aimed to assess the impact of socio-demographic factors, health literacy, and adherence on the overall hypertension management in a group of Malaysian hypertensive patients during the COVID-19 pandemic. An anonymous, online cross-sectional study was conducted over three months that involved a group of Malaysian adults with hypertension. A validated, self-administered 30-item questionnaire was prepared in Malay and English languages on Google Forms. The link was then distributed to participants on social media (Facebook and WhatsApp). Following survey validation, a pilot study with 30 participants who met the inclusion criteria was carried out. The total scores for health literacy, adherence, and pandemic impact on hypertension control were calculated and compared across all independent variables. In a total of 144 study participants, controlled blood pressure was reported in 77% (N = 111). There were good levels of adherence and health literacy scores but moderate levels of pandemic impact scores. The total adherence scores showed a statistically significant difference between age groups (χ2 = 6.48, p = 0.039) and those who reported having controlled and uncontrolled blood pressure (U = 1116, p = 0.001). Moreover, the analysis revealed statistically significant differences in total pandemic impact scores based on the age group (χ2 = 15.008, p = 0.001), household income (χ2 = 6.887, p = 0.032), employment (U = 1712, p = 0.006), and marital status (U = 520.5, p < 0.001). The youngest age group (18-39) years, the lowest income group, unemployed and unmarried individuals, had significantly higher pandemic impact scores. This denotes that those individuals were more prone to be negatively affected by the pandemic regarding their hypertension management. Most participants reported relatively controlled blood pressure and good levels of health literacy as well as adherence amidst the pandemic. To a moderate extent, study participants perceived that the pandemic had a negative effect on hypertension management. The perceived negative impact of the pandemic was attributed to several socio-demographic factors, such as age, household income, employment, and marital status.
  9. Eff ARY, Huri HZ, Radji M, Mun'im A, Suyatna FD, Eden Y
    BMC Complement Med Ther, 2023 Feb 20;23(1):56.
    PMID: 36803524 DOI: 10.1186/s12906-023-03889-x
    BACKGROUND: Mahkota Dewa [Phaleria macrocarpa (Scheff) Boerl.] fruit in vitro and in- vivo can decrease and prevent elevation of the blood pressure, lower plasma glucose levels, possess an antioxidant effect, and recover liver and kidney damage in rats. This study aimed to determine the structure and inhibitory activity of angiotensin-converting enzyme inhibitors (ACE) from the Mahkota Dewa fruit.

    METHODS: The fruit powder was macerated using methanol and then partitioned by hexane, ethyl acetate, n-butanol, and water. The fractions were chromatographed on the column chromatography and incorporated with TLC and recrystallization to give pure compounds. The structures of isolated compounds were determined by UV-Visible, FT-IR, MS, proton (1H-NMR), carbon (13C-NMR), and 2D-NMR techniques encompassing HMQC and HMBC spectra. The compounds were evaluated for their ACE inhibitory activity, and the strongest compound was determined by the kinetics enzyme inhibition.

    RESULTS: Based on the spectral data, the isolated compounds were determined as 6,4-dihydroxy-4-methoxybenzophenone-2-O-β-D-glucopyranoside (1), 4,4'-dihydroxy-6-methoxybenzophenone-2-O-β-D-glucopyranoside (2) and mangiferin (3). IC50 values of the isolated compounds 1, 2 and 3 were 0.055, 0.07, and 0.025 mM, respectively.

    CONCLUSION: The three compounds have ACE inhibitor and mangiferin demonstrated the best ACE inhibitory activity with competitive inhibition on ACE with the type of inhibition kinetics is competitive inhibition.

  10. Elnaem MH, Mohamed MHN, Huri HZ, Azarisman SM, Elkalmi RM
    J Pharm Bioallied Sci, 2017 Apr-Jun;9(2):80-87.
    PMID: 28717329 DOI: 10.4103/jpbs.JPBS_30_17
    Use of statin therapy in patients with type 2 diabetes mellitus (T2DM) has been recommended by most clinical guidelines. Cardiovascular disease (CVD) is a leading cause of morbidity and mortality among T2DM patients. It has been proved that statins are effective for primary or secondary CVD prophylaxis. Reports have highlighted the underutilization of statins in clinical practice and the suboptimal adherence to guideline recommendations. This review article points to summarize the current evidence confirming the role of statins in T2DM patients and to provide an overview of factors that may affect statins' prescribing patterns and compliance in clinical practice. Initiatives to enhance statin therapy prescribing should recognize the comprehensive nature of the prescribing process. Attempts to assure proper statin prescribing and utilization can help in achieving better clinical outcomes of statin therapy.
  11. Abousheishaa AA, Lazim NHM, Tang SL, Sulaiman AH, Huri HZ, Guan NC
    Patient Educ Couns, 2022 Jul;105(7):2466-2474.
    PMID: 34844812 DOI: 10.1016/j.pec.2021.11.007
    OBJECTIVES: This study aimed to develop and assess the effectiveness of an encounter decision aid for Malaysian patients with MDD to support treatment decision-making during the consultation.

    METHODS: The decision aid prototype was developed following a literature review and six focus groups. Alpha testing assessed its comprehensibility, acceptability, usability and desirability through user-centered cognitive interviews. Beta-testing evaluated preliminary evidence on its efficacy using the SDM Scale and PDMS. Feasibility was assessed by timing the consultation.

    RESULTS: The alpha testing demonstrated that the decision aid was patient-oriented, comprehensible, comprehensive, concise and objective with an appealing design. Beta-testing indicated that PtDA significantly increased patients satisfaction with SDM from patients' [83.32 (13.92) vs 85.76 (13.80); p 

  12. Elnaem MH, Nik Mohamed MH, Huri HZ
    PLoS One, 2019;14(9):e0220458.
    PMID: 31536502 DOI: 10.1371/journal.pone.0220458
    OBJECTIVE: Previous reports have highlighted the suboptimal utilization and prescription of statin therapy among patients with type 2 diabetes mellitus (T2DM) in the Malaysian clinical practice. This study aims to test the impact of a pharmacist-led academic detailing program on improving the overall statin therapy prescribing in Malaysian hospital and primary care settings.

    METHODS: As a quasi-experimental design with a control group and pre-tests., we examined 1,598 medical records of T2DM subjects in six healthcare facilities in the state of Pahang, Malaysia. In all study sites, there was a pre and post-intervention assessment of the percentage of appropriate statin therapy prescribing that complied with the clinical guidelines with no potential safety issues. The intervention was an academic detailing program offered to the health care providers in three study sites, while the other three sites served as the control group. A comparison of the overall percentage of appropriate statin therapy prescribing before and after the academic detailing was performed in all intervention and control sites.

    RESULTS: Overall, 797 medical records were examined in the pre-intervention phase, and 801 records were evaluated in the post-intervention phase. The academic detailing program was associated with a statistically significant difference in the proportion of appropriate statin therapy prescribing between the post-intervention phase compared to the pre-intervention phase (n = 246, 61.7% versus n = 188, 47.1%), p = 0.001. Whereas, the appropriate statin therapy prescribing in the control study sites experienced a modest change from 53.8% (214/398) to 56.7% (228/402), p = 0.220. The academic detailing showed significant increases in the proportions of appropriate statin therapy prescribing in both hospital and primary care settings.

    CONCLUSIONS: The academic detailing program was found to be significantly associated with a positive impact on the overall statin therapy prescribing among patients with T2DM in Malaysian hospital and primary care settings.

  13. Abu Bakar MH, Cheng KK, Sarmidi MR, Yaakob H, Huri HZ
    Molecules, 2015 May 07;20(5):8242-69.
    PMID: 25961164 DOI: 10.3390/molecules20058242
    Mitochondrial dysfunction and inflammation are widely accepted as key hallmarks of obesity-induced skeletal muscle insulin resistance. The aim of the present study was to evaluate the functional roles of an anti-inflammatory compound, celastrol, in mitochondrial dysfunction and insulin resistance induced by antimycin A (AMA) in human skeletal muscle cells. We found that celastrol treatment improved insulin-stimulated glucose uptake activity of AMA-treated cells, apparently via PI3K/Akt pathways, with significant enhancement of mitochondrial activities. Furthermore, celastrol prevented increased levels of cellular oxidative damage where the production of several pro-inflammatory cytokines in cultures cells was greatly reduced. Celastrol significantly increased protein phosphorylation of insulin signaling cascades with amplified expression of AMPK protein and attenuated NF-κB and PKC θ activation in human skeletal muscle treated with AMA. The improvement of insulin signaling pathways by celastrol was also accompanied by augmented GLUT4 protein expression. Taken together, these results suggest that celastrol may be advocated for use as a potential therapeutic molecule to protect against mitochondrial dysfunction-induced insulin resistance in human skeletal muscle cells.
  14. Perumalsamy S, Ahmad WAW, Huri HZ
    Biology (Basel), 2021 Sep 01;10(9).
    PMID: 34571734 DOI: 10.3390/biology10090858
    (1) Background: Insulin resistance (IR) is the fundamental cause of type 2 diabetes (T2D), which leads to endothelial dysfunction and alters systemic lipid metabolism. The changes in the endothelium and lipid metabolism result in atherosclerotic coronary artery disease (CAD). In insulin-resistant and atherosclerotic CAD states, serum cytokine retinol-binding protein-4 (RBP-4) levels are elevated. The adipocyte-specific deletion of glucose transporter 4 (GLUT4) results in higher RBP-4 expression and IR and atherosclerotic CAD progression. (2) Aim: This study aimed to investigate the association of RBP-4 and clinical factors with IR and the severity of CAD. (3) Methods: Patients were recruited from diabetes and cardiology clinics and divided into three subgroups, namely (i) T2D patients with CAD, (ii) T2D-only patients, and (iii) CAD-only patients. The severity of CAD was classified as either single-vessel disease (SVD), double-vessel disease (DVD), or triple-vessel disease (TVD). An enzyme-linked immunosorbent assay was conducted to assess the concentration of serum RBP-4. Univariate (preliminary analysis) and multivariate (secondary analysis) logistic regressions were applied to assess the associations of RBP-4 and clinical factors with IR and the severity of CAD. (4) Results: Serum RBP-4 levels were associated with IR and the severity of CAD in all the three groups (all p-values are less than 0.05). Specifically, serum RBP-4 levels were associated with IR (p = 0.030) and the severity of CAD (SVD vs. DVD, p = 0.044; SVD vs. TVD, p = 0.036) in T2D patients with CAD. The clinical factors fasting plasma glucose (FPG) and angiotensin-converting-enzyme inhibitor (ACEI) were also associated with both IR and the severity of CAD in T2D patients with CAD. (5) Conclusion: RBP-4, FPG, and ACEI are predictors of IR and severity of CAD in T2D patients with CAD.
  15. Perumalsamy S, Aqilah Mohd Zin NA, Widodo RT, Wan Ahmad WA, Vethakkan SRDB, Huri HZ
    Curr Pharm Des, 2017;23(25):3689-3698.
    PMID: 28625137 DOI: 10.2174/1381612823666170616081256
    BACKGROUND: Chemerin is an adipokine that induces insulin resistance by the mechanism of inflammation in adipose tissue but these are still unclear. A high level of chemerin in humans is considered as a marker of inflammation in insulin resistance and obesity as well as in type 2 diabetes mellitus. Despite the role of chemerin in insulin resistance progression, chemerin as one of the novel adipokines is proposed to be involved in high cancer risk and mortality.

    AIM: The aim of this paper was to review the role of CMKLR-1 receptor and the potential therapeutic target in the management of chemerin induced type 2 diabetes mellitus and cancer.

    PATHOPHYSIOLOGY: Increased chemerin secretion activates an inflammatory response. The inflammatory response will increase the oxidative stress in adipose tissue and consequently results in an insulin-resistant state. The occurrence of inflammation, oxidative stress and insulin resistance leads to the progression of cancers.

    CONCLUSION: Chemerin is one of the markers that may involve in development of both cancer and insulin resistance. Chemokine like receptor- 1 (CMKLR-1) receptor that regulates chemerin levels exhibits a potential therapeutic target for insulin resistance, type 2 diabetes and cancer treatment.

  16. Yugavathy N, Abdullah BM, Lim SK, Abdul Gafor AHB, Wong MG, Bavanandan S, et al.
    Curr Issues Mol Biol, 2023 Aug 07;45(8):6550-6563.
    PMID: 37623232 DOI: 10.3390/cimb45080413
    The study of anaemia is a well-developed discipline where the concepts of precision medicine have, in part, been researched extensively. This review discusses the treatment of erythropoietin (EPO) deficiency anaemia and resistance in cases of chronic kidney disease (CKD). Traditionally, erythropoietin-stimulating agents (ESAs) and iron supplementation have been used to manage anaemia in cases of CKD. However, these treatments pose potential risks, including cardiovascular and thromboembolic events. Newer treatments have emerged to address these risks, such as slow-release and low-dosage intravenous iron, oral iron supplementation, and erythropoietin-iron combination therapy. Another novel approach is the use of hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs). This review highlights the need for precision medicine targeting the genetic components of EPO deficiency anaemia in CKD and discusses individual variability in genes such as the erythropoietin gene (EPO), the interleukin-β gene (IL-β), and the hypoxia-inducible factor gene (HIF). Pharmacogenetic testing aims to provide targeted therapies and interventions that are tailored to the specific characteristics of an individual, thus optimising treatment outcomes and minimising resistance and adverse effects. This article concludes by suggesting that receptor modification has the potential to revolutionise the treatment outcomes of patients with erythropoietin deficiency anaemia through the integration of the mentioned approach.
  17. 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.
  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.
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