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  1. Abu Seman N, Witasp A, Wan Mohamud WN, Anderstam B, Brismar K, Stenvinkel P, et al.
    J Diabetes Res, 2013;2013:298019.
    PMID: 24350299 DOI: 10.1155/2013/298019
    Recent reports have demonstrated that elevated plasma long pentraxin 3 (PTX3) levels are associated with cardiovascular and chronic kidney diseases. In the current study, we investigated the plasma PTX3 levels in 296 Malay subjects including the subjects with normal glucose tolerance (NGT) and type 2 diabetes (T2DM) patients with or without DN by using an enzyme-linked immune-sorbent assay. Results showed that in males, plasma PTX3 levels in T2DM patients without DN were lower than that in the subjects with NGT (2.78 versus 3.98 ng/mL; P = 0.021). Plasma PTX3 levels in T2DM patients with DN were decreased compared to the patients without DN (1.63 versus 2.78 ng/mL; P = 0.013). In females, however, no significant alteration of plasma PTX3 levels among NGT subjects and T2DM patients with and without DN was detected. Furthermore, an inverse correlation between PTX3 and body mass index was found in male subjects with NGT (P = 0.012; r = -0.390), but not in male T2DM patients, neither in all females. The current study provided the first evidence that decreased plasma PTX3 levels are associated with T2DM and DN in Malay men and also suggested that PTX3 may have different effects in DN and chronic kidney diseases.
  2. Imam MU, Ismail M, Omar AR, Ithnin H
    J Diabetes Res, 2013;2013:134694.
    PMID: 23671850 DOI: 10.1155/2013/134694
    Germinated brown rice (GBR) is rich in bioactive compounds, which confer GBR with many functional properties. Evidence of its hypocholesterolemic effects is emerging, but the exact mechanisms of action and bioactive compounds involved have not been fully documented. Using type 2 diabetic rats, we studied the effects of white rice, GBR, and brown rice (BR) on lipid profile and on the regulation of selected genes involved in cholesterol metabolism. Our results showed that the upregulation of apolipoprotein A1 and low-density lipoprotein receptor genes was involved in the hypocholesterolemic effects of GBR. Additionally, in vitro studies using HEPG2 cells showed that acylated steryl glycoside, gamma amino butyric acid, and oryzanol and phenolic extracts of GBR contribute to the nutrigenomic regulation of these genes. Transcriptional and nontranscriptional mechanisms are likely involved in the overall hypocholesterolemic effects of GBR suggesting that it may have an impact on the prevention and/or management of hypercholesterolemia due to a wide variety of metabolic perturbations. However, there is need to conduct long-term clinical trials to determine the clinical relevance of the hypocholesterolemic effects of GBR determined through animal studies.
  3. Fernando HA, Chin HF, Ton SH, Abdul Kadir K
    J Diabetes Res, 2013;2013:190395.
    PMID: 23671857 DOI: 10.1155/2013/190395
    Chronic stress has been shown to have a strong link towards metabolic syndrome (MetS). Glycyrrhizic acid (GA) meanwhile has been shown to improve MetS symptoms caused by an unhealthy diet by inhibiting 11 β -HSD 1. This experiment aimed to determine the effects of continuous, moderate-intensity stress on rats with and without GA intake on systolic blood pressure (SBP) across a 28-day period, as well as glucose metabolism, and 11 β -HSD 1 and 2 activities at the end of the 28-day period. Adaptation to the stressor (as shown by SBP) resulted in no significant defects in glucose metabolism by the end of the experimental duration. However, a weakly significant increase in renal 11 β -HSD 1 and a significant increase in subcutaneous adipose tissue 11 β -HSD 1 activities were observed. GA intake did not elicit any significant benefit in glucose metabolism, indicating that the stress response may block its effects. However, GA-induced improvements in 11 β -HSD activities in certain tissues were observed, although it is uncertain if these effects are manifested after adaptation due to the withdrawal of the stress response. Hence the ability of GA to improve stress-induced disturbances in the absence of adaptation needs to be investigated further.
  4. Ghodsian N, Ismail P, Ahmadloo S, Heidari F, Haghvirdizadeh P, Ataollahi Eshkoor S, et al.
    J Diabetes Res, 2016;2016:8219543.
    PMID: 27314050 DOI: 10.1155/2016/8219543
    With-no-lysine (K) Kinase-4 (WNK4) consisted of unique serine and threonine protein kinases, genetically associated with an autosomal dominant form of hypertension. Argumentative consequences have lately arisen on the association of specific single nucleotide polymorphisms of WNK4 gene and essential hypertension (EHT). The aim of this study was to determine the association of Ala589Ser polymorphism of WNK4 gene with essential hypertensive patients in Malaysia. WNK4 gene polymorphism was specified utilizing mutagenically separated polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) method in 320 subjects including 163 cases and 157 controls. Close relation between Ala589Ser polymorphism and elevated systolic and diastolic blood pressure (SBP and DBP) was recognized. Sociodemographic factors including body mass index (BMI), age, the level of fasting blood sugar (FBS), low density lipoprotein (LDL), and triglyceride (TG) in the cases and healthy subjects exhibited strong differences (p < 0.05). The distribution of allele frequency and genotype of WNK4 gene Ala589Ser polymorphism showed significant differences (p < 0.05) between EHT subjects with or without type 2 diabetes mellitus (T2DM) and normotensive subjects, statistically. The WNK4 gene variation influences significantly blood pressure increase. Ala589Ser probably has effects on the enzymic activity leading to enhanced predisposition to the disorder.
  5. Ayadurai S, Hattingh HL, Tee LB, Md Said SN
    J Diabetes Res, 2016;2016:5897452.
    PMID: 27247949 DOI: 10.1155/2016/5897452
    Background. We conducted a review of current diabetes intervention studies in type 2 diabetes and identified opportunities for pharmacists to deliver quality diabetes care. Methods. A search on randomised controlled trials (RCT) on diabetes management by healthcare professionals including pharmacists published between 2010 and 2015 was conducted. Results and Discussion. Diabetes management includes multifactorial intervention which includes seven factors as outlined in diabetes guidelines, namely, glycaemic, cholesterol and blood pressure control, medication, lifestyle, education, and cardiovascular risk factors. Most studies do not provide evidence that the intervention methods used included all seven factors with exception of three RCT which indicated HbA1c (glycated hemoglobin) reduction range of 0.5% to 1.8%. The varied HbA1C reduction suggests a lack of standardised and consistent approach to diabetes care. Furthermore, the duration of most studies was from one month to two years; therefore long term outcomes could not be established. Conclusion. Although pharmacists' contribution towards improving clinical outcomes of diabetes patients was well documented, the methods used to deliver structured, consistent evidence-based care were not clearly stipulated. Therefore, approaches to achieving long term continuity of care are uncertain. An intervention strategy that encompass all seven evidence-based factors will be useful.
  6. Joyce-Tan SM, Zain SM, Abdul Sattar MZ, Abdullah NA
    J Diabetes Res, 2016;2016:2161376.
    PMID: 26682227 DOI: 10.1155/2016/2161376
    Genome-wide association studies (GWAS) have been successfully used to call for variants associated with diseases including type 2 diabetes mellitus (T2DM). However, some variants are not included in the GWAS to avoid penalty in multiple hypothetic testing. Thus, candidate gene approach is still useful even at GWAS era. This study attempted to assess whether genetic variations in the renin-angiotensin system (RAS) and their gene interactions are associated with T2DM risk. We genotyped 290 T2DM patients and 267 controls using three genes of the RAS, namely, angiotensin converting enzyme (ACE), angiotensinogen (AGT), and angiotensin II type 1 receptor (AGTR1). There were significant differences in allele frequencies between cases and controls for AGT variants (P = 0.05) but not for ACE and AGTR1. Haplotype TCG of the AGT was associated with increased risk of T2DM (OR 1.92, 95% CI 1.15-3.20, permuted P = 0.012); however, no evidence of significant gene-gene interactions was seen. Nonetheless, our analysis revealed that the associations of the AGT variants with T2DM were independently associated. Thus, this study suggests that genetic variants of the RAS can modestly influence the T2DM risk.
  7. Gooda Sahib Jambocus N, Saari N, Ismail A, Khatib A, Mahomoodally MF, Abdul Hamid A
    J Diabetes Res, 2016;2016:2391592.
    PMID: 26798649 DOI: 10.1155/2016/2391592
    The prevalence of obesity is increasing worldwide, with high fat diet (HFD) as one of the main contributing factors. Obesity increases the predisposition to other diseases such as diabetes through various metabolic pathways. Limited availability of antiobesity drugs and the popularity of complementary medicine have encouraged research in finding phytochemical strategies to this multifaceted disease. HFD induced obese Sprague-Dawley rats were treated with an extract of Morinda citrifolia L. leaves (MLE 60). After 9 weeks of treatment, positive effects were observed on adiposity, fecal fat content, plasma lipids, and insulin and leptin levels. The inducement of obesity and treatment with MLE 60 on metabolic alterations were then further elucidated using a (1)H NMR based metabolomics approach. Discriminating metabolites involved were products of various metabolic pathways, including glucose metabolism and TCA cycle (lactate, 2-oxoglutarate, citrate, succinate, pyruvate, and acetate), amino acid metabolism (alanine, 2-hydroxybutyrate), choline metabolism (betaine), creatinine metabolism (creatinine), and gut microbiome metabolism (hippurate, phenylacetylglycine, dimethylamine, and trigonelline). Treatment with MLE 60 resulted in significant improvement in the metabolic perturbations caused obesity as demonstrated by the proximity of the treated group to the normal group in the OPLS-DA score plot and the change in trajectory movement of the diseased group towards the healthy group upon treatment.
  8. Yida Z, Imam MU, Ismail M, Ooi DJ, Sarega N, Azmi NH, et al.
    J Diabetes Res, 2015;2015:760535.
    PMID: 26273674 DOI: 10.1155/2015/760535
    Edible bird's nest (EBN) is used traditionally in many parts of Asia to improve wellbeing, but there are limited studies on its efficacy. We explored the potential use of EBN for prevention of high fat diet- (HFD-) induced insulin resistance in rats. HFD was given to rats with or without simvastatin or EBN for 12 weeks. During the intervention period, weight measurements were recorded weekly. Blood samples were collected at the end of the intervention and oral glucose tolerance test conducted, after which the rats were sacrificed and their liver and adipose tissues collected for further studies. Serum adiponectin, leptin, F2-isoprostane, insulin, and lipid profile were estimated, and homeostatic model assessment of insulin resistance computed. Effects of the different interventions on transcriptional regulation of insulin signaling genes were also evaluated. The results showed that HFD worsened metabolic indices and induced insulin resistance partly through transcriptional regulation of the insulin signaling genes. Additionally, simvastatin was able to prevent hypercholesterolemia but promoted insulin resistance similar to HFD. EBN, on the other hand, prevented the worsening of metabolic indices and transcriptional changes in insulin signaling genes due to HFD. The results suggest that EBN may be used as functional food to prevent insulin resistance.
  9. Haghvirdizadeh P, Mohamed Z, Abdullah NA, Haghvirdizadeh P, Haerian MS, Haerian BS
    J Diabetes Res, 2015;2015:908152.
    PMID: 26448950 DOI: 10.1155/2015/908152
    Diabetes mellitus (DM) is a major worldwide health problem and its prevalence has been rapidly increasing in the last century. It is caused by defects in insulin secretion or insulin action or both, leading to hyperglycemia. Of the various types of DM, type 2 occurs most frequently. Multiple genes and their interactions are involved in the insulin secretion pathway. Insulin secretion is mediated through the ATP-sensitive potassium (KATP) channel in pancreatic beta cells. This channel is a heteromeric protein, composed of four inward-rectifier potassium ion channel (Kir6.2) tetramers, which form the pore of the KATP channel, as well as sulfonylurea receptor 1 subunits surrounding the pore. Kir6.2 is encoded by the potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) gene, a member of the potassium channel genes. Numerous studies have reported the involvement of single nucleotide polymorphisms of the KCNJ11 gene and their interactions in the susceptibility to DM. This review discusses the current evidence for the contribution of common KCNJ11 genetic variants to the development of DM. Future studies should concentrate on understanding the exact role played by these risk variants in the development of DM.
  10. Haghvirdizadeh P, Ramachandran V, Etemad A, Heidari F, Ghodsian N, Bin Ismail N, et al.
    J Diabetes Res, 2015;2015:289846.
    PMID: 26451383 DOI: 10.1155/2015/289846
    BACKGROUND: Type 2 diabetes mellitus (T2DM) is a complex polygenic disorder characterized by impaired insulin resistance, insulin secretion, and dysregulation of lipid and protein metabolism with environmental and genetic factors. ATP-binding cassette transporter A1 (ABCA1) gene polymorphisms are reported as the one of the genetic risk factors for T2DM in various populations with conflicting results. This study was conducted based on PCR-HRM to determine the frequency of ABCA1 gene by rs2230806 (R219K), rs1800977 (C69T), and rs9282541 (R230C) polymorphisms Malaysian subjects.

    METHODS: A total of 164 T2DM and 165 controls were recruited and their genotypes for ABCA1 gene polymorphisms were determined based on the real time high resolution melting analysis.

    RESULTS: There was a significant difference between the subjects in terms of age, BMI, FPG, HbA1c, HDL, LDL, and TG (P < 0.05). There was a significant association between HOM of R219K (P = 0.005), among Malaysian subjects; moreover, allele frequency revealed the significant difference in A allele of R219K (P = 0.003). But, there was no significant difference in genotypic and allelic frequencies of C69T and R230C polymorphism.

    CONCLUSION: R219K polymorphism of ABCA1 gene can be considered as a genetic risk factor for T2DM subjects among Malaysians.

  11. Gunggu A, Thon CC, Whye Lian C
    J Diabetes Res, 2016;2016:9158943.
    PMID: 27563681 DOI: 10.1155/2016/9158943
    Diabetes mellitus is a public health concern in Malaysia. Treatment of diabetes is costly and can lead to complications if disease is poorly controlled. Diabetes self-management (DSM) is found to be essential for optimal glycemic control. This cross-sectional study was conducted among samples from four randomly selected diabetes clinics in Sarawak, Malaysia. The aim was to determine the predictors for DSM. Face-to-face interview using questionnaire was used to collect data. Four hundred respondents with type 2 diabetes mellitus (T2DM) were recruited. Majority of the respondents were Sarawak Bumiputra (Iban and Bidayuh, 48.6%) and female (68.6%). The mean age was 58.77 years (SD = 11.46) and approximately half of the respondents (50.6%) had T2DM for six years (SD = 4.46). The mean fasting blood glucose (FBG) was 8.06 mmol/L (SD = 2.94), with majority (76.1%) having the level higher than 6.1 mmol/L. Multiple logistic regression tests showed significant linear relationship between DSM and belief in treatment effectiveness (p = 0.001), family support (p = 0.007), and self-efficacy (p = 0.027). Health care personnel must convince patients with T2DM of the effectiveness of the treatment, empower and enhance their self-efficacy, and enlist the family support so as to ensure patients sustain their DSM efforts.
  12. Gillani SW, Ansari IA, Zaghloul HA, Abdul MIM, Sulaiman SAS, Baig MR, et al.
    J Diabetes Res, 2018;2018:4079087.
    PMID: 29854822 DOI: 10.1155/2018/4079087
    Background: This study is aimed at investigating the various disease-specific and health-related psychosocial concepts of HRQOL among insulin-dependent diabetes mellitus (IDDM) and understanding the gender differences in HRQOL among IDDM patients.

    Methods: A cross-sectional observational study was conducted to assess the effect of health-related and psychosocial correlates on HRQOL of IDDM patients in Penang, Malaysia. The participants were recruited from five governmental diabetic clinics. Patients with insulin use only, IDDM diagnosed at least 1 year earlier, were identified from clinical registers. The sample was then age stratified for 20-64 years, and severe complications (e.g., end-stage renal failure, hemodialysis, and liver cirrhosis) were excluded; a total of 1003 participants were enrolled in the study. Multivariate regression analysis was used to predict the response.

    Results: A total of 853 (100%) participants were enrolled and completed the study. Women exhibited significantly higher/better mental health (p < 0.013) and health perception scores (p < 0.001) despite high prevalence of impaired role (49.2%), social (24.2%), and physical (40.5%) functionings as compared to men. Women with longer diabetes exposure and uncontrolled glycemic levels (HbA1c) have poorer HRQOL. Availability of social support showed no significant association with either HRQOL or diabetes distress levels. Diabetes distress levels remained not associated with social support. Women also showed significantly higher association with health perception (15% versus 13% men, p < 0.001) and mental health (13% versus 11% men, p < 0.001) in diabetes-specific psychosocial factors. Thus, among women alone, diabetes-related specific and psychosocial factors explained 15% and 13% of variations in HRQOL extents, respectively.

    Conclusion: Women exhibit extensive and significant patterns with health-related factors and diabetes-specific psychosocial factors (self-efficacy, social support, and DLC) to improve HRQOL. Also, women have significantly high reported distress levels and low social functioning compared to men.

  13. Azami G, Soh KL, Sazlina SG, Salmiah MS, Aazami S, Mozafari M, et al.
    J Diabetes Res, 2018;2018:4930157.
    PMID: 30225268 DOI: 10.1155/2018/4930157
    In recent years, great emphasis has been placed on the role of nonpharmacological self-management in the care of patients with diabetes. Studies have reported that nurses, compared to other healthcare professionals, are more likely to promote preventive healthcare seeking behaviors. The aim of this study was to investigate the effectiveness of a nurse-led diabetes self-management education on glycosylated hemoglobin. A two-arm parallel-group randomized controlled trial with the blinded outcome assessors was designed. One hundred forty-two adults with type 2 diabetes were randomized to receive either usual diabetes care (control group) or usual care plus a nurse-led diabetes self-management education (intervention group). Duration of the intervention was 12 weeks. The primary outcome was glycosylated hemoglobin (HbA1c values). Secondary outcomes were changes in blood pressure, body weight, lipid profiles, self-efficacy (efficacy expectation and outcome expectation), self-management behaviors, quality of life, social support, and depression. Outcome measures were assessed at baseline and at 12-week and 24-week postrandomizations. Patients in the intervention group showed significant improvement in HbA1c, blood pressure, body weight, efficacy expectation, outcome expectation, and diabetes self-management behaviors. The beneficial effect of a nurse-led intervention continued to accrue beyond the end of the trial resulting in sustained improvements in clinical, lifestyle, and psychosocial outcomes. This trial is registered with IRCT2016062528627N1.
  14. Bujang MA, Kuan PX, Tiong XT, Saperi FE, Ismail M, Mustafa FI, et al.
    J Diabetes Res, 2018;2018:4638327.
    PMID: 30116741 DOI: 10.1155/2018/4638327
    Aims: This study aims to determine the all-cause mortality and the associated risk factors for all-cause mortality among the prevalent type 2 diabetes mellitus (T2DM) patients within five years' period and to develop a screening tool to determine high-risk patients.

    Methods: This is a cohort study of T2DM patients in the national diabetes registry, Malaysia. Patients' particulars were derived from the database between 1st January 2009 and 31st December 2009. Their records were matched with the national death record at the end of year 2013 to determine the status after five years. The factors associated with mortality were investigated, and a prognostic model was developed based on logistic regression model.

    Results: There were 69,555 records analyzed. The mortality rate was 1.4 persons per 100 person-years. The major cause of death were diseases of the circulatory system (28.4%), infectious and parasitic diseases (19.7%), and respiratory system (16.0%). The risk factors of mortality within five years were age group (p < 0.001), body mass index category (p < 0.001), duration of diabetes (p < 0.001), retinopathy (p = 0.001), ischaemic heart disease (p < 0.001), cerebrovascular (p = 0.007), nephropathy (p = 0.001), and foot problem (p = 0.001). The sensitivity and specificity of the proposed model was fairly strong with 70.2% and 61.3%, respectively.

    Conclusions: The elderly and underweight T2DM patients with complications have higher risk for mortality within five years. The model has moderate accuracy; the prognostic model can be used as a screening tool to classify T2DM patients who are at higher risk for mortality within five years.
  15. Bujang MA, Adnan TH, Mohd Hatta NKB, Ismail M, Lim CJ
    J Diabetes Res, 2018;2018:5804687.
    PMID: 30327784 DOI: 10.1155/2018/5804687
    Background: Diabetes quality of life (DQoL) instrument has been widely used to measure quality of life among diabetes patients. This study aimed to develop a revised version of DQoL instrument that incorporated issues of redundancies in the items and strengthen the basis of validity of the instrument.

    Methods: This was a cross-sectional study where diabetes patients were recruited from December 1, 2014, until end of March 2015 at a public health clinic in Peninsular Malaysia. A questionnaire that included patients' information and DQoL instrument was distributed to patients. Item selection of DQoL instrument was conducted to screen and finalize the items based on issues of missing values and redundancy. Validity testing was conducted for the revised DQoL instrument based on exploratory factor analysis, confirmatory factor analysis, and Rasch analysis.

    Results: The pattern structure matrix yielded three domains similar to the original version with 18 items. The minimum factor loading from the structure matrix was 0.358. The item's and person's reliability was excellent with 0.92 and 0.84 for "satisfaction" domain, 0.98 and 0.60 for "impact" domain, and 0.99 and 0.57 for "worry" domain, respectively. Confirmatory factor analysis has dropped 5 items and the revised version of DQoL contained 13 items. Composite reliability of the revised version was computed for "satisfaction" domain (0.922; 95% CI: 0.909-0.936), "impact" domain (0.781; 95% CI: 0.745-0.818), and "worry" domain (0.794; 95% CI: 0.755-0.832).

    Conclusion: A revised version of DQoL that maintains the conceptualization of "satisfaction," "impact," and "worry" with 13 items was successfully developed.
  16. Duan D, Li H, Xu J, Wong L, Xu G, Kong F, et al.
    J Diabetes Res, 2019;2019:2591709.
    PMID: 30805371 DOI: 10.1155/2019/2591709
    Objective: To estimate the incident risk of ischemic stroke (IS) in newly diagnosed type 2 diabetes (T2D) subjects according to different body mass index (BMI) and height categories.

    Methods: A total of 25,130 newly diagnosed T2D subjects were included in this study. All T2D subjects were enrolled consecutively from the Chronic Disease Surveillance System (CDSS) of Ningbo. Standardized incidence ratio (SIR) and its 95% confidence interval (95% CI) stratified by BMI categories and height quartiles were used to estimate the incident risk of IS in T2D subjects.

    Results: In total, 22,795 subjects completed the follow-up. Among them, 1268 newly diagnosed IS cases were identified, with 149,675 person-years. The SIRs of normal BMI (18.5-24.0 kg/m2), overweight (24.0-28.0 kg/m2), and obese (≥28.0 kg/m2) in overall subjects were 2.56 (95% CI 1.90-3.13), 2.13 (95% CI 1.90-3.13), and 1.87 (95% CI 1.29-2.43), respectively (Ptrend < 0.01), comparing to the general population of Ningbo. For each 1 kg/m2 increment in BMI, the SIR was 0.948 (95% CI 0.903-0.999). For height quartiles, the SIRs of male subjects in quartile 1 (<160 cm), quartile 2 (161-165 cm), quartile 3 (165-170 cm), and quartile 4 (≥171 cm) were 2.27 (95% CI 1.99-2.56), 2.01 (95% CI 1.67-2.45), 1.37 (95% CI 1.05-1.68), and 0.91 (95% CI 0.40-1.32), respectively (Ptrend < 0.01). While for female subjects, the SIRs in quartile 1 (<155 cm), quartile 2 (156-160 cm), quartile 3 (161-165 cm), and quartile 4 (≥166 cm) were 3.57 (95% CI 3.11-3.49), 2.96 (95% CI 2.61-3.31), 1.94 (95% CI 1.51-2.36), and 1.71 (95% CI 0.95-2.47), respectively (Ptrend < 0.01).

    Conclusion: Compared to the general population of Ningbo, T2D subjects had a higher incident risk of IS. Furthermore, the IS incident risk was not only higher in newly diagnosed T2D subjects with normal BMI but also lower in taller newly diagnosed T2D subjects.

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