Displaying publications 1 - 20 of 33 in total

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  1. Mustaffa N, Ibrahim S, Abdullah WZ, Yusof Z
    Blood Coagul Fibrinolysis, 2011 Sep;22(6):512-20.
    PMID: 21537159 DOI: 10.1097/MBC.0b013e32834740ba
    Rosiglitazone is an oral hypoglycaemic agent of the thiazolidinedione group. This study aimed to assess changes in the diabetic prothrombotic state via plasminogen activity and changes in surrogate markers of atherosclerotic burden via ankle-brachial pressure index (ABPI) measurements after rosiglitazone was added to a pre-existing type 2 diabetes mellitus treatment regime. A nonblinded interventional study was designed. Fifty-nine patients were enrolled. Rosiglitazone-naïve patients were prescribed oral rosiglitazone 4 mg daily for 10 weeks. ABPI, plasminogen activity, glycosylated haemoglobin (HbA1c) and fasting lipid profile were measured pretreatment and post-treatment. Forty-eight patients completed the study. At the end of this study, mean plasminogen activity improvement was nearly 16% (P<0.05), mean ABPI improvement was 0.01 (P=0.439), mean HbA1c reduction was 0.51% (P<0.05), mean total cholesterol (TC) increase was 0.36 mmol/l (P<0.05), mean high-density lipoprotein cholesterol (HDL-C) increase was 0.15 mmol/l (P<0.05) and mean low-density lipoprotein cholesterol increased by 0.19 mmol/l (P=0.098). Rosiglitazone significantly improved plasminogen activity. There was also significant HbA1c reduction, and rise in both TC and HDL-C. Thus, rosiglitazone potentially improves the atherosclerotic burden and prothrombotic state. In future, more studies are needed to confirm the relationship between rosiglitazone, fibrinolytic system and atheromatous reduction in type 2 diabetes mellitus.
    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology
  2. Arshad N', Lin TS, Yahaya MF
    CNS Neurol Disord Drug Targets, 2018;17(8):595-603.
    PMID: 30047340 DOI: 10.2174/1871527317666180724143258
    BACKGROUND & OBJECTIVE: Metabolic syndrome (MetS) is an interconnected group of physiological, biochemical, clinical and metabolic factors that directly increase the risk of cardiovascular disease, type 2 diabetes mellitus (T2DM) and mortality. Rising evidence suggests that MetS plays a significant role in the progression of Alzheimer's disease and other neurodegenerative diseases. Nonetheless, the factors linking this association has not yet been elucidated. As we are facing an increasing incidence of obesity and T2DM in all stages of life, understanding the association of MetS and neurodegenerative diseases is crucial to lessen the burden of the disease.

    CONCLUSION: In this review, we will discuss the possible mechanisms which may relate the association between MetS and cognitive decline which include vascular damages, elevation of reactive oxygen species (ROS), insulin resistance and low-grade inflammation.

    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology
  3. Ahmad B, Vohra MS, Saleemi MA, Serpell CJ, Fong IL, Wong EH
    Biochimie, 2021 May;184:26-39.
    PMID: 33548390 DOI: 10.1016/j.biochi.2021.01.015
    Brown and beige adipose tissues are the primary sites for adaptive non-shivering thermogenesis. Although they have been known principally for their thermogenic effects, in recent years, it has emerged that, just like white adipose tissue (WAT), brown and beige adipose tissues also play an important role in the regulation of metabolic health through secretion of various brown adipokines (batokines) in response to various physiological cues. These secreted batokines target distant organs and tissues such as the liver, heart, skeletal muscles, brain, WAT, and perform various local and systemic functions in an autocrine, paracrine, or endocrine manner. Brown and beige adipose tissues are therefore now receiving increasing levels of attention with respect to their effects on various other organs and tissues. Identification of novel secreted factors by these tissues may help in the discovery of drug candidates for the treatment of various metabolic disorders such as obesity, type-2 diabetes, skeletal deformities, cardiovascular diseases, dyslipidemia. In this review, we comprehensively describe the emerging secretory role of brown/beige adipose tissues and the metabolic effects of various brown/beige adipose tissues secreted factors on other organs and tissues in endocrine/paracrine manners, and as well as on brown/beige adipose tissue itself in an autocrine manner. This will provide insights into understanding the potential secretory role of brown/beige adipose tissues in improving metabolic health.
    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology
  4. Daher AM, AlMashoor SH, Winn T
    PLoS One, 2016;11(10):e0163701.
    PMID: 27695086 DOI: 10.1371/journal.pone.0163701
    INTRODUCTION: Diabetes Mellitus (DM) is notorious for its metabolic effect, acute and chronic complications and impact on Quality of Life (QoL). Successful intervention to improve QoL necessitates a valid and reliable measurement tool to identify areas of concern to patients with diabetes.
    OBJECTIVES: To (1) assess the factor structure of the Malay Audit of Diabetes Dependent Quality of Life-18 (ADDQoL-18) questionnaire; (2) determine the impact of DM on QoL; and (3) identify areas of concern to patients with type 2 DM from three major ethnic groups in Malaysia.
    METHODS: Data was obtained from a cross sectional study involving 256 patients with type 2 DM attending the diabetes clinic of the National University of Malaysia Medical Centre. The Malay version of ADDQoL-18 survey was translated from its English version according to standard guidelines and administered by a trained research assistant. Exploratory Factor Analysis (EFA) with oblimin rotation was used to determine factor structure of the data. Confirmatory Factor Analysis (CFA) was used to confirm the factor structure. Hierarchical liner regression was used to determine factors associated with QoL.
    RESULTS: Unforced factor solution yielded two factors for the whole sample. Forced one factor solution was ascertained for the whole sample and for each ethnic group. Loadings ranged between 0.588 and 0.949. Reliability coefficients were all higher than 0.955. CFA showed that the two factor model had better fit statistics. QoL was associated with the use of insulin and desired glycaemic control, longer diabetes duration, worry about diabetes, and diabetes complications.
    CONCLUSIONS: The Malay ADDQoL-18 is a valid tool to be used among patients with diabetes from different ethnic groups in Malaysia. The use of insulin to achieve desired glycaemic control had more negative impact on QoL than the use of tablets and/or dietary changes.
    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology
  5. Trang NTH, Tang DYY, Chew KW, Linh NT, Hoang LT, Cuong NT, et al.
    Mol Biotechnol, 2021 Nov;63(11):1004-1015.
    PMID: 34185249 DOI: 10.1007/s12033-021-00362-3
    Various studies showed that the suppression of α-glucosidase activity can impede the glucose absorption in our body, and therefore, it can be used to treat type 2 diabetes. Hence, the compounds with anti-α-glucosidase have gained considerable attention because of their potential application in diabetes treatment. In previous literature studies, these anti-α-glucosidase compounds were extracted from plants and fungus. Less studies are being conducted to identify the anti-α-glucosidase compounds in the microbial community. In this study, 23 marine bacterial strains were screened for their potential to suppress the α-glucosidase activity. The highest inhibitory activity was exhibited by isolated L06 which was identified as Oceanimonas smirnovii EBL6. The cultivation conditions, such as temperature and pH, were optimized to increase the production of α-glucosidase inhibitors by Oceanimonas smirnovii EBL6 strain. The result findings showed that the highest yield of α-glucosidase inhibitors can be obtained at the culture time of 120 h, fermentation temperature of 30 °C, and pH 4.6. Under these conditions, the inhibitory activity of α-glucosidase can reach 81%. The IC50 of n-butanol extract was 13.89 μg/ml, while standard acarbose was 31.16 μg/ml. Overall, these findings suggest that Oceanimonas smirnovii produces α-glucosidase inhibitors and could been applied in the biochemical and medicinal fields in the future.
    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology
  6. Chong YB, Keng TC, Tan LP, Ng KP, Kong WY, Wong CM, et al.
    Ren Fail, 2012;34(3):323-8.
    PMID: 22250665 DOI: 10.3109/0886022X.2011.647302
    BACKGROUND:
    Type 2 diabetes mellitus (T2DM) is reportedly the leading cause of end-stage renal disease (ESRD) worldwide. However, non-diabetic renal diseases (NDRD) are not uncommon among T2DM patients with renal involvement. Our study aimed to examine the prevalence of NDRD in T2DM and clinical markers for diabetic nephropathy (DN) and NDRD and to determine the role of renal biopsy in T2DM patients and its impact on clinical practice.

    METHODS:
    We conducted a retrospective analysis of T2DM patients in whom renal biopsies were performed from January 2004 to March 2008 (n = 110).

    RESULTS:
    Biopsy results were divided into three groups: group I/pure DN (62.7%), group II/isolated NDRD (18.2%), and group III/mixed lesions (19.1%). The causes of NDRD in decreasing order of frequency were acute interstitial nephritis, glomerulonephritides, hypertensive renal disease, and acute tubular necrosis. Significant clinical markers for DN are presence of diabetic retinopathy and longer duration of diabetes. For NDRD, useful clinical markers include the presence of acute renal failure and microscopic hematuria. In the DN subgroup, Indians had significantly shorter duration of diabetes on biopsy compared with Malays and Chinese.

    CONCLUSIONS:
    NDRD is prevalent in T2DM patients, and given its potentially treatable nature, renal biopsy should be considered in T2DM patients with nephropathy, especially in those with atypical features.
    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology*
  7. Nazratun N, Mahmood AA, Kuppusamy UR, Ahmad TS, Tan SY
    Vasc Med, 2006 Nov;11(4):245-50.
    PMID: 17390548
    The excess accumulation of advanced glycation end products (AGEs) contributes to the chronic complications of type 2 diabetes mellitus (DM) and renal failure. Biopsy specimens (n = 184) of arterial (n = 92) and venous (n = 92) tissues were obtained (radial artery and cephalic vein) from end-stage renal disease (ESRD) patients with or without DM and normal healthy subjects (n = 12) requiring surgery (trauma patients). Immunohistochemical assessment of the blood vessels revealed the presence of pentosidine (AGE marker) in both veins and arteries in 72% of the ESRD patients. The percentage of arteries and veins that showed positive pentosidine staining in ESRD patients with type 2 DM alone was 100% and 92% respectively, in the non-diabetic ESRD patients it was < 70% (for arteries and veins), and in the ESRD patients with hypertension as an additional co-morbidity to type 2 DM it was 70% and 82%, respectively. The veins of ESRD patients with DM showed a strong (+++) positive staining and very strong (++++) positive staining was observed in the patients with DM and hypertension. Only mild (+) or moderate (++) pentosidine staining intensity was observed in the arteries of ESRD patients without or with comorbidities, respectively. The accumulation of AGE in the vein rather than the artery may be a better reflection of the extent of complications of ESRD.
    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology
  8. Giribabu N, Karim K, Kilari EK, Kassim NM, Salleh N
    Can J Diabetes, 2018 Apr;42(2):138-149.
    PMID: 28673757 DOI: 10.1016/j.jcjd.2017.04.005
    OBJECTIVES: Consumption of Vitis vinifera seed has been reported to ameliorate liver pathology in diabetes mellitus; however, the mechanisms underlying its effects remain unknown. In this study, the anti-inflammatory, anti-apoptotic and pro-proliferative effects of the ethanolic seed extract of V. vinifera (VVSEE) in the liver in cases of diabetes were identified.

    METHODS: Adult male rats with streptozotocin-nicotinamide-induced diabetes were given 50, 100 or 200 mg/kg body weight VVSEE orally for 28 days. At the end of the treatment, body weights were determined, and the blood was collected for analyses of fasting blood glucose, insulin and liver enzyme levels. Following sacrifice, livers were harvested and their wet weights and glycogen contents were measured. Histologic appearances of the livers were observed under light microscopy, and the expression and distribution of inflammatory, apoptosis and proliferative markers in the livers were identified by molecular biologic techniques.

    RESULTS: Treatment of rats with diabetes by VVSEE attenuates decreased body weight, liver weight and liver glycogen content. Additionally, increases in fasting blood glucose levels and liver enzyme levels and decreases in serum insulin levels were ameliorated. Lesser histopathologic changes were also observed: decreased inflammation and apoptosis, as indicated by decreased levels of inflammatory markers (TNF-α, NF-Kβ, IKK-β, IL-6, IL-1β) and apoptosis markers (caspase-3, caspase-9 and Bax). VVSEE treatment induces increase in hepatocyte regeneration, as indicated by increased PCNA and Ki-67 distribution in the livers of rats with diabetes. Several molecules identified in VVSEE via gas chromatography mass spectrometry might contribute to these effects.

    CONCLUSIONS: The anti-inflammatory, anti-apoptotic and pro-proliferative effects of VVSEE could account for its hepatoprotective actions in diabetes.

    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology
  9. Chew BH, Vos RC, Pouwer F, Rutten GEHM
    Diabetes Res Clin Pract, 2018 Aug;142:74-84.
    PMID: 29802952 DOI: 10.1016/j.diabres.2018.05.021
    AIMS: To examine whether diabetes distress (DD), when measured by three different instruments, was associated differently with self-efficacy, self-care activity, medication adherence and disease control in people with Type 2 diabetes mellitus.
    METHODS: A cross-sectional study in three health clinics. DD was assessed with the 17-item Diabetes Distress Scale, the 2-item DDS-2 (DDS-2) and the 5-item Problem Areas in Diabetes Scale (PAID-5). Dependent variables included self-efficacy, self-care activities, medication adherence, HbA1c, systolic and diastolic blood pressure (SBP, DBP). Multiple linear and logistic regression were used in analyses.
    RESULTS: In total 338 participants (56% women), with a mean age of 61 years and diabetes duration of 9.8 years, were included. DDS-2 was an independent determinant of SBP (β = 1.89, 95% CI 0.14, 3.64), DBP (β = 1.19, 95% CI 0.16, 2.21) and blood pressure target (OR = 2.09, 95% CI 1.12, 3.83). PAID-5 was an independent determinant of medication adherence (adjusted β = -0.05, 95% CI -0.08, -0.01) and self-care activities (OR = 0.50, 95% CI 0.26, 0.99).
    CONCLUSIONS: Associations of DD with important aspects of diabetes care are substantially influenced by confounders and depend on the way DD is measured. Our findings call for a judicious use of different DD measures in clinical practice and research. The study is registered on ClinicalTrials.gov (NCT02730754).
    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology
  10. Yusof MI, Al-Astani AD, Jaafar H, Rashid FA
    Singapore Med J, 2008 Feb;49(2):100-4.
    PMID: 18301834
    INTRODUCTION: This study was designed to evaluate the histopathological features of skin microvasculature in patients with a diabetic foot, specifically the number of blood vessels, number of endothelial cells and endothelial thickness.
    METHODS: This study involved 41 diabetic foot patients admitted to Hospital Universiti Sains Malaysia for surgical management of foot problems. Skin biopsies were taken for histological evaluation following surgical procedures, such as wound debridement or local foot amputation. The skin microvasculature features examined were the number of blood vessels, the endothelial thickness of the vessels and the cross-sectional endothelial cell count. The findings were compared with the similar parameters of non-diabetic patients (control) and analysed.
    RESULTS: The mean blood vessel count (BVC), endothelial cell thickness (ECT) and endothelial cell count (ECC) for the diabetic group were 12.56 +/- 2.77, 4.81 +/- 1.5 micrometres and 7.07 +/- 1.88, respectively. The mean BVC, ECT and ECC for the non-diabetic control group were 5.25 +/- 1.98, 1.9 +/- 0.55 micrometres and 4.11 +/- 1.17, respectively. The mean BVC, ECT and ECC for the diabetic group were significantly higher than those for the non-diabetic control group.
    CONCLUSION: The increased number of blood vessels to the skin and their endothelial cell number and thickness may be the contributing factors for problems related to the diabetic foot, such as tendency for skin ulceration, infection and poor wound-healing in these patients. These may also contribute to secondary changes of diabetic foot lesions, indicating failure of adequate vascularisation of the foot.
    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology
  11. Rahman S, Rahman T, Ismail AA, Rashid AR
    Diabetes Obes Metab, 2007 Nov;9(6):767-80.
    PMID: 17924861 DOI: 10.1111/j.1463-1326.2006.00655.x
    The complications associated with diabetic vasculopathy are commonly grouped into two categories: microvascular and macrovascular complications. In diabetes, macrovascular disease is the commonest cause of mortality and morbidity and is responsible for high incidence of vascular diseases such as stroke, myocardial infarction and peripheral vascular diseases. Macrovascular diseases are traditionally thought of as due to underlying obstructive atherosclerotic diseases affecting major arteries. Pathological changes of major blood vessels leading to functional and structural abnormalities in diabetic vessels include endothelial dysfunction, reduced vascular compliance and atherosclerosis. Besides, advanced glycation end product formation interacts with specific receptors that lead to overexpression of a range of cytokines. Haemodynamic pathways are activated in diabetes and are possibly amplified by concomitant systemic hypertension. Apart from these, hyperglycaemia, non-enzymatic glycosylation, lipid modulation, alteration of vasculature and growth factors activation contribute to development of diabetic vasculopathy. This review focuses on pathophysiology and pathogenesis of diabetes-associated macrovasculopathy.
    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology
  12. Swarna Nantha Y, Haque S, Paul Chelliah AA
    PLoS One, 2019;14(11):e0225534.
    PMID: 31770421 DOI: 10.1371/journal.pone.0225534
    BACKGROUND: An upward trend is observed in the prevalence of Type 2 diabetes (T2D) in South-East Asian and Western Pacific regions. These patterns incur a costly health burden to developing nations around the world. A clear understanding of the mechanics behind self-management practices of T2D patients might help overcome this impasse. This information can help unlock specific problem areas that warrant specific intervention. We aim to uncover prevailing T2D self-management habits and its deviations from optimal behaviour.

    METHODS: We adopted a Grounded Theory approach to guide in-depth interviews (IDI) with T2D patients and healthcare providers (HCP) at a regional primary care clinic in Malaysia. Twenty-four T2D patients and 10 HCPs were recruited through purposive sampling to examine their inner psychological narratives related to self-management practices. 2 focus group discussions (FGD) were conducted as a part of the data triangulation process.

    RESULTS: A functional framework for self-management practices in T2D patients was developed. Self-management behavior was characterized by 2 major processes- 1) helpful and, 2) unhelpful practices. Self-efficacy, taking responsibility and being rational define helpful behaviour in these patients. On the other hand, unhelpful traits (neglect, poor restraint, and experimentation) often trigger violations with regards to medication compliance and therapeutic lifestyle changes.

    CONCLUSIONS: We outlined a roadmap that navigates through the positive and negative mindset in relation to self-management practices of T2D patients. These results highlight the importance of devising individualized strategies by taking into account the personal challenges, emotions, and motivations that define the inner self of the patient.
    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology
  13. Taheri Rouhi SZ, Sarker MMR, Rahmat A, Alkahtani SA, Othman F
    BMC Complement Altern Med, 2017 Mar 14;17(1):156.
    PMID: 28288617 DOI: 10.1186/s12906-017-1667-6
    BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with hyperglycemia, inflammatory disorders and abnormal lipid profiles. Several functional foods have therapeutic potential to treat chronic diseases including diabetes. The therapeutic potential of pomegranate has been stated by multitudinous scientists. The present study aimed to evaluate the effects of pomegranate juice and seed powder on the levels of plasma glucose and insulin, inflammatory biomarkers, lipid profiles, and health of the pancreatic islets of Langerhans in streptozotocin (STZ)-nicotinamide (NAD) induced T2DM Sprague Dawley (SD) rats.

    METHODS: Forty healthy male SD rats were induced to diabetes with a single dose intra-peritoneal administration of STZ (60 mg/kg b.w.) - NAD (120 mg/kg b.w.). Diabetic rats were orally administered with 1 mL of pomegranate fresh juice (PJ) or 100 mg pomegranate seed powder in 1 mL distilled water (PS), or 5 mg/kg b.w. of glibenclamide every day for 21 days. Rats in all groups were sacrificed on day 22. The obtained data was analyzed by SPSS software (v: 22) using One-way analysis of variance (ANOVA).

    RESULTS: The results showed that PJ and PS treatment had slight but non-significant reduction of plasma glucose concentration, and no impact on plasma insulin compared to diabetic control (DC) group. PJ lowered the plasma total cholesterol (TC) and triglyceride (TG) significantly, and low-density lipoproteins (LDL) non-significantly compared to DC group. In contrast, PS treatment significantly raised plasma TC, LDL, and high-density lipoproteins (HDL) levels compared to the DC rats. Moreover, the administration of PJ and PS significantly reduced the levels of plasma inflammatory biomarkers, which were actively raised in diabetic rats. Only PJ treated group showed significant repairment and restoration signs in islets of Langerhans. Besides, PJ possessed preventative impact against 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals almost 2.5 folds more than PS.

    CONCLUSIONS: Our findings suggest that active constituents with high antioxidant properties present in PJ are responsible for its anti-hyperlipidemic and anti-inflammatory effects, likewise the restoration effect on the damaged islets of Langerhans in experimental rats. Hence, the pharmacological, biochemical, and histopathological profiles of PJ treated rats obviously indicated its helpful effects in amelioration of diabetes-associated complications.

    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology
  14. Chin CY, Ng PY, Ng SF
    Drug Deliv Transl Res, 2019 04;9(2):453-468.
    PMID: 29560587 DOI: 10.1007/s13346-018-0510-z
    Previously, Moringa oleifera leaf (MOL) standardised aqueous extract-loaded films were successfully developed and they showed potential wound healing activity in vitro. The objective of this study was to evaluate in vivo dermal safety as well as wound healing efficacy of these MOL film dressings (containing 0.1, 0.5 and 1% MOL) on diabetic rat model. The acute dermal toxicity was carried out on healthy rats, and signs of toxicity over 14 days were observed. For wound healing studies, excision and abrasion wounds were created out on the STZ/HFD-induced diabetic rat model and the wound healing was studied over 21 days. The wound healing evaluation determined by histology staining, hydroxyproline assay and ELISA assays on wound healing related-growth factors, cytokines and chemokines. MOL film formulations exhibited no signs of dermal toxicities. In excision wound model, 0.5% film significantly enhanced the wound closure by 77.67 ± 7.28% at day 7 compared to control group. While in abrasion wounds, 0.5% MOL films accelerated wound closure significantly at 81 ± 4.5% as compared to the control. The histology findings and hydroxyproline assay revealed that high collagen deposition and complete re-epithelialisation were observed for the wounds treated with 0.5 and 1% MOL films. All MOL film dressings had successfully tested non-toxic via in vivo safety dermal toxicity. It was concluded that the 0.5% MOL extract-loaded film had proven to be the most promising approach to accelerate diabetic wound healing process in both full-thickness excision and partial thickness abrasion wounds on the HFD/STZ-induced diabetic type II model.
    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology
  15. Yunus R, Ariff AR, Shuaib IL, Jelani AM, Alias NA, Abdullah J, et al.
    PMID: 17121310
    There is very little data regarding the factors related to intima-media thickness (IMT) of the common carotid artery in normal individuals in those with non-insulin diabetes mellitus and perimenopausal women in Southeast Asian countries. Ultrasound imaging evaluating the carotid artery IMT in those with diabetes and those on hormone replacement therapy (HRT) was performed beginning in August 2000 for a period of nearly two years at the Department of Radiology, Hospital Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia. A total of 153 participants were included. Significant differences between the women on HRT and not on HRT were IMT and systolic blood pressure. When comparing those with non-insulin dependent diabetes mellitus (NIDDM) and normal individuals, the significant differences were IMT, total cholesterol level, systolic blood pressure and diastolic blood pressure. IMT was high in those with NIDDM but not in those on HRT. Both those with NIDDM and those on HRT had associated dyslipidemia and systolic hypertension.
    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology*
  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.
    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology
  17. Mustapha S, Mohammed M, Azemi AK, Jatau AI, Shehu A, Mustapha L, et al.
    Molecules, 2021 Jul 19;26(14).
    PMID: 34299638 DOI: 10.3390/molecules26144362
    The endoplasmic reticulum (ER) plays a multifunctional role in lipid biosynthesis, calcium storage, protein folding, and processing. Thus, maintaining ER homeostasis is essential for cellular functions. Several pathophysiological conditions and pharmacological agents are known to disrupt ER homeostasis, thereby, causing ER stress. The cells react to ER stress by initiating an adaptive signaling process called the unfolded protein response (UPR). However, the ER initiates death signaling pathways when ER stress persists. ER stress is linked to several diseases, such as cancer, obesity, and diabetes. Thus, its regulation can provide possible therapeutic targets for these. Current evidence suggests that chronic hyperglycemia and hyperlipidemia linked to type II diabetes disrupt ER homeostasis, thereby, resulting in irreversible UPR activation and cell death. Despite progress in understanding the pathophysiology of the UPR and ER stress, to date, the mechanisms of ER stress in relation to type II diabetes remain unclear. This review provides up-to-date information regarding the UPR, ER stress mechanisms, insulin dysfunction, oxidative stress, and the therapeutic potential of targeting specific ER stress pathways.
    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology
  18. Hammad MA, Syed Sulaiman SA, Alghamdi S, Mangi AA, Aziz NA, Mohamed Noor DA
    Diabetes Metab Syndr, 2020 04 09;14(4):341-346.
    PMID: 32305775 DOI: 10.1016/j.dsx.2020.04.005
    BACKGROUND: Peripheral neuropathy (PN) is a complaint with often unidentified reasons. Some medicines, including statins therapy, are anticipated to be amongst the reasons for PN.

    AIMS: This study intended to assess the association of peripheral neuropathy with statins therapy amongst Type 2 diabetic patients.

    METHODS: At Penang General Hospital, 757 cases were categorized into two groups (564 with statins therapy and 193 without statins therapy). The diagnosis of PN was investigated retrospectively for a period of 10 years (2006-2016). Confounding risk factors as age, diabetes period, hypertension, glycemic control, other co-morbidity, and prescriptions were matched.

    RESULTS: About 129 (22.9%) cases from 564 statins users had PN. Only 30 (15.5%) subjects had PN from 193 statins non-users. Chi-square test showed a significant variance among statins treatment cohort and statin-free cohort in the occurrence of PN (P-value: 0.001). Spearman's investigation presented a positive correlation (r: 0.078, p-value: 0.031) among statins use and PN prevalence. Binary logistic regression was statistically significant for statins therapy as a predictor of peripheral neuropathy incidence (r2: 0.006, p-value: 0.027) amid diabetic patients. The relative risk of peripheral neuropathy connected with statins therapy is (RR: 1.47, 95% CI: 1.02-2.11). The excess relative risk is 47.1%. While the absolute risk (AR) is 7.3% and the number needed to harm (NNH) is 14.

    CONCLUSIONS: The study indicated a positive association between peripheral neuropathy and statins utilization. Peripheral neuropathy was higher amongst statins users than the statins-free group.

    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology
  19. Kuppusamy UR, Indran M, Ahmad T, Wong SW, Tan SY, Mahmood AA
    Clin Chim Acta, 2005 Jan;351(1-2):197-201.
    PMID: 15563890 DOI: 10.1016/j.cccn.2004.09.014
    BACKGROUND: Comparisons of oxidative indices and total antioxidant status between end-stage renal disease (ESRD) patients with or without diabetes is scant, especially in the Asian population.
    METHOD: The assays were carried out according to known established protocols.
    RESULT: The present study showed that ESRD patients with or without non-insulin-dependent diabetes mellitus (NIDDM) did not have any significant differences in antioxidant enzyme activities, advanced glycated end products (AGE), advanced oxidized protein products (AOPP) and ferric reducing ability of plasma (FRAP), indicating that hyperglycemia does not exacerbate oxidative damage in ESRD. The regulation of catalase and glutathione peroxidase is also altered in ESRD. Elevated FRAP was observed in both ESRD groups (with and without NIDDM). The dialysis process did not alter the antioxidant enzyme activities but decreased AGEs and FRAP and increased AOPP levels.
    CONCLUSION: Oxidative stress is present in ESRD but this is not significantly exacerbated by hyperglycemia. The contribution of components in the pathology of renal failure towards oxidative stress exceeds that of hyperglycemia.
    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology*
  20. Aminian A, Vidal J, Salminen P, Still CD, Nor Hanipah Z, Sharma G, et al.
    Diabetes Care, 2020 03;43(3):534-540.
    PMID: 31974105 DOI: 10.2337/dc19-1057
    OBJECTIVE: To characterize the status of cardiometabolic risk factors after late relapse of type 2 diabetes mellitus (T2DM) and to identify factors predicting relapse after initial diabetes remission following bariatric surgery to construct prediction models for clinical practice.

    RESEARCH DESIGN AND METHODS: Outcomes of 736 patients with T2DM who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) at an academic center (2004-2012) and had ≥5 years' glycemic follow-up were assessed. Of 736 patients, 425 (58%) experienced diabetes remission (HbA1c <6.5% [48 mmol/mol] with patients off medications) in the 1st year after surgery. These 425 patients were followed for a median of 8 years (range 5-14) to characterize late relapse of diabetes.

    RESULTS: In 136 (32%) patients who experienced late relapse, a statistically significant improvement in glycemic control, number of diabetes medications including insulin use, blood pressure, and lipid profile was still observed at long-term. Independent baseline predictors of late relapse were preoperative number of diabetes medications, duration of T2DM before surgery, and SG versus RYGB. Furthermore, patients who relapsed lost less weight during the 1st year after surgery and regained more weight afterward. Prediction models were constructed and externally validated.

    CONCLUSIONS: While late relapse of T2DM is a real phenomenon (one-third of our cohort), it should not be considered a failure, as the trajectory of the disease and its related cardiometabolic risk factors is changed favorably after bariatric surgery. Earlier surgical intervention, RYGB (compared with SG) and more weight loss (less late weight regain) are associated with less diabetes relapse in the long-term.

    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology*
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