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  1. Fulltext Glucose uptake and lipid metabolism are impaired in epicardial adipose tissue from heart failure patients with or without diabetes
    Burgeiro A, Fuhrmann A, Cherian S, Espinoza D, Jarak I, Carvalho RA, et al.
    Am J Physiol Endocrinol Metab, 2016 Apr 01;310(7):E550-64.
    PMID: 26814014 DOI: 10.1152/ajpendo.00384.2015
    Type 2 diabetes mellitus is a complex metabolic disease, and cardiovascular disease is a leading complication of diabetes. Epicardial adipose tissue surrounding the heart displays biochemical, thermogenic, and cardioprotective properties. However, the metabolic cross-talk between epicardial fat and the myocardium is largely unknown. This study sought to understand epicardial adipose tissue metabolism from heart failure patients with or without diabetes. We aimed to unravel possible differences in glucose and lipid metabolism between human epicardial and subcutaneous adipocytes and elucidate the potential underlying mechanisms involved in heart failure. Insulin-stimulated [(14)C]glucose uptake and isoproterenol-stimulated lipolysis were measured in isolated epicardial and subcutaneous adipocytes. The expression of genes involved in glucose and lipid metabolism was analyzed by reverse transcription-polymerase chain reaction in adipocytes. In addition, epicardial and subcutaneous fatty acid composition was analyzed by high-resolution proton nuclear magnetic resonance spectroscopy. The difference between basal and insulin conditions in glucose uptake was significantly decreased (P= 0.006) in epicardial compared with subcutaneous adipocytes. Moreover, a significant (P< 0.001) decrease in the isoproterenol-stimulated lipolysis was also observed when the two fat depots were compared, and it was strongly correlated with lipolysis, lipid storage, and inflammation-related gene expression. Moreover, the fatty acid composition of these tissues was significantly altered by diabetes. These results emphasize potential metabolic differences between both fat depots in the presence of heart failure and highlight epicardial fat as a possible therapeutic target in situ in the cardiac microenvironment.
    Matched MeSH terms: Diabetes Mellitus, Type 2/metabolism*
  2. Fulltext No effect of NOS inhibition on skeletal muscle glucose uptake during in situ hindlimb contraction in healthy and diabetic Sprague-Dawley rats
    Hong YH, Betik AC, Premilovac D, Dwyer RM, Keske MA, Rattigan S, et al.
    Am J Physiol Regul Integr Comp Physiol, 2015 May 15;308(10):R862-71.
    PMID: 25786487 DOI: 10.1152/ajpregu.00412.2014
    Nitric oxide (NO) has been shown to be involved in skeletal muscle glucose uptake during contraction/exercise, especially in individuals with Type 2 diabetes (T2D). To examine the potential mechanisms, we examined the effect of local NO synthase (NOS) inhibition on muscle glucose uptake and muscle capillary blood flow during contraction in healthy and T2D rats. T2D was induced in Sprague-Dawley rats using a combined high-fat diet (23% fat wt/wt for 4 wk) and low-dose streptozotocin injections (35 mg/kg). Anesthetized animals had one hindlimb stimulated to contract in situ for 30 min (2 Hz, 0.1 ms, 35 V) with the contralateral hindlimb rested. After 10 min, the NOS inhibitor, N(G)-nitro-l-arginine methyl ester (l-NAME; 5 μM) or saline was continuously infused into the femoral artery of the contracting hindlimb until the end of contraction. Surprisingly, there was no increase in skeletal muscle NOS activity during contraction in either group. Local NOS inhibition had no effect on systemic blood pressure or muscle contraction force, but it did cause a significant attenuation of the increase in femoral artery blood flow in control and T2D rats. However, NOS inhibition did not attenuate the increase in muscle capillary recruitment during contraction in these rats. Muscle glucose uptake during contraction was significantly higher in T2D rats compared with controls but, unlike our previous findings in hooded Wistar rats, NOS inhibition had no effect on glucose uptake during contraction. In conclusion, NOS inhibition did not affect muscle glucose uptake during contraction in control or T2D Sprague-Dawley rats, and this may have been because there was no increase in NOS activity during contraction.
    Matched MeSH terms: Diabetes Mellitus, Type 2/metabolism*
  3. Fulltext The role of lycopene for the amelioration of glycaemic status and peripheral antioxidant capacity among the Type II diabetes mellitus patients: a case-control study
    Leh HE, Mohd Sopian M, Abu Bakar MH, Lee LK
    Ann Med, 2021 12;53(1):1059-1065.
    PMID: 34180336 DOI: 10.1080/07853890.2021.1943515
    BACKGROUND: The use of lycopene as a complementary medicine for Type II diabetes mellitus (T2DM) is limited and controversial. This study evaluated the effect of lycopene intake on the changes of glycaemic status and antioxidant capacity among the T2DM patients.

    PATIENTS AND METHODS: This case-control study involved the participation of 87 patients and 122 healthy individuals. Lycopene intake was assessed by using a food frequency questionnaire. The peripheral antioxidant capacity among the T2DM patients was evaluated. Glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) were measured as indications of glycaemic status.

    RESULTS: Peripheral antioxidant capacity was significantly lower in the T2DM group. Direct positive correlations were found between the lycopene intake and peripheral antioxidant level among the T2DM patients. Contrarily, HbA1c and FPG levels decreased significantly with the higher lycopene intake.

    CONCLUSIONS: T2DM patients with a higher lycopene intake showed a greater peripheral antioxidant capacity and better glycaemic control. Lycopene may act to ameliorate oxidative stress and improve the pathophysiology of T2DM.

    Matched MeSH terms: Diabetes Mellitus, Type 2/metabolism*
  4. Fulltext Clinical Determinants of Diabetes Progression in Multiethnic Asians with Type 2 Diabetes - A 3-Year Prospective Cohort Study
    Liu S, Liu JJ, Gurung RL, Chan C, Yeo D, Ang K, et al.
    Ann Acad Med Singap, 2019 Jul;48(7):217-223.
    PMID: 31495867
    INTRODUCTION: The risk for diabetes progression varies greatly in individuals with type 2 diabetes mellitus (T2DM). We aimed to study the clinical determinants of diabetes progression in multiethnic Asians with T2DM.

    MATERIALS AND METHODS: A total of 2057 outpatients with T2DM from a secondary-level Singapore hospital were recruited for the study. Diabetes progression was defined as transition from non-insulin use to requiring sustained insulin treatment or glycated haemoglobin (HbA1c) ≥8.5% when treated with 2 or more oral hypoglycaemic medications. Multivariable logistic regression (LR) was used to study the clinical and biochemical variables that were independently associated with diabetes progression. Forward LR was then used to select variables for a parsimonious model.

    RESULTS: A total of 940 participants with no insulin use or indication for insulin treatment were analysed. In 3.2 ± 0.4 (mean ± SD) years' follow-up, 163 (17%) participants experienced diabetes progression. Multivariable LR revealed that age at T2DM diagnosis (odds ratio [95% confidence interval], 0.96 [0.94-0.98]), Malay ethnicity (1.94 [1.19-3.19]), baseline HbA1c (2.22 [1.80-2.72]), body mass index (0.96 [0.92-1.00]) and number of oral glucose-lowering medications (1.87 [1.39-2.51]) were independently associated with diabetes progression. Area under receiver operating characteristic curve of the parsimonious model selected by forward LR (age at T2DM diagnosis, Malay ethnicity, HbA1c and number of glucose-lowering medication) was 0.76 (95% CI, 0.72-0.80).

    CONCLUSION: Young age at T2DM diagnosis, high baseline HbA1c and Malay ethnicity are independent determinants of diabetes progression in Asians with T2DM. Further mechanistic studies are needed to elucidate the pathophysiology underpinning progressive loss of glycaemic control in patients with T2DM.
    Matched MeSH terms: Diabetes Mellitus, Type 2/metabolism
  5. Fulltext Metabolic control in type 2 diabetes correlates weakly with patient adherence to oral hypoglycaemic treatment
    Loke SC, Jong M
    Ann Acad Med Singap, 2008 Jan;37(1):15-20.
    PMID: 18265892
    INTRODUCTION: Patient adherence to treatment is viewed as essential to good metabolic control in diabetes. Our primary objective was to determine if self-reported patient adherence correlated strongly with metabolic control. Our secondary objective was to determine the natural grouping of factors which influence adherence.

    MATERIALS AND METHODS: Data were collected using a questionnaire set with 5-point Likert scales. Primary analysis was done using Spearman's correlation coefficient between self-reported composite adherence scores and HbA1c. Secondary analysis was done using exploratory factor analysis.

    RESULTS: The primary analysis suggests that patient adherence to the treatment regime is weakly correlated to metabolic control. Calculated Spearman's rho was 0.197, with a two-tailed P value of 0.027. The secondary analysis demonstrates the natural clustering of factors that influence patient adherence to treatment. A 6-factor solution was found to account for most of the variance in the data. We also found that feelings of frustration, anxiety, and depression were associated with a lack of knowledge about diabetes treatment. In addition, belief in traditional medicine correlated strongly with ethnicity.

    CONCLUSION: A good treatment regime for type 2 diabetes mellitus influences metabolic outcome far more than patient adherence.
    Matched MeSH terms: Diabetes Mellitus, Type 2/metabolism*
  6. Bariatric Surgery as a Long-Term Treatment for Type 2 Diabetes/Metabolic Syndrome
    Hanipah ZN, Schauer PR
    Annu Rev Med, 2020 01 27;71:1-15.
    PMID: 31986081 DOI: 10.1146/annurev-med-053117-123246
    Metabolic surgery is increasingly becoming recognized as a more effective treatment for patients with type 2 diabetes (T2D) and obesity as compared to lifestyle modification and medical management alone. Both observational studies and clinical trials have shown metabolic surgery to result in sustained weight loss (20-30%), T2D remission rates ranging from 23% to 60%, and improvement in cardiovascular risk factors such as hypertension and dyslipidemia. Metabolic surgery is cost-effective and relatively safe, with perioperative risks and mortality comparable to low-risk procedures such as cholecystectomy, hysterectomy, and appendectomy. International diabetes and medical organizations have endorsed metabolic surgery as a standard treatment for T2D with obesity.
    Matched MeSH terms: Diabetes Mellitus, Type 2/metabolism
  7. Obesity is a determinant of arterial stiffness independent of traditional risk factors in Asians with young-onset type 2 diabetes
    Liu JJ, Sum CF, Tavintharan S, Yeoh LY, Ng XW, Moh AM, et al.
    Atherosclerosis, 2014 Oct;236(2):286-91.
    PMID: 25112799 DOI: 10.1016/j.atherosclerosis.2014.07.017
    OBJECTIVE: Type 2 diabetes (T2DM) among the young population has become a serious concern globally, presumably due to the rising trend of obesity. Compared to other forms of diabetes, young-onset T2DM experiences more cardiovascular events and other vascular complications although the underlying mechanisms remain largely unknown. Increased arterial stiffness is a hallmark of vasculopathy. We aim to study the clinical and metabolic determinants of arterial stiffness in a cohort of multi-ethnic Asians with young-onset T2DM.
    METHODS: 179 subjects with T2DM onset age below 30 years old were selected in this cross sectional study. Arterial stiffness was assessed by carotid-femoral pulse wave velocity (PWV).
    RESULTS: PWV was correlated with age, duration of diabetes, systolic blood pressure, alanine aminotransferase, urinary albumin-to-creatinine ratio (ACR) and eGFR in bivariate correlation analysis. However, PWV was only significantly correlated with body mass index (BMI), waist circumference, urinary ACR and eGFR after adjustment for age. Overweight individuals with young-onset T2DM had significantly higher PWV levels compared to their lean counterparts (7.3 ± 2.4 m/s vs 6.4 ± 2.3 m/s, p = 0.072 and p < 0.0001 without and with adjustment for age, respectively). Multivariable regression models revealed that age, BMI, eGFR and usage of insulin were independently associated with PWV. These 4 variables explained 35.5% variance in PWV levels.
    CONCLUSION: Age, BMI, renal function and insulin usage are the main determinants of PWV levels in Asians with young-onset T2DM. Notably, obesity is a modifiable determinant of arterial stiffness independent of high blood pressure, dyslipidemia and hyperglycemia in this population.
    Matched MeSH terms: Diabetes Mellitus, Type 2/metabolism
  8. Fulltext Effect of Cosmos caudatus (Ulam raja) supplementation in patients with type 2 diabetes: Study protocol for a randomized controlled trial
    Cheng SH, Ismail A, Anthony J, Ng OC, Hamid AA, Yusof BN
    BMC Complement Altern Med, 2016 Feb 27;16:84.
    PMID: 26920910 DOI: 10.1186/s12906-016-1047-7
    BACKGROUND: Type 2 diabetes mellitus is a major health threat worldwide. Cosmos caudatus is one of the medicinal plants used to treat type 2 diabetes. Therefore, this study aims to determine the effectiveness and safety of C. caudatus in patients with type 2 diabetes. Metabolomic approach will be carried out to compare the metabolite profiles between C. Caudatus treated diabetic patients and diabetic controls.

    METHODS AND DESIGN: This is a single-center, randomized, controlled, two-arm parallel design clinical trial that will be carried out in a tertiary hospital in Malaysia. In this study, 100 patients diagnosed with type 2 diabetes will be enrolled. Diabetic patients who meet the eligibility criteria will be randomly allocated to two groups, which are diabetic C. caudatus treated(U) group and diabetic control (C) group. Primary and secondary outcomes will be measured at baseline, 4, 8, and 12 weeks. The serum and urine metabolome of both groups will be examined using proton NMR spectroscopy.

    DISCUSSION: The study will be the first randomized controlled trial to assess whether C. caudatus can confer beneficial effect in patients with type 2 diabetes. The results of this trial will provide clinical evidence on the effectiveness and safety of C. caudatus in patients with type 2 diabetes.

    TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02322268.

    Matched MeSH terms: Diabetes Mellitus, Type 2/metabolism
  9. Fulltext Expression profiling of genes related to endothelial cells biology in patients with type 2 diabetes and patients with prediabetes
    Moradipoor S, Ismail P, Etemad A, Wan Sulaiman WA, Ahmadloo S
    Biomed Res Int, 2016;2016:1845638.
    PMID: 27781209 DOI: 10.1155/2016/1845638
    Endothelial dysfunction appears to be an early sign indicating vascular damage and predicts the progression of atherosclerosis and cardiovascular disorders. Extensive clinical and experimental evidence suggests that endothelial dysfunction occurs in Type 2 Diabetes Mellitus (T2DM) and prediabetes patients. This study was carried out with an aim to appraise the expression levels in the peripheral blood of 84 genes related to endothelial cells biology in patients with diagnosed T2DM or prediabetes, trying to identify new genes whose expression might be changed under these pathological conditions. The study covered a total of 45 participants. The participants were divided into three groups: group 1, patients with T2DM; group 2, patients with prediabetes; group 3, control group. The gene expression analysis was performed using the Endothelial Cell Biology RT(2) Profiler PCR Array. In the case of T2DM, 59 genes were found to be upregulated, and four genes were observed to be downregulated. In prediabetes patients, increased expression was observed for 49 genes, with two downregulated genes observed. Our results indicate that diabetic and prediabetic conditions change the expression levels of genes related to endothelial cells biology and, consequently, may increase the risk for occurrence of endothelial dysfunction.
    Matched MeSH terms: Diabetes Mellitus, Type 2/metabolism*
  10. Brown/Beige adipose tissues and the emerging role of their secretory factors in improving metabolic health: The batokines
    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/metabolism*
  11. Homology modeling and molecular docking studies on Type II diabetes complications reduced PPARγ receptor with various ligand molecules
    Prabhu S, Vijayakumar S, Manogar P, Maniam GP, Govindan N
    Biomed Pharmacother, 2017 Aug;92:528-535.
    PMID: 28575810 DOI: 10.1016/j.biopha.2017.05.077
    Peroxisome proliferator-activated receptor gamma (PPARγ), a type II nuclear receptor present in adipose tissue, colon and macrophages. It reduces the hyperglycemia associated metabolic syndromes. Particularly, type II diabetes-related cardiovascular system risk in human beings. The fatty acid storage and glucose metabolism are regulated by PPARγ activation in human body. According to recent reports commercially available PPARγ activating drugs have been causing severe side effects. At the same time, natural products have been proved to be a promising area of drug discovery. Recently, many studies have been attempted to screen and identify a potential drug candidate to activate PPARγ. Hence, in this study we have selected some of the bio-active molecules from traditional medicinal plants. Molecular docking studies have been carried out against the target, PPARγ. We Results suggested that Punigluconin has a efficient docking score and it is found to have good binding affinities than other ligands. Hence, we concluded that Punigluconin is a better drug candidate for activation of PPARγ gene expression. Further studies are necessary to confirm their efficacy and possibly it can develop as a potential drug in future.
    Matched MeSH terms: Diabetes Mellitus, Type 2/metabolism*
  12. Fulltext Polyphenol-rich ethyl acetate fraction isolated from Molineria latifolia ameliorates insulin resistance in experimental diabetic rats via IRS1/AKT activation
    Ooi J, Adamu HA, Imam MU, Ithnin H, Ismail M
    Biomed Pharmacother, 2018 Feb;98:125-133.
    PMID: 29248832 DOI: 10.1016/j.biopha.2017.12.002
    This study aimed to evaluate the effect of ethyl acetate fraction (EAF) isolated from Molineria latifolia rhizome as dietary interventions for type 2 diabetes mellitus (T2DM) and its underlying molecular mechanisms in vivo. Experimental rats were induced by high fat diet feeding coupled with combined exposure to streptozotocin and nicotinamide. Treatment with EAF improved glucose tolerance and lipid profiles, but the insulin secretion was unaltered. Gene expression analyses on insulin/adipocytokine signalling-related genes demonstrated tissue-specific transcriptional responses. In skeletal muscle and liver tissues, Socs1, Tnf and Mapk8 showed consistent transcript regulation. Furthermore, hepatic translational analyses revealed sensitization on proximal insulin signalling, with reduced expression of IRS1 serine phosphorylation, increased IRS1 tyrosine phosphorylation and increased phospho-AKT (Ser473). The present findings suggested that EAF exerted its effect by modulating insulin signalling, potentially via IRS1/AKT activation. The pharmacological attributes of EAF may implicate its potential therapeutic applications for diabetes management.
    Matched MeSH terms: Diabetes Mellitus, Type 2/metabolism
  13. Synthesis, α-glucosidase inhibitory activity and in silico study of tris-indole hybrid scaffold with oxadiazole ring: As potential leads for the management of type-II diabetes mellitus
    Taha M, Rahim F, Imran S, Ismail NH, Ullah H, Selvaraj M, et al.
    Bioorg Chem, 2017 10;74:30-40.
    PMID: 28750203 DOI: 10.1016/j.bioorg.2017.07.009
    Discovery of α-glucosidase inhibitors has been actively pursued with the aim to develop therapeutics for the treatment of type-II diabetes mellitus and the other carbohydrate mediated disease. In continuation of our drug discovery research on potential antidiabetic agents, we synthesized novel tris-indole-oxadiazole hybrid analogs (1-21), structurally characterized by various spectroscopic techniques such as 1H NMR, EI-MS, and 13C NMR. Elemental analysis was found in agreement with the calculated values. All compounds were evaluated for α-glucosidase inhibiting potential and showed potent inhibitory activity in the range of IC50=2.00±0.01-292.40±3.16μM as compared to standard acarbose (IC50=895.09±2.04µM). The pharmacokinetic predictions of tris-indole series using descriptor properties showed that almost all compounds in this series indicate the drug aptness. Detailed binding mode analyses with docking simulation was also carried out which showed that the inhibitors can be stabilized by the formation of hydrogen bonds with catalytic residues and the establishment of hydrophobic contacts at the opposite side of the active site.
    Matched MeSH terms: Diabetes Mellitus, Type 2/metabolism
  14. The effects of high-fat diet and metformin on urinary metabolites in diabetes and prediabetes rat models
    Lee YF, Sim XY, Teh YH, Ismail MN, Greimel P, Murugaiyah V, et al.
    Biotechnol Appl Biochem, 2021 Oct;68(5):1014-1026.
    PMID: 32931602 DOI: 10.1002/bab.2021
    High-fat diet (HFD) interferes with the dietary plan of patients with type 2 diabetes mellitus (T2DM). However, many diabetes patients consume food with higher fat content for a better taste bud experience. In this study, we examined the effect of HFD on rats at the early onset of diabetes and prediabetes by supplementing their feed with palm olein oil to provide a fat content representing 39% of total calorie intake. Urinary profile generated from liquid chromatography-mass spectrometry analysis was used to construct the orthogonal partial least squares discriminant analysis (OPLS-DA) score plots. The data provide insights into the physiological state of an organism. Healthy rats fed with normal chow (NC) and HFD cannot be distinguished by their urinary metabolite profiles, whereas diabetic and prediabetic rats showed a clear separation in OPLS-DA profile between the two diets, indicating a change in their physiological state. Metformin treatment altered the metabolomics profiles of diabetic rats and lowered their blood sugar levels. For prediabetic rats, metformin treatment on both NC- and HFD-fed rats not only reduced their blood sugar levels to normal but also altered the urinary metabolite profile to be more like healthy rats. The use of metformin is therefore beneficial at the prediabetes stage.
    Matched MeSH terms: Diabetes Mellitus, Type 2/metabolism*
  15. Fulltext Boldine improves endothelial function in diabetic db/db mice through inhibition of angiotensin II-mediated BMP4-oxidative stress cascade
    Lau YS, Tian XY, Mustafa MR, Murugan D, Liu J, Zhang Y, et al.
    Br J Pharmacol, 2013 Nov;170(6):1190-8.
    PMID: 23992296 DOI: 10.1111/bph.12350
    Boldine is a potent natural antioxidant present in the leaves and bark of the Chilean boldo tree. Here we assessed the protective effects of boldine on endothelium in a range of models of diabetes, ex vivo and in vitro.
    Matched MeSH terms: Diabetes Mellitus, Type 2/metabolism*
  16. Interlink Between Insulin Resistance and Neurodegeneration with an Update on Current Therapeutic Approaches
    Bhattamisra SK, Shin LY, Saad HIBM, Rao V, Candasamy M, Pandey M, et al.
    CNS Neurol Disord Drug Targets, 2020;19(3):174-183.
    PMID: 32418534 DOI: 10.2174/1871527319666200518102130
    The interlink between diabetes mellitus and neurodegenerative diseases such as Alzheimer's Disease (AD) and Parkinson's Disease (PD) has been identified by several researchers. Patients with Type-2 Diabetes Mellitus (T2DM) are found to be affected with cognitive impairments leading to learning and memory deficit, while patients with Type-1 Diabetes Mellitus (T1DM) showed less severe levels of these impairments in the brain. This review aimed to discuss the connection between insulin with the pathophysiology of neurodegenerative diseases (AD and PD) and the current therapeutic approached mediated through insulin for management of neurodegenerative diseases. An extensive literature search was conducted using keywords "insulin"; "insulin resistance"; "Alzheimer's disease"; "Parkinson's disease" in public domains of Google scholar, PubMed, and ScienceDirect. Selected articles were used to construct this review. Studies have shown that impaired insulin signaling contributes to the accumulation of amyloid-β, neurofibrillary tangles, tau proteins and α-synuclein in the brain. Whereas, improvement in insulin signaling slows down the progression of cognitive decline. Various therapeutic approaches for altering the insulin function in the brain have been researched. Besides intranasal insulin, other therapeutics like PPAR-γ agonists, neurotrophins, stem cell therapy and insulin-like growth factor-1 are under investigation. Research has shown that insulin insensitivity in T2DM leads to neurodegeneration through mechanisms involving a variety of extracellular, membrane receptor, and intracellular signaling pathway disruptions. Some therapeutics, such as intranasal administration of insulin and neuroactive substances have shown promise but face problems related to genetic background, accessibility to the brain, and invasiveness of the procedures.
    Matched MeSH terms: Diabetes Mellitus, Type 2/metabolism
  17. Emerging Role of Adipocytokines in Type 2 Diabetes as Mediators of Insulin Resistance and Cardiovascular Disease
    Jaganathan R, Ravindran R, Dhanasekaran S
    Can J Diabetes, 2018 Aug;42(4):446-456.e1.
    PMID: 29229313 DOI: 10.1016/j.jcjd.2017.10.040
    Adipose tissue is an enormously active endocrine organ, secreting various hormones, such as adiponectin, leptin, resistin and visfatin, together with classical cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). All these adipocytokines play significant roles in the regulation of energy metabolism, glucose and lipid metabolism, reproduction, cardiovascular function and immunity. Adipocytokines are significantly regulated by nutritional status and can directly influence other organ systems, including brain, liver and skeletal muscle. Adiponectin plays a key role as an anti-inflammatory hormone. Upregulated expression of resistin, vaspin, apelin and TNF-α plays a significant role in induction of insulin resistance linked with obesity and type 2 diabetes. Ghrelin, the circulating peptide, has been found to stimulate appetite and regulate energy balance. Thus, it can be considered 1 of the candidate genes for obesity and type 2 diabetes. Omentin is a novel adipokine produced by visceral adipose tissue. Circulating levels of omentin are decreased in insulin-resistant states, for example, in obesity and diabetes. IL-6 plays a vital role in regulating the accumulation of lipids intramyocardially. Based on the biologic relevance of these adipocytokines, they can no longer be considered as energy storage sites alone but must also be considered in metabolic control. Hence, the present review summarizes the regulatory roles of adipocytokines in diabetes linked with obesity.
    Matched MeSH terms: Diabetes Mellitus, Type 2/metabolism*
  18. Fulltext High proportion of adults with type 2 diabetes and poor glycated hemoglobin perceived that their diabetes control was excellent
    Shahar MA, Omar AM, Loh HH
    Can J Diabetes, 2019 Mar;43(2):98-104.e7.
    PMID: 30145243 DOI: 10.1016/j.jcjd.2018.06.003
    OBJECTIVES: As is true for other chronic illnesses, perception of disease control is pivotal to patient empowerment in diabetes care. This study aimed to describe the perception of diabetes control by patients with poor glycated hemoglobin (A1C) levels so as to explore the relationship between perception and various sociodemographic and disease characteristics and to measure the patients' knowledge, attitudes and practices in diabetes care.
    METHODS: A cross-sectional study was made involving 276 patients with type 2 diabetes mellitus. After obtaining informed consent, their sociodemographics, medical histories and most recent available blood investigations were documented. Patients were asked about their perceptions of diabetes control-whether it was excellent, moderate or poor. A Malay-language knowledge, attitudes and practice questionnaire was administered to respondents. Analyses were descriptive and exploratory.
    RESULTS: The median age of the subjects and the durations of diabetes were 56 (interquartile range, 48-62) years and 8 (interquartile range, 4-13) years, respectively. The median A1C level was 9.5% (interquartile range, 8.3%-11.4%). Despite having poor A1C levels, 28.4% of patients perceived that their diabetes control was excellent; 58.9% perceived it as moderate, and only 12.7% accurately perceived it as poor. A significant number of those with higher education had wrong perceptions, indicating that other factors, such as effective communication, need to be considered. The absence of an association between perception and duration of diabetes suggests that information given over the years did not contribute to patients' understanding of disease control. Younger patients had better knowledge scores. Those with higher education levels had higher quartiles of knowledge and attitude but not practice scores.
    CONCLUSIONS: This study demonstrated discordance between perceived diabetes control and actual A1C levels, which may hinder effective diabetes care.
    Study site: a tertiary referral center and a primary care centre in Kuantan, Pahang, Malaysia
    Matched MeSH terms: Diabetes Mellitus, Type 2/metabolism
  19. Vitamin D status and oxidative stress in diabetes mellitus
    Lee WC, Mokhtar SS, Munisamy S, Yahaya S, Rasool AHG
    Cell Mol Biol (Noisy-le-grand), 2018 May 30;64(7):60-69.
    PMID: 29974854
    Diabetes mellitus is an epidemic that is gaining global concern. Chronic hyperglycemia in diabetes induces the excess production of free radicals. The deleterious effects of excess free radicals are encountered by endogenous antioxidant defense system. Imbalance between free radicals production and antioxidants defense mechanisms leads to a condition known as "oxidative stress". Diabetes mellitus is associated with augmented oxidative stress that induced micro- and macrovascular complications, which presents a significant risk for cardiovascular events. Low vitamin D levels in the body have also been reported to be associated with the pathogenesis of diabetes and enhanced oxidative stress. The article is to review available literature and summarize the relationship between oxidative stress and vitamin D levels in diabetes. We also review the effects of vitamin D analogs supplementation in improving oxidative stress in diabetics.
    Matched MeSH terms: Diabetes Mellitus, Type 2/metabolism*
  20. Evaluation of metabolic and immunological changes in streptozotocin-nicotinamide induced diabetic rats
    Mojani MS, Sarmadi VH, Vellasamy S, Sandrasaigaran P, Rahmat A, Peng LS, et al.
    Cell Immunol, 2014 May-Jun;289(1-2):145-9.
    PMID: 24791700 DOI: 10.1016/j.cellimm.2014.04.004
    Type 2 diabetes is a chronic disease with growing public health concern globally. Finding remedies to assist this health issue requires recruiting appropriate animal model for experimental studies. This study was designated to evaluate metabolic and immunologic changes in streptozotocin-nicotinamide induced diabetic rats as a model of type 2 diabetes. Male rats were induced diabetes using nicotinamide (110 mg/kg) and streptozotocin (65 mg/kg). Following 42 days, biochemical and immunological tests showed that diabetic rats had higher levels of blood glucose, WBC, certain abnormalities in lipid profile and insufficient mitogenic responses of lymphocytes (p<0.05). However, the status of the total antioxidant, inflammatory biomarkers and other parameters of full blood count (except HCT) were not significantly altered. Phenotyping assay indicated insignificant lymphocyte subtype imbalances excluding a significant rise in the level of CD4+CD25+ marker (p<0.05). This model of diabetic animals may represent some but not all symptoms of human type 2 diabetes.
    Matched MeSH terms: Diabetes Mellitus, Type 2/metabolism*
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