METHODS: The fruit powder was macerated using methanol and then partitioned by hexane, ethyl acetate, n-butanol, and water. The fractions were chromatographed on the column chromatography and incorporated with TLC and recrystallization to give pure compounds. The structures of isolated compounds were determined by UV-Visible, FT-IR, MS, proton (1H-NMR), carbon (13C-NMR), and 2D-NMR techniques encompassing HMQC and HMBC spectra. The compounds were evaluated for their ACE inhibitory activity, and the strongest compound was determined by the kinetics enzyme inhibition.
RESULTS: Based on the spectral data, the isolated compounds were determined as 6,4-dihydroxy-4-methoxybenzophenone-2-O-β-D-glucopyranoside (1), 4,4'-dihydroxy-6-methoxybenzophenone-2-O-β-D-glucopyranoside (2) and mangiferin (3). IC50 values of the isolated compounds 1, 2 and 3 were 0.055, 0.07, and 0.025 mM, respectively.
CONCLUSION: The three compounds have ACE inhibitor and mangiferin demonstrated the best ACE inhibitory activity with competitive inhibition on ACE with the type of inhibition kinetics is competitive inhibition.
METHODS: The study involved 235 Malaysian subjects who were randomly selected (66 normal weight subjects, 97 overweight, 59 obese subjects, and 13 subjects who were underweight). Serum sDPP4 and active GLP-1 levels were examined by enzyme-linked immunosorbent assay (ELISA). Also, body mass index kg/m(2) (BMI), lipid profiles, insulin and glucose levels were evaluated. Insulin resistance (IR) was estimated via the homeostasis model assessment for insulin resistance (HOMA-IR).
RESULTS: Serum sDPP4 levels were significantly higher in obese subjects compared to normal weight subjects (p=0.034), whereas serum levels of active GLP-1 were lower (p=0.021). In obese subjects, sDPP4 levels correlated negatively with active GLP-1 levels (r(2)=-0.326, p=0.015). Furthermore, linear regression showed that sDPP4 levels were positively associated with insulin resistance (B=82.28, p=0.023) in obese subjects.
CONCLUSION: Elevated serum sDPP4 levels and reduced GLP-1 levels were observed in obese subjects. In addition, sDPP4 levels correlated negatively with active GLP-1 levels but was positively associated with insulin resistance. This finding provides evidence that sDPP4 and GLP-1 may play an important role in the pathogenesis of obesity, suggesting that sDPP4 may be valuable as an early marker for the augmented risk of obesity and insulin resistance.
OBJECTIVE: This study aims to review the use of antidepressants for physical and psychological symptoms in cancer patients.
RESULTS: Our findings showed the mixed result of positive and negative findings in various symptoms associated with cancer patients. These studies are categorised according to the hierarchy of evidence from high to low level, namely randomised controlled trials, cohort studies, case-control studies, case series, case reports, as well as other type of publications. The majority of antidepressants used in cancer patients seem to be beneficial for the treatment of depression, anxiety, hot flashes and other symptoms such as sexual dysfunction, fatigue, nicotine dependence, vasomotor symptoms, executive functions, sleep problems, pruritus, as well as for hypochondriasis. While fluoxetine was found to be associated with the reduction of antiemetic property in ondansetron, mirtazapine was identified to be a good alternative in treating nausea and cachexia among cancer patients.
CONCLUSION: More research studies with adequate statistical power are warranted to validate the use of antidepressants among cancer patients in treating these physical and psychological symptoms.
AIM: The aim of this paper was to review the role of CMKLR-1 receptor and the potential therapeutic target in the management of chemerin induced type 2 diabetes mellitus and cancer.
PATHOPHYSIOLOGY: Increased chemerin secretion activates an inflammatory response. The inflammatory response will increase the oxidative stress in adipose tissue and consequently results in an insulin-resistant state. The occurrence of inflammation, oxidative stress and insulin resistance leads to the progression of cancers.
CONCLUSION: Chemerin is one of the markers that may involve in development of both cancer and insulin resistance. Chemokine like receptor- 1 (CMKLR-1) receptor that regulates chemerin levels exhibits a potential therapeutic target for insulin resistance, type 2 diabetes and cancer treatment.
PATIENTS AND METHODS: A prospective observational cohort study was conducted on 86 patients with T2DM who had been receiving metformin monotherapy for <1 year. Patients showing ≥0.5% reduction in HbA1c levels from baseline within 3 months and remained low for at least another 3 months were defined as responders while those patients with <0.5% reduction in HbA1c levels and/or those whom started a new class of glucose-lowering drug(s) because of unsatisfactory reduction were defined as non-responders. In addition, good glycemic control was observed when HbA1c ≤7.0%, and the above values were regarded as poor. Genotyping of rs72552763 SNP was performed using TaqMan® Drug Metabolism Enzyme Genotyping Assay and its association with metformin response and glycemic control were assessed by measuring the change in HbA1c and fasting blood glucose levels using Chi-square, logistic regression and Mann-Whitney U-test. Statistical significance was set at p <0.05.
RESULTS: The minor allele frequency of the rs72552763 SNP of SLC22A1 was 9.3%. Metformin response was significantly higher in deletion_GAT (del_G) genotypes as compared to the wild-type GAT_GAT (G_G) genotypes. Furthermore, a significantly lower median treatment HbA1 level was found in del_G genotypes as compared to G_G genotypes. However, the association of rs72552763 with metformin response was not replicated at the allele level. In contrast, the minor del_allele was significantly associated with good glycemic control compared to the G_allele, though not replicated at del_G genotypes level.
CONCLUSION: This study demonstrated that metformin response was significantly higher in study participants with a heterozygous carrier of M420del variants of SLC22A1 as compared to the wild-type G_G genotypes after 3 months of treatment.
METHODS: A total of 220 T2DM patients from the University of Malaya Medical Centre, Malaysia, who had at least one CV complication and who had been taking at least one antidiabetic drug for at least 3 months, were included. The associations of antidiabetics, cardiovascular diseases, laboratory parameters, concurrent medications, comorbidities, demographics, and clinical characteristics with glycemic control were investigated.
RESULTS: Sulfonylureas in combination (P=0.002) and sulfonylurea monotherapy (P<0.001) were found to be associated with good glycemic control, whereas insulin in combination (P=0.051), and combination biguanides and insulin therapy (P=0.012) were found to be associated with poor glycemic control. Stroke (P=0.044) was the only type of CVD that seemed to be significantly associated with good glycemic control. Other factors such as benign prostatic hyperplasia (P=0.026), elderly patients (P=0.018), low-density lipoprotein cholesterol levels (P=0.021), and fasting plasma glucose (P<0.001) were found to be significantly correlated with good glycemic control.
CONCLUSION: Individualized treatment in T2DM patients with CVDs can be supported through a better understanding of the association between glycemic control and CV profiles in T2DM patients.
PURPOSE: This study aimed to identify antidiabetic regimens as well as other factors that associated with glycemic control in T2DM patients with different stages of chronic kidney disease (CKD).
PATIENTS AND METHODS: This retrospective, cross-sectional study involved 242 T2DM inpatients and outpatients with renal complications from January 2009 to March 2014 and was conducted in a tertiary teaching hospital in Malaysia. Glycated hemoglobin (A1C) was used as main parameter to assess patients' glycemic status. Patients were classified to have good (A1C <7%) or poor glycemic control (A1C ≥7%) based on the recommendations of the American Diabetes Association.
RESULTS: Majority of the patients presented with CKD stage 4 (43.4%). Approximately 55.4% of patients were categorized to have poor glycemic control. Insulin (57.9%) was the most commonly prescribed antidiabetic medication, followed by sulfonylureas (43%). Of all antidiabetic regimens, sulfonylureas monotherapy (P<0.001), insulin therapy (P=0.005), and combination of biguanides with insulin (P=0.038) were found to be significantly associated with glycemic control. Other factors including duration of T2DM (P=0.004), comorbidities such as anemia (P=0.024) and retinopathy (P=0.033), concurrent medications such as erythropoietin therapy (P=0.047), α-blockers (P=0.033), and antigouts (P=0.003) were also correlated with A1C.
CONCLUSION: Identification of factors that are associated with glycemic control is important to help in optimization of glucose control in T2DM patients with renal complication.
OBJECTIVE: This study sought to identify demographic, clinical, and genetic factors that may contribute to increased insulin resistance or worsening of glycaemic control in patients with T2DM.
SETTING: This prospective cohort study included 156 patients with T2DM and severe or acute hyperglycaemia who were treated with insulin at any medical ward of the National University of Malaysia Medical Centre.
METHOD: Insulin resistance was determined using the homeostatic model assessment-insulin resistance index. Glycaemic control during the episode of hyperglycaemia was assessed as the degree to which the patient achieved the target glucose levels. The polymerase chain reaction-restriction fragment length polymorphism method was used to identify polymorphisms in insulin receptor substrate (IRS) genes.
MAIN OUTCOME MEASURE: Identification of possible predictors (demographic, clinical, or genetic) for insulin resistance and glycaemic control during severe/acute hyperglycaemia.
RESULTS: A polymorphism in IRS1, r.2963 G>A (p.Gly972Arg), was a significant predictor of both insulin resistance [odds ratios (OR) 4.48; 95 % confidence interval (CI) 1.2-16.7; P = 0.03) and worsening of glycaemic control (OR 6.04; 95 % CI 0.6-64.6; P = 0.02). The use of loop diuretics (P < 0.05) and antibiotics (P < 0.05) may indirectly predict worsening of insulin resistance or glycaemic control in patients with severe/acute hyperglycaemia.
CONCLUSION: Clinical and genetic factors contribute to worsening of insulin resistance and glycaemic control during severe/acute hyperglycaemia in patients with T2DM. Early identification of factors that may influence insulin resistance and glycaemic control may help to achieve optimal glycaemic control during severe/acute hyperglycaemia.
METHODS: The study encompassed a comprehensive three-stage approach to the development and validation of the PROM. Initially, during the preliminary design stage, the necessity for a new PROM was recognized, an expert panel was formed, and semi-structured qualitative interviews were carried out with GSM patients. In the second stage, the study used the five-step pre-validation methodology established by Prior et al. to generate and refine the PROM items. The third and final stage encompassed the determination of scale and item content validity indexes to ensure validity. Additionally, the reliability of each construct was evaluated using Cronbach's α.
RESULTS: The resulting PROM was named GSM-SVTAQ (GSM-symptoms and vaginal treatments acceptability questionnaire). It demonstrated excellent validity in assessing symptoms burden, health-related and sexual quality of life, and vaginal treatment acceptability, with high content validity indices and strong internal consistency. The scale content validity indices and Cronbach's α coefficients for the three domains were (0.926, 0.939), (0.875, 0.947), and (0.824, 0.855), respectively.
CONCLUSION: The GSM-SVTAQ stands as the first GSM-specific, valid, and reliable PROM capable of comprehensively measuring the three components of GSM and the acceptability of vaginal treatments. Its implementation has the potential to significantly enhance patient care and outcomes in GSM management.