Electrocardiogram abnormalities and renal impairment in patients with type 2 diabetes mellitus: A healthcare facilities-based cross-sectional study in Dang district of Nepal.

AIMS/INTRODUCTION: The global burden of diabetes mellitus is rising substantially, with a further increase in cardiovascular and kidney disease burden. These public health problems are highly prevalent in low- and middle-income countries, including Nepal. However, there is limited evidence on cardiac and renal conditions among patients with type 2 diabetes mellitus. We determined the status of electrocardiogram (ECG) abnormalities and renal impairment among patients with type 2 diabetes mellitus in Nepal. METHODS: We carried out a cross-sectional study in Tulsipur Sub-Metropolitan City of Nepal using a multistage stratified sampling technique to recruit patients with type 2 diabetes mellitus. We used World Health Organization stepwise approach to surveillance (WHO STEPS) questionnaires and carried out resting ECG to collect data of 345 patients with type 2 diabetes mellitus. Logistic regression analysis assessed the factors associated with ECG abnormalities and renal impairment. RESULTS: The study showed that 6.1% of participants had major ECG abnormalities (95% confidence interval [CI] 3.8-8.6%), which were associated with hypertension (P = 0.01%) and low socioeconomic status (P = 0.01). The proportion of major and/or minor ECG abnormalities was 47.8% (95% CI 40.5-51%), and were significantly associated with age (odds ratio [OR] 1.04, 95% CI 1.01-1.07), higher education (OR 3.50, 95% CI 1.31-9.33), unemployment (OR 3.02, 95% CI 1.08-8.48), body mass index (OR 1.09, 95% CI 1.02-1.17) and duration of type 2 diabetes mellitus >5 years (OR 2.42, 95% CI 1.19-4.93). The proportion of renal impairment was 3.5% (95% CI 1.5-4.5%) which was associated with older age (OR 1.08, 95% CI 1.00-1.17) and hypertension (OR 12.12, 95% CI 1.07-138.22). CONCLUSION: A significant proportion of patients with type 2 diabetes mellitus had ECG abnormalities and renal impairment, which were significantly associated with hypertension. Therefore, hypertension management and early screening are essential to prevent future cardiorenal complications among patients with type 2 diabetes mellitus.

Poor glycemic control, cardiovascular disease risk factors and their clustering among patients with type 2 diabetes mellitus: A cross-sectional study from Nepal.

BACKGROUND: Cardiovascular disease (CVD) is the most common complication of diabetes mellitus (DM). To prevent morbidity and mortality among patients with type 2 diabetes mellitus (T2DM), optimization of glycemic status and minimizing CVD risk factors is essential. As Nepal has limited data on these CVD risk parameters, we assessed the prevalence of poor glycemic control, CVD risk factors, and their clustering among patients with T2DM. METHODS: Using a cross-sectional study design, we collected data of 366 patients with T2DM. We applied a multistage cluster sampling technique and used the WHO STEPS tools. Binary logistic and Poisson regression was applied to calculate odds and prevalence ratio of clustering of risk factors, considering P< 0.05 statistically significant. RESULTS: The mean age of participants was 54.5±10.7 years and 208 (57%) were male. The prevalence of poor glycemic control was 66.4% (95% C.I: 61.5-71.2). The prevalence of smoking, alcohol users, inadequate fruit and vegetables intake and physical inactivity were 18% (95% C.I:14 to 21.9), 14.8% (95% C.I:11.1 to 18.4), 98.1% (95% C.I: 96.7-99.4), and 9.8% (95% C.I:6.7-12.8), respectively. Overall, 47.3% (95% C.I: 42.1-52.4) were overweight and obese, 59% (95% C.I: 52.9-63) were hypertensive, and 68% (95% C.I: 63.2-72.7) had dyslipidemia. Clustering of two, three, four, five and more than five risk factors was 12.6%, 30%, 30%,19%, and 8.7%, respectively. Four or more risk factors clustering was significantly associated with gender, age, level of education, T2DM duration, and use of medication. Risk factors clustering was significantly higher among males and users of anti-diabetic medications with prevalence ratio of 1.14 (95% C.I:1.05-1.23) and 1.09 (95% C.I: 1.09-1.18)], respectively. CONCLUSIONS: The majority of the patients with T2DM had poor glycemic control and CVD risk factors. Policies and programs focused on the prevention and better management of T2DM and CVD risk factors should be implemented to reduce mortality in Nepal.

Assessment of Effect of Different Sterilization Agents on Dimensional Accuracy of Different Impression Materials in Implant Prosthesis - An In vitro Study.

AIM: Sterilization of impression materials is of paramount importance. The present study was conducted to compare the effect of different disinfectants on dimensional accuracy of elastomeric impression materials used for implant prosthesis and other routine treatments. MATERIALS AND METHODS: The present study was conducted with polyvinyl siloxane (PVS) (regular body), PVS (medium body), PVS (heavy body), and polyether (medium body) impression materials. Glutaraldehyde (2%) and sodium hypochlorite (NaOCl, 0.525%) were the disinfectant solutions employed in the study. After 16 h, the specimens were measured under Leica WILD stereomicroscope and dimensions were compared with master die. RESULTS: The dimensional change in the Controls, 2% glutaraldehyde (Group I), and 0.525% NaOCl (Group II) was non significant where as Group III and Group IV showed statistically significant difference (P < 0.05). Results also showed significantly higher tear strength (newton/millimeter) in Control group followed by Group I and Group II. CONCLUSION: PVS (heavy body) was found to be most stable, and polyether was seen to be stable of all the impression materials.

Design, synthesis and docking studies on phenoxy-3-piperazin-1-yl-propan-2-ol derivatives as protein tyrosine phosphatase 1B inhibitors.

A series of substituted phenoxy-3-piperazin-1-yl-propan-2-ols has been synthesized and evaluated for PTP1B inhibitory activity in vitro and for antidiabetic activity in vivo. Two molecules viz. 4a and 5b showed PTP1B inhibition of 31.58% and 35.90% at 100 µM concentration. The compound 4a also showed 40.3% normalization of plasma glucose levels at 100mg/kg in Sugar-loaded model (SLM) and 32% activity in Streptozodocin model (STZ). The docking studies of these molecules revealed that hydrogen bond formation with Arg221 is important for activity.

Synthesis of protein tyrosine phosphatase 1B inhibitors: model validation and docking studies.

The designed and synthesized 2-(4-methoxyphenyl) ethyl] acetamide derivatives (3a, 3b and 3c) were evaluated for their PTP1B inhibitory activity where they showed IC(50) values 69 microM, 87 microM and 71 microM, respectively. These results correlated well with the docking studies and in vivo screening of the compounds for their antidiabetic activity in SLM and STZ models.

3D QSAR studies on protein tyrosine phosphatase 1B inhibitors: comparison of the quality and predictivity among 3D QSAR models obtained from different conformer-based alignments.

A set of 65 flexible peptidomimetic competitive inhibitors (52 in the training set and 13 in the test set) of protein tyrosine phosphatase 1B (PTP1B) has been used to compare the quality and predictive power of 3D quantitative structure-activity relationship (QSAR) comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models for the three most commonly used conformer-based alignments, namely, cocrystallized conformer-based alignment (CCBA), docked conformer-based alignment (DCBA), and global minima energy conformer-based alignment (GMCBA). These three conformers of 5-[(2S)-2-({(2S)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropanoyl}amino)3-oxo-3-pentylamino)propyl]-2-(carboxymethoxy)benzoic acid (compound number 66) were obtained from the X-ray structure of its cocrystallized complex with PTP1B (PDB ID: 1JF7), its docking studies, and its global minima by simulated annealing. Among the 3D QSAR models developed using the above three alignments, the CCBA provided the optimal predictive CoMFA model for the training set with cross-validated r2 (q2)=0.708, non-cross-validated r2=0.902, standard error of estimate (s)=0.165, and F=202.553 and the optimal CoMSIA model with q2=0.440, r2=0.799, s=0.192, and F=117.782. These models also showed the best test set prediction for the 13 compounds with predictive r2 values of 0.706 and 0.683, respectively. Though the QSAR models derived using the other two alignments also produced statistically acceptable models in the order DCBA>GMCBA in terms of the values of q2, r2, and predictive r2, they were inferior to the corresponding models derived using CCBA. Thus, the order of preference for the alignment selection for 3D QSAR model development may be CCBA>DCBA>GMCBA, and the information obtained from the CoMFA and CoMSIA contour maps may be useful in designing specific PTP1B inhibitors.

CoMFA and docking studies on glycogen phosphorylase a inhibitors as antidiabetic agents.

Glycogen phosphorylase (GP(a)) is a specific target for the design of inhibitors and may prevent glycogenolysis under high glucose conditions in type II diabetes. The carboxamides first reported by Hoover D. J. et al. (J. Med. Chem. 1998, 41, 2934-2938) are one of the major classes of GP(a) inhibitors other than glucose derivatives. The recent, X-ray crystallographic analyses (Oikonomakos et al. Biochim. Biophys. Acta 2003, 1647, 325-332) have revealed a distinct mechanism of action for these inhibitors, which bind at a new allosteric site away from the inhibitory and catalytic sites. To elucidate the essential structural and physicochemical requirements responsible for binding to the GP(a) enzyme and to develop predictive models, CoMFA and docking studies have been carried out on a series of indole-2-carboxamide derivates. The CoMFA model developed using pharmacophoric alignments and hydrogen-bonding fields demonstrated high predictive ability against the training (r2 = 0.98, q2 = 0.68) and the test set (r2pred = 0.85). Further the superimposition of PLS coefficient contour maps from CoMFA with the GP(a) active site (PDB: 1lwo) has shown a high level of compatibility.

Pharmacophore identification and 3D-QSAR studies in N-(2-benzoyl phenyl)-L-tyrosines as PPAR gamma agonists.

The identification of pharmacophore and three dimensional quantitative structure-activity studies have been performed on a set of N-(2-Benzoylphenyl)-L-tyrosine for their PPARgamma agonist activity by using the logico-structural based software Apex 3D-which describes the properties and distribution of primary and secondary biophore sites in the three dimensional space. Among several models, two models of comparable probability were selected on the basis of R(2)>0.60, chance 0.20. These models showed a good correlation between the observed and predicted biological activity both for training and test sets.