Impact of Anti-Diabetic Medications on Quality of Life in Persons with Type 2 Diabetes Mellitus.

Introduction: Type 2 diabetes mellitus (T2DM) has been found to be associated with poor quality of life (QOL). The aim of this study was to measure QOL in T2DM patients and examine if the patients' socio demographic, diabetes-related clinical characteristics and insulin usage are associated with better quality of life. Materials and Methods: This clinic based cross-sectional study analyzed data from outpatients with T2DM attending a referral clinic between January and June 2016. Association between Diabetes Attitudes, Wishes and Needs (DAWN) QOL and few demographic, socioeconomic, clinical and biochemical predictors were examined using multivariate logistic regression model. A total of 518 patients completed the interview. Results: The HbA1c level of insulin ± oral anti-diabetic (OAD) cohort was significantly lower (7.89 ± 1.98) than the OAD cohort (8.79 ± 1.96), P < 0.001. Compared to their counterparts in the OAD cohort, patients on insulin were older with longer duration of diabetes mellitus. Co-morbid confounders like obesity, hypoglycemia, and blood pressure control or socio demographic confounders like income, education were almost similar in both the cohorts. The incidence of hypertension, coronary artery disease (CAD) and statin usage was significantly higher in the insulin cohort. The overall composite DAWN QOL scores of the insulin ± OAD cohort (25.42 ± 4.35) was marginally higher than that of the OAD cohort (23.62 ± 5.06) (P = 0.067). Analog insulin users were also found to have significantly higher composite DAWN QOL scores compared to human insulin users (25.77 ± 5.73 vs.24.13 ± 4.88, P = 0.037). Conclusions: The insulin cohort, despite being older and having longer duration of diabetes, had significantly higher diet compliance score, and enhanced QOL owing to better diabetes-related knowledge and treatment adherence characteristics than non-insulin users. Questionnaires-based evaluation of QOL can provide better understanding of the patient's experience of the illness, self-care, psychological and emotional functioning, and choice of therapeutic modality enhancing the quality of care.

Determination of individual type 2 diabetes risk profile in the North East Indian population & its association with anthropometric parameters.

Background & objectives: Diabetes genomics research has illuminated single nucleotide polymorphism (SNP) in several genes including, fat mass and obesity associated (FTO) (rs9939609 and rs9926289), potassium voltage-gated channel subfamily J member 11 (rs5219), SLC30A 8 (rs13266634) and peroxisome proliferator-activated receptor gamma 2 (rs1805192). The present study was conducted to investigate the involvement of these polymorphisms in conferring susceptibility to type 2 diabetes (T2D) in the North East Indian population, and also to establish their association with anthropometric parameters. Methods: DNA was extracted from blood samples of 155 patients with T2D and 100 controls. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing. To confirm the association between the inheritance of SNP and T2D development, logistic regression analysis was performed. Results: For the rs9939609 variant (FTO), the dominant model AA/(AT+TT) revealed significant association with T2D [odds ratio (OR)=2.03, P=0.021], but was non-significant post correction for multiple testing (P=0.002). For the rs13266634 variant (SLC30A 8), there was considerable but non-significant difference in the distribution pattern of genotypic polymorphisms between the patients and the controls (P=0.004). Significant association was observed in case of the recessive model (CC+CT)/TT (OR=4.56 P=0.001), after adjusting for age, gender and body mass index. In addition, a significant association (P=0.001) of low-density lipoprotein (mg/dl) could be established with the FTO (rs9926289) polymorphism assuming dominant model. Interpretation & conclusions: The current study demonstrated a modest but significant effect of SLC30A8 (rs13266634) polymorphisms on T2D predisposition. Considering the burgeoning prevalence of T2D in the Indian population, the contribution of these genetic variants studied, to the ever-increasing number of T2D cases, appears to be relatively low. This study may serve as a foundation for performing future genome-wide association studies (GWAS) involving larger populations.

Effects of Resveratrol and Mangiferin on PPARγ and FALDH Gene Expressions in Adipose Tissue of Streptozotocin-Nicotinamide-Induced Diabetes in Rats.

Type 2 diabetes (T2D) is characterized by insufficient insulin secretion by the pancreatic beta cells and insulin resistance in liver, skeletal muscle, and white adipose tissue. Adipose tissue plays a major role in glucose homeostasis and lipid metabolism. Dietary antioxidants such as resveratrol and mangiferin may offer some protection against the early stage of diabetes mellitus. Therefore, an attempt has been made to investigate the effects of resveratrol and mangiferin on biochemical parameters and molecular mechanism of PPARγ and FALDH gene expression in adipose tissue of streptozotocin- (STZ-) nicotinamide- (NA-) induced diabetic rats. Albino Wister rats were randomly divided into five groups: control rats (Group 1), diabetic control rats (Group 2), diabetic rats given resveratrol (40 mg/kg body weight per day; Group 3), diabetic rats given mangiferin (40 mg/kg body weight per day; Group 4), diabetic rats given glibenclamide (0.6 mg/kg body weight per day; Group 5). Serum biochemical parameters-total cholesterol (TC), total triglyceride (TG), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, glycosylated hemoglobin (HbA1c), urea, and uric acid were analyzed. We found that the oral administration of resveratrol and mangiferin to STZ-NA-induced diabetic rats for 30 days showed the significant protective effect on all the biochemical parameters. A significant reduction in blood glucose and HbA1c levels was observed in rats treated with 40 mg/kg body weight per day of resveratrol or mangiferin. Moreover, both these antioxidants showed significant enhancement of PPARγ and FALDH gene expression in rat adipose tissue compared to control rats.

Comparative analysis of different dietary antioxidants on oxidative stress pathway genes in L6 myotubes under oxidative stress.

Enhanced oxidative stress plays an important role in the progression and onset of diabetes and its complications. Strategies or efforts meant to reduce the oxidative stress are needed which may mitigate these pathogenic processes. The present study aims to investigate the in vitro ameliorative potential of nine antioxidant molecules in L6 myotubes under oxidative stress condition induced by 4-hydroxy-2-nonenal and also to comprehend the gene expression patterns of oxidative stress genes upon the supplementation of different antioxidants in induced stress condition. The study results demonstrated a marked increase in the level of malondialdehyde and protein carbonyl content with a subsequent increase in the free radicals that was reversed by the pretreatment of different dietary antioxidant. From the expression analysis of the oxidative stress genes, it is evident that the expression of these genes is modulated by the presence of antioxidants. The highest expression was found in the cells treated with Insulin in conjugation with an antioxidant. Resveratrol is the most potent modulator followed by Mangiferin, Estragole, and Capsaicin. This comparative analysis ascertains the potency of Resveratrol along with Insulin in scavenging the reactive oxygen species (ROS) generated under induced stress conditions through antioxidant defense mechanism against excessive ROS production, contributing to the prevention of oxidative damage in L6 myotubes.

PfRIO-2 kinase is a potential therapeutic target of antimalarial protein kinase inhibitors.

Protein kinases (PKs) present in Plasmodium falciparum catalyze phosphorylation reaction to control growth and differentiation of the parasite throughout the life cycle. Protein kinase inhibitors are found to kill the parasite but their cellular target enzymes are not known. Protein kinase inhibitors are evaluated in an in sillico docking studies using plasmodium falciparum RIO-2 kinase (right open reading frame-2 protein kinase) as target enzyme. Most of the protein kinase inhibitors showed appropriate docking within the ATP binding domain of the PfRIO-2 kinase. The initial docking experiments were further validated by a substrate competition experiment to validate the preliminary screening results and test the potentials of these inhibitors under in vivo conditions. Docking and substrate competition study identifies wortmannin, enzastaurin, indirubin-3'-monoxime, apigenin, kaempferol and 8-hydroxy-4-methyl-9-nitro-2H-benzo[g]chromen-2-one as lead inhibitors against native/active form of the PfRIO-2 kinase. The top protein kinase inhibitors bind into the ATP binding site with a similar conformation as ATP. The docking result is in good agreement with the antimalarial schizonticidal IC50 (µg/ml) of an inhibitor and gives a correlation factor (R2) of 0.82 whereas top hit antimalarial inhibitors gives a correlation factor (R2) of 0.99. In summary, our work highlights the importance of PfRIO-2 kinase as a target behind the antimalarial action of protein kinase inhibitors and might help to design a new set of antimalarial remedies.