Comparison of gliclazide vs linagliptin on hypoglycemia and cardiovascular events in type 2 diabetes mellitus: A systematic review

BACKGROUND Cardiovascular outcome trials have demonstrated cardiovascular safety of glimepiride(a sulfonylureas) against dipeptidyl peptidase-4 inhibitor linagliptin.Gliclazide(another newer sulfonylureas) has shown similar glycemic efficacy and 50% decreased risk of hypoglycemia compared to glimepiride.AIM Considering the absence of cardiovascular outcome trials for gliclazide, we decided to conduct a systematic review of the literature to assess the cardiovascular(CV) safety by assessing the risk for major adverse CV events and hypoglycemia risk of gliclazide vs linagliptin in patients with type 2 diabetes(T2D).METHODS This systematic review followed the current Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to analyze all the clinical studies published from 2008 that compared the two drugs in patients with T2D with no risk of CV disease(CVD). We included only evidence designated high quality by the Oxford Center for Evidence-based Medicine-Levels of Evidence.RESULTS Eight clinical studies were included in the narrative descriptive analysis(gliclazide: 5 and linagliptin: 3). The CV safety of gliclazide in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation trial and of linagliptin in the Cardiovascular and Renal Microvascular Outcome Study With Linagliptin(CARMELINA) and CARdiovascular Outcome study of LINAgliptin vs glimepiride in patients with T2D(CAROLINA)trials were excluded from the comparative analysis as these trials demonstrated CV and hypoglycemia benefits in patients at high risk of CVD. However, since these are landmark trials,they were discussed in brief to show the CV benefits and low hypoglycemia risk of gliclazide and linagliptin. We did not find any study comparing gliclazide with linagliptin. Hence, direct comparison of their major adverse CV events and hypoglycemia risk could not be carried out.However, the literature meeting the inclusion criteria showed that both drugs were effective in achieving the desired glycemic control and had low major adverse CV events and hypoglycemia risk in adult patients with no history of CVD.CONCLUSION Gliclazide can be considered an effective and safe glucose-lowering drug in T2D patients with no established CVD but at high risk of CVD due to their T2D status. Future randomized controlled trials comparing gliclazide with linagliptin or dipeptidyl peptidase-4 inhibitors can confirm these findings.

A comprehensive evaluation of brain derived neurotropic growth factor gene on Bharatnatyam dancers

Research significance:Dance symbolizes rhythmic body movements to music intending expression of an idea or emotion that delights the performer.Bharatanatyam,an imperative form of Indian Classical dance,has therapeutic implications including enhancement of cognitive function.Neurotrophins belonging to the nerve growth factor family essentially regulate neuronal growth,development and maintenance.The Brain-Derived Neurotrophic Factor(BDNF)is a member of this family.Long-term memory and learning are vitally influenced by BDNF.In Bharatanatyam,new movements are learntand they are practiced until perfection.Every newly learntmovement initially stays in short-term memory and with practice,it reaches the long-term memory.And thus,a favorableincrease in plasma BDNF levels can be associated with Bharatanatyam.In the BDNF gene,rs6265 is a common single nucleotide polymorphism,which results in a valine(Val)being substituted with methionine(Met)in the prodomainat codon 66(Val66Met).This genetic variation affects the BDNF protein’s activity-dependent release.Research methods:With an intention to delve into the link between BDNF gene variants and Bharatanatyam,we conducted an observational research study on 93 participants with their due consent.The study group included 45 dancers and 48 non-dancers.Results anddiscussion:Genotype suggesting optimal BDNF production was proportionately higher in dancers(40%)than non-dancers.Many of the dancers with optimal BDNF genotype expressed a feeling of happiness as their mental status after one hour of dancing and also took up other exercises(like skating/badminton/basketball player etc)as well.While amongst dancers with sub-optimal BDNF genotype,most of them did not take up any other exercise(like skating/badminton/basketball player etc)andalso expressed a blank feeling as their mental status after one hour of dancing.Thus,BDNF has an evident role in the formation of new learning and memory.

The establishment of pancreatic islet isolation in India-an update on human pancreatic islet transplantation

Background:Diabetes is a widespread disease with increasing prevalence.Transplantation of islets of Langerhans is a viable treatment for a selected group of patients with repeated hypoglycemic episodes in type 1 diabetes.The countries where islet transplantation has not been explored suffer from insufficient knowledge concerning key elements of the isolation process.Donor and organ procurement parameters impact human islet yield,although for research purposes,islet yield may be secondary in importance to islet function.This paper will analyze the feasibility of research-only human islet isolation and signify parameters underlying a successful yield in the Indian population.This eventually can make islet transplantation a clinical reality in India.Method:After receiving the consent for procuring brain-dead pancreas from the first-degree of relatives,samples were collected and transported in a transportation buffer at 4℃.The procedure consists of a mechanically enhanced enzymatic digestion of the pancreas,after which it was taken for purification using Ficoll method,followed by islet quality testing.Results:Through 15 isolations done over a span of approximately 2 years during the COVID pandemic in India,we confirm that ischemic time and glycated hemoglobin,each have a negative impact on isolation purity and yield.Notably,extending cold ischemic tim beyond the typical clinical isolation cutoff of 12 hours(to≥18 h)had a huge impact on islet function and yield.Age had a negative correlation with islet yield;however other biological parameters(specifically body mass index)and isolation variables appear to make a significant contribution to the heterogeneity of human islet yield.Our current work demonstrates the feasibility of extending acceptable cold ischemic time for research-focused human islet isolation and highlights the biological variation in isolation of human islets from donors with and without diabetes.Conclusion:India requires establishment of an islet transplant program using the current standard methods of“islet isolation”and donor program and process.Research should focus on improving standards in the islet preparation process to increase the number of successful preparations,shorten the isolation time,and increase patient safety so that the theoretical risk involved can become a practical reality.

Exosome-based liquid biopsy in the management of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) commonly presents at an advanced stage due to the lack of efficient early screening tools. Early, non-invasive biomarkers useful in the diagnosis and prognosis of HCC would be of significant benefit for HCC management. Development of exosome-based liquid biopsy as a non-invasive method for the management of HCC has gained much traction. Exosomes are small membranous vesicles secreted by most cell types including HCC cells. Exosomes serve as couriers for the intercellular transfer of important biomolecules, including, protein, nucleic acids and lipids to nearby and distant cells in the body. The molecular cargos carried by exosome have been described to play significant roles in cancer progression. Herein, we will dissect how HCC-derived exosomes confer aggressive traits such as tumour growth, invasion, immune remodelling and drug resistance to HCC cells. We review the current literature concerning exosomes as biomarkers in a diagnostic setting, evaluating their prognostic, predictive and monitoring capabilities. This review will highlight and discuss emerging research in the utility of exosome-based liquid biopsies therapeutic tools in HCC management. Here we will also focus on advances in exosome biology in preclinical studies.