In this editorial,we comment on the article by Zeng et al published in the recent issue of the World Journal of Diabetes in 2024.We focus on the epidemiological,pathophysiological,and clinical interplay between obesit...In this editorial,we comment on the article by Zeng et al published in the recent issue of the World Journal of Diabetes in 2024.We focus on the epidemiological,pathophysiological,and clinical interplay between obesity and type 1 diabetes mellitus(T1DM).Overweight and obesity represent a growing threat for modern societies and people with T1DM could not be an exception to this rule.Chronic exogenous insulin administration,genetic and epigenetic factors,and psy-chosocial and behavioral parameters,along with the modern way of life that incorporates unhealthy eating patterns and physical inactivity,set the stage for the increasing obesity rates in T1DM.As our knowledge of the underlying mechanisms that lead to the development of obesity and hyperglycemia expands,it becomes clear that there are overlap zones in the pathophysiology of the two main types of diabetes.Stereotypes regarding strict dividing lines between“autoimmune”and“metabolic”phenotypes increase the risk of trapping physicians into ineffective therapeutic approaches,instead of individualized diabetes care.In this context,the use of adjuncts to insulin therapy that have the potential to alleviate cardiorenal risk and decrease body weight can reduce the burden of obesity in patients with T1DM.展开更多
With increasing incidence of diabetes, use of diabetes specific nutrition supplements (DSNS) is common for better management of the disease. To study effect of 12-week DSNS supplementation on glycemic markers, anthrop...With increasing incidence of diabetes, use of diabetes specific nutrition supplements (DSNS) is common for better management of the disease. To study effect of 12-week DSNS supplementation on glycemic markers, anthropometry, lipid profile, SCFAs, and gut microbiome in individuals with diabetes. Markers studied were glycemic [Fasting Blood Glucose (FBG), Post Prandial Glucose (PPG), HbA1c, Incremental Area under curve (iAUC), Mean Amplitude of Glycemic Excursions (MAGE), Time in/above Range (TIR/TAR)], anthropometry [weight, Body Mass Index (BMI), waist circumference (WC)], lipid profile, diet and gut health [plasma short chain fatty acids (SCFAs)]. N = 210 adults were randomized to receive either DSNS with standard care (DSNS + SC;n = 105) or standard care alone (SC alone;n = 105). After 12 weeks, significant differences between DSNS + SC versus SC alone was observed in FBG [−3 ± 6 vs 14 ± 6 mg/dl;p = 0.03], PPG [−35 ± 9 vs −3 ± 9 mg/dl;p = 0.01], weight [−0.6 ± 0.1 vs 0.2 ± 0.1 kg;p = 0.0001], BMI [−0.3 ± 0.1 vs 0.1 ± 0.1 kg/m2;p = 0.0001] and WC [−0.3 ± 0.2 vs 0.2 ± 0.2 cm;p = 0.01]. HbA1C and low-density lipoprotein (LDL) were significantly reduced in DSNS + SC [−0.2 ± 0.9;p = 0.04 and −5 mg/dl;p = 0.03] respectively with no change in control. Continuous Glucose Monitoring (CGM) reported significant differences between DSNS + SC versus SC alone for mean glucose [−12 ± 65 vs 28 ± 93 mg/dl;p < 0.01], TAR 180 [−9 ± 42 vs 7 ± 45 mg/dl;p = 0.04], TAR 250 [−3 ± 27 vs 9 ± 38 mg/dl;p = 0.05], iAUC [−192 (1.1) vs −48 (1.1) mg/dl;p = 0.03]. MAGE was significantly reduced for both DSNS + SC (−19 ± 67;p < 0.001) and SC alone (−8 ± 70;p = 0.04), with reduction being more pronounced for DSNS + SC. DSNS + SC reported a decrease in carbohydrate energy % [−9.4 (−11.3, −7.6) %;p < 0.0001] and amount [−47.4 (−67.1, −27.7) g;p < 0.0001], increased dietary fiber [9.5 (7.2, 11.8) g;p < 0.0001] and protein energy % [0.9 (0.5, 1.3) %;p < 0.0001] versus SC alone. DSNS + SC reported significant increases versus SC alone in total (0.3 ng/ml;p = 0.03) and individual plasma SCFAs. The consumption of DSNS significantly improves the glycemic, anthropometric, dietary, and gut health markers in diabetes.展开更多
Butyrylcholinesterase(BChE;EC 3.1.1.8),an enzyme structurally related to acetylcholinesterase,is widely distributed in the human body.It plays a role in the detoxification of chemicals such as succinylcholine,a muscle...Butyrylcholinesterase(BChE;EC 3.1.1.8),an enzyme structurally related to acetylcholinesterase,is widely distributed in the human body.It plays a role in the detoxification of chemicals such as succinylcholine,a muscle relaxant used in anesthetic practice.BChE is well-known due to variant forms of the enzyme with little or no hydrolytic activity which exist in some endogamous communities and result in prolonged apnea following the administration of succinylcholine.Its other functions include the ability to hydrolyze acetylcholine,the cholinergic neurotransmitter in the brain,when its primary hydrolytic enzyme,acetylcholinesterase,is absent.To assess its potential roles,BChE was studied in relation to insulin resistance,type 2 diabetes mellitus,cognition,hepatic disorders,cardiovascular and cerebrovascular diseases,and inflammatory conditions.Individuals who lack the enzyme activity of BChE are otherwise healthy,until they are given drugs hydrolyzed by this enzyme.Therefore,BChE is a candidate for the study of loss-of-function mutations in humans.Studying individuals with variant forms of BChE can provide insights into whether they are protected against metabolic diseases.The potential utility of the enzyme as a biomarker for Alzheimer’s disease and the response to its drug treatment can also be assessed.展开更多
Obesity is increasingly prevalent worldwide,with genetic factors contributing to its development.The hypothalamic leptin-melanocortin pathway is central to the regulation of appetite and weight;leptin activates the pr...Obesity is increasingly prevalent worldwide,with genetic factors contributing to its development.The hypothalamic leptin-melanocortin pathway is central to the regulation of appetite and weight;leptin activates the proopiomelanocortin neurons,leading to the production of melanocortin peptides;these in turn act on melanocortin 4 receptors(MC4R)which suppress appetite and increase energy expenditure.MC4R mutations are responsible for syndromic and non-syndromic obesity.These mutations are classified based on their impact on the receptor's life cycle:i.e.null mutations,intracellular retention,binding defects,signaling defects,and variants of unknown function.Clinical manifestations of MC4R mutations include early-onset obesity,hyperphagia,and metabolic abnormalities such as hyperinsulinemia and dyslipidemia.Management strategies for obesity due to MC4R mutations have evolved with the development of targeted therapies such as Setmelanotide,an MC4R agonist which can reduce weight and manage symptoms without adverse cardiovascular effects.Future research directions must include expansion of population studies to better understand the epidemiology of MC4R mutations,exploration of the molecular mechanisms underlying MC4R signaling,and development of new therapeutic agents.Understanding the interaction between MC4R and other genetic and environmental factors will be key to advancing both the prevention and treatment of obesity.展开更多
Childhood obesity,an escalating global health challenge,is intricately linked to the built environment in which children live,learn,and play.This review and perspective examined the multifaceted relationship between t...Childhood obesity,an escalating global health challenge,is intricately linked to the built environment in which children live,learn,and play.This review and perspective examined the multifaceted relationship between the built environment and childhood obesity,offering insights into potential interventions for prevention.Factors such as urbanization,access to unhealthy food options,sedentary behaviors,and socioeconomic disparities are critical contributors to this complex epidemic.Built environment encompasses the human-modified spaces such as homes,schools,workplaces,and urban areas.These settings can influence children’s physical activity levels,dietary habits,and overall health.The built environment can be modified to prevent childhood obesity by enhancing active transportation through the development of safe walking and cycling routes,creating accessible and inviting green spaces and play areas,and promoting healthy food environments by regulating fast-food outlet density.School design is another area for intervention,with a focus on integrating outdoor spaces and facilities that promote physical activity and healthy eating.Community engagement and education in reinforcing healthy behaviors is necessary,alongside the potential of technology and innovation in encouraging physical activity among children.Policy and legislative support are crucial for sustaining these efforts.In conclusion,addressing the built environment in the fight against childhood obesity requires the need for a comprehensive,multipronged approach that leverages the built environment as a tool for promoting healthier lifestyles among children,ultimately paving the way for a healthier,more active future generation.展开更多
The use of Artificial intelligence(AI)has evolved from its mid-20th century origins to playing a pivotal tool in modern medicine.It leverages digital data and computational hardware for diverse applications,including ...The use of Artificial intelligence(AI)has evolved from its mid-20th century origins to playing a pivotal tool in modern medicine.It leverages digital data and computational hardware for diverse applications,including diagnosis,prognosis,and treatment responses in gastrointestinal and hepatic conditions.AI has had an impact in diagnostic techniques,particularly endoscopy,ultrasound,and histopathology.AI encompasses machine learning,natural language processing,and robotics,with machine learning being central.This involves sophisticated algorithms capable of managing complex datasets,far surpassing traditional statistical methods.These algorithms,both supervised and unsupervised,are integral for interpreting large datasets.In liver diseases,AI's non-invasive diagnostic applications,particularly in non-alcoholic fatty liver disease,and its role in characterizing hepatic lesions is promising.AI aids in distinguishing between normal and cirrhotic livers and improves the accuracy of lesion characterization and prognostication of hepatocellular carcinoma.AI enhances lesion identification during endoscopy,showing potential in the diagnosis and management of early-stage esophageal carcinoma.In peptic ulcer disease,AI technologies influence patient management strategies.AI is useful in colonoscopy,particularly in detecting smaller colonic polyps.However,its applicability in nonacademic settings requires further validation.Addressing these issues is vital for harnessing the potential of AI.In conclusion,while AI offers transformative possibilities in gastroenterology,careful integration and balancing of technical possibilities with ethical and practical application,is essential for optimal use.展开更多
A previous diagnosis of gestational diabetes(GDM)carries a lifetime risk of progression to type 2 diabetes of up to 60%.Identification of those women at higher risk of progression to diabetes allows the timely introdu...A previous diagnosis of gestational diabetes(GDM)carries a lifetime risk of progression to type 2 diabetes of up to 60%.Identification of those women at higher risk of progression to diabetes allows the timely introduction of measures to delay or prevent diabetes onset.However,there is a large degree of variability in the literature with regard to the proportion of women with a history of GDM who go on to develop diabetes.Heterogeneity between cohorts with regard to diagnostic criteria used,duration of follow-up,and the characteristics of the study population limit the ability to make meaningful comparisons across studies.As the new International Association for Diabetes in Pregnancy Study Group criteria are increasingly adopted worldwide,the prevalence of GDM is set to increase by two-to three-fold.Here,we review the literature to examine the evolution of diagnostic criteria for GDM,the implications of changing criteria on the proportion of women with previous GDM progressing to diabetes,and how the use of different diagnostic criteria may influence the development of appropriate follow-up strategies.展开更多
Type 2 diabetes mellitus and Alzheimer's disease are both associated with increasing age,and each increases the risk of development of the other.Epidemiological,clinical,biochemical and imaging studies have shown ...Type 2 diabetes mellitus and Alzheimer's disease are both associated with increasing age,and each increases the risk of development of the other.Epidemiological,clinical,biochemical and imaging studies have shown that elevated glucose levels and diabetes are associated with cognitive dysfunction,the most prevalent cause of which is Alzheimer's disease.Cross sectional studies have clearly shown such an association,whereas longitudinal studies are equivocal,reflecting the many complex ways in which the two interact.Despite the dichotomy,common risk and etiological factors(obesity,dyslipidemia,insulin resistance,and sedentary habits) are recognized;correction of these by lifestyle changes and pharmacological agents can be expected to prevent or retard the progression of both diseases.Common pathogenic factors in both conditions span a broad sweep including chronic hyperglycemia per se,hyperinsulinemia,insulin resistance,acute hypoglycemic episodes,especially in the elderly,microvascular disease,fibrillar deposits(in brain in Alzheimer's disease and in pancreas in type 2 diabetes),altered insulin processing,inflammation,obesity,dyslipidemia,altered levels of insulin like growth factor and occurrence of variant forms of the protein butyrylcholinesterase.Of interest not only do lifestyle measures have a protective effect against the development of cognitive impairment due to Alzheimer's disease,but so do some of the pharmacological agents used in the treatment of diabetes such as insulin(especially when delivered intranasally),metformin,peroxisome proliferator-activated receptors γ agonists,glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors.Diabetes must be recognized as a risk for development of Alzheimer's disease;clinicians must ensure preventive care be given to control and postpone both conditions,and to identify cognitive impairment early to manage it appropriately.展开更多
Under normal metabolic conditions insulin stimulates microvascular perfusion(capillary recruitment) of skeletal muscle and subcutaneous adipose tissue and thus increases blood flow mainly after meal ingestion or physi...Under normal metabolic conditions insulin stimulates microvascular perfusion(capillary recruitment) of skeletal muscle and subcutaneous adipose tissue and thus increases blood flow mainly after meal ingestion or physical exercise.This helps the delivery of insulinitself but also that of substrates and of other signalling molecules to multiple tissues beds and facilitates glucose disposal and lipid kinetics.This effect is impaired in insulin resistance and type 2 diabetes early in the development of metabolic dysregulation and reflects early-onset endothelial dysfunction.Failure of insulin to increase muscle and adipose tissue blood flow results in decreased glucose handling.In fat depots,a blunted postprandial blood flow response will result in an insufficient suppression of lipolysis and an increased spill over of fatty acids in the circulation,leading to a more pronounced insulin resistant state in skeletal muscle.This defect in blood flow response is apparent even in the prediabetic state,implying that it is a facet of insulin resistance and exists long before overt hyperglycaemia develops.The following review intends to summarize the contribution of blood flow impairment to the development of the atherogenic dysglycemia and dyslipidaemia.展开更多
Synchrony of biological processes with environmental cues developed over millennia to match growth, reproduction and senescence. This entails a complex interplay of genetic, metabolic, chemical, light, hormonal andhed...Synchrony of biological processes with environmental cues developed over millennia to match growth, reproduction and senescence. This entails a complex interplay of genetic, metabolic, chemical, light, hormonal andhedonistic factors across life forms. Sleep is one of the most prominent rhythms where such a match is established. Over the past 100 years or so, it has been possible to disturb the synchrony between sleep-wake cycle and environmental cues. Development of electric lights, shift work and continual accessibility of the internet has disrupted this match. As a result, many noncommunicable diseases such as obesity, insulin resistance, type 2 diabetes, coronary artery disease and malignancies have been attributed in part to such disruption. In this presentation a review is made of the origin and evolution of sleep studies, the pathogenic mediators for such asynchrony, clinical evidence and relevance and suggested management options to deal with the disturbances.展开更多
Chromium is considered to have positive effects on insulin sensitivity and is marketed as an adjunctive therapy for inducing glucose tolerance in cases of insulin resistance("the glucose tolerance factor"). ...Chromium is considered to have positive effects on insulin sensitivity and is marketed as an adjunctive therapy for inducing glucose tolerance in cases of insulin resistance("the glucose tolerance factor"). Case reports on patients who received prolonged parenteral nutrition indeed showed that the absence of trivalent chromium caused insulin resistance and diabetes. However, whether patients with type 2 diabetes can develop a clinically relevant chromium deficiency is unclear. This review summarizes the available evidence regarding the potential effectiveness of chromium supplementation on glycemic control(Hemoglobin A1c levels) in patients with type 2 diabetes. No studies investigating the longterm safety of chromium in humans were found. All clinical trials that have been performed had a relative short follow-up period. None of the trials investigated whether the patients had risk factors for chromium deficiency.The evidence from randomized trials in patients with type 2 diabetes demonstrated that chromium supplementation does not effectively improve glycemic control. The meta-analyses showed that chromium supplementation did not improve fasting plasma glucose levels. Moreover, there were no clinically relevant chromium effects on body weight in individuals with or without diabetes. Future studies should focus on reliable methods to estimate chromium status to identify patients at risk for pathological alterations in their metabolism associated with chromium deficiency. Given the present data, there is no evidence that supports advising patients with type 2 diabetes to take chromium supplements.展开更多
Background:Individuals with diabetes have greater central arterial stiffness,wave reflections,and hemodynamics,all of which promote the accelerated cardiovascular pathology seen in this population.Acute aerobic exerci...Background:Individuals with diabetes have greater central arterial stiffness,wave reflections,and hemodynamics,all of which promote the accelerated cardiovascular pathology seen in this population.Acute aerobic exercise has been shown to be an effective strategy for reducing central arterial stiffness,wave reflections,and hemodynamics in healthy individuals;however,the effects of acute aerobic exercise in reducing these outcomes is not well established in people with diabetes.Recently,implementation of high-intensity interval exercise(HIIE)has shown superior improvements in cardiovascular health outcomes when compared to traditional aerobic exercise.Yet,the effect of HIIE on the aforementioned outcomes in people with diabetes is not known.The purpose of this study was to(i)describe the central arterial stiffness,wave reflections,and hemodynamic responses to a bout of HIIE and moderate-intensity continuous exercise(MICE)in adults with diabetes;and(ii)compare the effects of HIIE and MICE on the aforementioned outcomes.Methods:A total of 24 adult men and women(aged 29-59 years old)with type 1(n=12)and type 2(n=12)diabetes participated in a randomized cross-over study.All participants completed the following protocols:(i)HIIE:cycling for 4×4 min at 85%-95%of heart rate peak(HR_(peak)),interspersed with 3 min of active recovery at 60%-70%HR_(peak);(ii)MICE:33 min of continuous cycling at 60%-70%HR_(peak);and(iii)control(CON):lying quietly in a supine position for 30 min.Results:A significant group£time effect was found for changes in central systolic blood pressure(F=3.20,p=0.01)with a transient reduction for the HIIE group but not for the MICE or CON groups.There was a significant group£time effect for changes in augmentation index at a heart rate of 75 beats/min(F=2.32,p=0.04)with a decrease following for HIIE and MICE but not for CON.For all other measures of central arterial stiffness and hemodynamics,no significant changes were observed(p>0.05).Conclusion:A bout of HIIE appears to lead to a greater transient reduction in central systolic blood pressure than the reduction observed following MICE;however,both HIIE and MICE improved augmentation index at a heart rate of 75 beats/min in people with diabetes.There was no significant difference in response to HIIE and MICE in all outcomes.This provides preliminary evidence on the role of HIIE on such outcomes in people with diabetes.展开更多
BACKGROUND Risk factors such as hereditary, ecological, and metabolic are interrelated and contribute to the development of type 2 diabetes mellitus. Family history(FH) of diabetes mellitus, age, obesity, and physical...BACKGROUND Risk factors such as hereditary, ecological, and metabolic are interrelated and contribute to the development of type 2 diabetes mellitus. Family history(FH) of diabetes mellitus, age, obesity, and physical inactivity are some of the risk factors for the development of type 2 diabetes.AIM To study various aetiological determinants and risk factors for type 2 diabetes in Bangalore, India. This retrospective study examined questionnaire from patients attending the Diabetes Clinic.METHODS Data on various parameters were obtained through a questionnaire from 533 patients on the first visit to the diabetes clinic. Data regarding various aetiological determinants and risk factors viz.: Genetic risk factor and few modifiable risk factors were collected. Chi-squared test was used for statistical analysis.RESULTS A higher incidence of type 2 diabetes in males and younger population was observed in Bangalore, India. Obesity and FH were significant risk factors for not only type 2 diabetes but also early onset of diabetes. In addition, maternal history of type 2 diabetes and consanguinity increased incidence of early onset type 2 diabetes.CONCLUSION Risk factors such as obesity and FH(maternal history of type 2 diabetes) and consanguinity may play an important role in screening of family members of type 2 diabetes patients which may lead to early intervention and reduced risk of subsequent complications. Moreover, susceptible population can be counselled for the management of the type 2 diabetes including periodic investigation of blood glucose levels and lifestyle changes.展开更多
Limited joint mobility syndrome(LJMS) or diabetic cheiroarthropathy is a long term complication of diabetes mellitus. The diagnosis of LJMS is based on clinical features: progression of painless stiffness of hands and...Limited joint mobility syndrome(LJMS) or diabetic cheiroarthropathy is a long term complication of diabetes mellitus. The diagnosis of LJMS is based on clinical features: progression of painless stiffness of hands and fingers, fixed flexion contractures of the small hand and foot joints, impairment of fine motion and impaired grip strength in the hands. As the syndrome progresses, it can also affect other joints. It is important to properly diagnose such a complication as LJMS. Moreover, it is important to diagnose LJMS because it is known that the presence of LJMS is associated with micro- and macrovascular complications of diabetes. Due to the lack of curative treatment options, the suggested method to prevent or decelerate the development of LJMS is improving or maintaining good glycemic control. Daily stretching excercises of joints aim to prevent or delay progression of joint stiffness, may reduce the risk of inadvertent falls and will add to maintain quality of life.展开更多
BACKGROUND The diagnosis of type 2 diabetes(T2D)in younger adults,an increasingly common public health issue,is associated with a higher risk of cardiovascular complications and mortality,which may be due to a more ad...BACKGROUND The diagnosis of type 2 diabetes(T2D)in younger adults,an increasingly common public health issue,is associated with a higher risk of cardiovascular complications and mortality,which may be due to a more adverse cardiovascular risk profile in individuals diagnosed at a younger age.AIM To investigate the association between age at diagnosis and the cardiovascular risk profile in adults with T2D.METHODS A pooled dataset was used,comprised of data from five previous studies of adults with T2D,including 1409 participants of whom 196 were diagnosed with T2D under the age of 40 years.Anthropometric and blood biomarker measurements included body weight,body mass index(BMI),waist circumference,body fat percentage,glycaemic control(HbA1c),lipid profile and blood pressure.Univariable and multivariable linear regression models,adjusted for diabetes duration,sex,ethnicity and smoking status,were used to investigate the association between age at diagnosis and each cardiovascular risk factor.RESULTS A higher proportion of participants diagnosed with T2D under the age of 40 were female,current smokers and treated with glucose-lowering medications,compared to participants diagnosed later in life.Participants diagnosed with T2D under the age of 40 also had higher body weight,BMI,waist circumference and body fat percentage,in addition to a more adverse lipid profile,compared to participants diagnosed at an older age.Modelling results showed that each one year reduction in age at diagnosis was significantly associated with 0.67 kg higher body weight[95%confidence interval(CI):0.52-0.82 kg],0.18 kg/m^(2) higher BMI(95%CI:0.10-0.25)and 0.32 cm higher waist circumference(95%CI:0.14-0.49),after adjustment for duration of diabetes and other confounders.Younger age at diagnosis was also significantly associated with higher HbA1c,total cholesterol,low-density lipoprotein cholesterol and triglycerides.CONCLUSION The diagnosis of T2D earlier in life is associated with a worse cardiovascular risk factor profile,compared to those diagnosed later in life.展开更多
AIM:To evaluate metabolic control and health-related quality of life(HRQOL)in a type 1 diabetes mellitus(T1DM)population.METHODS:As part of a prospective cohort study,283T1DM patients treated with various insulin trea...AIM:To evaluate metabolic control and health-related quality of life(HRQOL)in a type 1 diabetes mellitus(T1DM)population.METHODS:As part of a prospective cohort study,283T1DM patients treated with various insulin treatment modalities including multiple daily injections(MDI)and continuous subcutaneous insulin infusion(CSII)were examined annually.HRQOL was measured using the SF-36 and EuroQol questionnaires.Data regarding HRQOL,glycaemic and metabolic control from baseline and follow-up measures in 2002 and 2010 were analysed.Linear mixed models were used to calculate estimated values and differences between the three moments in time and the three treatment modalities.RESULTS:Significant changes[meanΔ(95%CI)]in body mass index[2.4 kg/m2(1.0,3.8)],systolic blood pressure[-6.4 mmHg(-11.4,-1.3)]and EuroQol-VAS[-7.3(-11.4,-3.3)]were observed over time.In 2010,168 patients were lost to follow-up.Regarding mode of therapy,52 patients remained on MDI,28 remained on CSII,and 33 patients switched from MDI to CSII during follow-up.Among patients on MDI,HRQOL decreased significantly over time:mental component summary[-9.8(-16.3,-3.2)],physical component summary[-8.6(-15.3,-1.8)]and EuroQol-VAS[-8.1(-14.0,-2.3)],P<0.05 for all.For patients using CSII,the EuroQol-VAS decreased[-9.6(-17.5,-1.7)].None of the changes over time in HRQOL differed significantly with the changes over time within the other treatment groups.CONCLUSION:No differences with respect to metabolic and HRQOL parameters between the various insulin treatment modalities were observed after 15 years of follow-up in T1DM patients.展开更多
BACKGROUND Cardiovascular outcome trials have demonstrated cardiovascular safety of glimepiride(a sulfonylureas) against dipeptidyl peptidase-4 inhibitor linagliptin.Gliclazide(another newer sulfonylureas) has shown s...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.展开更多
文摘In this editorial,we comment on the article by Zeng et al published in the recent issue of the World Journal of Diabetes in 2024.We focus on the epidemiological,pathophysiological,and clinical interplay between obesity and type 1 diabetes mellitus(T1DM).Overweight and obesity represent a growing threat for modern societies and people with T1DM could not be an exception to this rule.Chronic exogenous insulin administration,genetic and epigenetic factors,and psy-chosocial and behavioral parameters,along with the modern way of life that incorporates unhealthy eating patterns and physical inactivity,set the stage for the increasing obesity rates in T1DM.As our knowledge of the underlying mechanisms that lead to the development of obesity and hyperglycemia expands,it becomes clear that there are overlap zones in the pathophysiology of the two main types of diabetes.Stereotypes regarding strict dividing lines between“autoimmune”and“metabolic”phenotypes increase the risk of trapping physicians into ineffective therapeutic approaches,instead of individualized diabetes care.In this context,the use of adjuncts to insulin therapy that have the potential to alleviate cardiorenal risk and decrease body weight can reduce the burden of obesity in patients with T1DM.
文摘With increasing incidence of diabetes, use of diabetes specific nutrition supplements (DSNS) is common for better management of the disease. To study effect of 12-week DSNS supplementation on glycemic markers, anthropometry, lipid profile, SCFAs, and gut microbiome in individuals with diabetes. Markers studied were glycemic [Fasting Blood Glucose (FBG), Post Prandial Glucose (PPG), HbA1c, Incremental Area under curve (iAUC), Mean Amplitude of Glycemic Excursions (MAGE), Time in/above Range (TIR/TAR)], anthropometry [weight, Body Mass Index (BMI), waist circumference (WC)], lipid profile, diet and gut health [plasma short chain fatty acids (SCFAs)]. N = 210 adults were randomized to receive either DSNS with standard care (DSNS + SC;n = 105) or standard care alone (SC alone;n = 105). After 12 weeks, significant differences between DSNS + SC versus SC alone was observed in FBG [−3 ± 6 vs 14 ± 6 mg/dl;p = 0.03], PPG [−35 ± 9 vs −3 ± 9 mg/dl;p = 0.01], weight [−0.6 ± 0.1 vs 0.2 ± 0.1 kg;p = 0.0001], BMI [−0.3 ± 0.1 vs 0.1 ± 0.1 kg/m2;p = 0.0001] and WC [−0.3 ± 0.2 vs 0.2 ± 0.2 cm;p = 0.01]. HbA1C and low-density lipoprotein (LDL) were significantly reduced in DSNS + SC [−0.2 ± 0.9;p = 0.04 and −5 mg/dl;p = 0.03] respectively with no change in control. Continuous Glucose Monitoring (CGM) reported significant differences between DSNS + SC versus SC alone for mean glucose [−12 ± 65 vs 28 ± 93 mg/dl;p < 0.01], TAR 180 [−9 ± 42 vs 7 ± 45 mg/dl;p = 0.04], TAR 250 [−3 ± 27 vs 9 ± 38 mg/dl;p = 0.05], iAUC [−192 (1.1) vs −48 (1.1) mg/dl;p = 0.03]. MAGE was significantly reduced for both DSNS + SC (−19 ± 67;p < 0.001) and SC alone (−8 ± 70;p = 0.04), with reduction being more pronounced for DSNS + SC. DSNS + SC reported a decrease in carbohydrate energy % [−9.4 (−11.3, −7.6) %;p < 0.0001] and amount [−47.4 (−67.1, −27.7) g;p < 0.0001], increased dietary fiber [9.5 (7.2, 11.8) g;p < 0.0001] and protein energy % [0.9 (0.5, 1.3) %;p < 0.0001] versus SC alone. DSNS + SC reported significant increases versus SC alone in total (0.3 ng/ml;p = 0.03) and individual plasma SCFAs. The consumption of DSNS significantly improves the glycemic, anthropometric, dietary, and gut health markers in diabetes.
文摘Butyrylcholinesterase(BChE;EC 3.1.1.8),an enzyme structurally related to acetylcholinesterase,is widely distributed in the human body.It plays a role in the detoxification of chemicals such as succinylcholine,a muscle relaxant used in anesthetic practice.BChE is well-known due to variant forms of the enzyme with little or no hydrolytic activity which exist in some endogamous communities and result in prolonged apnea following the administration of succinylcholine.Its other functions include the ability to hydrolyze acetylcholine,the cholinergic neurotransmitter in the brain,when its primary hydrolytic enzyme,acetylcholinesterase,is absent.To assess its potential roles,BChE was studied in relation to insulin resistance,type 2 diabetes mellitus,cognition,hepatic disorders,cardiovascular and cerebrovascular diseases,and inflammatory conditions.Individuals who lack the enzyme activity of BChE are otherwise healthy,until they are given drugs hydrolyzed by this enzyme.Therefore,BChE is a candidate for the study of loss-of-function mutations in humans.Studying individuals with variant forms of BChE can provide insights into whether they are protected against metabolic diseases.The potential utility of the enzyme as a biomarker for Alzheimer’s disease and the response to its drug treatment can also be assessed.
文摘Obesity is increasingly prevalent worldwide,with genetic factors contributing to its development.The hypothalamic leptin-melanocortin pathway is central to the regulation of appetite and weight;leptin activates the proopiomelanocortin neurons,leading to the production of melanocortin peptides;these in turn act on melanocortin 4 receptors(MC4R)which suppress appetite and increase energy expenditure.MC4R mutations are responsible for syndromic and non-syndromic obesity.These mutations are classified based on their impact on the receptor's life cycle:i.e.null mutations,intracellular retention,binding defects,signaling defects,and variants of unknown function.Clinical manifestations of MC4R mutations include early-onset obesity,hyperphagia,and metabolic abnormalities such as hyperinsulinemia and dyslipidemia.Management strategies for obesity due to MC4R mutations have evolved with the development of targeted therapies such as Setmelanotide,an MC4R agonist which can reduce weight and manage symptoms without adverse cardiovascular effects.Future research directions must include expansion of population studies to better understand the epidemiology of MC4R mutations,exploration of the molecular mechanisms underlying MC4R signaling,and development of new therapeutic agents.Understanding the interaction between MC4R and other genetic and environmental factors will be key to advancing both the prevention and treatment of obesity.
文摘Childhood obesity,an escalating global health challenge,is intricately linked to the built environment in which children live,learn,and play.This review and perspective examined the multifaceted relationship between the built environment and childhood obesity,offering insights into potential interventions for prevention.Factors such as urbanization,access to unhealthy food options,sedentary behaviors,and socioeconomic disparities are critical contributors to this complex epidemic.Built environment encompasses the human-modified spaces such as homes,schools,workplaces,and urban areas.These settings can influence children’s physical activity levels,dietary habits,and overall health.The built environment can be modified to prevent childhood obesity by enhancing active transportation through the development of safe walking and cycling routes,creating accessible and inviting green spaces and play areas,and promoting healthy food environments by regulating fast-food outlet density.School design is another area for intervention,with a focus on integrating outdoor spaces and facilities that promote physical activity and healthy eating.Community engagement and education in reinforcing healthy behaviors is necessary,alongside the potential of technology and innovation in encouraging physical activity among children.Policy and legislative support are crucial for sustaining these efforts.In conclusion,addressing the built environment in the fight against childhood obesity requires the need for a comprehensive,multipronged approach that leverages the built environment as a tool for promoting healthier lifestyles among children,ultimately paving the way for a healthier,more active future generation.
文摘The use of Artificial intelligence(AI)has evolved from its mid-20th century origins to playing a pivotal tool in modern medicine.It leverages digital data and computational hardware for diverse applications,including diagnosis,prognosis,and treatment responses in gastrointestinal and hepatic conditions.AI has had an impact in diagnostic techniques,particularly endoscopy,ultrasound,and histopathology.AI encompasses machine learning,natural language processing,and robotics,with machine learning being central.This involves sophisticated algorithms capable of managing complex datasets,far surpassing traditional statistical methods.These algorithms,both supervised and unsupervised,are integral for interpreting large datasets.In liver diseases,AI's non-invasive diagnostic applications,particularly in non-alcoholic fatty liver disease,and its role in characterizing hepatic lesions is promising.AI aids in distinguishing between normal and cirrhotic livers and improves the accuracy of lesion characterization and prognostication of hepatocellular carcinoma.AI enhances lesion identification during endoscopy,showing potential in the diagnosis and management of early-stage esophageal carcinoma.In peptic ulcer disease,AI technologies influence patient management strategies.AI is useful in colonoscopy,particularly in detecting smaller colonic polyps.However,its applicability in nonacademic settings requires further validation.Addressing these issues is vital for harnessing the potential of AI.In conclusion,while AI offers transformative possibilities in gastroenterology,careful integration and balancing of technical possibilities with ethical and practical application,is essential for optimal use.
文摘A previous diagnosis of gestational diabetes(GDM)carries a lifetime risk of progression to type 2 diabetes of up to 60%.Identification of those women at higher risk of progression to diabetes allows the timely introduction of measures to delay or prevent diabetes onset.However,there is a large degree of variability in the literature with regard to the proportion of women with a history of GDM who go on to develop diabetes.Heterogeneity between cohorts with regard to diagnostic criteria used,duration of follow-up,and the characteristics of the study population limit the ability to make meaningful comparisons across studies.As the new International Association for Diabetes in Pregnancy Study Group criteria are increasingly adopted worldwide,the prevalence of GDM is set to increase by two-to three-fold.Here,we review the literature to examine the evolution of diagnostic criteria for GDM,the implications of changing criteria on the proportion of women with previous GDM progressing to diabetes,and how the use of different diagnostic criteria may influence the development of appropriate follow-up strategies.
文摘Type 2 diabetes mellitus and Alzheimer's disease are both associated with increasing age,and each increases the risk of development of the other.Epidemiological,clinical,biochemical and imaging studies have shown that elevated glucose levels and diabetes are associated with cognitive dysfunction,the most prevalent cause of which is Alzheimer's disease.Cross sectional studies have clearly shown such an association,whereas longitudinal studies are equivocal,reflecting the many complex ways in which the two interact.Despite the dichotomy,common risk and etiological factors(obesity,dyslipidemia,insulin resistance,and sedentary habits) are recognized;correction of these by lifestyle changes and pharmacological agents can be expected to prevent or retard the progression of both diseases.Common pathogenic factors in both conditions span a broad sweep including chronic hyperglycemia per se,hyperinsulinemia,insulin resistance,acute hypoglycemic episodes,especially in the elderly,microvascular disease,fibrillar deposits(in brain in Alzheimer's disease and in pancreas in type 2 diabetes),altered insulin processing,inflammation,obesity,dyslipidemia,altered levels of insulin like growth factor and occurrence of variant forms of the protein butyrylcholinesterase.Of interest not only do lifestyle measures have a protective effect against the development of cognitive impairment due to Alzheimer's disease,but so do some of the pharmacological agents used in the treatment of diabetes such as insulin(especially when delivered intranasally),metformin,peroxisome proliferator-activated receptors γ agonists,glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors.Diabetes must be recognized as a risk for development of Alzheimer's disease;clinicians must ensure preventive care be given to control and postpone both conditions,and to identify cognitive impairment early to manage it appropriately.
文摘Under normal metabolic conditions insulin stimulates microvascular perfusion(capillary recruitment) of skeletal muscle and subcutaneous adipose tissue and thus increases blood flow mainly after meal ingestion or physical exercise.This helps the delivery of insulinitself but also that of substrates and of other signalling molecules to multiple tissues beds and facilitates glucose disposal and lipid kinetics.This effect is impaired in insulin resistance and type 2 diabetes early in the development of metabolic dysregulation and reflects early-onset endothelial dysfunction.Failure of insulin to increase muscle and adipose tissue blood flow results in decreased glucose handling.In fat depots,a blunted postprandial blood flow response will result in an insufficient suppression of lipolysis and an increased spill over of fatty acids in the circulation,leading to a more pronounced insulin resistant state in skeletal muscle.This defect in blood flow response is apparent even in the prediabetic state,implying that it is a facet of insulin resistance and exists long before overt hyperglycaemia develops.The following review intends to summarize the contribution of blood flow impairment to the development of the atherogenic dysglycemia and dyslipidaemia.
文摘Synchrony of biological processes with environmental cues developed over millennia to match growth, reproduction and senescence. This entails a complex interplay of genetic, metabolic, chemical, light, hormonal andhedonistic factors across life forms. Sleep is one of the most prominent rhythms where such a match is established. Over the past 100 years or so, it has been possible to disturb the synchrony between sleep-wake cycle and environmental cues. Development of electric lights, shift work and continual accessibility of the internet has disrupted this match. As a result, many noncommunicable diseases such as obesity, insulin resistance, type 2 diabetes, coronary artery disease and malignancies have been attributed in part to such disruption. In this presentation a review is made of the origin and evolution of sleep studies, the pathogenic mediators for such asynchrony, clinical evidence and relevance and suggested management options to deal with the disturbances.
文摘Chromium is considered to have positive effects on insulin sensitivity and is marketed as an adjunctive therapy for inducing glucose tolerance in cases of insulin resistance("the glucose tolerance factor"). Case reports on patients who received prolonged parenteral nutrition indeed showed that the absence of trivalent chromium caused insulin resistance and diabetes. However, whether patients with type 2 diabetes can develop a clinically relevant chromium deficiency is unclear. This review summarizes the available evidence regarding the potential effectiveness of chromium supplementation on glycemic control(Hemoglobin A1c levels) in patients with type 2 diabetes. No studies investigating the longterm safety of chromium in humans were found. All clinical trials that have been performed had a relative short follow-up period. None of the trials investigated whether the patients had risk factors for chromium deficiency.The evidence from randomized trials in patients with type 2 diabetes demonstrated that chromium supplementation does not effectively improve glycemic control. The meta-analyses showed that chromium supplementation did not improve fasting plasma glucose levels. Moreover, there were no clinically relevant chromium effects on body weight in individuals with or without diabetes. Future studies should focus on reliable methods to estimate chromium status to identify patients at risk for pathological alterations in their metabolism associated with chromium deficiency. Given the present data, there is no evidence that supports advising patients with type 2 diabetes to take chromium supplements.
文摘Background:Individuals with diabetes have greater central arterial stiffness,wave reflections,and hemodynamics,all of which promote the accelerated cardiovascular pathology seen in this population.Acute aerobic exercise has been shown to be an effective strategy for reducing central arterial stiffness,wave reflections,and hemodynamics in healthy individuals;however,the effects of acute aerobic exercise in reducing these outcomes is not well established in people with diabetes.Recently,implementation of high-intensity interval exercise(HIIE)has shown superior improvements in cardiovascular health outcomes when compared to traditional aerobic exercise.Yet,the effect of HIIE on the aforementioned outcomes in people with diabetes is not known.The purpose of this study was to(i)describe the central arterial stiffness,wave reflections,and hemodynamic responses to a bout of HIIE and moderate-intensity continuous exercise(MICE)in adults with diabetes;and(ii)compare the effects of HIIE and MICE on the aforementioned outcomes.Methods:A total of 24 adult men and women(aged 29-59 years old)with type 1(n=12)and type 2(n=12)diabetes participated in a randomized cross-over study.All participants completed the following protocols:(i)HIIE:cycling for 4×4 min at 85%-95%of heart rate peak(HR_(peak)),interspersed with 3 min of active recovery at 60%-70%HR_(peak);(ii)MICE:33 min of continuous cycling at 60%-70%HR_(peak);and(iii)control(CON):lying quietly in a supine position for 30 min.Results:A significant group£time effect was found for changes in central systolic blood pressure(F=3.20,p=0.01)with a transient reduction for the HIIE group but not for the MICE or CON groups.There was a significant group£time effect for changes in augmentation index at a heart rate of 75 beats/min(F=2.32,p=0.04)with a decrease following for HIIE and MICE but not for CON.For all other measures of central arterial stiffness and hemodynamics,no significant changes were observed(p>0.05).Conclusion:A bout of HIIE appears to lead to a greater transient reduction in central systolic blood pressure than the reduction observed following MICE;however,both HIIE and MICE improved augmentation index at a heart rate of 75 beats/min in people with diabetes.There was no significant difference in response to HIIE and MICE in all outcomes.This provides preliminary evidence on the role of HIIE on such outcomes in people with diabetes.
文摘BACKGROUND Risk factors such as hereditary, ecological, and metabolic are interrelated and contribute to the development of type 2 diabetes mellitus. Family history(FH) of diabetes mellitus, age, obesity, and physical inactivity are some of the risk factors for the development of type 2 diabetes.AIM To study various aetiological determinants and risk factors for type 2 diabetes in Bangalore, India. This retrospective study examined questionnaire from patients attending the Diabetes Clinic.METHODS Data on various parameters were obtained through a questionnaire from 533 patients on the first visit to the diabetes clinic. Data regarding various aetiological determinants and risk factors viz.: Genetic risk factor and few modifiable risk factors were collected. Chi-squared test was used for statistical analysis.RESULTS A higher incidence of type 2 diabetes in males and younger population was observed in Bangalore, India. Obesity and FH were significant risk factors for not only type 2 diabetes but also early onset of diabetes. In addition, maternal history of type 2 diabetes and consanguinity increased incidence of early onset type 2 diabetes.CONCLUSION Risk factors such as obesity and FH(maternal history of type 2 diabetes) and consanguinity may play an important role in screening of family members of type 2 diabetes patients which may lead to early intervention and reduced risk of subsequent complications. Moreover, susceptible population can be counselled for the management of the type 2 diabetes including periodic investigation of blood glucose levels and lifestyle changes.
文摘Limited joint mobility syndrome(LJMS) or diabetic cheiroarthropathy is a long term complication of diabetes mellitus. The diagnosis of LJMS is based on clinical features: progression of painless stiffness of hands and fingers, fixed flexion contractures of the small hand and foot joints, impairment of fine motion and impaired grip strength in the hands. As the syndrome progresses, it can also affect other joints. It is important to properly diagnose such a complication as LJMS. Moreover, it is important to diagnose LJMS because it is known that the presence of LJMS is associated with micro- and macrovascular complications of diabetes. Due to the lack of curative treatment options, the suggested method to prevent or decelerate the development of LJMS is improving or maintaining good glycemic control. Daily stretching excercises of joints aim to prevent or delay progression of joint stiffness, may reduce the risk of inadvertent falls and will add to maintain quality of life.
基金Supported by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (NIHR201165)by the NIHR Leicester Biomedical Research Centrethe NIHR Applied Research Collaboration East Midlands
文摘BACKGROUND The diagnosis of type 2 diabetes(T2D)in younger adults,an increasingly common public health issue,is associated with a higher risk of cardiovascular complications and mortality,which may be due to a more adverse cardiovascular risk profile in individuals diagnosed at a younger age.AIM To investigate the association between age at diagnosis and the cardiovascular risk profile in adults with T2D.METHODS A pooled dataset was used,comprised of data from five previous studies of adults with T2D,including 1409 participants of whom 196 were diagnosed with T2D under the age of 40 years.Anthropometric and blood biomarker measurements included body weight,body mass index(BMI),waist circumference,body fat percentage,glycaemic control(HbA1c),lipid profile and blood pressure.Univariable and multivariable linear regression models,adjusted for diabetes duration,sex,ethnicity and smoking status,were used to investigate the association between age at diagnosis and each cardiovascular risk factor.RESULTS A higher proportion of participants diagnosed with T2D under the age of 40 were female,current smokers and treated with glucose-lowering medications,compared to participants diagnosed later in life.Participants diagnosed with T2D under the age of 40 also had higher body weight,BMI,waist circumference and body fat percentage,in addition to a more adverse lipid profile,compared to participants diagnosed at an older age.Modelling results showed that each one year reduction in age at diagnosis was significantly associated with 0.67 kg higher body weight[95%confidence interval(CI):0.52-0.82 kg],0.18 kg/m^(2) higher BMI(95%CI:0.10-0.25)and 0.32 cm higher waist circumference(95%CI:0.14-0.49),after adjustment for duration of diabetes and other confounders.Younger age at diagnosis was also significantly associated with higher HbA1c,total cholesterol,low-density lipoprotein cholesterol and triglycerides.CONCLUSION The diagnosis of T2D earlier in life is associated with a worse cardiovascular risk factor profile,compared to those diagnosed later in life.
文摘AIM:To evaluate metabolic control and health-related quality of life(HRQOL)in a type 1 diabetes mellitus(T1DM)population.METHODS:As part of a prospective cohort study,283T1DM patients treated with various insulin treatment modalities including multiple daily injections(MDI)and continuous subcutaneous insulin infusion(CSII)were examined annually.HRQOL was measured using the SF-36 and EuroQol questionnaires.Data regarding HRQOL,glycaemic and metabolic control from baseline and follow-up measures in 2002 and 2010 were analysed.Linear mixed models were used to calculate estimated values and differences between the three moments in time and the three treatment modalities.RESULTS:Significant changes[meanΔ(95%CI)]in body mass index[2.4 kg/m2(1.0,3.8)],systolic blood pressure[-6.4 mmHg(-11.4,-1.3)]and EuroQol-VAS[-7.3(-11.4,-3.3)]were observed over time.In 2010,168 patients were lost to follow-up.Regarding mode of therapy,52 patients remained on MDI,28 remained on CSII,and 33 patients switched from MDI to CSII during follow-up.Among patients on MDI,HRQOL decreased significantly over time:mental component summary[-9.8(-16.3,-3.2)],physical component summary[-8.6(-15.3,-1.8)]and EuroQol-VAS[-8.1(-14.0,-2.3)],P<0.05 for all.For patients using CSII,the EuroQol-VAS decreased[-9.6(-17.5,-1.7)].None of the changes over time in HRQOL differed significantly with the changes over time within the other treatment groups.CONCLUSION:No differences with respect to metabolic and HRQOL parameters between the various insulin treatment modalities were observed after 15 years of follow-up in T1DM patients.
文摘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.