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Cardiovascular implications of metabolic dysfunction-associated fatty liver disease and type 2 diabetes mellitus:A meta-analysis 认领 引用 被引量：4
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作者 Sahana Shetty Renuka Suvarna +2 位作者 Vanessa Ambrose Fistus Shivam Modi Joseph M Pappachan 《World Journal of Hepatology》 2025年第5期198-208,共11页
BACKGROUND Metabolic dysfunction-associated fatty liver disease(MAFLD)and type 2 diabetes mellitus(T2DM)are independent risk factors for the development of cardiovascular disease(CVD)and an exaggerated CVD risk is exp... BACKGROUND Metabolic dysfunction-associated fatty liver disease(MAFLD)and type 2 diabetes mellitus(T2DM)are independent risk factors for the development of cardiovascular disease(CVD)and an exaggerated CVD risk is expected when both diseases co-exist.Therefore,thorough risk stratification is important to inform better clinical practice decisions based on good quality evidence for patient with MAFLD and T2DM.AIM To identify the CVD and cardiovascular event(CVE)risk in a systematic review when MAFLD and T2DM co-exist to inform better clinical practice decisions.METHODS A systematic review was performed by compiling data by searching PubMed,EMBASE and Cochrane Library databases.Quality appraisal of retrieved studies and the meta-analysis were performed using Joanna Briggs Institute(JBI)tool and RevMan 5.4 software respectively.The effect indicators for CVE and CVD risk were expressed as odds ratios(OR)and 95%CI with P-values<0.05 as significant.RESULTS Fourteen(5 cohort and 9 cross-sectional)studies with 370013 participants were included in this review.The metaanalysis of CVE showed that the risk of CVE in T2DM was higher in the MAFLD group when compared to the non-MAFLD group[OR 1.28(95%CI,1.04-1.56)P=0.02]with follow up duration ranging between 5-6 years.The prevalence of CVD in the metanalysis of cross-sectional studies was found to be higher[OR 1.47(95%CI,1.21-1.78)P=0.0001]in T2DM with MAFLD when compared to T2DM without MAFLD.Significant heterogeneity exists due to variations in study design,methodologies,and MAFLD diagnostic criteria,which may have influenced the study's findings.CONCLUSION The presence of MAFLD in T2DM increased the risk of CVE.The prevalence of CVD is higher in T2DM with MAFLD as compared to T2DM without MAFLD.Large well-designed multicentric long-term prospective studies are necessary to appropriately risk stratify the cardiovascular effect of the MAFLD in T2DM patients. 展开更多
关键词 Cardiovascular disease Cardiovascular events Insulin resistance Metabolic dysfunction-associated fatty liver disease Type 2 diabetes mellitus
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Effect of beinaglutide,a thrice-daily GLP-1 receptor agonist,on body weight and metabolic parameters:A systematic review and metaanalysis 认领 引用 被引量：2
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作者 Abul Bashar Mohammad Kamrul-Hasan Vanishri Ganakumar +3 位作者 Lakshmi Nagendra Deep Dutta M Rafiqul Islam Joseph M Pappachan 《World Journal of Diabetes》 SCIE 2025年第5期374-387,共14页
BACKGROUND Beinaglutide,a short-acting glucagon-like polypeptide-1 receptor agonist,has shown variable efficacy in weight reduction and metabolic control in randomized controlled trials(RCTs).AIM To summarize the ther... BACKGROUND Beinaglutide,a short-acting glucagon-like polypeptide-1 receptor agonist,has shown variable efficacy in weight reduction and metabolic control in randomized controlled trials(RCTs).AIM To summarize the therapeutic effects of beinaglutide in patients with overweight/obesity with/without type 2 diabetes.METHODS RCTs involving patients receiving beinaglutide in the intervention arm and placebo or active comparator in the control arm were searched through multiple electronic databases.The change from baseline in body weight was the primary outcome;secondary outcomes included changes in body mass index(BMI),waist circumference(WC),blood pressure,glycemic parameters,lipids,and adverse events(AEs).RevMan web was used to conduct meta-analysis using random-effects models.Outcomes were presented as mean differences(MDs),odds ratios(ORs),or risk ratios(RRs)with 95%confidence intervals(95%CIs).RESULTS Six RCTs(n=800)with mostly some concerns about the risk of bias were included.Over 12-24 weeks,beinaglutide 0.1-0.2 mg thrice daily was superior to the control group in reducing total(MD=-3.25 kg,95%CI:-4.52 to-1.98,I2=84%,P<0.00001)and percent(MD=-4.13%,95%CI:-4.87 to-3.39,I2=54%,P<0.00001)body weight reduction.Beinaglutide also outperformed the control group in achieving weight loss by 5%(OR 4.61)and 10%(OR=5.34).The superiority of beinaglutide vs the control group was also found in reducing BMI(MD=-1.22 kg/m2,95%CI:-1.67 to-0.77)and WC(MD=-2.47 cm,95%CI:-3.74 to-1.19]).Beinaglutide and the control group had comparable impacts on blood pressure,glycemic parameters,insulin resistance,hepatic transaminases,and lipid profile.Beinaglutide posed higher risks of treatment discontinuation due to AEs(RR=3.15),nausea(RR=4.51),vomiting(RR=8.19),palpitation(RR=3.95),headache(RR=2.87),and dizziness(RR=6.07)than the control.However,the two groups had identical risks of total and serious AEs,diarrhea,fatigue,and hypoglycemia.CONCLUSION Short-term data from RCTs suggested that beinaglutide causes modest benefits in reducing body weight,BMI,and WC,with no significant difference in glycemic and other metabolic endpoints compared to the control arm.Safety data were consistent with those of the other drugs in the glucagon-like polypeptide-1 receptor agonist class.Larger RCTs are warranted to prove the longer-term metabolic benefits of beinaglutide. 展开更多
关键词 Beinaglutide Glucagon-like polypeptide-1 receptor agonist Obesity Type 2 diabetes Weight reduction Metaanalysis
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Pharmacological management of type 2 diabetes mellitus in children and adolescents: A systematic review and network meta-analysis 认领 引用 被引量：1
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作者 Charles A Gagnon Katherine Buchanan +5 位作者 Jill M Deaver Jessica A Schmitt Ian M Lahart Sahana Shetty Ambika P Ashraf Joseph M Pappachan 《World Journal of Diabetes》 SCIE 2025年第7期328-341,共14页
BACKGROUND The incidence of type 2 diabetes mellitus(T2DM)in children and adolescents is increasing,yet there is limited information on the available pharmacological interventions to combat T2DM and prevent associated... BACKGROUND The incidence of type 2 diabetes mellitus(T2DM)in children and adolescents is increasing,yet there is limited information on the available pharmacological interventions to combat T2DM and prevent associated comorbidities.AIM To assess the effectiveness of current pharmacological treatments in managing T2DM in children and adolescents.The protocol of the study was registered in PROSPERO(CRD42022382165).METHODS Searches were performed in PubMed,EMBASE,Scopus,and ClinicalTrials.gov for publications between 1990 to September 2024 without language restrictions.Randomized control trials(RCTs)of pharmacotherapy in children and adolescents with T2DM(aged<19 years)were included.The primary outcome was a change in glycated hemoglobin(HbA1c)from baseline to follow-up.Secondary outcomes were changes in body weight,body mass index(BMI),total cholesterol,triglycerides,high density lipoprotein,and low-density lipoprotein from baseline,and incidence of adverse events during study periods.Screening,full-text review,data extraction,and assessments of risk of bias were done by two reviewers.Conflicts on each step were resolved by a third reviewer.Data analysis was performed using Review Manager Version 6.5(RevMan 6.5)and‘R’software via RStudio,‘meta’and‘netmeta’.RESULTS A total of 12 studies having low to moderate risk of bias with 1658 participants,and follow-up duration 12-52 weeks were included.In our network meta-analysis,compared to control(s),the reduction of HbA1c was sig-nificantly larger for dulaglutide[mean difference(MD),95%confidence interval:-1.20,-2.12 to-0.28],followed by dapagliflozin(-0.94,-1.44 to-0.44),liraglutide(-0.91,-1.37 to-0.45),empagliflozin(-0.87,-1.40 to-0.34),exenatide(-0.59,-1.07 to-0.11)and linagliptin(-0.45,-0.87 to-0.02)while other drugs had little or no effect.While liraglutide was associated with a change in body weight[MD-2.41(-4.68,-0.14)kg],no other drug treatment was associated with significant changes in body weight,BMI,and lipids.Apart from level 1 hypoglycemia with liraglutide[risk difference(RD):0.20,0.04-0.37]and minor adverse events with dulaglutide(RD:0.24,0.08-0.40),no other treatment was associated with excess risk of hypoglycemia or minor or major adverse events.CONCLUSION Pharmacotherapy of T2DM with dulaglutide,dapagliflozin,liraglutide,empagliflozin,exenatide,and linagliptin in children is associated with modest reduction of HbA1c.Larger RCTs with longer follow-up durations are needed to guide better therapeutic decision making. 展开更多
关键词 Type 2 diabetes mellitus Pharmacotherapy Children Adolescents Obesity Diabesity Glycemic control
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Renal effects and safety of tirzepatide in subjects with and without diabetes:A systematic review and meta-analysis 认领 引用 被引量：1
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作者 ABM Kamrul-Hasan Shinjan Patra +4 位作者 Deep Dutta Lakshmi Nagendra AFM Muntahi-Reza Sanja Borozan Joseph M Pappachan 《World Journal of Diabetes》 SCIE 2025年第2期270-283,共14页
BACKGROUND Type 2 diabetes(T2D),as well as obesity,are risk factors for chronic kidney disease(CKD)and end-stage renal disease.The renal impacts of glucose-lowering and weight-lowering drugs and their potential benefi... BACKGROUND Type 2 diabetes(T2D),as well as obesity,are risk factors for chronic kidney disease(CKD)and end-stage renal disease.The renal impacts of glucose-lowering and weight-lowering drugs and their potential benefits in preventing CKD often guide clinicians in choosing them appropriately.Only limited data based on randomized controlled trials(RCTs)is currently available on the renal effects and safety profile of tirzepatide.AIM To explore the renal benefits and safety of tirzepatide vs controls.METHODS RCTs involving patients receiving tirzepatide for any indication in the intervention arm and placebo or active comparator in the control arm were searched through multiple electronic databases.The co-primary outcomes were percent change from baseline(CFB)in urine albumin-to-creatinine ratio(UACR)and absolute CFB in estimated glomerular filtration rate(eGFR;in mL/min/1.73 m2);the secondary outcome was tirzepatide’s renal safety profile.RevMan web was used to conduct meta-analysis using random-effects models.Outcomes were presented as mean differences(MD)or risk ratios with 95%confidence intervals.RESULTS Fifteen RCTs(n=14471)with mostly low risk of bias(RoB)were included.Over 26-72 weeks,tirzepatide 10 mg[MD-26.95%(-40.13,-13.76),P0.05 for all vs insulin.Tirzepatide(pooled and separate doses)did not increase the risks of adverse renal events,urinary tract infection,nephrolithiasis,acute kidney injury,and renal cancer compared to the placebo,insulin,and glucagon-like peptide-1 receptor agonists.CONCLUSION Short-term data from RCTs with low RoB suggests that tirzepatide positively impacts UACR without detrimental effects on eGFR in subjects with T2D and obesity without T2D,with a reassuring renal safety profile.Larger RCTs are warranted to prove the longer-term renal benefits of tirzepatide,which might also prevent eGFR decline and worsening of CKD. 展开更多
关键词 Tirzepatide Type 2 diabetes Obesity Urine albumin creatinine ratio Estimated glomerular filtration rate Renal safety Acute kidney injury Chronic kidney disease
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Efficacy and safety of incretin co-agonists:Transformative advances in cardiometabolic healthcare 认领 引用 被引量：1
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作者 Sowrabha Bhat Cornelius J Fernandez +1 位作者 Vijaya Lakshmi Joseph M Pappachan 《World Journal of Cardiology》 2025年第8期9-25,共17页
The ground-breaking development of the incretin agonists by manipulation of the incretin system,including the gut hormones glucagon-like peptide-1(GLP-1)and glucose-dependent insulinotropic polypeptide(GIP),as well as... The ground-breaking development of the incretin agonists by manipulation of the incretin system,including the gut hormones glucagon-like peptide-1(GLP-1)and glucose-dependent insulinotropic polypeptide(GIP),as well as the pancreatic hor-mone glucagon,has led to the emergence of promising pharmacotherapy for metabolic health.The GLP-1 receptor agonists(GLP-1RAs),namely liraglutide,dulaglutide,albiglutide,exenatide,and semaglutide,have been found to have beneficial effects on glycated hemoglobin,weight,lipid profile,and liver fat and thereby improving cardiometabolic health.Other drugs of the same group in development include Orforglipron,which has a high weight loss efficacy(-15%weight reduction).Long-acting GLP-1RAs in trials are Ecnoglutide,Efpeglenatide,TG103,and Visepegenatide.Many of these have cardiovascular benefits in terms of reduction in MACE(Non-fatal MI,Non-fatal stroke,and mortality).Tirzepatide is a dual GIP/GLP-1RA,the first drug of the group to be approved for diabetes and obesity with remarkably lower gastrointestinal side effects compared to GLP-1 monoagonists.The dual GLP-1/glucagon co-agonists cause tremendous weight loss due to the synergistic action.Most drugs in this class are long-acting and developed for once-weekly administration.The revolutionary triple agonists at the GLP-1,GIP,and Glucagon receptors have demonstrated the highest achievable weight loss with pharmaco-therapy.Retatrutide and Efocipegtrutide belong to this novel group of drugs.The newer drugs in the broad category of incretin co-agonists include the GLP-1/amylin receptor agonist like CagriSema and Amycretin,oral GLP-1 agonists other than semaglutide,and the peptide YY/GLP-1 receptor dual agonists.The profound bioche-mical and weight loss outcomes associated with incretin co-/poly-agonists are expected to translate into outstanding cardiometabolic benefits,the theme of this evidence review. 展开更多
关键词 Incretin co-agonists Incretin poly-agonists Metabolic health Type 2 diabetes mellitus Obesity Cardiovascular safety
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Current perspectives and the future of disease-modifying therapies in type 1 diabetes 认领 引用 被引量：1
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作者 Sunetra Mondal Joseph M Pappachan 《World Journal of Diabetes》 SCIE 2025年第1期12-21,共10页
Use of immunomodulating agents to prevent the progression of autoimmuneβ-cell damage leading to type 1 diabetes mellitus(T1DM)is an interesting area for research.These include non-specific anti-inflammatory agents,im... Use of immunomodulating agents to prevent the progression of autoimmuneβ-cell damage leading to type 1 diabetes mellitus(T1DM)is an interesting area for research.These include non-specific anti-inflammatory agents,immunologic vaccination and anti-inflammatory agents targeting specific immune cells or cytokines.Teplizumab is an anti-CD3-molecule that binds to and leads to the disappearance of the CD3/TCR complex and rendering the T cell anergic to its target antigen.Preclinical and clinical trials have demonstrated its efficacy in reducing the decline in serum C-peptide levels and the need for insulin therapy if used early in the disease process of T1DM.The benefits have been apparent as early as six months to as long as seven years after therapy.It has recently been approved by the Food and Drug Administration to delay the onset of clinical(stage 3)type 1 diabetes in children above 8 years of age.In their recent metaanalysis published in the World Journal of Diabetes,Ma et al found that those in the teplizumab treatment group have a greater likelihood of reduction in insulin use,change in C-peptide response,and better glycemic control compared to the control group with a good safety profile.However,all the included randomized control trials have been conducted in high-income countries.High cost of therapy and unknown utility of the molecule in stage 3 disease limit its widespread use. 展开更多
关键词 Teplizumab Type 1 diabetes mellitus Disease modifying therapy β-cell function C-peptide Immunotherapy
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Glycemic control,weight-loss effects,and safety of cotadutide in individuals with type 2 diabetes:A systematic review and metaanalysis 认领 引用
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作者 Abul Bashar Mohammad Kamrul-Hasan Deep Dutta +4 位作者 Lakshmi Nagendra Sindhu Doddabokikere Basavarajappa Harish Bukkasagar Girijashankar Ameya Joshi Joseph M Pappachan 《World Journal of Diabetes》 SCIE 2025年第12期211-226,共16页
BACKGROUND Cotadutide(MEDI0382)is a twincretin that acts as an agonist for both the glucagon-like peptide-1 and glucagon receptors.Several randomized controlled trials(RCTs)have been published evaluating the use of co... BACKGROUND Cotadutide(MEDI0382)is a twincretin that acts as an agonist for both the glucagon-like peptide-1 and glucagon receptors.Several randomized controlled trials(RCTs)have been published evaluating the use of cotadutide in individuals with type 2 diabetes(T2D),showing promising results.However,the efficacy and safety of the drug use have been inadequately explored by systematic reviews and meta-analyses.AIM To assess the clinical efficacy and safety of cotadutide in individuals with T2D having overweight or obesity.METHODS The systematic reviews and meta-analyses have been registered with International Prospective Register of Systematic Reviews(CRD42024511703),and the protocol summary can be accessed online.Several databases and registries,including MEDLINE(via PubMed),Scopus,Web of Science,the Cochrane Central Register of Controlled Trials,and ClinicalTrials.gov,were systematically searched using related terms from their inception to May 15,2025,for RCTs involving individuals with T2D receiving cotadutide in the intervention group.Review Manager web was used to conduct meta-analysis using random-effects models.The co-primary outcomes of interest were the changes in glycated hemoglobin(HbA1c)and the percent changes in body weight from baseline.The results of the outcomes were expressed as mean differences(MDs)or risk ratios(RRs)with 95%confidence intervals(CIs).The analysis of outcomes was stratified according to whether the control group received a placebo,denoted as the placebo control group(PCG),or an active comparator,referred to as the active control group(ACG).RESULTS Nine RCTs(mostly phase 2 RCTs,n=1525)with study durations varying from 28 days to 54 weeks that met all the inclusion criteria were analyzed;five studies had a low overall risk of bias,while the other four had some concerns.Compared to the PCG,greater reductions in HbA1c were achieved with cotadutide 100μg(MD-0.77%,95%CI:-1.06 to-0.47),200μg(MD-0.68%,95%CI:-1.12 to-0.23),300μg(MD-0.67%,95%CI:-0.79 to-0.56),and 600μg(MD-0.69%,95%CI:-0.97 to-0.41).Cotadutide 100μg(MD-1.74%,95%CI:-3.23 to-0.25),200μg(MD-2.56%,95%CI:-3.37 to-1.75),300μg(MD-3.49%,95%CI:-4.14 to-2.84),and 600μg(MD-5.45%,95%CI:-7.17 to-3.73)achieved greater percent reductions in body weight from baseline.However,the certainty of evidence for HbA1c and percent body weight reductions was very low to low.Cotadutide,at all doses,also outperformed PCG in reducing fasting plasma glucose and absolute body weight.The changes in HbA1c,percent body weight,fasting plasma glucose,and absolute body weight were similar between the cotadutide group and the ACG.Compared to PCG,pooled doses of cotadutide increased the risks of treatment-emergent adverse events(AEs),treatment-related AEs,and discontinuation of the study drug due to AEs,but not for serious AEs.More subjects experienced overall gastrointestinal AEs,dyspepsia,nausea,vomiting,constipation,and decreased appetite with cotadutide than with PCG.Compared to the ACG,none of the AEs showed increased risk in the cotadutide group.CONCLUSION Cotadutide demonstrated glycemic control and weight-loss benefits in short-term,small RCTs(mostly phase 2).However,small sample sizes,very low to low certainty of evidence,and the absence of data on long-term cardiovascular and renal outcomes highlight substantial uncertainties,warranting cautious interpretation and further investigation in larger,longer-term trials to establish its safety and efficacy profile. 展开更多
关键词 Cotadutide Type 2 diabetes Obesity Diabesity Glycated hemoglobin Body weight Adverse events
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Role of automated insulin delivery in managing insulin-treated outpatients with type 2 diabetes: A systematic review and metaanalysis 认领 引用
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作者 Abul Bashar Mohammad Kamrul-Hasan Joseph M Pappachan +4 位作者 Lakshmi Nagendra Nazma Akter Sweekruti Jena Deep Dutta Sunil Nair 《World Journal of Diabetes》 SCIE 2025年第10期385-401,共17页
BACKGROUND Automated insulin delivery(AID)systems have demonstrated benefits in managing patients with type 2 diabetes(T2D),but data are still limited.Moreover,the efficacy and safety of the AID systems in these patie... BACKGROUND Automated insulin delivery(AID)systems have demonstrated benefits in managing patients with type 2 diabetes(T2D),but data are still limited.Moreover,the efficacy and safety of the AID systems in these patients have been inadequately explored by systematic reviews and meta-analyses.AIM To provide a comprehensive understanding of the optimal use of AID in managing insulin-treated outpatients with T2D.METHODS A systematic search of multiple databases and registries,including MEDLINE,Scopus,Web of Science,Cochrane Library,and ClinicalTrials.gov,was conducted from inception to May 15,2025,to identify studies on AID use for outpatients with T2D.The co-primary outcomes were the change in glycated hemoglobin(HbA1c)and continuous glucose monitoring(CGM)metrics.Statistical analyses were conducted using Review Manager Web software with random-effects models and the inverse variance statistical method.The results were presented as mean differences(MDs)or risk ratios(RRs)with 95%CI.RESULTS A total of 15 studies with 28985 participants were identified,including 6 randomized trials(n=748;3 crossover and 3 parallel-group trials)and 9 single-arm studies.All included randomized trials raised some concerns,and the single-arm studies had serious risks of overall bias.Meta-analysis of randomized trials showed that AID is more effective than the control group in lowering HbA1c(MD:-0.89%,95%CI:-1.32 to-0.46,P10 mmol/L(MD:-19.48%,95%CI:-27.14 to-11.82,P<0.00001,I2=73%);however,time below range remained similar between the two groups.The mean sensor glucose level was lower in the AID group;however,the coefficient of variation of glucose was the same in both groups.AID use also led to a reduction in insulin dose,but this is not a consistent finding across all study designs.The risks of serious adverse events(AEs)and severe hypoglycemia were similar in both groups;however,AID use raised the risk of device deficiency.Single-arm studies with participants using AID systems also demonstrated reductions in HbA1c(ranging from 0.7%to 2.07%)and improvements in CGM metrics,along with acceptable safety data.CONCLUSION Based on short-term study data,the use of AID systems in outpatients with T2D appears to improve glycemic outcomes and CGM metrics,with no significant AEs.Larger and longer-term randomized controlled trials involving diverse populations,along with a cost-benefit analysis,are needed to guide more informed clinical practice decisions. 展开更多
关键词 Automated insulin delivery Type 2 diabetes Time in range Glycated hemoglobin Meta-analysis
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Prevalence of diabetes distress among people with type 2 diabetes in South Asia:A systematic review and meta-analysis 认领 引用
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作者 Abul Bashar Mohammad Kamrul-Hasan Joseph M Pappachan +8 位作者 Lakshmi Nagendra Dimuthu Muthukuda Deep Dutta Saptarshi Bhattacharya Dina Shrestha Guru Prasad Dhakal Manilka Sumanatilleke Syed Abbas Raza Sanjay Kalra 《World Journal of Diabetes》 SCIE 2025年第8期316-330,共15页
BACKGROUND Diabetes distress(DD),an emotional problem arising from the challenges of living with diabetes and the relentless burden of daily self-management,is common among patients with type 2 diabetes(T2D).South Asi... BACKGROUND Diabetes distress(DD),an emotional problem arising from the challenges of living with diabetes and the relentless burden of daily self-management,is common among patients with type 2 diabetes(T2D).South Asia has a high T2D burden,and many studies have reported varying prevalence rates of DD in this area.AIM To estimate the pooled prevalence of DD among patients with T2D in South Asia,as it is crucial for developing effective therapeutic strategies.METHODS This systematic review and meta-analysis included cross-sectional studies conducted in South Asian countries involving adults with T2D and reported the prevalence of DD.The studies were identified by searching multiple electronic databases and registries from the inception of each database to January 30,2025,using prespecified search terms.Four authors screened and extracted data independently.Meta-analyses were conducted using RStudio software with a random-effects model.The primary outcome was the pooled prevalence of DD.RESULTS Thirty-seven cross-sectional studies(28 from India,five from Bangladesh,and two each from Pakistan and Sri Lanka)with mostly high methodological quality involving 11500 subjects were included.The pooled prevalence of DD was 44%(95%confidence interval:35-53,I2=97.4%).The prevalence of DD was highest in Pakistan(85%),followed by India and Bangladesh(42%each),and Sri Lanka(25%).Emotional burden was the most prevalent form of DD(60%),followed by treatment regimen-related distress(51%),interpersonal distress(31%),and physician-related distress(17%).Meta-regression analysis revealed no significant associations between the prevalence of DD and publication year,sample size,proportion of females,age,duration of diabetes,insulin usage,glycated hemoglobin levels,or diabetic complications.CONCLUSION South Asians with T2D seem to experience a relatively high burden of DD,and the emotional burden is the most common form of DD in this area.Larger studies utilizing unique tools and involving a broader participant base from the region would provide better epidemiological data for effectively planning high-quality diabetes care in South Asian countries. 展开更多
关键词 Type 2 diabetes Diabetes distress South Asia Prevalence Systematic reviews
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Safety and efficacy of glucagon-like peptide-1 receptor agonists in individuals with type 2 diabetes mellitus fasting during Ramadan:a systematic review and meta-analysis 认领 引用
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作者 Abul Bashar Mohammad Kamrul-Hasan Joseph M Pappachan +4 位作者 Hamid Ashraf Lakshmi Nagendra Deep Dutta Mohammad Shafi Kuchay Shehla Shaikh 《World Journal of Methodology》 2025年第4期374-384,共11页
BACKGROUND Data on the use of glucagon-like peptide-1 receptor agonists(GLP-1RAs)in individuals with type 2 diabetes mellitus(T2DM)during Ramadan fasting is limited.No meta-analysis has summarized the safety and effec... BACKGROUND Data on the use of glucagon-like peptide-1 receptor agonists(GLP-1RAs)in individuals with type 2 diabetes mellitus(T2DM)during Ramadan fasting is limited.No meta-analysis has summarized the safety and effectiveness of GLP-1RAs in these situations.AIM To evaluate the safety and efficacy of GLP-1RA in patients with T2DM fasting during Ramadan.METHODS Electronic databases were systematically searched for relevant studies that featured GLP-1RA in the intervention arm and other glucose-lowering medications in the control arm.The primary outcome was adverse events(AEs)during Ramadan for both groups;other outcomes included changes in glycemic and anthropometric measures during the peri-Ramadan period.RESULTS Four studies[three randomized-controlled trials with low risk of bias(RoB)and one prospective observational study with serious RoB]involving 754 subjects were analyzed.GLP-1RA group achieved greater glycated hemoglobin reduction than the non-GLP-1RA group[mean difference(MD):-0.31%,95%CI:-0.61 to-0.01,P=0.04,I2=77%]with a lower risk of documented symptomatic hypoglycemia(risk ratio=0.38,95%CI:0.16 to 0.88,P=0.02).Any AEs,serious AEs,or AEs that led to treatment discontinuation were comparable between the two groups.The GLP-1RA group experienced greater weight loss compared to the non-GLP-1RA group(MD:-2.0 kg,95%CI:-3.37 to-0.63,P=0.004,I2=95%).There were comparable changes in blood pressure and lipid profile between the two groups.GLP-1RA users experienced higher risks of gastrointestinal AEs,nausea,and vomiting;however,the risks of heartburn,abdominal pain,and diarrhea were similar in both groups.CONCLUSION Limited evidence suggests that GLP-1RAs are safe for T2DM management during Ramadan,offering modest benefits in blood sugar control and weight loss.Large multicenter trials are needed to confirm their safety and efficacy in at-risk populations,improving clinical practice decision-making. 展开更多
关键词 Type 2 diabetes mellitus Glucagon-like peptide-1 receptor agonist Ramadan Religious fasting Safety Metaanalysis
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Diabetic ketoacidosis in patients with type 2 diabetes:Risk factors for mortality and adverse outcomes 认领 引用 被引量：1
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作者 Vishnu Chandrabalan Timothy Howcroft +3 位作者 Mohammed Khalid Alkhalifah Noorulanne Younis Ebrahim Aldhafiri Joseph M Pappachan 《World Journal of Experimental Medicine》 2026年第1期161-170,共10页
BACKGROUND Diabetic ketoacidosis(DKA)resulting from type 2 diabetes mellitus(T2DM)is less common,and the factors associated with adverse outcomes and mortality are not well established based on large-scale studies.AIM... BACKGROUND Diabetic ketoacidosis(DKA)resulting from type 2 diabetes mellitus(T2DM)is less common,and the factors associated with adverse outcomes and mortality are not well established based on large-scale studies.AIM To identify the risk factors for adverse outcomes and mortality in treated patients with DKA in T2DM.METHODS Retrospective analysis of patients admitted to a tertiary-care hospital in the United Kingdom with DKA and T2DM for inpatient management between January 2010 to September 2024 to identify the clinical profile,demographic features,and laboratory parameters impacting treatment outcomes and survival.RESULTS Four hundred and sixty-four patients were included.Of these 395(85.13%)were White,266(57.3%)were males with a mean age at presentation of 61.3(17.6)years,median inpatient hospital stay of 5(interquartile range:3-10.3)days,and a mean glycated HbA1c of 89.3(30)mmol/mol.The 30-day and 90-day mortality were 13.4%and 11%respectively after the index DKA event.The long-term survival after the DKA event was only 58.6%.Presence of cerebrovascular disease[odds ratio(OR):6.75;95%CI:0.76-12.74],use of sodium glucose cotransporter 2 inhibitors(OR:5.8;95%CI:1.32-9.62),chronic obstructive pulmonary disease(OR:3.6;95%CI:2.14-6.44),higher national early warning score 2 score(OR:1.14;95%CI:0.10-2.18)and low systolic blood pressure(OR:-0.18;95%CI:-0.32 to-0.04)at admission were the significant predictors of longer inpatient stay.Coexistent peripheral vascular disease(PVD;OR:46.43)and congestive heart failure(CHF;OR:30.83),and lower estimated glomerular filtration rate(eGFR;OR:0.98)were the important predictors of mortality during the hospital treatment.The significant predictors on 30-day mortality were:Age(OR:1.06),eGFR(0.97)and index of multiple deprivation(IMD)decile(0.74).The factors associated with long-term mortality risk were dementia(20.54-fold higher),continued use of sulfonylurea/metformin,and older age(4%higher with each additional year).CONCLUSION DKA carries a serious risk of mortality in both the short and long term in T2DM patients.Factors such as older age,dementia,PVD,CHF,low eGFR define the riskiest groups.These groups of patients may benefit from closer follow-up and more aggressive metabolic and comorbidity management after discharge. 展开更多
关键词 Type 2 diabetes mellitus Diabetic ketoacidosis Dementia Peripheral vascular disease Heart failure Mortality risk
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Glucagon-like peptide-1 receptor agonists in type 2 diabetes:Evidence for disease modification and therapeutic switching 认领 引用
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作者 Vanishri Ganakumar Cornelius J Fernandez Joseph M Pappachan 《World Journal of Diabetes》 SCIE 2026年第6期1-10,共10页
The discovery of the incretin system and the subsequent development of pharmacotherapeutic agents to manipulate incretin hormones,such as glucagon-like peptide-1(GLP-1)and glucose-dependent insulinotropic polypeptide,... The discovery of the incretin system and the subsequent development of pharmacotherapeutic agents to manipulate incretin hormones,such as glucagon-like peptide-1(GLP-1)and glucose-dependent insulinotropic polypeptide,as well as glucagon,with various drugs,have revolutionised the management of type 2 diabetes mellitus(T2DM)in the 21st century.The first few drug molecules in this group were the GLP-1 receptor agonists(GLP-1RA),which have been used for treating patients with T2DM in the past 2 decades,and newer molecules,including incretin polyagonists,are being added to the growing list of incretinbased drugs in recent years.Generally,these newer molecules possess longer biological half-lives and dosing intervals,better weight loss potentials,higher efficacy in glycemic control and possibly improved disease-modifying properties such as a higher chance for T2DM remission and better cardiometabolic outcomes.Therefore,newer incretin-based medications are currently preferred by many diabetologists and switching from older molecules to the newer ones is not uncommon in day-to-day clinical practice.However,outside the remit of randomised controlled trial settings,there is only limited evidence emerging from real-world data.A study by Kassem et al published in the World Journal of Diabetes provides us with robust evidence from a large real-world study of 18047 patients with T2DM from Israel on the benefits of switching from an old GLP-1RA to a newer agent,with a remarkable improvement in glycemic control.With the most up-to-date evidence,we update the rationale for switching GLP-1RA molecules in managing T2DM with a detailed review of the therapeutic benefits,including the anticipated cardiometabolic outcomes and cost benefit analysis from such switching in this editorial. 展开更多
关键词 Glucagon-like peptide-1 receptor agonists Incretin polyagonists Type 2 diabetes mellitus Switching glucagonlike peptide-1 receptor agonist Glycemic control
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Management of metabolic-associated fatty liver disease: The diabetology perspective 认领 引用 被引量：12
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作者 Mohammad Sadiq Jeeyavudeen Shahanas K A Khan +1 位作者 Sherouk Fouda Joseph M Pappachan 《World Journal of Gastroenterology》 SCIE CAS 2023年第1期126-143,共18页
The metabolic syndrome as a consequence of the obesity pandemic resulted in a substantial increase in the prevalence of metabolic-associated fatty live disease(MAFLD)and type 2 diabetes mellitus(T2DM).Because of the s... The metabolic syndrome as a consequence of the obesity pandemic resulted in a substantial increase in the prevalence of metabolic-associated fatty live disease(MAFLD)and type 2 diabetes mellitus(T2DM).Because of the similarity in pathobiology shared between T2DM and MAFLD,both disorders coexist in many patients and may potentiate the disease-related outcomes with rapid progression and increased complications of the individual diseases.In fact,awareness about this coexistence and the risk of complications are often overlooked by both hepatologists and diabetologists.Management of these individual disorders in a patient should be addressed wholistically using an appropriate multidisciplinary team approach involving both the specialists and,when necessary,liaising with dieticians and surgeons.This comprehensive review is to compile the current evidence from a diabetologist's perspective on MAFLD and T2DM and to suggest optimal management strategies. 展开更多
关键词 Metabolic syndrome Metabolic-associated fatty liver disease Type 2 diabetes mellitus Nonalcoholic fatty liver disease Nonalcoholic steatohepatitis Diabetology perspective Obesity
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Helicobacter pylori and diabetic complications:Stronger evidence for the interlink 认领 引用
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作者 Sanja Medenica Cornelius J Fernandez Joseph M Pappachan 《World Journal of Diabetes》 SCIE 2026年第6期62-71,共10页
An association between Helicobacter pylori(H.pylori)infection and various systemic diseases,including diabetes mellitus(DM),has been well known for several years.H.pylori infection can result in metabolic dysregulatio... An association between Helicobacter pylori(H.pylori)infection and various systemic diseases,including diabetes mellitus(DM),has been well known for several years.H.pylori infection can result in metabolic dysregulation through the contribution to the development of insulin resistance,β-cell dysfunction,systemic inflammation,and hormonal signalling with alterations in glucose and lipid homeostasis.This can result in metabolic syndrome and type 2 DM.An association between H.pylori and immune-mediated diseases such as autoimmune thyroiditis and type 1 DM has been identified.Emerging evidence also points to a strong bidirectional relationship between type 2 DM and H.pylori infection,leading to worsening of either disease and/or its complications.Therefore,DM patients with H.pylori infection are likely to have more aggressive disease with the development of various end-organ complications of diabetes early in their disease course,mandating rigorous monitoring.A recent basic study investigating the interlink between H.pylori infection and DM provides strong evidence of worse damage to the stomach,liver,and kidneys in diabetic mouse models.In this article,we outline our current understanding of the association between H.pylori disease and diabetic complications. 展开更多
关键词 Autoimmune disorders Helicobacter pylori Metabolic dysregulation Type 1 diabetes mellitus Type 2 diabetes mellitus
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Management of diabesity:Current concepts 认领 引用 被引量：15
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作者 Maria Michaelidou Joseph M Pappachan Mohammad Sadiq Jeeyavudeen 《World Journal of Diabetes》 SCIE 2023年第4期396-411,共16页
The global prevalence of obesity is increasing rapidly with an exponential rise in incidence of type 2 diabetes mellitus in recent years.‘Diabesity’,the term coined to show the strong interlink between obesity and d... The global prevalence of obesity is increasing rapidly with an exponential rise in incidence of type 2 diabetes mellitus in recent years.‘Diabesity’,the term coined to show the strong interlink between obesity and diabetes,is the direct cons-equence of the obesity pandemic,and poses significant challenges in the management of the disease.Without addressing the clinical and mechanistic complications of obesity such as metabolic-associated fatty liver disease and obstructive sleep apnoea,a rational management algorithm for diabesity cannot be developed.Several classes of anti-diabetic medications including insulins,sulphonylureas,thiazolidinediones and meglitinides are associated with the risk of weight gain and may potentially worsen diabesity.Therefore,appropriate selection of antidiabetic drug regimen is crucial in the medical management of diabesity.The role of non-pharmacological measures such as dietary adjustments,exercise interventions and bariatric procedures should also be emphasised.Unfortunately,the importance of appropriate and optimal management of diabesity is often overlooked by medical professionals when achieving adequate glycemic control which results in inappropriate management of the disease and its complications.This review provides a narrative clinical update on the evidence behind the management of diabesity. 展开更多
关键词 Obesity Diabesity Metabolic-associated fatty liver disease Antidiabetic medications Glycemic control Metabolic surgery
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Incretin polyagonists as an alternative to bariatric surgery to manage obesity 认领 引用
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作者 Rohit Jacob Manoj Cornelius J Fernandez +1 位作者 Sunil Nair Joseph M Pappachan 《World Journal of Gastrointestinal Pathophysiology》 2026年第1期16-26,共11页
Incretins are gut hormones involved in maintaining metabolic homeostasis in the human body,and disorders of the incretin system are recognized as contributing to the pathobiology of metabolic dysfunction and obesity.I... Incretins are gut hormones involved in maintaining metabolic homeostasis in the human body,and disorders of the incretin system are recognized as contributing to the pathobiology of metabolic dysfunction and obesity.Incretin polyagonists are transforming the landscape of obesity treatment by offering potent,non-surgical alternatives to bariatric procedures.Acting on multiple incretin and related receptors,these novel pharmacological agents harness the synergistic effects of gut hormones such as glucagon-like peptide-1,glucose-dependent insulinotropic polypeptide,and glucagon to achieve unprecedented weight loss and metabolic improvements.Recent clinical trials demonstrate that dual and triple agonists can produce weight reductions comparable to,or in some cases approaching,those seen with bariatric surgery,while simultaneously improving glycemic control,lipid profiles,liver fat,and cardiovascular risk factors.Unlike conventional monotherapies,these polyagonists address the complexity of energy homeostasis and metabolic dysfunction in obesity,with some agents displaying a favorable side effect profile and thereby enhancing patient tolerability.Practical considerations,such as ease of administration,cost,long-term safety,and accessibility,remain evolving challenges;yet,incretin polyagonists have rapidly gained prominence in clinical guidelines for the management of obesity and type 2 diabetes mellitus.As evidence mounts regarding their efficacy,safety,and potential to modify cardiometabolic disease risk,incretin polyagonists emerge as promising alternatives,especially for patients unable or unwilling to undergo bariatric surgery.Ongoing research will further define their long-term role,comparative effectiveness,and optimal integration into multidisciplinary obesity care.This review discusses the current evidence-base for optimal use of incretin polyagonists as an alternative to bariatric surgery. 展开更多
关键词 Incretin polyagonists Obesity Bariatric surgery Weight loss Metabolic health Tirzepatide Type 2 diabetes mellitus
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Rising tide: The global surge of type 2 diabetes in children and adolescents demands action now 认领 引用 被引量：2
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作者 Joseph M Pappachan Cornelius James Fernandez Ambika P Ashraf 《World Journal of Diabetes》 SCIE 2024年第5期797-809,共13页
Childhood-onset obesity has emerged as a major public healthcare challenge across the globe,fueled by an obesogenic environment and influenced by both genetic and epigenetic predispositions.This has led to an exponent... Childhood-onset obesity has emerged as a major public healthcare challenge across the globe,fueled by an obesogenic environment and influenced by both genetic and epigenetic predispositions.This has led to an exponential rise in the incidence of type 2 diabetes mellitus in children and adolescents.The looming wave of diabetes-related complications in early adulthood is anticipated to strain the healthcare budgets in most countries.Unless there is a collective global effort to curb the devastation caused by the situation,the impact is poised to be pro-found.A multifaceted research effort,governmental legislation,and effective social action are crucial in attaining this goal.This article delves into the current epidemiological landscape,explores evidence concerning potential risks and consequences,delves into the pathobiology of childhood obesity,and discusses the latest evidence-based management strategies for diabesity. 展开更多
关键词 Childhood obesity Diabesity Type 2 diabetes mellitus Adolescence Cardiovascular disease Pharmacotherapy
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Clinical implications of COVID-19 in patients with metabolicassociated fatty liver disease 认领 引用 被引量：1
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作者 Mohammad Sadiq Jeeyavudeen Rahul Chaudhari +1 位作者 Joseph M Pappachan Sherouk Fouda 《World Journal of Gastroenterology》 SCIE CAS 2023年第3期487-502,共16页
People across the world are affected by the"coronavirus disease 2019(COVID-19)",brought on by the"SARS-CoV type-2 coronavirus".Due to its high incidence in individuals with diabetes,metabolic syndr... People across the world are affected by the"coronavirus disease 2019(COVID-19)",brought on by the"SARS-CoV type-2 coronavirus".Due to its high incidence in individuals with diabetes,metabolic syndrome,and metabolic-associated fatty liver disease(MAFLD),COVID-19 has gained much attention.The metabolic syndrome's hepatic manifestation,MAFLD,carries a significant risk of type-2-diabetes.The link between the above two conditions has also drawn increasing consideration since MAFLD is intricately linked to the obesity epidemic.Independent of the metabolic syndrome,MAFLD may impact the severity of the viral infections,including COVID-19 or may even be a risk factor.An important question is whether the present COVID-19 pandemic has been fueled by the obesity and MAFLD epidemics.Many liver markers are seen elevated in COVID-19.MAFLD patients with associated comorbid conditions like obesity,cardiovascular disease,renal disease,malignancy,hypertension,and old age are prone to develop severe disease.There is an urgent need for more studies to determine the link between the two conditions and whether it might account for racial differences in the mortality and morbidity rates linked to COVID-19.The role of innate and adaptive immunity alterations in MAFLD patients may influence the severity of COVID-19.This review investigates the implications of COVID-19 on liver injury and disease severity and viceversa.We also addressed the severity of COVID-19 in patients with prior MAFLD and its potential implications and therapeutic administration in the clinical setting. 展开更多
关键词 Metabolic-associated fatty liver disease COVID-19 Metabolic syndrome Non-alcoholic steatohepatitis Angiotensin converting enzyme 2
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Management of male obesity-related secondary hypogonadism:A clinical update 认领 引用
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作者 Mohan T Shenoy Sunetra Mondal +1 位作者 Cornelius James Fernandez Joseph M Pappachan 《World Journal of Experimental Medicine》 2024年第2期11-28,共18页
The global obesity pandemic has resulted in a rise in the prevalence of male obesity-related secondary hypogonadism(MOSH)with emerging evidence on the role of testosterone therapy.We aim to provide an updated and prac... The global obesity pandemic has resulted in a rise in the prevalence of male obesity-related secondary hypogonadism(MOSH)with emerging evidence on the role of testosterone therapy.We aim to provide an updated and practical approach towards its management.We did a comprehensive literature search across MEDLINE(via PubMed),Scopus,and Google Scholar databases using the keywords“MOSH”OR“Obesity-related hypogonadism”OR“Testosterone replacement therapy”OR“Selective estrogen receptor modulator”OR“SERM”OR“Guidelines on male hypogonadism”as well as a manual search of references within the articles.A narrative review based on available evidence,recommendations and their practical implications was done.Although weight loss is the ideal therapeutic strategy for patients with MOSH,achievement of significant weight reduction is usually difficult with lifestyle changes alone in real-world practice.Therefore,androgen administration is often necessary in the management of hypogonadism in patients with MOSH which also improves many other comorbidities related to obesity.However,there is conflicting evidence for the appropriate use of testosterone replacement therapy(TRT),and it can also be associated with complications.This evidence-based review updates the available evidence including the very recently published results of the TRAVERSE trial and provides comprehensive clinical practice pearls for the management of patients with MOSH.Before starting testosterone replacement in functional hypogonadism of obesity,it would be desirable to initiate lifestyle modification to ensure weight reduction.TRT should be coupled with the management of other comorbidities related to obesity in MOSH patients.Balancing the risks and benefits of TRT should be considered in every patient before and during longterm management. 展开更多
关键词 Male obesity-related secondary hypogonadism Androgen therapy Testosterone replacement therapy Obesity Cardiovascular benefits
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Metabolic complications of hepatitis C virus infection 认领 引用 被引量：10
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作者 Rahul Chaudhari Sherouk Fouda +1 位作者 Ashik Sainu Joseph M Pappachan 《World Journal of Gastroenterology》 SCIE CAS 2021年第13期1267-1282,共16页
Hepatitis C virus(HCV) infection is a systemic disease that is implicated in multiple extrahepatic organ dysfunction contributing to its protean manifestations. HCV is associated with diverse extrahepatic disorders in... Hepatitis C virus(HCV) infection is a systemic disease that is implicated in multiple extrahepatic organ dysfunction contributing to its protean manifestations. HCV is associated with diverse extrahepatic disorders including atherosclerosis, glucose and lipid metabolic disturbances, alterations in the iron metabolic pathways, and lymphoproliferative diseases over and above the traditional liver manifestations of cirrhosis and hepatocellular carcinoma. The orchestration between HCV major proteins and the liver-muscle-adipose axis, poses a major burden on the global health of human body organs, if not adequately addressed. The close and inseparable associations between chronic HCV infection, metabolic disease, and cardiovascular disorders are specifically important considering the increasing prevalence of obesity and metabolic syndrome, and their economic burden to patients, the healthcare systems, and society. Cellular and molecular mechanisms governing the interplay of these organs and tissues in health and disease are therefore of significant interest. The coexistence of metabolic disorders and chronic hepatitis C infection also enhances the progression to liver fibrosis and hepatocellular carcinoma. The presence of metabolic disorders is believed to influence the chronicity and virulence of HCV leading to liver disease progression. This comprehensive review highlights current knowledge on the metabolic manifestations of hepatitis C and the potential pathways in which these metabolic changes can influence the natural history of the disease. 展开更多
关键词 Chronic hepatitis C infection Insulin resistance Metabolic syndrome Cardiovascular diseases Fatty liver Diabetes mellitus
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