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monogenic diabetes in children:An underdiagnosed and poorly managed clinical dilemma

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World Journal of Diabetes 2024年第6期15卷 1051-1059页

作者： Saptarshi Bhattacharya joseph m pappachan Department of Endocrinology Indraprastha Apollo HospitalsDelhi 110076India Department of Endocrinology and metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine and HealthThe University of ManchesterManchester M139PLUnited Kingdom

monogenic diabetes,constituting 1%-2%of global diabetes cases,arises from single gene defects with distinctive inheritance *** over 50 associated genetic disorders,accurate diagnoses and management of monogenic diabetes remain inadequate,underscoring insufficient clinician *** disease spectrum encompasses maturity-onset diabetes of the young(mODY),characterized by distinct genetic mutations affecting insulin secretion,and neonatal diabetes mellitus(NDm)-a heterogeneous group of severe hyperglycemic disorders in *** diabetes,autoimmune monogenic diabetes,genetic insulin resistance and lipodystrophy syndromes further diversify the monogenic diabetes landscape.A tailored approach based on phenotypic and biochemical factors to identify candidates for genetic screening is recommended for suspected cases of *** diagnosis warrants immediate molecular genetic testing for infants under six *** these genetic defects presents a unique opportunity for precision *** research aimed to develop cost-effective genetic testing methods and gene-based therapy can facilitate appropriate identification and optimize clinical *** and study of new genes offer a valuable opportunity to gain deeper insights into pancreatic cell biology and the pathogenic mechanisms underlying common forms of *** clinical review published in the recent issue of World Journal of Diabetes is such an attempt to fill-in our knowledge gap about this enigmatic disease.

关键词： monogenic diabetes maturity-onset diabetes of the young Neonatal diabetes mitochondrial diabetes Insulin resistance syndromes Genetic testing Next generation sequencing

Periodontitis:An often-neglected complication of diabetes

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World Journal of Diabetes 2024年第3期15卷 318-325页

作者： marina G Kudiyirickal joseph m pappachan Primary Care Dental Practice The Smile ClinicPreston PR16PZUnited Kingdom Department of Endocrinology and metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine and HealthThe University of ManchesterManchester M139PLUnited Kingdom

The bidirectional association between type 2 diabetes mellitus(T2Dm)and periodontitis is now well established,resulting in periodontal disease being considered as the 6th major complication of diabetes mellitus(Dm)after cardiovascular disease,eye disease,neuropathy,nephropathy,and peripheral vascular *** can worsen the virulence and invasiveness of pathogenic oral microbial flora aggravating the local inflammation and infection in those with periodontal *** the other hand,the chemical and immunological mediators released into the circulation as part of periodontal inflammation worsen the systemic insulin resistance with worsening of *** if undiagnosed or left untreated can also result in eventual tooth loss.A study by Xu et al in the World Journal of Diabetes examined the predictive factors associated with periodontitis in Chinese patients with *** prevalence of periodontitis was found to be 75.7%in this *** on logistic regression analysis,the predictive factors for higher risk were low tooth brushing frequency[odds ratio(OR)=4.3],high triglycerides(TG;OR=3.31),high total cholesterol(TC;OR=2.87),higher glycated hemoglobin(HbA1c;OR=2.55),and higher age(OR=1.05)while higher education level was protective(OR=0.53).However,the most influential variables were HbA1c followed by age,TC,TG,low education level,brushing frequency,and sex on the random forest model(this model showed higher sensitivity for predicting the risk).A good understanding of the predictors for periodontitis in T2Dm patients is important in prevention,early detection of susceptible patients,and intervention to improve periodontal health and enable long-term glycaemic control as observed by Xu et al.

关键词： Diabetes mellitus Periodontitis Predictive factors Cardiovascular disease Glycaemic control

Bariatric and endo-bariatric interventions for diabetes:What is the current evidence?

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World Journal of Diabetes 2024年第11期15卷 2255-2263页

作者： Sunetra mondal Vanessa Ambrose Fistus joseph m pappachan Department of Endocrinology NRS Medical College and HospitalKolkata 700014West BengalIndia Department of medicine Royal Preston HospitalLancashire Teaching Hospitals NHS TrustPreston PR29HTLancashireUnited Kingdom Department of Endocrinology and metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTLancashireUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Department of Endocrinology Kasturba Medical CollegeManipal UniversityManipal 576104India

Bariatric interventions have shown the best therapeutic benefits in individuals with *** can be classified into surgical procedures(bariatric/metabolic surgery)and endoscopic *** surgical procedures include sleeve gastrectomy,Roux-en-Y gastric bypass,bilio-pancreatic diversion with or without duodenal switch and Stomach Intestinal Pylorus Sparing *** procedures include intragastric balloons,transpyloric shuttle,endoscopic gastroplasties,aspiration therapy,duodenal mucosal resurfacing,duodeno-jejunal bypass liner,gastro-duodeno-jejunal bypass and incisionless magnetic anastomosis system among ***,these procedures are limited by lack of wide availability,high costs,immediate and long-term complications and poor acceptability in some *** re-gain is a common concern and revisional metabolic surgery is often *** pre-operative evaluation and correction of nutritional deficiencies post-surgery are very *** most appropriate procedure for a person would depend on multiple factors like the intended magnitude of weight-loss,comorbidities and surgical fitness,as well as choice of the ***,glucagon-like insulinotropic peptide-1 receptor agonists(GLP)and the GLP-1/gastric inhibitory polypeptide co-agonist-Tirzepatide have shown remarkable weight loss potential,which is at par with bariatric interventions in some *** far these can help in avoiding invasive bariatric procedures in near future remains to be *** updated and comprehensive clinical review by He et al in the recent issue of World Journal of Diabetes address has addressed the avenues and challenges of currently available bariatric surgeries which will enable clinicians to make better decisions in their practice,including their applicability in special populations like the elderly and pediatric age groups,type 1 diabetes mellitus,and non-diabetics.

关键词： Bariatric surgery Bariatric endoscopy Obesity Type 2 diabetes mellitus metabolic benefits

Diabetes and tuberculosis:An emerging dual threat to healthcare

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World Journal of Diabetes 2024年第7期15卷 1409-1416页

作者： Sahana Shetty joseph m pappachan Cornelius James Fernandez Department of Endocrinology Kasturba Medical CollegeManipalManipal Academy of Higher EducationManipal 576104KarnatakaIndia Department of Endocrinology and metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine and HealthThe University of ManchesterManchester M139PLUnited Kingdom Department of Endocrinology&metabolism Pilgrim HospitalUnited Lincolnshire Hospitals NHS TrustBoston PE219QSUnited Kingdom

Tuberculosis(TB)remains a huge global healthcare challenge even in the 21^(st) century though the prevalence has dropped in developed countries in recent *** mellitus(Dm)is an important risk factor for the development and perpetuation of TB owing to the immune dysfunction in patients with *** coexistence of both diseases in the same individual also aggravates disease severity,complications,and chance of treatment failure because of gross immune alterations posed by Dm as well as *** complex cellular and humoral immunological factors are involved in the dangerous interaction between TB and Dm,some of which remain unknown even *** is highly important to identify the risk factors for TB in patients with Dm,and vice versa,to ensure early diagnosis and management to prevent complications from this ominous *** their research study published in the recent issue of the World Journal of Diabetes,Shi et al elaborate on the factors associated with the development of TB in a large cohort of Dm patients from *** such research output from different regions of the world is expected to improve our knowledge to fight the health devastation posed by TB in patients with diabetes.

关键词： Tuberculosis Diabetes mellitus Immune dysfunction Treatment failure multi-drug resistant tuberculosis

metabolic complications of hepatitis C virus infection

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World Journal of Gastroenterology 2021年第13期27卷 1267-1282页

作者： Rahul Chaudhari Sherouk Fouda Ashik Sainu joseph m pappachan Department of medicine Pennsylvania Hospital of the University of PennsylvaniaPennsylvaniaPA 19104United States School of Health and Biomedical Sciences RMIT UniversityMelbourne VIC 3000Australia Department of Gastroenterology and Hepatology Aster Oman HospitalAl GhubraMuscat OM 133Oman Department of Endocrinology and metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine and HealthThe University of ManchesterManchester M139PLUnited Kingdom

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.

关键词： Chronic hepatitis C infection Insulin resistance metabolic syndrome Cardiovascular diseases Fatty liver Diabetes mellitus

Acute worsening of microvascular complications of diabetes mellitus during rapid glycemic control:The pathobiology and therapeutic implications

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World Journal of Diabetes 2024年第3期15卷 311-317页

作者： Dania Blaibel Cornelius James Fernandez joseph m pappachan Department of Endocrinology and metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Department of Endocrinology and metabolism Pilgrim HospitalUnited Lincolnshire Hospitals NHS TrustBoston PE219QSUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine and HealthThe University of ManchesterManchester M139PLUnited Kingdom

While chronic hyperglycaemia resulting from poorly controlled diabetes mellitus(Dm)is a well-known precursor to complications such as diabetic retinopathy,neuropathy(including autonomic neuropathy),and nephropathy,a paradoxical intensification of these complications can rarely occur with aggressive glycemic management resulting in a rapid reduction of glycated ***,acute onset or worsening of retinopathy and treatment induced neuropathy of diabetes are more common among these complications,rarely other problems such as albuminuria,diabetic kidney disease,Charcot’s neuroarthropathy,gastroparesis,and urinary bladder dysfunction are also *** World Journal of Diabetes recently published a rare case of all these complications,occurring in a young type 1 diabetic female intensely managed during pregnancy,as a case report by Huret et *** is essential to have a comprehensive understanding of the pathobiology,prevalence,predisposing factors,and management strategies for acute onset,or worsening of microvascular complications when rapid glycemic control is achieved,which serves to alleviate patient morbidity,enhance disease management compliance,and possibly to avoid medico-legal issues around this rare clinical *** editorial delves into the dynamics surrounding the acute exacerbation of microvascular complications in poorly controlled Dm during rapid glycaemic control.

关键词： Diabetes mellitus microvascular complications Diabetic retinopathy Treatment induced neuropathy of diabetes Diabetic nephropathy Charcot’s neuropathy

management of diabesity:Current concepts

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World Journal of Diabetes 2023年第4期14卷 396-411页

作者： maria michaelidou joseph m pappachan mohammad Sadiq Jeeyavudeen Department of Endocrinology and metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine and HealthThe University of ManchesterManchester M139PLUnited Kingdom Department of Endocrinology&metabolism University Hospitals of EdinburghEdinburgh EH164SAUnited Kingdom

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 *** 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 *** classes of anti-diabetic medications including insulins,sulphonylureas,thiazolidinediones and meglitinides are associated with the risk of weight gain and may potentially worsen ***,appropriate selection of antidiabetic drug regimen is crucial in the medical management of *** role of non-pharmacological measures such as dietary adjustments,exercise interventions and bariatric procedures should also be ***,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 *** review provides a narrative clinical update on the evidence behind the management of diabesity.

关键词： Obesity Diabesity metabolic-associated fatty liver disease Antidiabetic medications Glycemic control metabolic surgery

Diabetic cardiomyopathy:Emerging therapeutic options

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World Journal of Diabetes 2024年第8期15卷 1677-1682页

作者： Cornelius James Fernandez Sahana Shetty joseph m pappachan Department of Endocrinology&metabolism Pilgrim HospitalUnited Lincolnshire Hospitals NHS TrustBoston PE219QSUnited Kingdom Department of Endocrinology Kasturba Medical CollegeManipal Academy of Higher EducationManipal 576104KarnatakaIndia Department of Endocrinology and metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine and HealthThe University of ManchesterManchester M139PLUnited Kingdom

Diabetic cardiomyopathy(DbCm)is a common but underrecognized complication of patients with diabetes mellitus(Dm).Although the pathobiology of other cardiac complications of diabetes such as ischemic heart disease and cardiac autonomic neuropathy are mostly known with reasonable therapeutic options,the mechanisms and management options for DbCm are still not fully *** its early stages,DbCm presents with diastolic dysfunction followed by heart failure(HF)with preserved ejection fraction that can progress to systolic dysfunction and HF with reduced ejection fraction in its advanced stages unless appropriately *** from prompt control of Dm with lifestyle changes and antidiabetic medications,disease-modifying therapy for DbCm includes prompt control of hypertension and dyslipidemia inherent to patients with Dm as in other forms of heart diseases and the use of treatments with proven efficacy in HF.A basic study by Zhang et al,in a recent issue of the World Journal of Diabetes elaborates the potential pathophysiological alterations and the therapeutic role of teneligliptin in diabetic mouse models with *** this preliminary basic study might help to improve our understanding of DbCm and offer a potential new management option for patients with the disease,the positive results from such animal models might not always translate to clinical practice as the pathobiology of DbCm in humans could be ***,such experimental studies can encourage more scientific efforts to find a better solution to treat patients with this enigmatic disease.

关键词： Diabetic cardiomyopathy Diabetic cardiomyopathy Heart failure Pathobiology Teneligliptin

Non-pharmacological interventions for diabetic peripheral neuropathy:Are we winning the battle?

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World Journal of Diabetes 2024年第4期15卷 579-585页

作者： Dania Blaibel Cornelius James Fernandez joseph m pappachan Department of Endocrinology and metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Department of Endocrinology&metabolism Pilgrim HospitalUnited Lincolnshire Hospitals NHS TrustBoston PE219QSUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine&HealthThe University of ManchesterManchester M139PLUnited Kingdom

Despite the advent of relatively reliable modalities of diagnosing diabetic peripheral neuropathy(DPN),such as nerve conduction studies,there is still a knowledge gap about the pathophysiology,and thus limited available in-terventions for symptom control and curtailing disease *** pharma-cologic aspect of management is mainly centred on pain control,however,there are several important aspects of DPN such as loss of vibration sense,pressure sense,and proprioception which are associated with risks to lower limb health,which pharmacotherapy does not ***,published evidence suggests non-pharmacologic interventions such as glycaemic control through dietary modification and exercise need to be combined with other measures such as psychotherapy,to reach a desired,however modest *** is emerging as an important treatment modality for several chronic medical conditions including neuropathic and other pain *** their study published in the World Journal of Diabetes on the potential of acupuncture to reduce DPN symptoms and enhance nerve conduction parameters,Hoerder et al have been able to demonstrate that acupuncture improves sensory function and that this effect is likely sustained two months after treatment *** previous studies also support these findings,larger multi-center randomized control trials including a sham-controlled arm accounting for a placebo effect are ***,given the satisfactory safety profile and the positive results found in these studies,it is likely that acupuncture may become an important aspect of the repertoire of effective DPN management.

关键词： Diabetic peripheral neuropathy Diabetes mellitus Pharmacotherapy Acupuncture Neuropathic pain Nonpharmacological intervention