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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

Effects of exercise training on glucose metabolism indicators and inflammatory markers in obese children and adolescents:A metaanalysis

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World Journal of Diabetes 2024年第6期15卷 1353-1366页

作者： Le-Yang Li Song-Mei Li Bo-Xian Pang Jun-Ping Wei Qiu-Hong Wang department of endocrinology Guang’anmen HospitalChina Academy of Chinese Medical SciencesBeijing 100053China Graduate School Beijing University of Chinese MedicineBeijing 100029China

BACKGROUND Obesity in children and adolescents is a serious problem,and the efficacy of exercise therapy for these patients is *** To assess the efficacy of exercise training on overweight and obese children based on glucose metabolism indicators and inflammatory *** The PubMed,Web of Science,and Embase databases were searched for randomized controlled trials related to exercise training and obese children until October *** meta-analysis was conducted using RevMan 5.3 software to evaluate the efficacy of exercise therapy on glucose metabolism indicators and inflammatory markers in obese *** In total,1010 patients from 28 studies were *** therapy reduced the levels of fasting blood glucose(FBG)[standardized mean difference(SMD):-0.78;95%confidence interval(CI):-1.24 to-0.32,P=0.0008],fasting insulin(FINS)(SMD:-1.55;95%CI:-2.12 to-0.98,P<0.00001),homeostatic model assessment for insulin resistance(HOMA-IR)(SMD:-1.58;95%CI:-2.20 to-0.97,P<0.00001),interleukin-6(IL-6)(SMD:-1.31;95%CI:-2.07 to-0.55,P=0.0007),C-reactive protein(CRP)(SMD:-0.64;95%CI:-1.21 to-0.08,P=0.03),and leptin(SMD:-3.43;95%CI:-5.82 to-1.05,P=0.005)in overweight and obese *** training increased adiponectin levels(SMD:1.24;95%CI:0.30 to 2.18,P=0.01)but did not improve tumor necrosis factor-alpha(TNF-α)levels(SMD:-0.80;95%CI:-1.77 to 0.18,P=0.11).CONCLUSION In summary,exercise therapy improves glucose metabolism by reducing levels of FBG,FINS,HOMA-IR,as well as improves inflammatory status by reducing levels of IL-6,CRP,leptin,and increasing levels of adiponectin in overweight and obese *** was no statistically significant effect between exercise training and levels of TNF-α.Additional long-term trials should be conducted to explore this therapeutic perspective and confirm these results.

关键词： Exercise training Obesity Children and adolescents Glucose metabolism Inflammatory markers Meta-analysis

Myosteatosis is associated with coronary artery calcification in patients with type 2 diabetes

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World Journal of Diabetes 2024年第3期15卷 429-439页

作者： Fu-Peng Liu Mu-Jie Guo Qing Yang Yan-Ying Li Yan-Gang Wang Mei Zhang The Affiliated Hospital of Medical College Qingdao University Qingdao UniversityQingdao 266071Shandong ProvinceChina department of endocrinology The Affiliated Hospital of Jining Medical UniversityJining 272029Shandong ProvinceChina department of Medical Imaging The Affiliated Hospital of Jining Medical UniversityJining 272029Shandong ProvinceChina department of Clinical Nutrition The Affiliated Hospital of Jining Medical UniversityJining 272029Shandong ProvinceChina department of endocrinology The Affiliated Hospital of Qingdao UniversityQingdao 266003Shandong ProvinceChina

BACKGROUND Myosteatosis,rather than low muscle mass,is the primary etiologic factor of sarcopenia in patients with type 2 diabetes mellitus(T2DM).Myosteatosis may lead to a series of metabolic dysfunctions,such as insulin resistance,systematic inflammation,and oxidative stress,and all these dysfunctions are closely associated with the acceleration of T2DM and *** To investigate the association between myosteatosis and coronary artery calcification(CAC)in patients with *** Patients with T2DM,who had not experienced major cardiovascular events and had undergone both abdominal and thoracic computed tomography(CT)scans,were *** mean skeletal muscle attenuation was assessed using abdominal CT images at the L3 *** CAC score was determined from thoracic CT images using the Agatston scoring *** was diagnosed according to Martin’s *** CAC(SCAC)was defined when the CAC score exceeded *** regression and decision tree analyses were *** A total of 652 patients with T2DM were *** them,167(25.6%)patients had *** regression analysis demonstrated that myosteatosis,age,duration of diabetes,cigarette smoking,and alcohol consumption were independent risk factors of *** was significantly associated with an increased risk of SCAC(OR=2.381,P=0.003).The association between myosteatosis and SCAC was significant in the younger patients(OR=2.672,95%CI:1.477-4.834,P=0.002),but not the older patients(OR=1.456,95%CI:0.863-2.455,P=0.188),and was more prominent in the population with lower risks of *** decision tree analyses prioritized older age as the primary variable for *** older patients,cigarette smoking was the main contributing factor for SCAC,while in younger patients,it was *** Myosteatosis is a novel risk factor for atherosclerosis in patients with T2DM,especially in the population with younger ages and fewer traditional ri

关键词： Type 2 diabetes Myosteatosis Muscle quality Coronary artery calcification Atherosclerosis Cardiovascular diseases

Maternal High-Fat Diet Impairs Offspring Glucose Metabolism and Programs Hepatic DNA Methylation Linked to NK Cell-Mediated Cytotoxicity Signaling Pathway at Weaning

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Food Science and Human Wellness 2024年

作者： Sheng Zheng Ling Zhang Shixuan Zhang Guanyu Hu Yikai Li Jia Zheng department of Traditional Chinese Orthopedics and Traumatology， Center for Orthopedic Surgery， The Third Affiliated Hospital of Southern Medical University department of endocrinology， Peking University First Hospital

Maternal consumption of a high-fat diet has been linked to increased risks of obesity and impaired glucose metabolism in offspring. However， the precise epigenetic mechanisms governing these intergenerational effects， particularly during the early stages of offspring development， remain poorly understood. In this study， female C57BL/6J mice were randomly assigned to either a high-fat diet or normal chow diet throughout gestation and lactation. Methylated DNA immunoprecipitation (MeDIP) coupled with microarray analysis was employed to identify differentially methylated genes in the livers of offspring at weaning age. We found that maternal high-fat diet feeding predisposes offspring to obesity and impaired glucose metabolism as early as the weaning period. DNA methylation profile analysis unveiled a significant enrichment of differentially methylated genes within the natural killer (NK) cell-mediated cytotoxicity pathway. MeDIP-PCR validated reduced methylation levels of specific genes within this pathway， including TNFα， PI3K， and SHC1. Consistently， the expressions of TNFα， PI3K， and SHC1 were significantly upregulated， accompanied by elevated serum TNFα and IL-6 levels in offspring from dams fed with high-fat diet. Moreover， we assessed the expressions of genes associated with NK cell activities， uncovering a notable rise in hepatic granzyme B levels and a trend towards increased CD107a expression in offspring from dams fed a high-fat diet. In addition， methylation levels of TNFα， PI3K， and SHC1 promoters were inversely correlated with glucose response during glucose tolerance testing. In conclusion， our findings underscore the critical role of the NK cell-mediated cytotoxicity signaling pathway in mediating DNA methylation patterns， thereby contributing to the programming effects of maternal high-fat diet consumption on offspring glucose metabolism as early as the weaning period.

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Assessment of pathogenicity and functional characterization of APPL1 gene mutations in diabetic patients

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World Journal of Diabetes 2024年第2期15卷 275-286页

作者： Ping Shi Yang Tian Feng Xu Lu-Na Liu Wan-Hong Wu Ying-Zhou Shi An-Qi Dai Hang-Yu Fang Kun-Xia Li Chao Xu department of endocrinology Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250021Shandong ProvinceChina department of Pediatric Yantai Yuhuangding Hospital Affiliated to Qingdao UniversityYantai 264099Shandong ProvinceChina

BACKGROUND Adaptor protein,phosphotyrosine interacting with PH domain and leucine zipper 1(APPL1)plays a crucial role in regulating insulin signaling and glucose *** in the APPL1 gene have been associated with the development of maturity-onset diabetes of the young type 14(MODY14).Currently,only two mutations[c.1655T>A(***552*)and c.281G>A p.(Asp94Asn)]have been identified in association with this *** the limited understanding of MODY14,it is imperative to identify additional cases and carry out comprehensive research on MODY14 and APPL1 *** To assess the pathogenicity of APPL1 gene mutations in diabetic patients and to characterize the functional role of the APPL1 *** Patients exhibiting clinical signs and a medical history suggestive of MODY were screened for the *** exome sequencing was performed on the patients as well as their family *** pathogenicity of the identified APPL1 variants was predicted on the basis of bioinformatics *** addition,the pathogenicity of the novel APPL1 variant was preliminarily evaluated through in vitro functional ***,the impact of these variants on APPL1 protein expression and the insulin pathway were assessed,and the potential mechanism underlying the interaction between the APPL1 protein and the insulin receptor was further *** A total of five novel mutations were identified,including four missense mutations(Asp632Tyr,Arg633His,Arg532Gln,and Ile642Met)and one intronic mutation(1153-16A>T).Pathogenicity prediction analysis revealed that the Arg532Gln was pathogenic across all *** Asp632Tyr and Arg633His variants also had pathogenicity based on *** addition,multiple alignment of amino acid sequences showed that the Arg532Gln,Asp632Tyr,and Arg633His variants were conserved across different ***,in in vitro functional experiments,both the c.1894G>T(at Asp632Tyr)and c.1595G>A(at Arg532Gln)mutations

关键词： Adaptor protein,phosphotyrosine interacting with PH domain and leucine zipper 1 Maturity-onset diabetes of the young Bioinformatics analysis Gene mutation Domain

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World Journal of Gastroenterology 2024年第26期30卷 3206-3209页

作者： Mo-Wei Kong Xin-Rui Li Yu Gao Ting-Fang Yang department of Cardiology Guiqian International General HospitalGuiyang 550018Guizhou ProvinceChina department of endocrinology The Affiliated Hospital of Chengde Medical CollegeChengde 067000Hebei ProvinceChina department of Oncology Guiqian International General HospitalGuiyang 550018Guizhou ProvinceChina

In this editorial,we review the work of Razali et al published in World J Gas-troenterology,with a particular focus on the effect of rs10889677 variation in the phosphatidylinositol 3-kinase(PI3K)pathway and buparlisib on colitis-associated *** role of PI3K in promoting cancer progression has been widely recognized,as it is involved in regulating the survival,differentiation,and prolif-eration of cancer *** complement Clq/TNF-related protein 6(CTRP6)is a newer tumor-associated *** studies have revealed the pro-tumor effect of CTRP6 in gastric cancer,hepatocellular carcinoma,colorectal cancer,and other gastrointestinal tumors through the PI3K *** article attempts to reveal the mechanism through which the CTRP6 affects the development of digestive system tumors through the PI3K pathway by summarizing recent research.

关键词： Phosphatidylinositol 3-kinase Complement Clq/TNF-related protein 6 Gastric cancer Colorectal cancer Tumor-related factor

Corticosteroid-Induced Adrenal Insufficiency in Africa: Report of Nine Cases at the Internal Medicine/endocrinology-Diabetology department of Pikine NHC

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Open Journal of Endocrine and Metabolic Diseases 2020年第12期10卷 155-163页

作者： Nafy Ndiaye Ngone Diaba Diack Yakham Mohamed Leye Abdou Dieng Mamadou Ba Abdoulaye Leye Internal Medicine/endocrinology-Diabetology department Teaching Hospital of Pikine Dakar Senegal

Introduction: Prolonged corticosteroid therapy is labeled as the main cause of corticotropic adrenal insufficiency. However, the current frequency of this complication remains unknown. The objective of our study was to assess its epidemiologic, diagnostic, therapeutic, and evolutionary aspects of our practice. Methodology: A 60-month retrospective study was performed from May 2014 to April 2020 in the Pikine National Hospital Centre. Data were obtained from the medical records of patients with corticosteroid-induced adrenal insufficiency. Epidemiologic, diagnostic, therapeutic, and evolutionary parameters, and data related to corticotherapy were recorded. Patients with basal plasma cortisol levels Results: Medical records were obtained from nine patients, comprising six women and three men. The mean age of the patients was 48 years. Long-term corticosteroid therapy was used for self-medication in six patients and artificial bleaching in the remaining three patients. Betamethasone was the most commonly used drug in four patients, followed by clobetasol in three patients. Corticotropic insufficiency was revealed as a result of acute decompensation in five patients. All patients presented with a pseudo-cushingoid pattern. Diagnosis of corticotropic adrenal insufficiency was confirmed by measuring basal plasma cortisol levels of <50 ng/ml in seven patients. A standard Synachtene test was performed on two patients. All patients benefited from hydrocortisone supplementation. In the short-term, the outcome was unremarkable for all patients. Medium and long-term progression could be assessed in only three patients. Two patients showed persistent suppression with a 6- and 9-month follow-up. One patient was readmitted after one month due to an adrenal cris

关键词： Adrenal Insufficiency Corticotherapy Artificial Depigmentation Self-Medication

Prevalence and impact of diabetes and prediabetes on presentation and complications of primary hyperaldosteronism at diagnosis

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World Journal of Clinical Cases 2024年第18期12卷 3332-3339页

作者： Debmalya Sanyal Pradip Mukhopadhyay Sujoy Ghosh department of endocrinology NHRTIICS&KPC Medical CollegeKolkata 700032West BengalIndia department of endocrinology IPGME&R and SSKM HospitalKolkata 700020West BengalIndia department of endocrinology IPGME&RKolkata 700020West BengalIndia

BACKGROUND Primary hyperaldosteronism(PH)is considered to contribute to increased risk of developing type 2 diabetes mellitus(T2DM)and *** PH and DM are associated with increased risk for hypertension,cardiovascular diseases,and chronic kidney ***,data on prevalence of T2DM and prediabetes in PH,and impact of T2DM and prediabetes on presentation and cardio renal complications in PH at presentation is *** To determine the prevalence of T2DM and prediabetes in PH at diagnosis and impact on presentation and complications of *** A retrospective cohort study was conducted in tertiary care settings in individuals with confirmed diagnosis of PH at *** variables,clinical presentations,duration and degree of hypertension,complications,laboratory parameters including sodium,potassium levels,plasma aldosterone concentration(PAC),plasma renin activity(PRA),and aldosterone to renin ratio(ARR)and cardio-renal parameters were *** was done between three groups:PH with no DM(Group A)or with pre-diabetes(Group B)or with T2DM(Group C).P<0.05 was statistically *** Among 78 individuals with confirmed PH,62%had pre-diabetes or diabetes;with 37%having *** duration of T2DM was 5.97±4.7 *** mean levels of glycaemic parameters among the group A vs B vs C individuals were fasting plasma glucose(mg/dL):87.9±6.5,105.4±9.02,130.6±21.1;post prandial plasma glucose(mg/dL):122.7±9.8,154.9±14,196.7±38.0;glycated haemoglobin(%)(5.3±0.2,5.9±0.2,7.5±0.6,P<0.05),*** was no significant difference in the biochemical parameters(PAC,PRA,ARR,sodium,potassium levels),presentation and complications between the *** renal parameters or degree and duration of hypertension were comparable between the *** Significant prevalence of T2DM and prediabetes in PH at diagnosis does not impact its presentation or *** screening for undetected PH in T2DM and prediabete

关键词： Primary hyperaldosteronism Diabetes Prediabetes Hypertension Aldosterone Aldosterone to renin ratio

Experience of humanistic nursing in hemodialysis nursing for patients with diabetic kidney disease

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World Journal of Diabetes 2024年第2期15卷 186-195页

作者： Xiao-Ying Chai Xiao-Yan Bao Ying Dai Xing-Xing Dai Yu Zhang Yu-Ling Yang department of Nephrology The Affiliated Hospital of Jiangnan UniversityWuxi 214000Jiangsu ProvinceChina department of Hemodialysis The Affiliated Hospital of Jiangnan UniversityWuxi 214000Jiangsu ProvinceChina department of endocrinology The Affiliated Hospital of Jiangnan UniversityWuxi 214000Jiangsu ProvinceChina

BACKGROUND Diabetic kidney disease(DKD)is a prevalent complication of diabetes that often requires hemodialysis for *** the field of nursing,there is a growing recognition of the importance of humanistic care,which focuses on the holistic needs of patients,including their emotional,psychological,and social ***,the application of humanistic nursing in the context of hemodialysis for DKD patients remains relatively *** To explore the experience of humanistic nursing in hemodialysis nursing for DKD *** Ninety-six DKD patients treated with hemodialysis from March 2020 to June 2022 were included in the study and divided into the control cluster(48 cases)and the study cluster(48 cases)according to different nursing methods;the control cluster was given routine nursing and the study cluster was given humanized *** variances of negative emotion mark,blood glucose,renal function,the incidence of complications,life mark and nursing satisfaction before and after nur-sing were contrasted between the two *** No significant difference in negative emotion markers between the two clusters were observed before nursing(P>0.05),and the negative emotion markers of the two clusters decreased after *** Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale markers were lower in the study cluster than the control *** healing rate of patients in the study cluster was significantly higher than the control cluster(97.92%vs 85.42%,P0.05).However,after nursing,blood urea nitrogen and serum creatinine(SCr)levels in the study cluster were lower than those in the control cluster(P<0.05).The incidence rate of complications was significantly lower in the study group compared to the control cluster(6.25%vs 20.83%,P<0.05).There was no significant difference in the life markers between the two clusters be

关键词： Diabetic kidney disease Hemodialysis Humanistic nursing Incidence of complication Effect