Clinical and genetic analysis of five pedigree with maturity-onset diabetes of the young type 2 / 中华内分泌代谢杂志

Objective:To explore the clinical and molecular genetic characteristics of patients with maturity-onset diabetes of the young type 2(MODY2).Methods:Clinical data and laboratory results were collected from five MODY2 patients and their family members diagnosed in the Department of Endocrinology, Genetics, and Metabolism of Xi ′an Children′s Hospital in the recent two years. Whole exome sequencing was carried out on every proband to identify potential variants, then the suspected variants were verified with Sanger sequencing in family numbers.Results:Among the 5 probands, except for proband 4 who presented with polydipsia and polyuria, hyperglycemia in the rest of the children was accidentally identified. Urine routine, urinary protein, and blood lipid of the five probands were all normal, and HbA 1C was between 5.96% and 8.15%. Moreover, an important discovery in this study was that proband 5 had insulin resistance(IRS), which was different from previous studies. It was confirmed by genetic analysis that a glucokinase(GCK) gene variant existed in every MODY2 pedigree. There were four GCK variants in this study, including c. 146C>T(p.T49I), c. 1237T>G(p.Y413D), c. 683C>T(p.T228M) and c. 952G>T(p.G318W), among which the C. 1237T>G(P.y413d) and C. 952G>T(P.G318W) had not been reported till now. All probands received lifestyle intervention, and the blood glucose control was relatively stable. Conclusion:There is MODY2 patient complicated with IRS. MODY2 patients can be controlled well by lifestyle interventions. In addition, we discovered two novel variants of GCK, which extend the mutation spectrum of this gene.

Development of General Practice in Communities From the Perspective of Supply and Demand / 中国医学科学院学报

Objective To put forward suggestions for improving the scheme of general practice for functional communities from the perspective of supply and demand,guide the efficient use of the resources of general practice by the communities,and incorporate the general practice of communities into hierarchical diagnosis and treatment management. Methods In July 2021,stratified random sampling was employed to conduct the questionnaire surveys of the young and middle-aged (demand side) and the general practitioners (supply side),respectively.SPSS 20.0 was used for data analysis. Results The two sides had the same cognition about the main reasons for not signing a contract with a family doctor,which were the lack of knowledge about general practitioners and the lack of face-to-face communication opportunities.They had the same response about the form of services,with high acceptance of medical services via WeChat,outpatient consultation,and the internet.There were differences in service content between the two sides.The top three demands of the young and middle-aged were appointment registration and referral in superior hospitals,medication guidance,and massage,acupuncture,and moxibustion.The top service self-rated by general practitioners was personalized guidance and report interpretation of physical examination,and the bottom was massage,acupuncture,and moxibustion. Conclusions The general practice varies between the demand and supply sides.General practitioners should be encouraged to enter and learn functional communities and provide personalized services,thus improving the general medical service in functional communities.

When do we need to suspect maturity onset diabetes of the young in patients with type 2 diabetes mellitus?

ABSTRACT Objetivo: Maturity onset diabetes of the young (MODY) patients have clinical heterogeneity as shown by many studies. Thus, often it is misdiagnosed to type 1 or type 2 diabetes(T2DM). The aim of this study is to evaluate MODY mutations in adult T2DM patients suspicious in terms of MODY, and to show clinical and laboratory differences between these two situations. Subjects and methods: In this study, we analyzed 72 type 2 diabetic patients and their relatives (35F/37M) who had been suspected for MODY and referred to genetic department for mutation analysis. The gene mutations for MODY have been assessed in the laboratory of Marmara University genetics. Totally 67 (32F/35M; median age 36.1) diabetic patients were analyzed for 7 MODY mutations. Twelve patients who have uncertain mutation (VUS) were excluded from study for further evaluation. MODY(+) (n:30) patients and T2DM patients (n:25) were compared for clinical and laboratory parameters. Results: In MODY(+) subjects, mutations in GCK (MODY 2) (n:12; 40%) were the most common followed by HNF4A (MODY 1) (n:4; 13.3%). Diabetes diagnosis age was younger in MODY(+) group but not statistically significant. Sixty-six percent of MODY(+) subjects had diabetes history at 3-consecutive generations in their family compared with 28% of T2DM patients statistically significant (p:0.006). Gender, BMI, C-peptide, HbA1c, lipid parameters, creatinine, GFR, microalbuminuria, vitamin D and calcium were not statistically different between the groups. Conclusion: According to present study results, MODY mutation positivity is most probable in young autoantibody (-) diabetic patients diagnosed before 30 years of age, who have first degree family history of diabetes.

Changing trends of patients undergoing thrombolysis for acute ST-elevated myocardial infarction in tertiary care hospital in Maharashtra, India

Background: Coronary artery disease (CAD) is becoming a major cause of morbidity and mortality burden in the developing world. Indians have been associated with a more severe form of CAD that has its onset at a younger age group with a male predominance. Reperfusion of the occluded coronary artery at the earliest is the most important aim of management of acute ST-elevation myocardial infarction (STEMI). Aim: The aims of this work were to (1) study the changing trends in patients presenting with STEMI, (2) the outcomes of patients undergoing thrombolysis in a tertiary care hospital, and (3) the increasing trend of CAD in young (CADY). Materials and Methods: A total of 500 patients undergoing thrombolysis between January 2017 and December 2019 were studied retrospectively. We studied the age of presentation, sex, agents used for thrombolysis, their angiography findings, and their management and outcome. Results: CADY in less than 45 years of age was noted in 26.2% in our study. It was more common in men. Left anterior descending coronary artery (LAD) was the most common artery to be involved in single-vessel coronary artery disease (SVCAD) patients followed by the right coronary artery (RCA). Door to needle time in our study was 28 min. Conclusion: The prevalence of CADY Indians in our study was significantly high. The most common age group of men presenting with STEMI was 51–55 years, followed by 45–50 years. The most common age group of women presenting with CAD was 61–65 years.

MODY11 induced by heterozygous mutations of a novel B lymphocyte kinase / 中华内分泌代谢杂志

To characterize the clinical and molecular features of a patient with maturity-onset diabetes of the young 11(MODY11) and literature review. The patient was a 30-year-old female with hyperglycemia for 2 years. Failure to thrivea, primary amenorrhea, intellectual impairment, and severe hyperlipidemia were present at the same time. A novel mutations of the B lymphocyte kinase gene(BLK) c. 1025C>T(p.A342V) was found in the patient. Literature review revealed that there were more than ten mutation sites in BLK-MODY11. Some of them had hyperglycemia, over weight or systemic lupus erythematosus. To date, the clinical characteristics of the patient, such as growth retardation, primary amenorrhea, and intellectual impairment have not been reported in MODY11. Our clinical report further expands the clinical presentations and variabilities of MODY11.

Post-coital internal carotid artery dissection associated with acute cerebral infarction in a Filipino female: A case report

@#Carotid arterial dissections may result from spontaneous or traumatic causes. Postcoital arterial dissections have been reported in both the vertebral and coronary arteries. We report a rare case of spontaneous dissection on the extracranial internal carotid artery in a Filipino female after sexual intercourse, leading to a fulminant middle cerebral artery (MCA) territory infarct. Although postcoital carotid artery dissection is a very rare cause of neck vessel dissections, its rapid progressive course can lead to massive cerebral infarction and prompt management must be initiated.

Clinical characterization and genetic analysis of 5 Chinese families with glucokinase gene mutations / 中华内分泌代谢杂志

Objective:To summarize the clinical manifestations and molecular genetic characteristics of 5 families with maturity-onset diabetes mellitus of the young 2 (MODY2) caused by glucokinase (GCK) gene mutations.Methods:Clinical data and biochemical results of probands were collected. Peripheral blood samples of probands and first-degree family members were collected and whole exome gene was detected using second-generation sequencing. After comparing against the database, the suspected pathogenic sites were selected for Sanger sequencing verification.Results:All the 5 probands presented with mild fasting hyperglycemia, HbA 1C<7.5%, and no symptoms of thirst, polydipsia or polyuria. There were 6 mutants in 5 families, including M1: c.555delT (P.leu186CysFS Ter19) and M3: c. 263T>A (p.Met88Lys) which haven′t been reported before. During the follow-up, all probands received life-style intervention, except 2 pregnant women who should consider insulin treatment if necessary according to fetal genotypes. Conclusion:Among patients who meet the diagnostic criteria for MODY, MODY2 screening should be performed for children or pregnant women with mild hyperglycemia and family history. GCK gene detection is the gold standard for diagnosis, and accurate diagnosis will be conducive to the selection of appropriate treatment.

Hyperglycemia in pediatric age: could it be maturity onset diabetes of the young? Case reports and review of the literature

Maturity Onset Diabetes of the Young (MODY) includes a clinically and genetically heterogeneous group of diabetes subtypes with MODY-2 being the second most prevalent form. We report 2 cases of MODY-2 identified during the investigation of asymptomatic hyperglycemia. A 12-year-old girl with a familiar history of diabetes (mother, maternal aunt, and maternal grandfather) was referred due to hypercholesterolemia, abnormal fasting glucose (114 mg/dL), and increased levels of glycated haemoglobin (HbA(1c)) (6%) presenting with negative β-cell antibodies. A glucokinase (GCK) heterozygous missense mutation c.364C>T (p.Leu122Phe) in exon 4 was identified in the index patient and in the 3 family members. An obese 9-year-old boy was investigated for elevated fasting glycemic levels (99–126 mg/dL), HbA(1c) rise (6.6%–7.6%), and negative β-cell antibodies. The patient's father, paternal aunt, and paternal grandfather had a history of diabetes during their childhood. A GCK heterozygous missense mutation c.698G>A (p.Cys233Tyr) in exon 7 was identified in the index patient. This variant was only described in another family strongly affected by both MODY and classic autoimmune mediated diabetes, contrary to our case. MODY-2 should be suspected in the presence of early onset of persistent mild fasting hyperglycemia and negative β-cell antibodies associated with a positive family history of diabetes. These cases illustrate the challenging aspects of MODY diagnosis due to possible phenotypic overlap with other types of diabetes. The diagnosis requires a high level of suspicion and GCK genetic screening should be performed in the presence of compatible features. An early diagnosis allows for appropriate management, genetic counselling, and the identification of affected family members.

Association of related knowledge level and compliance of young and middle-aged hypertensive patients / 现代临床护理

Objective To evaluate the relevant knowledge level and compliance of young and middle-aged hypertensive patients,and explore the association of them. Method A total of 276 young and middle-aged hypertensive patients were surveyed using a hypertension knowledge level scale and treatment compliance questionnaire. Results The average score of young and middle-aged hypertensive patients on relevant knowledge was (62.55 ± 17.79). From different dimensions, the hypertensive patients got the highest score in the knowledge of their lifestyle,while they got the lowest score in their knowledge for complication.The average score of young and middle-aged hypertensive patients on treatment compliance was (71.53±9.87).From different dimensions,the hypertensive patients got the highest score in medication adherence,while they got the lowest score in exercise and pressure-relieving compliance.It showed that medication and drug compliance knowledge of middle-aged hypertensive patients was closely associated with treatment compliance(r=0.648, P<0.001)). Conclusions Both knowledge level and treatment compliance of young and middle-aged hypertensive patients should be improved.We should strengthen the population of knowledge about hypertension among young and middle-aged patients,especially the guidance of drug knowledge to improve their compliance.

Diabetes mellitus por mutación en el gen de glucokinasa: caso clínico / Diabetes mellitus caused by a mutation of glucokinase gene: report of an affected family

Maturity-Onset Diabetes of the Young (MODY) refers to a heterogeneous group of monogenic diabetes. Unlike other types of MODY characterized by genetic defects in transcription factors, MODY 2 is triggered by metabolic alterations caused by mutations of glucokinase (GCK), the first enzyme of the glycolytic pathway. We report a three-generation Chilean family with multiple cases affected with this disease. The index case is a patient who presented severe neonatal hyperglycemia (831 mg/dl, without ketosis) requiring continuous infusion of insulin, which was suspended after 48 hours with normalization of blood glucose. Subsequently, continuous glucose monitoring at 4 months of age revealed 47% of tissue glucose levels above 140 mg/dl, with fasting glucose levels between 120 and 166 mg/dl. The genetic analysis revealed a previously reported mutation in heterozygous state of the GCK gene (c.148C>T; p.His50Tyr). This mutation was also identified in more than one affected relative in the last two generations, with a transmission pattern suggestive of dominant inheritance. GCK gene sequencing led to a correct molecular diagnosis of MODY 2 while bioinformatic analysis indicated the possible molecular causes of the enzyme dysfunction. The knowledge of the molecular diagnosis allowed an adequate medical treatment for this disease.

Identification of Maturity-Onset Diabetes of the Young Caused by Glucokinase Mutations Detected Using Whole-Exome Sequencing

Glucokinase maturity-onset diabetes of the young (GCK-MODY) represents a distinct subgroup of MODY that does not require hyperglycemia-lowering treatment and has very few diabetes-related complications. Three patients from two families who presented with clinical signs of GCK-MODY were evaluated. Whole-exome sequencing was performed and the effects of the identified mutations were assessed using bioinformatics tools, such as PolyPhen-2, SIFT, and in silico modeling. We identified two mutations: p.Leu30Pro and p.Ser383Leu. In silico analyses predicted that these mutations result in structural conformational changes, protein destabilization, and thermal instability. Our findings may inform future GCK-MODY diagnosis; furthermore, the two mutations detected in two Korean families with GCK-MODY improve our understanding of the genetic basis of the disease.

The molecular diagnosis and their detailed clinical presentations in 5 cases of maturity-onset diabetes of the young / 中华实用儿科临床杂志

Objective To analyze the genetic changes and detailed clinical presentations of 5 maturity-onset diabetes of the young (MODY) cases in order to enhance the knowledge about MODY in children.Methods Seventy-eight patients initially diagnosed as diabetes mellitus between January 1 and December 31,2015 in Capital Institute of Pediatrics were retrospectively studied.Nine of them were suspected of MODY,and 5 patients were diagnosed as MODY through gene test.Clinical informations were collected including age,gender,main complaint,family history,body mass index (BMI),fasting blood glucose,fasting blood insulin,2-hour blood glucose and insulin after oral glucose tolerance test and glycosylated hemoglobin.The blood glucose was monitored dynamically in 2 patients.Targeted capture panel was designed to capture the 16 genes related to MODY,including 12 genes from MODY1 to MODY13 type and 4 genes with weak evidence of MODY according to Human Gene Mutation Database Exome capture,and Next-Generation sequencing on a HiSeq2000 (Illumina) was performed.After bioinformatics analysis,all prioritized variants detected in patients were validated by Sanger sequencing,including the probands and their parents.Results Five patients were confirmed as MODY by molecular diagnosis,accounting for 6.4％ of all the 78 patients in 2015.The ratio of male to female was 2 ∶ 3.The ages at diagnosis ranged from 2 to 11 years old,and the median age was 3 years old.Two cases were found to have abnormal blood glucose in physical examination.The rest 3 cases were discovered with abnormal blood glucose during hospitalization because of pneumonia (1 case)or diarrhea (2 cases).In 4 cases,their mothers had gestational diabetes history,in 1 case the father suffering from diabetes.BMI ranged 15.68-23.40 kg/m2.Fasting blood glucose was 6.3-7.2 mmol/L.Fasting blood insulin was 0.5-8.0 IU/L.Glucose tolerance test results showed that blood glucose of the patients was 8.6-10.8 mmol/L after 2 hours.The level of glycosylated hemoglobin was 5.5％-6.7％.Blood glucose was 3.9-13.0 mmol/L.All the 5 confirmed patients were caused by GCK gene mutation (MODY2 type).The mutations detected were located at Exon7 (2 cases),Exon4 (1 case),Exon5 (1 case),and Exon10 (1 case).Conclusions All the confirmed MODY patients were identified either through medical exam or infectious disease,and all had positive family history.Their BMI ranged widely.Fasting blood glucose was slightly elevated and glycosylated hemoglobin was normal or slightly elevated,but fasting blood insulin was normal in all the patients.Abnormal glucose tolerance test results were found in all 5 patients.Glycosylated hemoglobin was normal or slightly elevated.MODY2 was the only subtype detected in this group,which indicated that the common type in children was different from that in adults.

Progress of diagnosis and treatment for maturity-onset diabetes of the young / 中华实用儿科临床杂志

Maturity-onsetdiabetesoftheyoung(MODY),amonogenicformofdiabetes,hasmorethan8 well-known subtypes:MODY1( hepatocyte nuclear factor - 4A,HNF4A ),MODY2( glucokinase,GCK ),MODY3 (hepatocyte nuclear factor-1A,HNFIA),MODY4(pancreatic and duodenal homeobox,PDX),MODY5(hepatocyte nuclear factor-1B,HNFIB),MODY6(neuronal differentiation 1,NEUR0DI),MODY7(carboxyl ester lipase,CEL) and MODY8( insulin,INS). The molecular pathology,clinical manifestations and treatment of MODYs are different and reviewed.

Maturity-Onset Diabetes of the Young: What Do Clinicians Need to Know?

Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes that is characterized by an early onset, autosomal dominant mode of inheritance and a primary defect in pancreatic beta-cell function. MODY represents less than 2% of all diabetes cases and is commonly misdiagnosed as type 1 or type 2 diabetes mellitus. At least 13 MODY subtypes with distinct genetic etiologies have been identified to date. A correct genetic diagnosis is important as it often leads to personalized treatment for those with diabetes and enables predictive genetic testing for their asymptomatic relatives. Next-generation sequencing may provide an efficient method for screening mutations in this form of diabetes as well as identifying new MODY genes. In this review, I discuss a current update on MODY in the literatures and cover the studies that have been performed in Korea.

Analysis of clinicopathological characteristics and prognostic survival factors of primary hepatic carcinoma after hepatic resection in young patients / 西安交通大学学报(医学版)

Objective To analyze the clinicopathological characteristics and the prognostic survival factors of young patients who have undergone hepatectomy for primary hepatic carcinoma.Methods Clinicopathological da-ta and treatment outcomes in 79 young (≤40 years old)and 67 elderly (≥65 years old)patients who underwent hep-atectomy for primary hepatic carcinoma between 2008 and 2012 were retrospectively collected and compared using various parameters.Then the survival rate and prognostic factors of the younger patients were analyzed using Kap-lan-Meier and COX multivariate proportional hazards model.Results The positive rate of HBs-antigen and alpha-fetoprotein level were significantly higher in the younger patients than in the elderly patients (P0.05).The overall survival rate was similar between the two groups.COX multivariate proportional hazards model analysis showed that the independent prognostic factors of overall survival were pre-operative albumin level <3 5 g/L and maximum tumor diameter ≥5 cm.Conclusion Hepatectomy is a safe and feasible treatment for young and elderly patients with primary hepatic carcinoma.The independent prognostic factors of survival for young patients are pre-operative albumin level <3 5 g/L and the maximum tumor diameter ≥5 cm.

Intermediate Evaluation of Clinical Efficacy of Improved Surgical Method Combined with Chinese Medicine for Treatment of Young and Middle-aged Femoral Neck Fractures / 广州中医药大学学报

Objective To explore the effect of improved surgical method of intramedullary fibular allograft together with cannulated screw fixation combined with blood-activating and stasis-resolving Chinese medicine on the quality of life (QOL) of young and middle-aged fresh femoral neck fractures at intermediate stage. Methods A retrospective analysis was carried out in the articular orthopedics department of the First Affiliated Hospital of Guangzhou University of Chinese Medicine. The study involved 80 cases of young and middle-aged fresh femoral neck fractures receiving intramedullary fibular allograft together with cannulated screw fixation, and 50 qualified cases receiving cannulated screw fixation alone ( control group) . After the operation, all of the patients were given oral use of blood-activating and stasis-resolving Chinese medicine. After the last follow-up, Harris hip scoring, SF-36 scoring and radiographic evaluation were performed for the evaluation of clinical efficacy. Results The clinical application of intramedullary fibular allograft together with cannulated screw fixation combined with Chinese medicine was fulfilled in 80 hips of 80 cases. The follow-up period ranged from 48 to 84 months, averaging 62.68 ± 12.43 months. The improved surgical method group had an excellent and good rate of 93.75%, presented excellent-grade Harris scores and SF-36 scores, and had higher QOL scores than the control group (P<0.05) . After treatment, the two groups had statistically significant differences in the scores of SF-36 items of physical function ( PF) , bodily pain ( BP) , mental health ( MH) , vitality ( VT) , and general health ( GH) ( P<0.05 or P<0.01) , and also had significant differences in Harris scoring of pain, function and daily activities as well as the joint range-of-motion ( P<0.05 or P<0.01) . Conclusion The improved surgical method of intramedullary fibular allograft together with cannulated screw fixation combined with blood-activating and stasis-resolving Chinese medicine shows satisfactory therapeutic effect for young and middle-aged fresh femoral neck fractures at intermediate stages, which has the advantages of lower collapse rate after femoral head necrosis, less joint replacement, higher scores of the quality of life and Harris scoring, and better radiographic indicators than cannulated screw fixation alone.

Serum metabonomic study of two Uyghur families with maturity-onset diabetes of the young / 中华内分泌代谢杂志

ObjectiveTo study the characteristics of serum metabolites in two Uyghur families with maturityonset diabetes of the young(MODY).MethodsTwo MODY families were composed of four generations of Uyghur with 52 members collected from Kashgar region,Xinjiang Uyghur Autonomous Region.The general information,blood glucose and lipid levels,and blood pressure were analyzed.Using 1H nuclear magnetic resonance (1H NMR )spectroscopy,serum metabolites were measured for each subject.After having conducted data pretreatment on the spectrogram,orthogonal partial least squares discriminant analysis ( OPLS-DA ) was used to interpret data.The subjects were divided into two groups according to blood glucose ( diabetes and non-diabetes ),blood pressure,body mass index ( BMI ) for comparing differences in the metabolites.The differences of serum metabolic components between two groups were determined using pearson correlation coefficients with significant difference detection and two-dimensional spectrum technology.Results lsoleucine and tyrosine levels in diabetes group were decreased significantly,while α-glucose and β-glucose levels were increased significantly compared with non-diabetes group( all P＜0.05 ).Citrate,phaseomannite,1 -methyl histidine,and tyrosine levels in hypertension group were all decreased significantly compared with normal blood pressure group( all P＜0.05 ).No significant metabonomic differences were observed between normal BMI group and high BMI group.ConclusionsMetabonomic changes in diabetic patients from MODY families indicate that diabetic patients suffer from disordered tricarboxylic acid cycle ( TCA cycle )metabolism,with reduced glycolysis of glycogen in liver and muscle.There exist the metabolic disorder in TCA cycle and obstruction of fat metabolism in patients with hypertension from the MODY families.

MODY Syndrome / 대한소아내분비학회지

Maturity-onset diabetes of the young (MODY) is a heterogenous form of diabetes characterized by the early onset of diabetes, autosomal dominant inheritance, and impaired insulin secretion. MODY is mostly caused by mutations of the hepatocyte nuclear factor 1-alpha (HNF1-alpha) and glucokinase genes in Caucasians. However most Korean, Japanese, and Chinese patients with MODY do not express known MODY genes. The cause of MODY in Asians has not yet been elucidated clearly. This review focuses on studies on Asian patients with MODY.

Screening for Mutations of MODY 1-5 Genes in Chinese Families with Early-onset Type 2 Diabetes / 中山大学学报(医学科学版)

[Objective] The aim of our study was to seek the mutations in MODY1～5 genes in Chinese population by direct sequencing in probands from families with early-onset type 2 diabetes.[Methods] Variants screening in MODY 1-5 genes were performed by PCR and direct sequencing in 19 probands from early-onset type 2 diabetes families.[Results] We found no mutation but many polymorphisms.There were 6,5,15,1,and 1 variants in MODY 1-5 genes respectively.[Conclusion] Our negative results in MODY genes suggest the genetic heterogeneity of different populations.Mutations in MODY 1-5 genes might not be the cause of diabetes in those 19 families.

Identification of a novel glucokinase-E339K mutation in a Chinese maturity onset diabetes of the young 2 pedigree / 中华内科杂志

ovel GCK-E339K mutation might be linked to this MODY2 pedigree.