BACKGROUND Maturity-onset diabetes of the young(MODY)is a monogenic genetic disease often clinically misdiagnosed as type 1 or type 2 diabetes.MODY type 9(MODY9)is a rare subtype caused by mutations in the PAX4 gene.C...BACKGROUND Maturity-onset diabetes of the young(MODY)is a monogenic genetic disease often clinically misdiagnosed as type 1 or type 2 diabetes.MODY type 9(MODY9)is a rare subtype caused by mutations in the PAX4 gene.Currently,there are limited reports on PAX4-MODY,and its clinical characteristics and treatments are still unclear.In this report,we described a Chinese patient with high autoimmune antibodies,hyperglycemia and a site mutation in the PAX4 gene.CASE SUMMARY A 42-year-old obese woman suffered diabetes ketoacidosis after consuming substantial amounts of beverages.She had never had diabetes before,and no one in her family had it.However,her autoantibody tested positive,and she managed her blood glucose within the normal range for 6 mo through lifestyle interventions.Later,her blood glucose gradually increased.Next-generation sequencing and Sanger sequencing were performed on her family.The results revealed that she and her mother had a heterozygous mutation in the PAX4 gene(c.314G>A,p.R105H),but her daughter did not.The patient is currently taking liraglutide(1.8 mg/d),and her blood glucose levels are under control.Previous cases were retrieved from PubMed to investigate the relationship between PAX4 gene mutations and diabetes.CONCLUSION We reported the first case of a PAX4 gene heterozygous mutation site(c.314G>A,p.R105H),which does not appear pathogenic to MODY9 but may facilitate the progression of latent autoimmune diabetes in adults.展开更多
BACKGROUND Maturity-onset diabetes of the young(MODY)is the most common monogenic type of diabetes.Recently,14 gene mutations have been found to be associated with MODY.In addition,the KLF11 gene mutation is the patho...BACKGROUND Maturity-onset diabetes of the young(MODY)is the most common monogenic type of diabetes.Recently,14 gene mutations have been found to be associated with MODY.In addition,the KLF11 gene mutation is the pathogenic gene of MODY7.To date,the clinical and functional characteristics of the novel KLF11mutation c.G31A have not yet been reported.CASE SUMMARY We report of a 30-year-old male patient with a one-year history of nonketosisprone diabetes and a 3-generation family history of diabetes.The patient was found to carry a KLF11 gene mutation.Therefore,the clinical data of family members were collected and investigated.A total of four members of the family were found to have heterozygous mutations in the KLF11 gene c.G31A,which resulted in a change in the corresponding amino acid p.D11N.Three patients had diabetes mellitus,and one patient had impaired glucose tolerance.CONCLUSION The heterozygous mutation of the KLF11 gene c.G31A(p.D11N)is a new mutation site of MODY7.Subsequently,the main treatment included dietary interventions and oral drugs.展开更多
Maturity-onset diabetes of the young 10 caused by the c.4G>A (p.Ala2Thr)mutation is extremely rare, with only two reported studies to date. Herein, wereport another case that differs from previous cases in phenotyp...Maturity-onset diabetes of the young 10 caused by the c.4G>A (p.Ala2Thr)mutation is extremely rare, with only two reported studies to date. Herein, wereport another case that differs from previous cases in phenotype.CASE SUMMARYThe proband developed diabetes at the age of 27 years, despite having a normalbody mass index (BMI). She exhibited partial impairment of islet function, testedpositive for islet antibodies, and required high doses of insulin. Her sister alsocarried the c.4G>A (p.Ala2Thr) mutation, and their mother was stronglysuspected to carry the mutated gene. Her sister developed diabetes around 40years of age and required high doses of insulin, while the mother was diagnosedin her 20s and was managed with oral hypoglycemic agents;neither of them wereobese.CONCLUSION p.Ala2Thr mutation carriers often experience relatively later onset and normalBMI. Treatment regimens vary between individuals.展开更多
BACKGROUND Maturity-onset diabetes of the young 3(MODY3),caused by mutations in the HNF1A gene,is the most common subtype of MODY.The diagnosis of MODY3 is critical because a low dose of sulfonylurea agents can achiev...BACKGROUND Maturity-onset diabetes of the young 3(MODY3),caused by mutations in the HNF1A gene,is the most common subtype of MODY.The diagnosis of MODY3 is critical because a low dose of sulfonylurea agents can achieve glucose control.CASE SUMMARY We describe a patient with MODY3 involving a novel splicing mutation,in whom low-dose gliclazide was sufficient to control clinically significant hyperglycemia.Sanger sequencing identified a splicing HNF1A mutation in 12q24 NM_000545.5 Intron5 c.1108-1G>A.Glycemic control has been maintained without insulin therapy for 28 mo after the diagnosis of diabetes.CONCLUSION This case report highlights a novel HNF1A gene mutation in MODY3 that is responsive to sulfonylurea therapy.展开更多
BACKGROUND Intravenous steroid pulse therapy is the treatment of choice for acute exacerbation of multiple sclerosis(MS).Although steroid administration is generally welltolerated,cases of cardiac arrhythmia have been...BACKGROUND Intravenous steroid pulse therapy is the treatment of choice for acute exacerbation of multiple sclerosis(MS).Although steroid administration is generally welltolerated,cases of cardiac arrhythmia have been reported.Herein,we describe a young woman who developed marked sinus bradycardia and T-wave abnormalities after corticosteroid administration.We also present plausible explanations for the abnormalities observed in this patient.CASE SUMMARY An 18-year-old woman experienced vertiginous dizziness and binocular diplopia 1 wk prior to admission.Neurological examination revealed left internuclear ophthalmoplegia with left peripheral-type facial palsy.The initial laboratory results were consistent with those of type 2 diabetes.Brain magnetic resonance imaging revealed multifocal,non-enhancing,symptomatic lesions and multiple enhancing lesions.She was diagnosed with MS and maturity-onset diabetes of the young.Intravenous methylprednisolone was administered.On day 5 after methylprednisolone infusion,marked bradycardia with T-wave abnormalities were observed.Genetic evaluation to elucidate the underlying conditions revealed a hepatocyte nuclear factor 4-alpha(HNF4A)gene mutation.Steroid treatment was discontinued under suspicion of corticosteroid-induced bradycardia.Her electrocardiogram changes returned to normal without complications two days after steroid discontinuation.CONCLUSION Corticosteroid-induced bradycardia may have a significant clinical impact,especially in patients with comorbidities,such as HNF4A mutations.展开更多
BACKGROUND Maturity-onset diabetes of the young(MODY)is the most common form of monogenic diabetes.The disease is transmitted in autosomal dominant mode and diabetes is usually diagnosed before age 25 year.MODY 3 is c...BACKGROUND Maturity-onset diabetes of the young(MODY)is the most common form of monogenic diabetes.The disease is transmitted in autosomal dominant mode and diabetes is usually diagnosed before age 25 year.MODY 3 is caused by mutation of hepatocyte nuclear factor(HNF)1A genes and is the most common MODY subtype.Diagnosis of MODY 3 is crucial since glycemic control can be accomplished by very low dose of sulfonylurea.In this report we described a Thai MODY 3 patient who had excellence plasma glucose control by treating with glicazide 20 mg per day and insulin therapy can be discontinued.CASE SUMMARY A 31-year-old woman was diagnosed diabetes mellitus at 14 years old.The disease was transmitted from her grandmother and mother compatible with autosomal dominant inheritance.Sanger sequencing of proband’s DNA identified mutation of HNF1A at codon 203 which changed amino acid from arginine to cysteine(R203C).This mutation was carried only by family members who have diabetes.The patient has been treated effectively with a combination of oral hypoglycemic agents and must include a very low dose of glicazide(20 mg/d).Insulin therapy was successfully discontinued.CONCLUSION We demonstrated a first case of pharmacogenetics in Thai MODY 3 patient.Our findings underscore the essential role of molecular genetics in diagnosis and guidance of appropriate treatment of diabetes mellitus in particular patient.展开更多
Background:Maturity-onset diabetes of the young(MODY)is the most common monogenic diabetes.The aim of this study was to assess the prevalence of MODY in phenotypic type 2 diabetes(T2DM)among Chinese young adults.Metho...Background:Maturity-onset diabetes of the young(MODY)is the most common monogenic diabetes.The aim of this study was to assess the prevalence of MODY in phenotypic type 2 diabetes(T2DM)among Chinese young adults.Methods:From April 2015 to October 2017,this cross-sectional study involved 2429 consecutive patients from 46 hospitals in China,newly diagnosed between 15 years and 45 years,with T2DM phenotype and negative for standardized glutamic acid decarboxylase antibody at the core laboratory.Sequencing using a custom monogenic diabetes gene panel was performed,and variants of 14 MODY genes were interpreted as per current guidelines.Results:The survey determined 18 patients having genetic variants causing MODY(6 HNF1A,5 GCK,3 HNF4A,2 INS,1 PDX1,and 1 PAX4).The prevalence of MODY was 0.74%(95%confidence interval[CI]:0.40-1.08%).The clinical characteristics of MODY patients were not specific,72.2%(13/18)of them were diagnosed after 35 years,47.1%(8/17)had metabolic syndrome,and only 38.9%(7/18)had a family history of diabetes.No significant difference in manifestations except for hemoglobin A1c levels was found between MODY and non-MODY patients.Conclusion:The prevalence of MODY in young adults with phenotypic T2DM was 0.74%,among which HNF1A-,GCK-,and HNF4A-MODY were the most common subtypes.Clinical features played a limited role in the recognition of MODY.展开更多
Objective: The purpose of this study is to understand the current situation of knowledge, attitude, and practice of self-management in young patients with type 2 diabetes mellitus (T2DM) and to explore the relationshi...Objective: The purpose of this study is to understand the current situation of knowledge, attitude, and practice of self-management in young patients with type 2 diabetes mellitus (T2DM) and to explore the relationship between general conditions (personal, social, and environment, clinical factors) and their knowledge, attitude, and practices (KAP) of diabetes self-management, This aims to provide patients with high-quality nursing care management and services, as well as to provide relevant recommendations for effective self-management. Methods: This study is a descriptive correlational study that used the purposive sampling method to investigate 359 patients with T2DM aged 18-25 years in four designated tertiary hospitals in Shandong Province. Results: Knowledge of self-management was correlated with sex, age, education level, occupation and work situation, monthly household income, medical payment method, family and friend support, frequency of diabetes health education, and diabetes complications. The attitude subscale was correlated with sex, age, education level, work situation, and family and friend support. The practice subscale was associated with age, education level, work situation, family and friend support, frequency of diabetes health education, and HbA1c values. Conclusion: Young adults aged 18-25 with T2DM have positive attitudes towards diabetes self-management, but there are still deficiencies in knowledge acquisition and behavioral practice. The KAP of self-management of diabetes is influenced by personal factors such as sex, age, and education level, and socio-environmental factors such as family income and family or friends’ social support. Additionally, clinical factors such as complications and HbA1c values significantly impacted the patient’s disease self-management ability.展开更多
Monogenic diabetes,constituting 1%-2%of global diabetes cases,arises from single gene defects with distinctive inheritance patterns.Despite over 50 associated genetic disorders,accurate diagnoses and management of mon...Monogenic diabetes,constituting 1%-2%of global diabetes cases,arises from single gene defects with distinctive inheritance patterns.Despite over 50 associated genetic disorders,accurate diagnoses and management of monogenic diabetes remain inadequate,underscoring insufficient clinician awareness.The 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 infants.Mitochondrial 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 MODY.NDM diagnosis warrants immediate molecular genetic testing for infants under six months.Identifying these genetic defects presents a unique opportunity for precision medicine.Ongoing research aimed to develop cost-effective genetic testing methods and gene-based therapy can facilitate appropriate identification and optimize clinical outcomes.Identification 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 diabetes.The 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.展开更多
Pregnancy in women with monogenic diabetes is potentially complex,with significant implications for both maternal and fetal health.Among these,maturity-onset diabetes of the young(MODY)stands out as a prevalent monoge...Pregnancy in women with monogenic diabetes is potentially complex,with significant implications for both maternal and fetal health.Among these,maturity-onset diabetes of the young(MODY)stands out as a prevalent monogenic diabetes subtype frequently encountered in clinical practice.Each subtype of MODY requires a distinct approach tailored to the pregnancy,diverging from management strategies in non-pregnant individuals.Glucokinase MODY(GCK-MODY)typically does not require treatment outside of pregnancy,but special considerations arise when a woman with GCK-MODY becomes pregnant.The glycemic targets in GCK-MODY pregnancies are not exclusively dictated by the maternal/paternal MODY genotype but are also influenced by the genotype of the developing fetus.During pregnancy,the choice between sulfonylurea or insulin for treating hepatocyte nuclear factor 1-alpha(HNF1A)-MODY and HNF4A-MODY depends on the mother’s specific circumstances and the available expertise.Management of other rarer MODY subtypes is individu-alized,with decisions made on a case-by-case basis.Therefore,a collaborative approach involving expert diabetes and obstetric teams is crucial for the compre-hensive management of MODY pregnancies.展开更多
BACKGROUND This study presents the clinical and genetic mutation characteristics of an unusual case of adult-onset diabetes mellitus occurring in adolescence,featuring a unique mutation in the peroxisome proliferator-...BACKGROUND This study presents the clinical and genetic mutation characteristics of an unusual case of adult-onset diabetes mellitus occurring in adolescence,featuring a unique mutation in the peroxisome proliferator-activated receptor gamma(PPARG)gene.Data Access Statement:Research data supporting this publication are available from the NN repository at www.NNN.org/download/.CASE SUMMARY The methodology employed entailed meticulous collection of comprehensive clinical data from the probands and their respective family members.Additionally,high-throughput sequencing was conducted to analyze the PPARG genes of the patient,her siblings,and their offspring.The results of this investigation revealed that the patient initially exhibited elevated blood glucose levels during pregnancy,accompanied by insulin resistance and hypertriglyceridemia.Furthermore,these strains displayed increased susceptibility to diabetic kidney disease without any discernible aggregation patterns.The results from the gene detection process demonstrated a heterozygous mutation of guanine(G)at position 284 in the coding region of exon 2 of PPARG,which replaced the base adenine(A)(exon2c.284A>Gp.Tyr95Cys).This missense mutation resulted in the substitution of tyrosine with cysteine at the 95th position of the translated protein.Notably,both of her siblings harbored a nucleotide heterozygous variation at the same site,and both were diagnosed with diabetes.CONCLUSION The PPARG gene mutation,particularly the p.Tyr95Cys mutation,may represent a newly identified subtype of maturity-onset diabetes of the young.This subtype is characterized by insulin resistance and lipid metabolism disorders.展开更多
Background: Diabetic retinopathy is among the most common diabetic complications, and is one of the leading causes of blindness in the world. Recent studies have linked vitamin D to the pathogenesis of diabetes and th...Background: Diabetic retinopathy is among the most common diabetic complications, and is one of the leading causes of blindness in the world. Recent studies have linked vitamin D to the pathogenesis of diabetes and there is growing evidence that vitamin D can interfere with the mechanisms involved in diabetes and its complications. Despite improvements in treatment, diabetic retinopathy remains a significant complication of type 1 diabetes mellitus. Identification of early treatable predictors of diabetic retinopathy such as vitamin D deficiency, may allow more aggressive management of those at high risk. Purpose: To assess the association of vitamin D deficiency with diabetic retinopathy in young people with type 1 diabetes mellitus. Design: Observational study with case control design. Method: 60 young people with type 1 diabetes aged between 11 to 24 years were included in this study. Among them, 30-young people have diabetic retinopathy and 30-young people do not have diabetic retinopathy. Purposive sampling technique was applied as per inclusion criteria. Statistical analysis of the results was done by using computer-based software, SPSS version 26. P value of less than 0.05 was considered as statistically significant. Results: Vitamin D deficiency was present in 83% of the young people with diabetic retinopathy and in 53% without diabetic retinopathy. The mean vitamin D level in young people with and without diabetic retinopathy was 17.38 ± 3.77 ng/ml and 20.15 ± 5.06 ng/ml respectively and the difference was statistically significant (p = 0.019). Vitamin D deficiency was increased with the severity of diabetic retinopathy. Univariate and multivariate logistic regression showed vitamin D deficiency was independently associated with diabetic retinopathy with a crude odds ratio of 5.69 with a p value of 0.008 and adjusted odds ratio of 16.08 with a p value of 0.002 respectively. Conclusion: Result of the study revealed that vitamin D deficiency was strongly associated with diabetic retinopathy in young people with type 1 diabetes mellitus.展开更多
Monogenic diabetes is caused by one or even more genetic variations, which maybe uncommon yet have a significant influence and cause diabetes at an early age.Monogenic diabetes affects 1 to 5% of children, and early d...Monogenic diabetes is caused by one or even more genetic variations, which maybe uncommon yet have a significant influence and cause diabetes at an early age.Monogenic diabetes affects 1 to 5% of children, and early detection and geneticallyfocused treatment of neonatal diabetes and maturity-onset diabetes of theyoung can significantly improve long-term health and well-being. The etiology ofmonogenic diabetes in childhood is primarily attributed to genetic variationsaffecting the regulatory genes responsible for beta-cell activity. In rare instances,mutations leading to severe insulin resistance can also result in the developmentof diabetes. Individuals diagnosed with specific types of monogenic diabetes,which are commonly found, can transition from insulin therapy to sulfonylureas,provided they maintain consistent regulation of their blood glucose levels.Scientists have successfully devised materials and methodologies to distinguishindividuals with type 1 or 2 diabetes from those more prone to monogenicdiabetes. Genetic screening with appropriate findings and interpretations isessential to establish a prognosis and to guide the choice of therapies andmanagement of these interrelated ailments. This review aims to design a comprehensiveliterature summarizing genetic insights into monogenetic diabetes inchildren and adolescents as well as summarizing their diagnosis and management.展开更多
BACKGROUND Adaptor protein,phosphotyrosine interacting with PH domain and leucine zipper 1(APPL1)plays a crucial role in regulating insulin signaling and glucose metabolism.Mutations in the APPL1 gene have been associ...BACKGROUND Adaptor protein,phosphotyrosine interacting with PH domain and leucine zipper 1(APPL1)plays a crucial role in regulating insulin signaling and glucose metabolism.Mutations 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(p.Leu552*)and c.281G>A p.(Asp94Asn)]have been identified in association with this disease.Given the limited understanding of MODY14,it is imperative to identify additional cases and carry out comprehensive research on MODY14 and APPL1 mutations.AIM To assess the pathogenicity of APPL1 gene mutations in diabetic patients and to characterize the functional role of the APPL1 domain.METHODS Patients exhibiting clinical signs and a medical history suggestive of MODY were screened for the study.Whole exome sequencing was performed on the patients as well as their family members.The pathogenicity of the identified APPL1 variants was predicted on the basis of bioinformatics analysis.In addition,the pathogenicity of the novel APPL1 variant was preliminarily evaluated through in vitro functional experiments.Finally,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 explored.RESULTS 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 predictions.The Asp632Tyr and Arg633His variants also had pathogenicity based on MutationTaster.In addition,multiple alignment of amino acid sequences showed that the Arg532Gln,Asp632Tyr,and Arg633His variants were conserved across different species.Moreover,in in vitro functional experiments,both the c.1894G>T(at Asp632Tyr)and c.1595G>A(at Arg532Gln)mutations were found to downregulate the expression of APPL1 on both protein and mRNA levels,indicating their pathogenic nature.Therefore,based on the patient’s clinical and family history,combined with the results from bioinformatics analysis and functional experiment,the c.1894G>T(at Asp632Tyr)and c.1595G>A(at Arg532Gln)mutations were classified as pathogenic mutations.Importantly,all these mutations were located within the phosphotyrosinebinding domain of APPL1,which plays a critical role in the insulin sensitization effect.CONCLUSION This study provided new insights into the pathogenicity of APPL1 gene mutations in diabetes and revealed a potential target for the diagnosis and treatment of the disease.展开更多
Diabetes mellitus is a complicated disease characterized by a complex interplay of genetic,epigenetic,and environmental variables.It is one of the world's fastestgrowing diseases,with 783 million adults expected t...Diabetes mellitus is a complicated disease characterized by a complex interplay of genetic,epigenetic,and environmental variables.It is one of the world's fastestgrowing diseases,with 783 million adults expected to be affected by 2045.Devastating macrovascular consequences(cerebrovascular disease,cardiovascular disease,and peripheral vascular disease)and microvascular complications(like retinopathy,nephropathy,and neuropathy)increase mortality,blindness,kidney failure,and overall quality of life in individuals with diabetes.Clinical risk factors and glycemic management alone cannot predict the development of vascular problems;multiple genetic investigations have revealed a clear hereditary component to both diabetes and its related complications.In the twenty-first century,technological advancements(genome-wide association studies,nextgeneration sequencing,and exome-sequencing)have led to the identification of genetic variants associated with diabetes,however,these variants can only explain a small proportion of the total heritability of the condition.In this review,we address some of the likely explanations for this"missing heritability",for diabetes such as the significance of uncommon variants,gene-environment interactions,and epigenetics.Current discoveries clinical value,management of diabetes,and future research directions are also discussed.展开更多
Non insulin dependent diabetes mellitus (NIDDM) as a most common form of diabetes is a major public health problem;there is a subgroup of NIDDM patients who develop the disease at an early age and show a dominant mode...Non insulin dependent diabetes mellitus (NIDDM) as a most common form of diabetes is a major public health problem;there is a subgroup of NIDDM patients who develop the disease at an early age and show a dominant mode of inheritance. This type is nominates Maturity onset diabetes of the young (MODY). The prevalence of MODY is difficult to access, and patients with MODY genes mutations are often identified during routine screening for other purposes. MODY2 was linked to glucokinase gene (GCK) mutations, and accounted for 8% to 56% of MODY, with the highest prevalence found in the southern Europe. The aim of this study was to examine the prevalence and nature of mutations in GCK gene in Iranian paients. We have screened GCK mutations by polymerase chain reaction (PCR);single stranded conformation polymorphism (SSCP) technique in 12 Iranian families with clinical diagnosis of MODY, included 30 patients (8 males and 22 females) and their 21 family members. PCR products with abnormal mobility in denaturing gradient gel electrophoresis (DGGE) were directly sequenced. We identified 6 novel mutations in GCK gene in Iranian families (corresponding to 36.6% prevalence). Our findings and the last study on MODY1 highlight that in addition to GCK, other MODY genes such as MODY3 and MODYX may play a significant role in diabetes characterized by monogenic autosomal dominant transmission. There is an important point that the genetic recognation can be used to pre-symptomatically identify family members at risk for developing MODY.展开更多
Much has been published on the characteristics of type 2 diabetes mellitus and its association with the epidemic of obesity.But relatively little is known about the incidence of lean diabetes,progression of disease an...Much has been published on the characteristics of type 2 diabetes mellitus and its association with the epidemic of obesity.But relatively little is known about the incidence of lean diabetes,progression of disease and fate of the patients with low-normal body mass index(< 25).Studies in developing countries have shown that the clinical characteristics of these patients include history of childhood malnutrition,poor socioeconomic status,relatively early age of onset and absence of ketosis on withdrawal of insulin.In the United States,recent studies showed that the lean,normal weight diabetes is not rare especially among minority populations.They showed that these patients are mainly males,have higher prevalence of insulin use indicating rapid beta cell failure.They might have increased total,cardiovascular and non cardiovascular mortality when compared to obese diabetic patients.In this review,the epidemiologic and clinical features of lean diabetes are presented.The potential causal mechanisms of this emerging diabetes type that may include genetic,autoimmune,acquired and behavioral factors are discussed.The need for studies to further elucidate the causation as well as specific prevention and treatment of lean diabetes is emphasized.展开更多
BACKGROUND Risk factors such as hereditary, ecological, and metabolic are interrelated and contribute to the development of type 2 diabetes mellitus. Family history(FH) of diabetes mellitus, age, obesity, and physical...BACKGROUND Risk factors such as hereditary, ecological, and metabolic are interrelated and contribute to the development of type 2 diabetes mellitus. Family history(FH) of diabetes mellitus, age, obesity, and physical inactivity are some of the risk factors for the development of type 2 diabetes.AIM To study various aetiological determinants and risk factors for type 2 diabetes in Bangalore, India. This retrospective study examined questionnaire from patients attending the Diabetes Clinic.METHODS Data on various parameters were obtained through a questionnaire from 533 patients on the first visit to the diabetes clinic. Data regarding various aetiological determinants and risk factors viz.: Genetic risk factor and few modifiable risk factors were collected. Chi-squared test was used for statistical analysis.RESULTS A higher incidence of type 2 diabetes in males and younger population was observed in Bangalore, India. Obesity and FH were significant risk factors for not only type 2 diabetes but also early onset of diabetes. In addition, maternal history of type 2 diabetes and consanguinity increased incidence of early onset type 2 diabetes.CONCLUSION Risk factors such as obesity and FH(maternal history of type 2 diabetes) and consanguinity may play an important role in screening of family members of type 2 diabetes patients which may lead to early intervention and reduced risk of subsequent complications. Moreover, susceptible population can be counselled for the management of the type 2 diabetes including periodic investigation of blood glucose levels and lifestyle changes.展开更多
BACKGROUND The diagnosis of type 2 diabetes(T2D)in younger adults,an increasingly common public health issue,is associated with a higher risk of cardiovascular complications and mortality,which may be due to a more ad...BACKGROUND The diagnosis of type 2 diabetes(T2D)in younger adults,an increasingly common public health issue,is associated with a higher risk of cardiovascular complications and mortality,which may be due to a more adverse cardiovascular risk profile in individuals diagnosed at a younger age.AIM To investigate the association between age at diagnosis and the cardiovascular risk profile in adults with T2D.METHODS A pooled dataset was used,comprised of data from five previous studies of adults with T2D,including 1409 participants of whom 196 were diagnosed with T2D under the age of 40 years.Anthropometric and blood biomarker measurements included body weight,body mass index(BMI),waist circumference,body fat percentage,glycaemic control(HbA1c),lipid profile and blood pressure.Univariable and multivariable linear regression models,adjusted for diabetes duration,sex,ethnicity and smoking status,were used to investigate the association between age at diagnosis and each cardiovascular risk factor.RESULTS A higher proportion of participants diagnosed with T2D under the age of 40 were female,current smokers and treated with glucose-lowering medications,compared to participants diagnosed later in life.Participants diagnosed with T2D under the age of 40 also had higher body weight,BMI,waist circumference and body fat percentage,in addition to a more adverse lipid profile,compared to participants diagnosed at an older age.Modelling results showed that each one year reduction in age at diagnosis was significantly associated with 0.67 kg higher body weight[95%confidence interval(CI):0.52-0.82 kg],0.18 kg/m^(2) higher BMI(95%CI:0.10-0.25)and 0.32 cm higher waist circumference(95%CI:0.14-0.49),after adjustment for duration of diabetes and other confounders.Younger age at diagnosis was also significantly associated with higher HbA1c,total cholesterol,low-density lipoprotein cholesterol and triglycerides.CONCLUSION The diagnosis of T2D earlier in life is associated with a worse cardiovascular risk factor profile,compared to those diagnosed later in life.展开更多
Diabetes mellitus is a complex condition with far reaching physical, psychological and psychosocial effects. These outcomes can be significant when considering the care of a youth transferring from paediatric through ...Diabetes mellitus is a complex condition with far reaching physical, psychological and psychosocial effects. These outcomes can be significant when considering the care of a youth transferring from paediatric through to adult diabetes services. The art of mastering a smooth care transfer is crucial if not pivotal to optimising overall diabetic control. Quite often the nature of consultation varies between the two service providers and the objectives and outcomes will mirror this. The purpose of this review is to analyse the particular challenges and barriers one might expect to encounter when transferring these services over to an adult care provider. Particular emphasis is paid towards the psychological aspects of this delicate period, which needs to be recognised and appreciated appropriately in order to understand the particular plights a young diabetic child will be challenged with. We explore the approaches that can be positively adopted in order to improve the experience for child, parents and also the multi- disciplinary team concerned with the overall delivery of this care. Finally we will close with reflection on the potential areas for future development that will ultimately aim to improve long-term outcomes and experiences of the young adolescent confronted with diabetes as well as the burden of disease and burden of cost of disease.展开更多
基金Supported by the National Natural Science Foundation of China,No.81300702the Natural Science Foundation Project of Chongqing CSTC,No.cstc2018jcyjAXO210.
文摘BACKGROUND Maturity-onset diabetes of the young(MODY)is a monogenic genetic disease often clinically misdiagnosed as type 1 or type 2 diabetes.MODY type 9(MODY9)is a rare subtype caused by mutations in the PAX4 gene.Currently,there are limited reports on PAX4-MODY,and its clinical characteristics and treatments are still unclear.In this report,we described a Chinese patient with high autoimmune antibodies,hyperglycemia and a site mutation in the PAX4 gene.CASE SUMMARY A 42-year-old obese woman suffered diabetes ketoacidosis after consuming substantial amounts of beverages.She had never had diabetes before,and no one in her family had it.However,her autoantibody tested positive,and she managed her blood glucose within the normal range for 6 mo through lifestyle interventions.Later,her blood glucose gradually increased.Next-generation sequencing and Sanger sequencing were performed on her family.The results revealed that she and her mother had a heterozygous mutation in the PAX4 gene(c.314G>A,p.R105H),but her daughter did not.The patient is currently taking liraglutide(1.8 mg/d),and her blood glucose levels are under control.Previous cases were retrieved from PubMed to investigate the relationship between PAX4 gene mutations and diabetes.CONCLUSION We reported the first case of a PAX4 gene heterozygous mutation site(c.314G>A,p.R105H),which does not appear pathogenic to MODY9 but may facilitate the progression of latent autoimmune diabetes in adults.
文摘BACKGROUND Maturity-onset diabetes of the young(MODY)is the most common monogenic type of diabetes.Recently,14 gene mutations have been found to be associated with MODY.In addition,the KLF11 gene mutation is the pathogenic gene of MODY7.To date,the clinical and functional characteristics of the novel KLF11mutation c.G31A have not yet been reported.CASE SUMMARY We report of a 30-year-old male patient with a one-year history of nonketosisprone diabetes and a 3-generation family history of diabetes.The patient was found to carry a KLF11 gene mutation.Therefore,the clinical data of family members were collected and investigated.A total of four members of the family were found to have heterozygous mutations in the KLF11 gene c.G31A,which resulted in a change in the corresponding amino acid p.D11N.Three patients had diabetes mellitus,and one patient had impaired glucose tolerance.CONCLUSION The heterozygous mutation of the KLF11 gene c.G31A(p.D11N)is a new mutation site of MODY7.Subsequently,the main treatment included dietary interventions and oral drugs.
基金National Natural Science Foundation of China,No.82270881.
文摘Maturity-onset diabetes of the young 10 caused by the c.4G>A (p.Ala2Thr)mutation is extremely rare, with only two reported studies to date. Herein, wereport another case that differs from previous cases in phenotype.CASE SUMMARYThe proband developed diabetes at the age of 27 years, despite having a normalbody mass index (BMI). She exhibited partial impairment of islet function, testedpositive for islet antibodies, and required high doses of insulin. Her sister alsocarried the c.4G>A (p.Ala2Thr) mutation, and their mother was stronglysuspected to carry the mutated gene. Her sister developed diabetes around 40years of age and required high doses of insulin, while the mother was diagnosedin her 20s and was managed with oral hypoglycemic agents;neither of them wereobese.CONCLUSION p.Ala2Thr mutation carriers often experience relatively later onset and normalBMI. Treatment regimens vary between individuals.
基金Supported by National Natural Science Foundation of China,No.81870593 and No.82170865Quality Improvement of Postgraduate Education in Shandong Province,No.SDYAL19156.
文摘BACKGROUND Maturity-onset diabetes of the young 3(MODY3),caused by mutations in the HNF1A gene,is the most common subtype of MODY.The diagnosis of MODY3 is critical because a low dose of sulfonylurea agents can achieve glucose control.CASE SUMMARY We describe a patient with MODY3 involving a novel splicing mutation,in whom low-dose gliclazide was sufficient to control clinically significant hyperglycemia.Sanger sequencing identified a splicing HNF1A mutation in 12q24 NM_000545.5 Intron5 c.1108-1G>A.Glycemic control has been maintained without insulin therapy for 28 mo after the diagnosis of diabetes.CONCLUSION This case report highlights a novel HNF1A gene mutation in MODY3 that is responsive to sulfonylurea therapy.
文摘BACKGROUND Intravenous steroid pulse therapy is the treatment of choice for acute exacerbation of multiple sclerosis(MS).Although steroid administration is generally welltolerated,cases of cardiac arrhythmia have been reported.Herein,we describe a young woman who developed marked sinus bradycardia and T-wave abnormalities after corticosteroid administration.We also present plausible explanations for the abnormalities observed in this patient.CASE SUMMARY An 18-year-old woman experienced vertiginous dizziness and binocular diplopia 1 wk prior to admission.Neurological examination revealed left internuclear ophthalmoplegia with left peripheral-type facial palsy.The initial laboratory results were consistent with those of type 2 diabetes.Brain magnetic resonance imaging revealed multifocal,non-enhancing,symptomatic lesions and multiple enhancing lesions.She was diagnosed with MS and maturity-onset diabetes of the young.Intravenous methylprednisolone was administered.On day 5 after methylprednisolone infusion,marked bradycardia with T-wave abnormalities were observed.Genetic evaluation to elucidate the underlying conditions revealed a hepatocyte nuclear factor 4-alpha(HNF4A)gene mutation.Steroid treatment was discontinued under suspicion of corticosteroid-induced bradycardia.Her electrocardiogram changes returned to normal without complications two days after steroid discontinuation.CONCLUSION Corticosteroid-induced bradycardia may have a significant clinical impact,especially in patients with comorbidities,such as HNF4A mutations.
基金Supported by Mahidol University Research Grant,Nos.R015810001and 016120003(to Nattachet Plengvidhya)Siriraj Research Grant for Research and Development,Faculty of Medicine Siriraj Hospital,Mahidol University,No.R015934015(to Tassanee Narkdontri and Watip Tangjittipokin)Thailand Research Fund grants,Nos.TRG5780113(to Watip Tangjittipokin),BRG5280008(to Nattachet Plengvidhya),and IRG5980006(to Pa-thai Yenchitsomanus)
文摘BACKGROUND Maturity-onset diabetes of the young(MODY)is the most common form of monogenic diabetes.The disease is transmitted in autosomal dominant mode and diabetes is usually diagnosed before age 25 year.MODY 3 is caused by mutation of hepatocyte nuclear factor(HNF)1A genes and is the most common MODY subtype.Diagnosis of MODY 3 is crucial since glycemic control can be accomplished by very low dose of sulfonylurea.In this report we described a Thai MODY 3 patient who had excellence plasma glucose control by treating with glicazide 20 mg per day and insulin therapy can be discontinued.CASE SUMMARY A 31-year-old woman was diagnosed diabetes mellitus at 14 years old.The disease was transmitted from her grandmother and mother compatible with autosomal dominant inheritance.Sanger sequencing of proband’s DNA identified mutation of HNF1A at codon 203 which changed amino acid from arginine to cysteine(R203C).This mutation was carried only by family members who have diabetes.The patient has been treated effectively with a combination of oral hypoglycemic agents and must include a very low dose of glicazide(20 mg/d).Insulin therapy was successfully discontinued.CONCLUSION We demonstrated a first case of pharmacogenetics in Thai MODY 3 patient.Our findings underscore the essential role of molecular genetics in diagnosis and guidance of appropriate treatment of diabetes mellitus in particular patient.
基金Science and Technology Innovation Program of Hunan Province(No.2020RC4044)National Science and Technology Infrastructure Program(No.2013BAI09B12)
文摘Background:Maturity-onset diabetes of the young(MODY)is the most common monogenic diabetes.The aim of this study was to assess the prevalence of MODY in phenotypic type 2 diabetes(T2DM)among Chinese young adults.Methods:From April 2015 to October 2017,this cross-sectional study involved 2429 consecutive patients from 46 hospitals in China,newly diagnosed between 15 years and 45 years,with T2DM phenotype and negative for standardized glutamic acid decarboxylase antibody at the core laboratory.Sequencing using a custom monogenic diabetes gene panel was performed,and variants of 14 MODY genes were interpreted as per current guidelines.Results:The survey determined 18 patients having genetic variants causing MODY(6 HNF1A,5 GCK,3 HNF4A,2 INS,1 PDX1,and 1 PAX4).The prevalence of MODY was 0.74%(95%confidence interval[CI]:0.40-1.08%).The clinical characteristics of MODY patients were not specific,72.2%(13/18)of them were diagnosed after 35 years,47.1%(8/17)had metabolic syndrome,and only 38.9%(7/18)had a family history of diabetes.No significant difference in manifestations except for hemoglobin A1c levels was found between MODY and non-MODY patients.Conclusion:The prevalence of MODY in young adults with phenotypic T2DM was 0.74%,among which HNF1A-,GCK-,and HNF4A-MODY were the most common subtypes.Clinical features played a limited role in the recognition of MODY.
文摘Objective: The purpose of this study is to understand the current situation of knowledge, attitude, and practice of self-management in young patients with type 2 diabetes mellitus (T2DM) and to explore the relationship between general conditions (personal, social, and environment, clinical factors) and their knowledge, attitude, and practices (KAP) of diabetes self-management, This aims to provide patients with high-quality nursing care management and services, as well as to provide relevant recommendations for effective self-management. Methods: This study is a descriptive correlational study that used the purposive sampling method to investigate 359 patients with T2DM aged 18-25 years in four designated tertiary hospitals in Shandong Province. Results: Knowledge of self-management was correlated with sex, age, education level, occupation and work situation, monthly household income, medical payment method, family and friend support, frequency of diabetes health education, and diabetes complications. The attitude subscale was correlated with sex, age, education level, work situation, and family and friend support. The practice subscale was associated with age, education level, work situation, family and friend support, frequency of diabetes health education, and HbA1c values. Conclusion: Young adults aged 18-25 with T2DM have positive attitudes towards diabetes self-management, but there are still deficiencies in knowledge acquisition and behavioral practice. The KAP of self-management of diabetes is influenced by personal factors such as sex, age, and education level, and socio-environmental factors such as family income and family or friends’ social support. Additionally, clinical factors such as complications and HbA1c values significantly impacted the patient’s disease self-management ability.
文摘Monogenic diabetes,constituting 1%-2%of global diabetes cases,arises from single gene defects with distinctive inheritance patterns.Despite over 50 associated genetic disorders,accurate diagnoses and management of monogenic diabetes remain inadequate,underscoring insufficient clinician awareness.The 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 infants.Mitochondrial 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 MODY.NDM diagnosis warrants immediate molecular genetic testing for infants under six months.Identifying these genetic defects presents a unique opportunity for precision medicine.Ongoing research aimed to develop cost-effective genetic testing methods and gene-based therapy can facilitate appropriate identification and optimize clinical outcomes.Identification 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 diabetes.The 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.
文摘Pregnancy in women with monogenic diabetes is potentially complex,with significant implications for both maternal and fetal health.Among these,maturity-onset diabetes of the young(MODY)stands out as a prevalent monogenic diabetes subtype frequently encountered in clinical practice.Each subtype of MODY requires a distinct approach tailored to the pregnancy,diverging from management strategies in non-pregnant individuals.Glucokinase MODY(GCK-MODY)typically does not require treatment outside of pregnancy,but special considerations arise when a woman with GCK-MODY becomes pregnant.The glycemic targets in GCK-MODY pregnancies are not exclusively dictated by the maternal/paternal MODY genotype but are also influenced by the genotype of the developing fetus.During pregnancy,the choice between sulfonylurea or insulin for treating hepatocyte nuclear factor 1-alpha(HNF1A)-MODY and HNF4A-MODY depends on the mother’s specific circumstances and the available expertise.Management of other rarer MODY subtypes is individu-alized,with decisions made on a case-by-case basis.Therefore,a collaborative approach involving expert diabetes and obstetric teams is crucial for the compre-hensive management of MODY pregnancies.
文摘BACKGROUND This study presents the clinical and genetic mutation characteristics of an unusual case of adult-onset diabetes mellitus occurring in adolescence,featuring a unique mutation in the peroxisome proliferator-activated receptor gamma(PPARG)gene.Data Access Statement:Research data supporting this publication are available from the NN repository at www.NNN.org/download/.CASE SUMMARY The methodology employed entailed meticulous collection of comprehensive clinical data from the probands and their respective family members.Additionally,high-throughput sequencing was conducted to analyze the PPARG genes of the patient,her siblings,and their offspring.The results of this investigation revealed that the patient initially exhibited elevated blood glucose levels during pregnancy,accompanied by insulin resistance and hypertriglyceridemia.Furthermore,these strains displayed increased susceptibility to diabetic kidney disease without any discernible aggregation patterns.The results from the gene detection process demonstrated a heterozygous mutation of guanine(G)at position 284 in the coding region of exon 2 of PPARG,which replaced the base adenine(A)(exon2c.284A>Gp.Tyr95Cys).This missense mutation resulted in the substitution of tyrosine with cysteine at the 95th position of the translated protein.Notably,both of her siblings harbored a nucleotide heterozygous variation at the same site,and both were diagnosed with diabetes.CONCLUSION The PPARG gene mutation,particularly the p.Tyr95Cys mutation,may represent a newly identified subtype of maturity-onset diabetes of the young.This subtype is characterized by insulin resistance and lipid metabolism disorders.
文摘Background: Diabetic retinopathy is among the most common diabetic complications, and is one of the leading causes of blindness in the world. Recent studies have linked vitamin D to the pathogenesis of diabetes and there is growing evidence that vitamin D can interfere with the mechanisms involved in diabetes and its complications. Despite improvements in treatment, diabetic retinopathy remains a significant complication of type 1 diabetes mellitus. Identification of early treatable predictors of diabetic retinopathy such as vitamin D deficiency, may allow more aggressive management of those at high risk. Purpose: To assess the association of vitamin D deficiency with diabetic retinopathy in young people with type 1 diabetes mellitus. Design: Observational study with case control design. Method: 60 young people with type 1 diabetes aged between 11 to 24 years were included in this study. Among them, 30-young people have diabetic retinopathy and 30-young people do not have diabetic retinopathy. Purposive sampling technique was applied as per inclusion criteria. Statistical analysis of the results was done by using computer-based software, SPSS version 26. P value of less than 0.05 was considered as statistically significant. Results: Vitamin D deficiency was present in 83% of the young people with diabetic retinopathy and in 53% without diabetic retinopathy. The mean vitamin D level in young people with and without diabetic retinopathy was 17.38 ± 3.77 ng/ml and 20.15 ± 5.06 ng/ml respectively and the difference was statistically significant (p = 0.019). Vitamin D deficiency was increased with the severity of diabetic retinopathy. Univariate and multivariate logistic regression showed vitamin D deficiency was independently associated with diabetic retinopathy with a crude odds ratio of 5.69 with a p value of 0.008 and adjusted odds ratio of 16.08 with a p value of 0.002 respectively. Conclusion: Result of the study revealed that vitamin D deficiency was strongly associated with diabetic retinopathy in young people with type 1 diabetes mellitus.
文摘Monogenic diabetes is caused by one or even more genetic variations, which maybe uncommon yet have a significant influence and cause diabetes at an early age.Monogenic diabetes affects 1 to 5% of children, and early detection and geneticallyfocused treatment of neonatal diabetes and maturity-onset diabetes of theyoung can significantly improve long-term health and well-being. The etiology ofmonogenic diabetes in childhood is primarily attributed to genetic variationsaffecting the regulatory genes responsible for beta-cell activity. In rare instances,mutations leading to severe insulin resistance can also result in the developmentof diabetes. Individuals diagnosed with specific types of monogenic diabetes,which are commonly found, can transition from insulin therapy to sulfonylureas,provided they maintain consistent regulation of their blood glucose levels.Scientists have successfully devised materials and methodologies to distinguishindividuals with type 1 or 2 diabetes from those more prone to monogenicdiabetes. Genetic screening with appropriate findings and interpretations isessential to establish a prognosis and to guide the choice of therapies andmanagement of these interrelated ailments. This review aims to design a comprehensiveliterature summarizing genetic insights into monogenetic diabetes inchildren and adolescents as well as summarizing their diagnosis and management.
基金Supported by the National Natural Science Foundation,No.81974124and Taishan Scholar Project,No.tsqn20161071.
文摘BACKGROUND Adaptor protein,phosphotyrosine interacting with PH domain and leucine zipper 1(APPL1)plays a crucial role in regulating insulin signaling and glucose metabolism.Mutations 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(p.Leu552*)and c.281G>A p.(Asp94Asn)]have been identified in association with this disease.Given the limited understanding of MODY14,it is imperative to identify additional cases and carry out comprehensive research on MODY14 and APPL1 mutations.AIM To assess the pathogenicity of APPL1 gene mutations in diabetic patients and to characterize the functional role of the APPL1 domain.METHODS Patients exhibiting clinical signs and a medical history suggestive of MODY were screened for the study.Whole exome sequencing was performed on the patients as well as their family members.The pathogenicity of the identified APPL1 variants was predicted on the basis of bioinformatics analysis.In addition,the pathogenicity of the novel APPL1 variant was preliminarily evaluated through in vitro functional experiments.Finally,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 explored.RESULTS 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 predictions.The Asp632Tyr and Arg633His variants also had pathogenicity based on MutationTaster.In addition,multiple alignment of amino acid sequences showed that the Arg532Gln,Asp632Tyr,and Arg633His variants were conserved across different species.Moreover,in in vitro functional experiments,both the c.1894G>T(at Asp632Tyr)and c.1595G>A(at Arg532Gln)mutations were found to downregulate the expression of APPL1 on both protein and mRNA levels,indicating their pathogenic nature.Therefore,based on the patient’s clinical and family history,combined with the results from bioinformatics analysis and functional experiment,the c.1894G>T(at Asp632Tyr)and c.1595G>A(at Arg532Gln)mutations were classified as pathogenic mutations.Importantly,all these mutations were located within the phosphotyrosinebinding domain of APPL1,which plays a critical role in the insulin sensitization effect.CONCLUSION This study provided new insights into the pathogenicity of APPL1 gene mutations in diabetes and revealed a potential target for the diagnosis and treatment of the disease.
文摘Diabetes mellitus is a complicated disease characterized by a complex interplay of genetic,epigenetic,and environmental variables.It is one of the world's fastestgrowing diseases,with 783 million adults expected to be affected by 2045.Devastating macrovascular consequences(cerebrovascular disease,cardiovascular disease,and peripheral vascular disease)and microvascular complications(like retinopathy,nephropathy,and neuropathy)increase mortality,blindness,kidney failure,and overall quality of life in individuals with diabetes.Clinical risk factors and glycemic management alone cannot predict the development of vascular problems;multiple genetic investigations have revealed a clear hereditary component to both diabetes and its related complications.In the twenty-first century,technological advancements(genome-wide association studies,nextgeneration sequencing,and exome-sequencing)have led to the identification of genetic variants associated with diabetes,however,these variants can only explain a small proportion of the total heritability of the condition.In this review,we address some of the likely explanations for this"missing heritability",for diabetes such as the significance of uncommon variants,gene-environment interactions,and epigenetics.Current discoveries clinical value,management of diabetes,and future research directions are also discussed.
文摘Non insulin dependent diabetes mellitus (NIDDM) as a most common form of diabetes is a major public health problem;there is a subgroup of NIDDM patients who develop the disease at an early age and show a dominant mode of inheritance. This type is nominates Maturity onset diabetes of the young (MODY). The prevalence of MODY is difficult to access, and patients with MODY genes mutations are often identified during routine screening for other purposes. MODY2 was linked to glucokinase gene (GCK) mutations, and accounted for 8% to 56% of MODY, with the highest prevalence found in the southern Europe. The aim of this study was to examine the prevalence and nature of mutations in GCK gene in Iranian paients. We have screened GCK mutations by polymerase chain reaction (PCR);single stranded conformation polymorphism (SSCP) technique in 12 Iranian families with clinical diagnosis of MODY, included 30 patients (8 males and 22 females) and their 21 family members. PCR products with abnormal mobility in denaturing gradient gel electrophoresis (DGGE) were directly sequenced. We identified 6 novel mutations in GCK gene in Iranian families (corresponding to 36.6% prevalence). Our findings and the last study on MODY1 highlight that in addition to GCK, other MODY genes such as MODY3 and MODYX may play a significant role in diabetes characterized by monogenic autosomal dominant transmission. There is an important point that the genetic recognation can be used to pre-symptomatically identify family members at risk for developing MODY.
文摘Much has been published on the characteristics of type 2 diabetes mellitus and its association with the epidemic of obesity.But relatively little is known about the incidence of lean diabetes,progression of disease and fate of the patients with low-normal body mass index(< 25).Studies in developing countries have shown that the clinical characteristics of these patients include history of childhood malnutrition,poor socioeconomic status,relatively early age of onset and absence of ketosis on withdrawal of insulin.In the United States,recent studies showed that the lean,normal weight diabetes is not rare especially among minority populations.They showed that these patients are mainly males,have higher prevalence of insulin use indicating rapid beta cell failure.They might have increased total,cardiovascular and non cardiovascular mortality when compared to obese diabetic patients.In this review,the epidemiologic and clinical features of lean diabetes are presented.The potential causal mechanisms of this emerging diabetes type that may include genetic,autoimmune,acquired and behavioral factors are discussed.The need for studies to further elucidate the causation as well as specific prevention and treatment of lean diabetes is emphasized.
文摘BACKGROUND Risk factors such as hereditary, ecological, and metabolic are interrelated and contribute to the development of type 2 diabetes mellitus. Family history(FH) of diabetes mellitus, age, obesity, and physical inactivity are some of the risk factors for the development of type 2 diabetes.AIM To study various aetiological determinants and risk factors for type 2 diabetes in Bangalore, India. This retrospective study examined questionnaire from patients attending the Diabetes Clinic.METHODS Data on various parameters were obtained through a questionnaire from 533 patients on the first visit to the diabetes clinic. Data regarding various aetiological determinants and risk factors viz.: Genetic risk factor and few modifiable risk factors were collected. Chi-squared test was used for statistical analysis.RESULTS A higher incidence of type 2 diabetes in males and younger population was observed in Bangalore, India. Obesity and FH were significant risk factors for not only type 2 diabetes but also early onset of diabetes. In addition, maternal history of type 2 diabetes and consanguinity increased incidence of early onset type 2 diabetes.CONCLUSION Risk factors such as obesity and FH(maternal history of type 2 diabetes) and consanguinity may play an important role in screening of family members of type 2 diabetes patients which may lead to early intervention and reduced risk of subsequent complications. Moreover, susceptible population can be counselled for the management of the type 2 diabetes including periodic investigation of blood glucose levels and lifestyle changes.
基金Supported by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (NIHR201165)by the NIHR Leicester Biomedical Research Centrethe NIHR Applied Research Collaboration East Midlands
文摘BACKGROUND The diagnosis of type 2 diabetes(T2D)in younger adults,an increasingly common public health issue,is associated with a higher risk of cardiovascular complications and mortality,which may be due to a more adverse cardiovascular risk profile in individuals diagnosed at a younger age.AIM To investigate the association between age at diagnosis and the cardiovascular risk profile in adults with T2D.METHODS A pooled dataset was used,comprised of data from five previous studies of adults with T2D,including 1409 participants of whom 196 were diagnosed with T2D under the age of 40 years.Anthropometric and blood biomarker measurements included body weight,body mass index(BMI),waist circumference,body fat percentage,glycaemic control(HbA1c),lipid profile and blood pressure.Univariable and multivariable linear regression models,adjusted for diabetes duration,sex,ethnicity and smoking status,were used to investigate the association between age at diagnosis and each cardiovascular risk factor.RESULTS A higher proportion of participants diagnosed with T2D under the age of 40 were female,current smokers and treated with glucose-lowering medications,compared to participants diagnosed later in life.Participants diagnosed with T2D under the age of 40 also had higher body weight,BMI,waist circumference and body fat percentage,in addition to a more adverse lipid profile,compared to participants diagnosed at an older age.Modelling results showed that each one year reduction in age at diagnosis was significantly associated with 0.67 kg higher body weight[95%confidence interval(CI):0.52-0.82 kg],0.18 kg/m^(2) higher BMI(95%CI:0.10-0.25)and 0.32 cm higher waist circumference(95%CI:0.14-0.49),after adjustment for duration of diabetes and other confounders.Younger age at diagnosis was also significantly associated with higher HbA1c,total cholesterol,low-density lipoprotein cholesterol and triglycerides.CONCLUSION The diagnosis of T2D earlier in life is associated with a worse cardiovascular risk factor profile,compared to those diagnosed later in life.
文摘Diabetes mellitus is a complex condition with far reaching physical, psychological and psychosocial effects. These outcomes can be significant when considering the care of a youth transferring from paediatric through to adult diabetes services. The art of mastering a smooth care transfer is crucial if not pivotal to optimising overall diabetic control. Quite often the nature of consultation varies between the two service providers and the objectives and outcomes will mirror this. The purpose of this review is to analyse the particular challenges and barriers one might expect to encounter when transferring these services over to an adult care provider. Particular emphasis is paid towards the psychological aspects of this delicate period, which needs to be recognised and appreciated appropriately in order to understand the particular plights a young diabetic child will be challenged with. We explore the approaches that can be positively adopted in order to improve the experience for child, parents and also the multi- disciplinary team concerned with the overall delivery of this care. Finally we will close with reflection on the potential areas for future development that will ultimately aim to improve long-term outcomes and experiences of the young adolescent confronted with diabetes as well as the burden of disease and burden of cost of disease.
