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
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
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
目的·筛查青少年的成人起病型糖尿病(maturity-onset diabetes of the young,MODY)家系中NEUROD1基因突变,分析突变与中国人MODY6发病的相关性及其潜在的致病机制。方法·采用PCR-直接测序法对96例GCK/MODY2、HNF1A/MODY3、HNF...目的·筛查青少年的成人起病型糖尿病(maturity-onset diabetes of the young,MODY)家系中NEUROD1基因突变,分析突变与中国人MODY6发病的相关性及其潜在的致病机制。方法·采用PCR-直接测序法对96例GCK/MODY2、HNF1A/MODY3、HNF1B/MODY5突变阴性的中国MODY先证者进行NEUROD1突变筛查,同时比较96例MODY先证者与100例非糖尿病对照者NEUROD1基因变异的基因型频率。采用从头建模法构建NEUROD1蛋白野生型和突变体的3D结构,采用双荧光素酶报告基因系统检测野生型和突变体蛋白对胰岛素基因转录活性的影响。结果·在一个MODY家系中发现NEUROD1基因杂合错义突变Glu59Gln (NM_002500.5,c.175G>C)。3D结构分析发现,该突变将野生型中带负电荷的Glu59转化为突变中不带电荷的Gln59,导致两个盐桥键Glu59-Arg54和Glu59-Lys88缺失,并形成一个新的氢键Gln59-Arg54。与野生型相比,Glu59Gln突变体的胰岛素基因转录活性下降36.3%(P<0.05)。与非糖尿病对照相比,96例MODY先证者中Ala45Thr (G-A)变异的AA+GA基因型频率显著升高(P=0.002)。结论·Glu59Gln突变改变了NEUROD1蛋白N端的分子构象,导致其胰岛素基因转录活性显著下降,是该家系突变携带者胰岛素分泌缺陷的原因。Ala45Thr变异与MODY6先证者糖尿病发病年龄的提前有关。展开更多
目的初步评估葡萄糖激酶(glucokinase,GCK)基因突变引起的青少年发病的成年型糖尿病2型(maturity onset diabetes of the young 2,MODY2)在妊娠期血糖异常人群中的比例,建立一种识别GCK基因突变的筛查方法。方法回顾性分析2016年1月1日...目的初步评估葡萄糖激酶(glucokinase,GCK)基因突变引起的青少年发病的成年型糖尿病2型(maturity onset diabetes of the young 2,MODY2)在妊娠期血糖异常人群中的比例,建立一种识别GCK基因突变的筛查方法。方法回顾性分析2016年1月1日至2018年12月31日在首都医科大学附属北京潞河医院进行孕期检查的妊娠妇女,以孕早期、孕中期及孕后期空腹静脉血糖均≥5.5 mmol/L,血清三酰甘油至少1次≤1.43 mmol/L,妊娠24~28周75 g葡萄糖耐量试验2 h增量小于4.6 mmol/L为筛查条件,对受试者进行葡萄糖激酶基因序列测定。结果共纳入2454例受试者,符合GCK基因筛查条件者12例,获得外周血DNA标本5例,发现1例GCK基因突变者。结论妊娠期间3次空腹静脉血糖均≥5.5 mmol/L且血清三酰甘油至少1次≤1.43 mmol/L且口服葡萄糖耐量试验2 h血糖增量<4.6 mmol/L的方法,可以发现GCK基因突变,该类型糖尿病在妊娠期血糖异常人群中比较罕见。展开更多
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.
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.
文摘目的·筛查青少年的成人起病型糖尿病(maturity-onset diabetes of the young,MODY)家系中NEUROD1基因突变,分析突变与中国人MODY6发病的相关性及其潜在的致病机制。方法·采用PCR-直接测序法对96例GCK/MODY2、HNF1A/MODY3、HNF1B/MODY5突变阴性的中国MODY先证者进行NEUROD1突变筛查,同时比较96例MODY先证者与100例非糖尿病对照者NEUROD1基因变异的基因型频率。采用从头建模法构建NEUROD1蛋白野生型和突变体的3D结构,采用双荧光素酶报告基因系统检测野生型和突变体蛋白对胰岛素基因转录活性的影响。结果·在一个MODY家系中发现NEUROD1基因杂合错义突变Glu59Gln (NM_002500.5,c.175G>C)。3D结构分析发现,该突变将野生型中带负电荷的Glu59转化为突变中不带电荷的Gln59,导致两个盐桥键Glu59-Arg54和Glu59-Lys88缺失,并形成一个新的氢键Gln59-Arg54。与野生型相比,Glu59Gln突变体的胰岛素基因转录活性下降36.3%(P<0.05)。与非糖尿病对照相比,96例MODY先证者中Ala45Thr (G-A)变异的AA+GA基因型频率显著升高(P=0.002)。结论·Glu59Gln突变改变了NEUROD1蛋白N端的分子构象,导致其胰岛素基因转录活性显著下降,是该家系突变携带者胰岛素分泌缺陷的原因。Ala45Thr变异与MODY6先证者糖尿病发病年龄的提前有关。
