2型糖尿病家系成员血清皮质醇水平的影响因素

检测2型糖尿病家系成员口服葡萄糖耐量试验各时间点血清皮质醇水平,结果显示2型糖尿病患者空腹和餐后皮质醇水平均明显高于一级亲属和正常对照者,家系成员空腹皮质醇水平与空腹血糖正相关,提示2型糖尿病患者同时存在肾上腺皮质功能紊乱.     

早发2型糖尿病家系NeuroD1基因突变筛查与功能研究

目的 在中国人早发2型糖尿病家系先证者中筛查NeuroD1基因突变/变异,并研究其功能及携带者家系的临床表型和遗传特点.方法 用PCR-直接测序法检测85例早发、95例晚发2型糖尿病家系先证者和87名非糖尿病对照者NeuroD1基因突变/变异,比较筛查到的组间突变/变异的基因型及等位基因频率的差异.分别构建含小鼠NeuroD1(mND1)基因cDNA的野生型、突变型表达质粒载体和与人胰岛素基因启动子相连的荧光素酶报告基因质粒载体,共转染至大鼠INS-1细胞.分别检测荧光素酶活性,比较野生型、突变体蛋白对人胰岛素基因转录活性的影响.结果 在一早发先证者发现新突变S159P(T→C),它与来自父方的4例携带突变的糖尿病患者遗传上呈共分离;与野生型相比,S159P突变体导致胰岛素基因转录活性下降25%;检测到常见多态A45T(G→A),与非糖尿病组及晚发2型糖尿病组相比,早发组该变异的AA+GA基因型频率显著增加(P=0.006和P=0.014).结论 NeuroD1基因S159P突变促进该早发2型糖尿病家系的发病.A45T变异增加中国人早发2型糖尿病的易感性,或与之呈连锁不平衡,该变异可能影响中国人2型糖尿病的发病方式,即早发而不是晚发.     

2型糖尿病家系硒代谢紊乱与胰岛素抵抗

为了揭示硒与糖尿病的关系 ,我们进行了 2型糖尿病家系成员血浆硒水平及硒酶 (谷胱甘肽过氧化物酶 )的检测 ,并分析其与胰岛素抵抗的关系。一、对象和方法1.对象 :对有糖尿病家族史的 2型糖尿病先证者的 4 9个核心家系进行了三代血统成员调查。分组 :(1)正常组 :无糖尿病与高血压家族史 ,OGTT结果正常。 (2 )一级亲属糖耐量正常 (NGT)组 :家系中糖尿病患者的非糖尿病子代或同胞 ,其 OGTT结果正常。 (3)新诊断 2型糖尿病组 (新糖尿病组 ) :家系中通过 OGTT新诊断或病程在 1年以内者的 2型糖尿病患者。(4)原诊断 2型糖尿病患者 (原糖尿…     

2型糖尿病家系中患者与一级亲属血脂异常紊乱的研究

目的 探讨2型糖尿病（T2DM）家系人群中患者与一级亲属血脂紊乱异常类型、聚集程度的差异及血脂紊乱的影响因素。方法 对351例T2DM患者和300例非糖尿病一级亲属按血脂指标异常的项目数分为5组，并将血脂紊乱分为8种类型。比较家系两组人群异常血脂指标聚集性和血脂紊乱类型。在糖尿病患者中以血脂正常者为对照组，用Logistic回归分析年龄、体脂等和血脂的关系。结果 家系两组人群中的血脂紊乱类型的差异无统计学意义（x^2=4．294，P=0．7451），但患者组血脂紊乱的比例高于未患糖尿病亲属组（72．6％vs．57．7％，x^2=16．123，P=0．0000）。多因素分析发现年龄与TG的升高和HDL的降低有关，腰臀比的增大与TG有关[Exp（B）=1．799，P=0．012]。结论 糖尿病患者中存在异常血脂指标的聚集，但患者与其亲属的血脂紊乱类型相似。糖尿病患者腹部体脂的增加与总胆固醇水平有关。     

2型糖尿病患者的家系调查研究

按照ADA标准选择59个符合要求的2型糖尿病核心家系,进行问卷调查、OGTT试验、测胰岛素、C肽、血脂.将所获得资料汇成系谱图.结果①男女之比为11.58(P＜0.01);②母亲患病人数显著高于父亲(32.2%对13.6%,P＜0.91);③同胞对中47%人是患者;④患糖尿病的父母亲中子女的糖尿病患病串无明显差异(43.7%对46.9%P＞0.05).结论糖尿病具有明显的遗传倾向,家族性2型糖尿病遗传方式似不支持多基因遗传,母亲患者在遗传学上具有重要作用.     

2型糖尿病患者的家系调查研究

按照ADA标准选择59个符合要求的2型糖尿病核心家系,进行问卷调查、OGTT试验、测胰岛素、C肽、血脂。将所获得资料汇成系谱图。结果：①男女之比为1：1.58(P＜0.01);②母亲患病人数显高于父亲（32.2%对13.6%,P＜0.91);③同胞对中47%人是患;④患糖尿病的父母新中子女的糖尿病患病串无明显差异（43.7%对46.9%P＞0.05)。结论：糖尿病具有明显的遗传倾向,家庭性2型糖尿病遗传方式似不支持多基因遗传,母亲患在遗传学上具有重要作用。     

中国人2型糖尿病家系中糖尿病患者及其一级亲属血脂和载脂蛋白的研究

目的　探讨 2型糖尿病家系中 2型糖尿病患者及其正常糖耐量的一级亲属 (NFDR)的血脂和载脂蛋白 (Apo)水平变化的临床意义。方法　测定 2 9个中国人 2型糖尿病家系中的 62例 2型糖尿病患者和 67名NFDR ,以及 45名无糖尿病家族史的正常糖耐量对照者 (NC)的甘油三酯 (TG) ,总胆固醇(TC) ,高密度脂蛋白胆固醇 (HDL C) ,ApoAⅠ ,ApoB10 0 ,ApoCⅢ和ApoE水平。 结果　 (1) 2型糖尿病患者的TG显著高于NFDR和NC ,NFDR的TG水平也显著高于NC〔3组分别为 (1.85± 1.3 1)、(1.3 9± 0 .91)、(0 .92± 0 .45 )mmol/L ,均P <0 .0 5〕。 (2 ) 2型糖尿病患者和NFDR的HDL C水平都显著低于NC组〔3组分别为 (1.17± 0 .2 9)、(1.2 3± 0 .2 8)、(1.43± 0 .2 7)mmol/L ,均P <0 .0 5〕。 (3 ) 2型糖尿病患者ApoCⅢ水平显著高于NFDR与NC〔3组分别为 (0 .14± 0 .0 9)、(0 .11± 0 .0 4)、(0 .10± 0 .0 3 ) g/L ,均P <0 .0 5〕。(4 )糖尿病组TC、LDL C、ApoB10 0 虽高于NFDR和NC ,ApoAⅠ水平低于NC ,但均无统计学意义 ,ApoE在 3组间差异无显著性。 (5 ) 2型糖尿病患者与其子女配对后 ,其TC、LDL C和ApoB10 0 显著高于其子女 (均P <0 .0 5 ) ,而TG、ApoCⅢ有升高趋势 ,HDL C有降低趋势。 结论　 2型糖尿病患者的NFDR有着和 2型     

2型糖尿病家系一级亲属代谢状况的调查

目的探讨2型糖尿病家系一级亲属的代谢状况。方法比较2型糖尿病家系先证者（DM组）、一级亲属糖耐量异常者（IGR组）、一级亲属糖耐量正常者（NGT组）及无糖尿病家族史的正常人群（NC组）的代谢指标。结果 DM组高血压及脂质代谢紊乱的发生率明显高于其他三组（P〈0.05）,IGR组高于NGT组及NC组（P〈0.05）;NGT组收缩压、腰围、臀围、腰臀比、总胆固醇显著低于DM组及IGR组,NGT组、NC组甘油三酯、低密度脂蛋白、尿酸显著低于IGR组（P〈0.05）;NGT组及NC组0、120 min血糖均显著低于DM组、IGR组（P〈0.05）,NGT组血糖较NC组有增高趋势,但两者之间并无统计学差异。而DM组及NGT组高密度脂蛋白均显著低于NC组（P〈0.05）;HDL水平与空腹血糖呈负相关（r=-0.171,P〈0.05）。结论 2型糖尿病家系一级亲属存在着早期的代谢紊乱。     

2型糖尿病家系一级亲非糖尿病同胞的血脂水平研究

目的 研究２型糖尿病（２型ＤＭ）家系一级亲非ＤＭ同胞的血脂变化。方法 收集江浙籍２型ＤＭ家系３２０个。在排除ＤＭ和糖耐量减退（ＩＧＴ）的前提下,选择先让者同胞为观察组（３４７例）,先证者或其同胞的配偶为对照组（３２６例）,并按年龄和ＢＭＩ分成亚型,进行血脂水平比较。结果 ２型ＤＭ家系一级亲非ＤＭ同胞ＴＧ、ＴＣ,ＬＤＬ水平升高,ＨＤＬ水平降低,年龄超过４０岁以后尤其明显。结论 ２型ＤＭ家系一级亲在糖     

2型糖尿病家系一级亲人群代谢综合征患病情况及与肥胖相关指标的关系

目的 比较美国国家胆固醇教育计划成人治疗疗案第三次报告(ATPⅢ)2005年、国际糖尿病联盟(IDF)2005年、中华医学会糖尿病学分会(CDS)2004年和<中国成人血脂异常防治指南>制定联合委员会(JCDCG)2007年建议的代谢综合征(MS)工作定义中不同的肥胖标准在2型糖尿病家系一级亲人群中应用的差异及与肥胖相关指标的关系.方法 对715个2型糖尿病家系中有完整血压、血脂及血糖资料的2 372名一级亲成员.分别用ATeⅢ、IDF、CDS和JCDCG定义诊断MS及肥胖.结果 (1)四种定义诊断的一级亲MS患病率分别为45.40%、38.74%、25.08%和39.29%,按ATPⅢ、IDF定义诊断时,女性MS患病率明显高于男性(均P<0.01);(2)除CDS定义在女性中最常见的组合是血脂紊乱+高血压+高血糖外,其余定义下MS的常见异常组合均表现为四种代谢异常同时存在;(3)四种定义诊断的一级亲中具备肥胖组分的比例分别为58.18%、58.18%、33.90%和42.96%;肥胖患者中分别有66.59%、66.59%、54.85%和68.99%伴有MS;(4)应用ATPⅢ/IDF以及JCDCG定义中腹型肥胖的诊断切割点,分别有28.58%及16.78%个体表现为体重指数(BMI)<25 kg/m2,但已旱腹型肥胖,其中女性的比例明显高于男性(38.90% vs 15.02%,21.01% vs 11.22%,均P<0.01).结论 (1)MS及肥胖的发病有明显家族聚集倾向,2型糖尿病家系一级亲人群是其高危人群;(2)采用腰围作为MS中肥胖组分的判别指标,较BMI可能更有助于临床早期识别和防治MS.     

2型糖尿病家系发病特征与危险因素初步调查

目的 对2型糖尿病家系中的遗传特征、危险因素进行调查分析,为系统研究2型糖尿病及制定干预措施提供依据.方法 根据1997年美国糖尿病学会(ADA)标准,利用口服葡萄糖耐量试验确诊糖尿病,根据胰岛素功能测定和血清谷氨酸脱羧酶抗体(GADAb)、胰岛细胞抗体(ICA)和胰岛素自身抗体(IAA)检测及临床特征排除1型糖尿病,根据遗传特征及临床特点排除年轻的成年发病型糖尿病(MODY),根据母系遗传伴耳聋等临床特征排除线粒体基因突变家系,最终筛选出2型糖尿病家系182个(实际调查865例)并进行分析.结果 182个家系中男女2型糖尿病患病率(男性42.59%、女性48.18%)、新诊断率(男性9.89%、女性1 1.82%)差异无统计学意义(P＞0.05).家系第1代277例患者发病年龄为(63.3±12.4)岁,其中男性为(64.4±12.5)岁,女性为(62.3±10.3)岁;第2代468例患者发病年龄为(47.1 ±8.7)岁,其中男性为(48.2±9.3)岁,女性为(46.1±8.1)岁;第3代120例患者发病年龄为(29.6±10.2)岁,其中男性为(28.9 ±9.5)岁,女性为(30.0±10.4)岁.新诊断2型糖尿病组、新诊断糖调节受损(IGR)组分别与非患病亲属组比较,高血压病史、高脂血症史、吸烟史、活动量差异均有统计学意义;5年前体重、1年前体重、目前体重、腰围、腰臀比差异也有统计学意义,股围差异无统计学意义.结论 2型糖尿病发病无性别差异.肥胖、高血压病、吸烟、高脂血症、活动量较少与2型糖尿病、IGR相关.活动量较多可能是家族中的非患病亲属及IGR患者较晚进入糖尿病期的原因之一.

Abstract：

Objective To explore the characteristics and risk factors of type 2 diabetes mellitus (T2DM) onset in pedigrees. Methods A total of 865 subjects were screened and diagnosed by oral glucose tolerance test (OGTT) based on American Diabetes Association (ADA) criteria. Type 1 diabetes mellitus (T1DM) , maturity onset diabetes of the young (MODY) and chondriosome diabetes were excluded by clinical features and laboratory test of insulin and autoantibodies including glutamic acid decarboxylase antibody, insular cellular antibody and insulin autoantibody. A total of 182 pedigrees of T2DM were obtained. Results No gender difference was found in the prevalence of T2DM (42. 59% in male and 48. 18% in female respectively, P ＞0. 05) , nor was the newly diagnosed rate(9. 89% in male and 11. 82%in female, P ＞ 0. 05). The onset age was (63. 3 ± 12. 4) years old in the first generation [(64. 4 ± 12. 5)years in male and (62. 3 ± 10. 3) years in female] , (47. 1 ± 8. 7) years old in the second generation [(48. 2 ±9. 3)years in male and (46. 1 ± 8. 1) years in female] , (29. 6 ± 10. 2) years old in the third generation [(28. 9 ±9. 5)years in male and (30. 0 ± 10. 4)years in female]. Compared with normal glucose tolerance (NGT) subjects , newly diagnosed T2DM and impaired glucose regulation (IGR) subjects had higher prevalence of hypertension, hyperlipidemia and smoking but less physical activities. Statistical differences were shown in body weight five years before diagnosis, one years before diagnosis and at diagnosis in newly diagnosed T2DM[(68. 4 ±12. 4)kg, (69. 5 ± 11. 0)kg and (69. 1 ±9. 6)kg] and IGR[(66. 1 ±10.7)kg, (65.9 ± 10.7) kg and(65.7 ± 10.4) kg] , when compared with NGT [(61.0 ± 10.2) kg,(59. 5 ±11.0) kg and (60. 1 ± 10. 4) kg, all P ＜ 0. 05] . The same results were obtained with waist circumference and waist-hip ratio [(4. 1 ± 12. 5) cm and 0. 92 ± 0. 36 in newly diagnosed T2DM while (89. 1 ± 10. 7) cm and 0. 90 ± 0. 64 in IGR] , when compared with NGT[(82. 5 ± 10. 1) cm and 0. 82 ±0. 25] , all P ＜0. 05. Conclusions No gender difference was found in the onset characteristics of T2DM.High prevalence of obesity, hypertension, hyperlipidemia and smoking with less physical activities were associated with T2DM.     

2型糖尿病家系成员中的胰岛素抵抗与胰岛β—细胞功能状态的研究

目的研究胰岛素抵抗及胰岛紊分泌功能在2型糖尿病(DM)发生、发展中的作用.方法在2型DM家系成员中,对已诊断DM者按病程中位数分组,病程≤4年组153例,＜4年组129例.经口服葡萄糖耐量试验(OGTT),按1999年WHO糖尿病诊断标准,新诊断DM组72例.非DM者按HbAlc分组,HbAlc≤5.5%组78例,HbAlc＜5.5%组110例,计算各组HOMA模型胰岛素抵抗指数(HOMAIR)、β细胞功能指数(HOMAβ)及胰岛素敏感性指数(ISI),与无DM家族史的正常人98例比较.结果除HbAlc≤5.5%组外,家系各组HOMAIR均值高于正常对照,差异有显著性(P＜0.01).家系非DM两组HOMAβ高于正常对照(P＜0.01),DM各组HOMAβ低于正常对照(P＜0.01).结论北京地区2型DM家系中非DM一级亲属的胰岛素抵抗及糖耐量异常可能继发于胰岛素分泌功能异常增高,胰岛素分泌功能降低和胰岛素抵抗是发生糖尿病的主要机制.     

2型糖尿病家系肝细胞核因子1β基因1968A/G的多态性

糖尿病组中肝细胞核因子1β基因的G等位基因携带者的空腹C肽、△I10／△G30均明显低于AA基因型纯合子。一级亲属组中G等位基因携带者的空腹及餐后3h血糖，空腹、餐后2h及3h胰岛素明显高于AA基因型纯合子。     

2型糖尿病家系发病特征与危险因素初步调查

Objective To explore the characteristics and risk factors of type 2 diabetes mellitus (T2DM) onset in pedigrees. Methods A total of 865 subjects were screened and diagnosed by oral glucose tolerance test (OGTT) based on American Diabetes Association (ADA) criteria. Type 1 diabetes mellitus (T1DM) , maturity onset diabetes of the young (MODY) and chondriosome diabetes were excluded by clinical features and laboratory test of insulin and autoantibodies including glutamic acid decarboxylase antibody, insular cellular antibody and insulin autoantibody. A total of 182 pedigrees of T2DM were obtained. Results No gender difference was found in the prevalence of T2DM (42. 59% in male and 48. 18% in female respectively, P ＞0. 05) , nor was the newly diagnosed rate(9. 89% in male and 11. 82%in female, P ＞ 0. 05). The onset age was (63. 3 ± 12. 4) years old in the first generation [(64. 4 ± 12. 5)years in male and (62. 3 ± 10. 3) years in female] , (47. 1 ± 8. 7) years old in the second generation [(48. 2 ±9. 3)years in male and (46. 1 ± 8. 1) years in female] , (29. 6 ± 10. 2) years old in the third generation [(28. 9 ±9. 5)years in male and (30. 0 ± 10. 4)years in female]. Compared with normal glucose tolerance (NGT) subjects , newly diagnosed T2DM and impaired glucose regulation (IGR) subjects had higher prevalence of hypertension, hyperlipidemia and smoking but less physical activities. Statistical differences were shown in body weight five years before diagnosis, one years before diagnosis and at diagnosis in newly diagnosed T2DM[(68. 4 ±12. 4)kg, (69. 5 ± 11. 0)kg and (69. 1 ±9. 6)kg] and IGR[(66. 1 ±10.7)kg, (65.9 ± 10.7) kg and(65.7 ± 10.4) kg] , when compared with NGT [(61.0 ± 10.2) kg,(59. 5 ±11.0) kg and (60. 1 ± 10. 4) kg, all P ＜ 0. 05] . The same results were obtained with waist circumference and waist-hip ratio [(4. 1 ± 12. 5) cm and 0. 92 ± 0. 36 in newly diagnosed T2DM while (89. 1 ± 10. 7) cm and 0. 90 ± 0. 64 in IGR] , when compared with NGT[(82. 5 ± 10. 1) cm and 0. 82 ±0. 25] , all P ＜0. 05. Conclusions No gender difference was found in the onset characteristics of T2DM.High prevalence of obesity, hypertension, hyperlipidemia and smoking with less physical activities were associated with T2DM.     

2型糖尿病家系发病特征与危险因素初步调查

Objective To explore the characteristics and risk factors of type 2 diabetes mellitus (T2DM) onset in pedigrees. Methods A total of 865 subjects were screened and diagnosed by oral glucose tolerance test (OGTT) based on American Diabetes Association (ADA) criteria. Type 1 diabetes mellitus (T1DM) , maturity onset diabetes of the young (MODY) and chondriosome diabetes were excluded by clinical features and laboratory test of insulin and autoantibodies including glutamic acid decarboxylase antibody, insular cellular antibody and insulin autoantibody. A total of 182 pedigrees of T2DM were obtained. Results No gender difference was found in the prevalence of T2DM (42. 59% in male and 48. 18% in female respectively, P ＞0. 05) , nor was the newly diagnosed rate(9. 89% in male and 11. 82%in female, P ＞ 0. 05). The onset age was (63. 3 ± 12. 4) years old in the first generation [(64. 4 ± 12. 5)years in male and (62. 3 ± 10. 3) years in female] , (47. 1 ± 8. 7) years old in the second generation [(48. 2 ±9. 3)years in male and (46. 1 ± 8. 1) years in female] , (29. 6 ± 10. 2) years old in the third generation [(28. 9 ±9. 5)years in male and (30. 0 ± 10. 4)years in female]. Compared with normal glucose tolerance (NGT) subjects , newly diagnosed T2DM and impaired glucose regulation (IGR) subjects had higher prevalence of hypertension, hyperlipidemia and smoking but less physical activities. Statistical differences were shown in body weight five years before diagnosis, one years before diagnosis and at diagnosis in newly diagnosed T2DM[(68. 4 ±12. 4)kg, (69. 5 ± 11. 0)kg and (69. 1 ±9. 6)kg] and IGR[(66. 1 ±10.7)kg, (65.9 ± 10.7) kg and(65.7 ± 10.4) kg] , when compared with NGT [(61.0 ± 10.2) kg,(59. 5 ±11.0) kg and (60. 1 ± 10. 4) kg, all P ＜ 0. 05] . The same results were obtained with waist circumference and waist-hip ratio [(4. 1 ± 12. 5) cm and 0. 92 ± 0. 36 in newly diagnosed T2DM while (89. 1 ± 10. 7) cm and 0. 90 ± 0. 64 in IGR] , when compared with NGT[(82. 5 ± 10. 1) cm and 0. 82 ±0. 25] , all P ＜0. 05. Conclusions No gender difference was found in the onset characteristics of T2DM.High prevalence of obesity, hypertension, hyperlipidemia and smoking with less physical activities were associated with T2DM.     

2型糖尿病家系发病特征与危险因素初步调查

Objective To explore the characteristics and risk factors of type 2 diabetes mellitus (T2DM) onset in pedigrees. Methods A total of 865 subjects were screened and diagnosed by oral glucose tolerance test (OGTT) based on American Diabetes Association (ADA) criteria. Type 1 diabetes mellitus (T1DM) , maturity onset diabetes of the young (MODY) and chondriosome diabetes were excluded by clinical features and laboratory test of insulin and autoantibodies including glutamic acid decarboxylase antibody, insular cellular antibody and insulin autoantibody. A total of 182 pedigrees of T2DM were obtained. Results No gender difference was found in the prevalence of T2DM (42. 59% in male and 48. 18% in female respectively, P ＞0. 05) , nor was the newly diagnosed rate(9. 89% in male and 11. 82%in female, P ＞ 0. 05). The onset age was (63. 3 ± 12. 4) years old in the first generation [(64. 4 ± 12. 5)years in male and (62. 3 ± 10. 3) years in female] , (47. 1 ± 8. 7) years old in the second generation [(48. 2 ±9. 3)years in male and (46. 1 ± 8. 1) years in female] , (29. 6 ± 10. 2) years old in the third generation [(28. 9 ±9. 5)years in male and (30. 0 ± 10. 4)years in female]. Compared with normal glucose tolerance (NGT) subjects , newly diagnosed T2DM and impaired glucose regulation (IGR) subjects had higher prevalence of hypertension, hyperlipidemia and smoking but less physical activities. Statistical differences were shown in body weight five years before diagnosis, one years before diagnosis and at diagnosis in newly diagnosed T2DM[(68. 4 ±12. 4)kg, (69. 5 ± 11. 0)kg and (69. 1 ±9. 6)kg] and IGR[(66. 1 ±10.7)kg, (65.9 ± 10.7) kg and(65.7 ± 10.4) kg] , when compared with NGT [(61.0 ± 10.2) kg,(59. 5 ±11.0) kg and (60. 1 ± 10. 4) kg, all P ＜ 0. 05] . The same results were obtained with waist circumference and waist-hip ratio [(4. 1 ± 12. 5) cm and 0. 92 ± 0. 36 in newly diagnosed T2DM while (89. 1 ± 10. 7) cm and 0. 90 ± 0. 64 in IGR] , when compared with NGT[(82. 5 ± 10. 1) cm and 0. 82 ±0. 25] , all P ＜0. 05. Conclusions No gender difference was found in the onset characteristics of T2DM.High prevalence of obesity, hypertension, hyperlipidemia and smoking with less physical activities were associated with T2DM.