遗传因素与脑胶质细胞瘤的相关意义

背景：脑肿瘤的危险因素已经有许多流行病学调查研究，同时从群体遗传学角度对其研究尚需探讨。目的：揭示脑胶质细胞瘤是否与遗传因素有关及关联的程度和遗传的方式等。设计：以诊断为依据的病例对照研究。地点与对象：选择1989-09／2000-09在黑龙江省六大医院神经外科住院的80例患者为病例组，所有患者经外科摘除手术和病理诊断为原发、初发脑胶质细胞瘤，在上述医院其他外科病房选择同期住院、性别相同、年龄同一段(&;#177;2．5岁)、居住地相同或相近、排除肿瘤和头部疾病的其他患者(共160例)作为对照组。方法：采用1：2配比病例对照研究方法，按标准化调查表中项目当面采访。主要观察指标：与对照组比较家族史、曾患率，与人群比较发病率，估算遗传率。结果：在80例脑胶质细胞瘤患者中，有家族史者3例，而在160例对照中，无家族史存在(P=0．036)；病例组一级亲属该病曾患率为4．73／10000，对照组一级亲属中无人患病(P=0．037)；病例组一级亲属该病曾患率与人群发病率比较，差异有显著性意义(u=231．56，P&;lt;0．0005)；病例组一级亲属该病遗传率为56％。结论：脑胶质细胞瘤具有遗传倾向，且不符合单基因显性遗传的1／2或隐性遗传的1／4规律，可能与多基因遗传有关，环境因素的作用也不容忽视。     

遗传因素在青年脑梗死发病中的作用

目的:探讨遗传因素在青年脑梗死发生中的作用。方法:采用询问方式收集216例青年脑梗死患者及健康对照组心脑血管病(包括高血压、冠心病、脑血管病)家族史资料,收集病例及对照组一级亲属(除外儿女)脑梗死患病情况。采用病例—对照研究,对有家族史青年患脑梗死的危险度进行定量评估,计算脑梗死遗传度。结果:69.9%的青年脑梗死病例有家族史,明显高于对照组18.67%(χ2=137.25,P<0.001),无论男性或女性病例对心脑血管病家族史暴露率均明显高于对照组(P<0.001)。青年脑梗死病例的母亲心脑血管病患病率51.85%明显高于父亲的患病率18.06%(χ2=71.18,P<0.001),脑梗死遗传度为(72±5)%。55.56%青年脑梗死病例有高血压家族史,而对照组只有11.33%,两者差异有非常显著性意义(χ2=117.29,P<0.001)。结论:心脑血管病家族史是青年脑梗死发病的危险因素,在青年脑梗死发病中,遗传因素是不可忽视的因素。     

社交焦虑障碍的家系对照研究

目的 探讨社交焦虑障碍的家庭聚集性及遗传因素在社交焦虑障碍的发生中的作用.方法 采取以人群为基础的病例对照家系研究,调查76例社交焦虑障碍患者及76例正常对照者的一级亲属社交焦虑障碍患病及家族史等情况,比较两组亲属社交焦虑障碍的患病比例,检验社交焦虑障碍家庭聚集性;采用Falconer法估计其遗传度;采用Li-Mantel-Gart法计算分离比.结果 社交焦虑障碍先证者一级亲属患病比例（8.94％）高于对照者一级亲属患病比例（3.76％）,差异有统计学意义（x2 =3.91,P＜0.05）,证明存在家族聚集性;社交焦虑障碍先证者一级亲属遗传度为37.8％;根据社交焦虑障碍在家系中的分布情况进行分离分析得到分离比为0.1466（P ＜0.25）,表明社交焦虑障碍可能属于多因子遗传病.结论 遗传因素在社交焦虑障碍发病中起着重要作用,社交焦虑障碍家族史增加社交焦虑障碍发病风险.     

单相抑郁症患者自杀行为遗传效应及其遗传方式的研究

背景遗传因素在抑郁症自杀行为的发生中占有一定的地位,以往的关注的重点主要为双相抑郁自杀的遗传效应,单相抑郁症自杀行为的遗传方式和遗传效应有何特征?目的探讨单相抑郁症自杀行为的遗传效应及遗传方式.设计回顾性调查.单位一所市级精神卫生中心.对象单相抑郁症组(n=115)为1983-06-01/2002-05-31无锡市精神卫生中心门诊和住院诊断为抑郁症的患者.诊断均符合中国精神障碍分类与诊断标准第3版抑郁发作及美国精神障碍诊断与统计手册第4版重性抑郁发作标准,且抑郁发作次数≥3次或发作一两次已缓解≥8年者.方法以符合入组标准的单相抑郁症患者为先证者,由2名主治医师及其以上医师对每一家系进行调查,填写自行编制的精神病家系调查表,内容主要包括患者及一级亲属所有成员社会人口学资料、疾病发作特点及次数、以往治疗及自杀情况.由2名主治医师或以上医师对每一患者进行再诊断,并由1名主任医师核查,一致确诊的病例则予入组.对所有现存活的先症者(107例)及一级亲属中有自杀行为者(14例)进行面检;对无自杀行为的一级亲属(337名)进行面检和信函调查(380名);死亡者(患者8例,一级亲属5例)的资料由一两名一级亲属提供有关情况填写调查表.对照组由2名研究者进行面检,同时询问一级亲属情况并填写家系调查表.对所得资料行单因素分析,用多基因阈值理论Falconer模式估算自杀行为的遗传率和标准误,用医学遗传数学方法中分离分析法和多基因阈值理论进行遗传方式的探讨.主要观察指标单相抑郁症患者自杀行为的遗传效应和遗传方式.结果单相抑郁症患者自杀危险性51.30%(59/115)较其一级亲属2.58%(19/736)高(x2=283.16,P＜0.01),单相抑郁症患者一级亲属自杀危险性2.58%(19/736)较对照组0.12%(3/2469)高(x2=50.36,P＜0.01),有自杀行为患者的一级亲属自杀危险性3.8%(14/372)较无自杀行为患者的一级亲属自杀危险性1.4%(5/363)高(x2=4.14,P＜0.05).单相抑郁症自杀行为的加权平均遗传率及标准误为(70.16±0.79)%;多基因遗传方式验证显示,多基因遗传方式验证显示一级亲属自杀行为预期发病率为3.1%,实际发病率为2.6%,两者差异无显著性意义(u=0.766,P＞0.05).结论单相抑郁症自杀行为有明显的遗传效应,其遗传方式符合多基因遗传.     

直立性低血压的家族临床遗传特征

目的 探讨直立性低血压(OH)的家族临床遗传特征.方法 2001-01～2010-04在中南大学湘雅二医院晕厥专科门诊就诊或住院的不明原因晕厥或头晕患者1681例进行直立倾斜试验(HUTT),符合OH诊断者73例,年龄6.0~70.0岁,平均(22.30±18.77)岁,男34例,女39例,<18岁45例,≥18岁28例.详细询问OH患者现病史及家族史.结果 ①性别差异:73例OH患者中,19例存在家族遗传史(26.0%),其中男6例(一级亲属5例),女13例(一级亲属10例).女(13/19,68.4%)与男(6/19,31.6%)比较差异无统计学意义(χ2=2.32,P>0.05).②年龄差异:<18岁OH患者存在家族史15例(15/19,78.9%),其中3例为二级亲属;≥18岁OH患者存在家族史4例(4/19,21.1%),其中1例为二级亲属,两组比较差异无统计学意义(χ2=3.25,P>0.05).结论 OH存在一定的家族临床遗传性,一级亲属OH患者后代患该病的比率增加.     

头颈部肿瘤患者及一级亲属细胞突变后染色单体断裂率与五加皮的干预效应

背景头颈部肿瘤与遗传因素密切相关,但其一级亲属是否为肿瘤高风险人群?中药五加皮有抗突变的染色体稳定剂,能否提高一级亲属的抗癌能力?目的探讨头颈部肿瘤的遗传因素及五加皮对其染色体的稳定作用.设计以人外周血为对象的对照实验.单位吉林大学基础医学院医学遗传学教研室及第一医院耳鼻咽喉科,英国华威(沃瑞克)大学.对象对象来源时间为2001-10/2002-03.头颈肿瘤患者及其一级亲属均来自吉林大学第一医院耳鼻喉科,健康人群来自长春市中心血站健康献血者.实验对象共110例,分为3组.①对照组50例,男25例,女25例;来自健康献血者;均无癌家族史,身体健康,无癌症和病史.②患者组30例,男22例,女8例;喉癌20例,鼻咽癌10例;未经放射治疗及抗肿瘤药物治疗.③一级亲属组30例,男19例,女11例;为喉癌、鼻咽癌患者的一级亲属;除有癌家族史外,身体健康.以上参与者均知情同意.方法采集实验对象外周血,进行淋巴细胞培养,培养周期为72 h,在67 h时加入致诱变剂博来霉素(15 mg/L),抗诱变实验加入博来霉素的同时加入五加皮(800mg/L).继续培养72 h收获细胞,常规方法制片,吉姆萨不显带染色.选择分散好的分裂相,观察染色体的断裂情况.计算平均每细胞染色单体断裂率(即等于本组中所有染色单体断裂的总和除以所有观察的细胞总数).主要观察指标每细胞染色单体断裂率.结果患者3组110例进入结果分析.①应用博来霉素所致的每细胞染色单体断裂率对照组明显低于患者组及一级亲属组(0.16±0.06,0.48±0.14,0.42±0.12,P＜0.01),但患者组及一级亲属组比较无差异(P＞0.05).②应用五加皮和博来霉素后与单纯应用博来霉素所致每细胞染色单体断裂率的比较患者组及一级亲属组均显著降低(0.48±0.14,0.15±0.08,0.42±0 12,0.17±0.11,P＜0 01).结论头颈部肿瘤患者的一级亲属应列为肿瘤易患高风险人群,加入五加皮发挥了染色体稳定剂的作用,对博来霉素所致的患者及一级亲属每细胞染色单体断裂率有明显的抑制作用.     

遗传因素在青年脑梗死发病中的作用

目的：探讨遗传因素在青年脑梗死发生中的作用。方法：采用询问方式收集216例青年脑梗死患者及健康对照组心脑血管病(包括高血压、冠心病、脑血管病)家族史资料，收集病例及对照组一级亲属(除外儿女)脑梗死患病情况。采用病例一对照研究，对有家族史青年患脑梗死的危险度进行定量评估，计算脑梗死遗传度。结果：69．9％的青年脑梗死病例有家族史，明显高于对照组18，67％(X^2=137.25，P&;lt;0．001)，无论男性或女性病例对心脑血管病家族史暴露率均明显高于对照组(P&;lt;0．001)青年脑梗死病例的母亲心脑血管病患病率51．85％明显高于父亲的患病率18．06％(X^2=71．18，P&;lt;0．001)，脑梗死遗传度为(72&;#177;5)％。55．56％青年脑梗死病例有高血压家族史，而对照组只有11．33％，两者差异有非常显著性意义(X^2=117．29，P&;lt;0．001)。结论：心脑血管病家族史是青年脑梗死发病的危险因素，在青年脑梗死发病中，遗传因素是不可忽视的因素。     

精神病患者一级亲属个性特征对照研究

目的 探讨精神病患者一级亲属的个性特征,为研究精神疾病的发病机制提供依据.方法 将197例精神病患者和509名一级亲属设为研究组,依据不同状况分为3组:A组(高发家族)77名,B组(有阳性家族史)297名,C组(无阳性家族史)332名.抽取同期当地小学以上文化程度的居民,且均无严重躯体疾病、精神疾病史家庭的父母及其子女设为对照组,共入组195名.采用艾森克个性问卷对两组进行测评分析.结果 研究组一级亲属个性内向和倾向内向、情绪不稳定和倾向不稳定比率均显著高于对照组,而中间型个性和情绪比率均显著低于对照组(P＜0.05或0.01);研究组A组、B组中父母组个性外向比率均显著低于对照组(P＜0.05),情绪不稳定比率均显著高于C组父母组(χ2=5.31、6.24,P＜0.05),中间型个性及情绪比率均显著低于C组父母组(χ2=6.41、6.27,P＜0.05),同胞组个性内向和情绪不稳定比率显著低于患者组和父母组(P＜0.05).精神分裂症患者个性内向和倾向内向比率显著高于心境障碍患者(χ2=7.53、6.86,P＜0.01),倾向外向和外向比率显著低于心境障碍患者(χ2=7.26、6.37,P＜0.05或0.01),而情绪稳定比率差异无显著性(P＞0.05).结论 精神病患者及其一级亲属具有独特的个性特征,不同群体具有差异性;精神分裂症患者和一级亲属个性以倾向内向和内向者居多,情感障碍患者及一级亲属以倾向外向和外向者居多;这种家系性的易罹病素质可能是精神病发病的生物学基础.     

有肺癌家族史的肺癌患者一级亲属的肺癌认知、态度及筛查行为特征

目的分析有肺癌家族史的肺癌患者一级亲属的肺癌相关知识、态度及筛查行为特征。方法 2020年9月至2022年2月, 应用自行设计的调查问卷对吉林省肿瘤医院诊治的有肺癌家族史的肺癌患者一级亲属进行调查, 分析该人群的肺癌相关知识、对肺癌的态度及低剂量螺旋CT(LDCT)筛查情况, 探讨肺癌筛查行为的影响因素。结果共调查有肺癌家族史的肺癌患者一级亲属298例, 其中较高认知159例(53.35%), 部分认知111例(37.25%), 较低认知28例(9.40%)。60例(20.13%)接受过LDCT检查, 单因素分析表明, 性别、年龄、文化程度、婚姻状况、家庭人均月收入、是否有商业保险、血亲亲属中患肺癌人数、是否吸烟、肺癌认知水平是肺癌筛查行为的影响因素;Logistic回归分析显示, 性别(OR=2.203, 95%CI:1.005～4.289)、是否有商业保险(OR=5.272, 95%CI:1.292～21.529)和婚姻状况(OR=7.822, 95%CI:1.954～31.317)是肺癌患者一级亲属肺癌筛查行为的影响因素(均P<0.05)。结论应根据有肺癌家族史的肺癌患者一...     

神经系统软体征中运动协调因子在精神分裂症 病理表型中的价值

目的:探讨神经系统软体征(NSS)中运动协调因子在精神分裂症患者病理表型中的价值。方法:精神分裂症患者、其非患病的一级亲属及健康对照者各50例,分别纳入精神分裂症组、非患病亲属组、健康对照组。采用剑桥神经科检查(CNI)量表对3组进行NSS评估。结果:精神分裂症组NSS有13项异常率高于健康对照组(P0.05),4项异常率高于非患病亲属组(P0.05);非患病亲属组NSS有1项异常率高于健康对照组(P0.05)。精神分裂症组的运动协调因子、感觉整合因子和NSS总得分显著高于健康对照组和非患病亲属组(均P0.05);非患病亲属组运动协调因子和NSS总得分显著高于健康对照组(P0.05)。结论:精神分裂症患者NSS大部分指标异常率高于健康对照,小部分NSS异常率高于其一级非患病亲属。NSS中运动协调因子可能是精神分裂症的内表型之一。     

Association of family history of epilepsy with earlier age at seizure onset in patients with focal cortical dysplasia

OBJECTIVE: To establish the contribution of family history of epilepsy to seizure onset in patients with focal cortical dysplasia (FCD). PATIENTS AND METHODS: From January 1998 to January 2001, we prospectively evaluated 19 consecutive patients (10 male, 9 female) with a diagnosis of FCD based on magnetic resonance imaging. All patients and at least 1 family member were directly interviewed by the same observer after completion of a semistructured questionnaire. Initially, we classified patients into 2 groups: presence or absence of family history of epilepsy. Patients with a family history of epilepsy were subdivided into 2 groups: patients with a family history of epilepsy in first-degree relatives or multiple relatives (n=5) and patients with a family history of epilepsy in relatives who were not first-degree (n=4). Statistical analysis was performed with use of the nonparametric tests Kruskal-Wallis and Kaplan-Meier (survival analysis). P=.05 was considered statistically significant. RESULTS: The ages of the patients ranged from 3 to 41 years (mean, 15.6 years). All patients had similar type and extent of cortical dysgenesis. Ages at seizure onset varied from 1 month to 22 years, with a mean of 5.8 years. Nine patients had a family history of epilepsy. The mean age at the first seizure in patients with a family history of epilepsy was 2.6 years compared with 8.5 years in those with no relatives having epilepsy (P=.02). When patients with a family history of epilepsy were classified further, the mean age at first seizure was 1.9 years for patients with a family history of epilepsy in first-degree or multiple relatives and 3.9 years for patients with a family history of epilepsy in relatives who were not first-degree compared with 8.5 years for patients with no family history of epilepsy (P=.04). CONCLUSION: Our results show that a family history of epilepsy is associated with an earlier age at seizure onset in patients with FCD. Although this is a preliminary finding and a larger sample is needed to confirm these results, we believe these observations provide evidence that genetic modifiers could become an important issue in the clinical presentation of patients with dysplastic lesions.     

Inflammation, insulin resistance, and adiposity: a study of first-degree relatives of type 2 diabetic subjects

OBJECTIVE: Inflammatory markers such as C-reactive protein (CRP) are associated with insulin resistance, adiposity, and type 2 diabetes. Whether inflammation causes insulin resistance or is an epiphenomenon of obesity remains unresolved. We aimed to determine whether first-degree relatives of type 2 diabetic subjects differ in insulin sensitivity from control subjects without a family history of diabetes, whether first-degree relatives of type 2 diabetic subjects and control subjects differ in CRP, adiponectin, and complement levels, and whether CRP is related to insulin sensitivity independently of adiposity. RESEARCH DESIGN AND METHODS: We studied 19 young normoglycemic nonobese first-degree relatives of type 2 diabetic subjects and 22 control subjects who were similar for age, sex, and BMI. Insulin sensitivity (glucose infusion rate [GIR]) was measured by the euglycemic-hyperinsulinemic clamp. Dual-energy X-ray absorptiometry determined total and abdominal adiposity. Magnetic resonance imaging measured abdominal adipose tissue volumes. RESULTS: First-degree relatives of type 2 diabetic subjects had a 20% lower GIR than the control group (51.8 +/- 3.9 vs. 64.9 +/- 4.6 micromol x min(-1) x kg fat-free mass(-1), P = 0.04). However, first-degree relatives of subjects with type 2 diabetes and those without a family history of diabetes had normal and comparable levels of CRP, adiponectin, and complement proteins. When the cohort was examined as a whole, CRP was inversely related to GIR (r = -0.33, P = 0.04) and adiponectin (r = -0.34, P = 0.03) and positively related to adiposity (P < 0.04). However, CRP was not related to GIR independently of fat mass. In contrast to C3 (r = 0.41, P = 0.009) and factor B (r = 0.43, P = 0.005), CRP was unrelated to factor D. CONCLUSIONS: The insulin-resistant state is not associated with changes in inflammatory markers or complement proteins in subjects at high risk of type 2 diabetes. Our study confirms a strong relationship between CRP and fat mass. Increasing adiposity and insulin resistance may interact to raise CRP levels.     

Elevated proinsulin levels related to islet cell antibodies in first-degree relatives of IDDM patients.

OBJECTIVE--To assess whether proinsulin levels are elevated in first-degree relatives of insulin-dependent diabetes mellitus (IDDM) patients and whether there is a relationship between proinsulin levels and the occurrence of immunological markers. RESEARCH DESIGN AND METHODS--Fasting proinsulin concentrations were measured in 85 first-degree relatives (54 siblings, 20 parents, 11 children) of IDDM patients and in 90 age- and weight-matched control subjects with no family history of diabetes mellitus. RESULTS--Fasting proinsulin levels (median, 25th, and 75th percentiles) were 8 pM (range 3.2-14 pM) in first-degree relatives and 1.7 pM (range 1.7-4 pM) in control subjects (P less than 0.0001). Proinsulin was significantly elevated in siblings (7.2 pM, range 3.8-15 pM; P less than 0.0001), parents (9.8 pM, range 6.4-13 pM; P less than 0.0001), and children (6.6 pM, range 1.8-12 pM, P = 0.04) compared with control subjects but without differences between these groups. Islet cell antibody positive (ICA+) IDDM relatives had significantly higher proinsulin levels than ICA- (16 pM; range 7.2-25 vs. 6.9 pM, range 3.1-12 pM; P = 0.02). There was no difference between individuals with and without insulin autoantibodies. No difference in proinsulin levels was observed if the relatives were subdivided according to HLA-DR sharing with the diabetic proband. CONCLUSIONS--Fasting proinsulin concentrations were raised not only in siblings but also in parents and children of IDDM patients. Because proinsulin is more elevated in ICA+ than in ICA- subjects, increased proinsulin levels could reflect minor beta-cell damage due to previous immunological attack.     

Familial occurrence of migraine with aura in a population-based study

OBJECTIVE: To better define a possible genetic basis for migraine with aura (MWA). METHODS: We investigated the familial occurrence of migraine with aura in a sample of (MWA) subjects recruited from an epidemiologic study of migraine with aura involving the general population. The sample with migraine with aura (n = 26) was selected out of a total of 1392 subjects (842 women and 550 men) representative of the general population aged 18 to 65 years in the southern Italian town of San Severo. A family history of migraine with aura was determined via direct interviews with all living first-degree relatives of the 26 subjects who could be reached by investigators, 119 people: 71 women and 48 men. The diagnosis of migraine with aura was made according to the 1988 International Headache Society (IHS) criteria. RESULTS: Of the 26 subjects with migraine with aura, 7 (6 women and 1 man) had a positive family history, with a total of 7 first-degree relatives affected by the disease (1 mother, 2 fathers, 1 brother, 1 sister, and 2 children). Based on the lifetime prevalence rate of migraine with aura (1.6%) in the San Severo general population, the relative risk of migraine with aura in the first-degree relatives of the subjects was 3.68 (4.16 for women and 2.77 for men). CONCLUSION: Our subjects' relative risk rate for familial occurrence of migraine with aura was similar to that reported by one investigator, but markedly lower than that reported by another group.     

Extrapancreatic autoimmune manifestations in type 1 diabetes patients and their first-degree relatives: a multicenter study

OBJECTIVE: To investigate the prevalence of autoimmune diseases in young patients (probands) with type 1 diabetes and their first-degree relatives, and to determine the spectrum of extrapancreatic manifestations in these subjects. RESEARCH DESIGN AND METHODS: The study population included 109 probands age 13 +/- 4.9 years and 412 first-degree relatives age 28.7 +/- 16.2 years. The prevalence rates of autoimmune thyroiditis and celiac disease were determined in all probands and in 100 of the 412 first-degree relatives. Control groups included 78 subjects age 14.9 +/- 10.4 years for the prevalence of autoimmune thyroiditis and 120,000 youth ages 16-17 years for the prevalence of celiac disease. Thyroiditis and celiac disease were diagnosed by abnormally high thyroid peroxidase (TPO), thyroglobulin (TG), antigliadin, and antiendomysial antibody titers. Celiac was confirmed by biopsy. A questionnaire was used to interview probands and relatives to determine the spectrum of autoimmune manifestations. RESULTS: The prevalence of autoimmune thyroiditis determined by high TPO and/or TG titers was 27 and 25% for probands and relatives, respectively. These rates were higher than those for control subjects (P < 000.1). The prevalence of celiac disease among probands and screened relatives was 8.3 and 6%, respectively. These rates were higher than those for control subjects and the 312 family members interviewed only (0.1 and 0.3%, respectively; P < 0.0001). Interviews of participants revealed a wide range of associated autoimmune diseases. The risk of developing an autoimmune disease was higher (P < 0.001) in families with a proband who had an additional autoimmune manifestation. CONCLUSIONS: Screening for autoimmune thyroiditis and celiac disease should be performed in patients with type 1 diabetes and their first-degree relatives, especially when the probands have an additional autoimmune manifestation.     

Different patterns of insulin resistance in relatives of type 1 diabetic patients with retinopathy or nephropathy: the Genesis France-Belgium Study

OBJECTIVE: Insulin resistance may be a risk factor for diabetic microangiopathy, which may have a familial component. We carried out a family-based study to determine which components of the insulin resistance syndrome are associated with diabetic retinopathy and nephropathy in type 1 diabetes. RESEARCH DESIGN AND METHODS: The Genesis France-Belgium Study is a multicenter binational study designed to investigate the genetic factors involved in the microvascular complications of type 1 diabetes using a family-based design. Probands were type 1 diabetic patients with diabetic retinopathy (classified as background, preproliferative, or proliferative) and possibly diabetic nephropathy (absent, incipient, established, or advanced). The insulin resistance score of their first-degree relatives was calculated according to their BMI and history of arterial hypertension, lipid disorders, and type 2 diabetes. RESULTS: The insulin resistance score of relatives was positively correlated with the albumin excretion rate (P = 0.0009) and fasting plasma glucose (P = 0.0003) and HbA(1c) (P < 0.0001) concentrations. This score was higher in the relatives of probands with than in those without diabetic nephropathy (P = 0.0370). Similarly, it was higher in relatives of subjects with proliferative diabetic retinopathy than in those of probands without, even after controlling for subjects with versus without diabetic nephropathy (P = 0.0379). However, the components of the insulin resistance score in relatives differed according to the severity of diabetic retinopathy or nephropathy in the probands. Obesity and history of arterial hypertension were most common in relatives of probands with proliferative diabetic retinopathy, whereas obesity and history of lipid disorders were most common in the relatives of probands with diabetic nephropathy. CONCLUSIONS: Familial insulin resistance segregates with diabetic complications: lipid disorders and obesity segregate with diabetic nephropathy, whereas arterial hypertension and obesity segregate with diabetic retinopathy.     

Comparative analysis of organ-specific autoantibodies and celiac disease--associated antibodies in type 1 diabetic patients, their first-degree relatives, and healthy control subjects

OBJECTIVE: In type 1 diabetes the coexistence with other endocrine diseases and organ-specific autoantibodies has been frequently reported leading to the concept of autoimmune polyendocrine syndrome (APS). In addition, an association of type 1 diabetes with celiac disease has been described. These disorders share a similar genetic background, and first-degree relatives of type 1 diabetic patients may also be affected significantly. Screening for specific antibodies allows early diagnosis of these disorders. RESEARCH DESIGN AND METHODS: In the present cross-sectional study, we analyzed sera from 197 recent-onset type 1 diabetic patients at the time of diagnosis, 882 first-degree relatives, and sera of 150 healthy control subjects for prevalence and co-occurence of the following antibodies (method): insulin autoantibodies (radioimmunoassay); GAD and IA-2 antibodies (radioligand assay); islet cell antibody, anti-adrenal cortex antibodies, and anti-gastric parietal cell antibodies (indirect immunofluorescence); anti-thyroglobulin and anti-thyroid peroxidase antibodies; and gliadin IgG/A and tissue-transglutaminase IgA (enzyme-linked immunosorbent assay). RESULTS: The overall frequency of gastric patietal cell antibodies and adrenal antibodies did not differ significantly among groups. In contrast, type 1 diabetes-associated antibodies and thyroid antibodies were significantly more frequent both in recent-onset type 1 diabetic patients and in the group of first-degree relatives (P < 0.05). The prevalence of gliadin IgG/IgA and transglutaminase IgA was significantly higher in the group of recent-onset type 1 diabetic patients (P < 0.05), but the difference between first-degree relatives and control subjects did not reach statistical significance. Focusing on the coexistence of antibodies, the group of recentonset type 1 diabetic patients presented with 27.4% of the subjects testing antibody-positive-specific for two or more of the envisaged disorders (i.e., type 1 diabetes, autoimmune thyroiditis, and celiac disease) compared with 3.1% in the group of first-degree relatives and 0 of 150 in the control population (P < 0.05). CONCLUSIONS: We conclude that, in an active case-finding strategy, recent-onset type 1 diabetic patients should be routinely screened at least for concomitant autoimmune thyroid disease and additionally for celiac disease. Screening in their first-degree relatives should include at a minimum the search for thyroid autoimmunity in addition to screening for pre-type 1 diabetes.