Diabetes. 1997 Nov;46(11):1829-39.
We investigated familial clustering of diabetic retinopathy and nephropathy in the families of 372 subjects from the Diabetes Control and Complications Trial (DCCT). These subjects had 467 first-degree relatives with IDDM or NIDDM. Family sizes ranged from two to six. A complete data set was obtained from 241 relatives of 217 DCCT subjects. Among the DCCT subjects, 53% were in the intensive treatment group and 47% were in the conventional group; 44% were from the primary prevention cohort (no retinopathy or microalbuminuria at the DCCT baseline) and 56% were from the secondary intervention cohort (mild-to-moderate nonproliferative retinopathy and <200 mg/24 h albumin excretion rate [AER] at baseline). Retinopathy and nephropathy were assessed with seven-field stereo fundus photography and timed urinary AER measurements. Retinopathy was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. ETDRS scores and AERs were adjusted for the DCCT treatment group and for significant covariates from among sex, age, diabetes duration, HbA1c value, and body weight. Familial associations were assessed by comparing the prevalence of retinopathy and nephropathy in diabetic relatives of the respective positive versus negative DCCT subjects. To determine family clustering of the severity of retinopathy or nephropathy, the intraclass (familial) correlation was computed from the log-adjusted retinopathy and nephropathy scores of DCCT subjects and their relatives for all family members and sib-sib relationships. For parent-offspring, mother-child, and father-child relationships, the pairwise estimate of the correlations was computed. A correlation of 0.2 was considered to be biologically meaningful a priori. Among families of patients in the intensive and conventional groups combined, there was an increased risk of severe retinopathy (an ETDRS score > or =47, clinically significant macular edema, or laser treatment in either eye) among relatives of retinopathy-positive vs. retinopathy-negative DCCT subjects in the secondary intervention cohort (odds ratio [OR], 3.1; 95% CI 1.2-7.8; P < 0.05). There was no increase in the risk of retinopathy of any severity (microaneurysms or worse) in the relatives of retinopathy-positive vs. retinopathy-negative DCCT subjects of the primary prevention cohort. There was an increased risk of nephropathy (AER >40 mg/24 h) in relatives of nephropathy-positive versus nephropathy-negative DCCT subjects of the secondary intervention cohort (OR, 5.4; 95% CI 2.2-13.7; P < 0.001). The risk of severe retinopathy in the relatives of positive versus negative subjects from the conventional treatment group alone (OR, 4.3; 95% CI 1.01-18.6; P < 0.05) was statistically significant and somewhat greater than that among relatives of the subjects in intensive treatment group (OR, 2.4; 95% CI 0.7-8.1), which was not significant. Correlations for the severity of retinopathy were 0.187 (all family members), 0.327 (parent-offspring), 0.249 (father-child), 0.391 (mother-child), and 0.060 (sib-sib), using the combined treatment group families. All these correlations were statistically significant (P < 0.05), except for sib-sib. The results showed similar trends when the families from the conventional and intensive treatment groups were analyzed separately. Correlations for nephropathy in the combined treatment group families were 0.063 (all family members), 0.138 (parent-offspring), 0.170 (father-child), 0.103 (mother-child), and 0.107 (sib-sib). None of these correlations is statistically significant. The lack of significant correlation for the severity of nephropathy may reflect the relatively short duration of diabetes in the offspring of these families and the known high intrasubject variability of AERs. These data provide the first available evidence that the severity of diabetic retinopathy is influenced by familial (possibly genetic) factors and confirmatory evidence that such factors influence the development
我们对糖尿病控制与并发症试验（DCCT）中372名受试者的家族性糖尿病视网膜病变和肾病聚集情况进行了研究。这些受试者有467名患有胰岛素依赖型糖尿病（IDDM）或非胰岛素依赖型糖尿病（NIDDM）的一级亲属。家庭规模从2人到6人不等。从217名DCCT受试者的241名亲属那里获得了完整的数据集。在DCCT受试者中，53%属于强化治疗组，47%属于常规治疗组；44%来自一级预防队列（DCCT基线时无视网膜病变或微量白蛋白尿），56%来自二级干预队列（基线时为轻度至中度非增殖性视网膜病变且白蛋白排泄率[AER]<200mg/24小时）。通过七视野立体眼底照相和定时尿AER测量来评估视网膜病变和肾病。使用早期糖尿病视网膜病变治疗研究（ETDRS）量表评估视网膜病变。对ETDRS评分和AER进行了DCCT治疗组以及性别、年龄、糖尿病病程、糖化血红蛋白（HbA1c）值和体重等显著协变量的校正。通过比较各自DCCT阳性与阴性受试者的糖尿病亲属中视网膜病变和肾病的患病率来评估家族关联。为了确定视网膜病变或肾病严重程度的家族聚集情况，根据DCCT受试者及其亲属针对所有家庭成员以及同胞 - 同胞关系的对数校正视网膜病变和肾病评分计算组内（家族性）相关性。对于亲子、母子和父子关系，计算相关性的成对估计值。先验地认为相关性为0.2具有生物学意义。在强化治疗组和常规治疗组合并的患者家庭中，二级干预队列中视网膜病变阳性与阴性DCCT受试者的亲属中，严重视网膜病变（ETDRS评分≥47、临床上显著的黄斑水肿或任何一只眼睛接受激光治疗）的风险增加（优势比[OR]为3.1；95%置信区间为1.2 - 7.8；P<0.05）。一级预防队列中视网膜病变阳性与阴性DCCT受试者的亲属中，任何严重程度（微动脉瘤或更严重）的视网膜病变风险没有增加。二级干预队列中肾病阳性与阴性DCCT受试者的亲属中，肾病（AER>40mg/24小时）的风险增加（OR为5.4；95%置信区间为2.2 - 13.7；P<0.001）。仅常规治疗组中阳性与阴性受试者的亲属中严重视网膜病变的风险（OR为4.3；95%置信区间为1.01 - 18.6；P<0.05）具有统计学意义，且略高于强化治疗组受试者亲属中的风险（OR为2.4；95%置信区间为0.7 - 8.1），后者无统计学意义。使用合并治疗组家庭的数据，视网膜病变严重程度的相关性在所有家庭成员中为0.187，亲子关系中为0.327，父子关系中为0.249，母子关系中为0.391，同胞 - 同胞关系中为0.060。除同胞 - 同胞关系外，所有这些相关性均具有统计学意义（P<0.05）。当分别分析常规治疗组和强化治疗组的家庭时，结果显示出类似趋势。合并治疗组家庭中肾病的相关性在所有家庭成员中为0.063，亲子关系中为0.138，父子关系中为0.170，母子关系中为0.103，同胞 - 同胞关系中为0.107。这些相关性均无统计学意义。肾病严重程度缺乏显著相关性可能反映了这些家庭后代中糖尿病病程相对较短以及已知的AERs较高的个体内变异性。这些数据提供了首个现有证据表明糖尿病视网膜病变的严重程度受家族性（可能是遗传性）因素影响，并证实了此类因素影响其发展
