Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.
Diabetes. 2010 Feb;59(2):416-22. doi: 10.2337/db09-0747. Epub 2009 Oct 28.
To evaluate the significance of GAD antibodies (GADAs) and family history for type 1 diabetes (FH(T1)) or type 2 diabetes (FH(T2)) in nondiabetic subjects.
GADAs were analyzed in 4,976 nondiabetic relatives of type 2 diabetic patients or control subjects from Finland. Altogether, 289 (5.9%) were GADA(+)-a total of 253 GADA(+) and 2,511 GADA(-) subjects participated in repeated oral glucose tolerance tests during a median time of 8.1 years. The risk of progression to diabetes was assessed using Cox regression analysis.
Subjects within the highest quartile of GADA(+) (GADA(+)(high)) had more often first-degree FH(T1) (29.2 vs. 7.9%, P < 0.00001) and GADA(+) type 2 diabetic (21.3 vs. 13.7%, P = 0.002) or nondiabetic (26.4 vs. 13.3%, P = 0.010) relatives than GADA(-) subjects. During the follow-up, the GADA(+) subjects developed diabetes significantly more often than the GADA(-) subjects (36/253 [14.2%] vs. 134/2,511 [5.3%], P < 0.00001). GADA(+)(high) conferred a 4.9-fold increased risk of diabetes (95% CI 2.8-8.5) compared with GADA(-)-seroconversion to positive during the follow-up was associated with 6.5-fold (2.8-15.2) and first-degree FH(T1) with 2.2-fold (1.2-4.1) risk of diabetes. Only three subjects developed type 1 diabetes, and others had a non-insulin-dependent phenotype 1 year after diagnosis. GADA(+) and GADA(-) subjects did not clinically differ at baseline, but they were leaner and less insulin resistant after the diagnosis of diabetes.
GADA positivity clusters in families with type 1 diabetes or latent autoimmune diabetes in adults. GADA positivity predicts diabetes independently of family history of diabetes, and this risk was further increased with high GADA concentrations.
评估谷氨酸脱羧酶抗体（GADAs）和一级亲属糖尿病史（FH（T1））或 2 型糖尿病史（FH（T2））对非糖尿病患者的意义。
分析了来自芬兰的 4976 名 2 型糖尿病患者或对照受试者的非糖尿病亲属的 GADAs。共有 289 名（5.9%）为 GADA（+），共有 253 名 GADA（+）和 2511 名 GADA（-）受试者在中位时间为 8.1 年的情况下接受了重复口服葡萄糖耐量试验。使用 Cox 回归分析评估进展为糖尿病的风险。
GADA（+）最高四分位的受试者（GADA（+）（高））更常具有一级亲属 1 型糖尿病史（29.2% vs. 7.9%，P < 0.00001）和 GADA（+）2 型糖尿病史（21.3% vs. 13.7%，P = 0.002）或非糖尿病史（26.4% vs. 13.3%，P = 0.010）亲属比 GADA（-）受试者更常见。在随访期间，GADA（+）受试者比 GADA（-）受试者更频繁地发生糖尿病（36/253 [14.2%] vs. 134/2511 [5.3%]，P < 0.00001）。与 GADA（-）-随访期间转为阳性相比，GADA（+）（高）使糖尿病的风险增加了 4.9 倍（95%CI 2.8-8.5），而一级亲属 1 型糖尿病史使糖尿病的风险增加了 2.2 倍（1.2-4.1），一级亲属糖尿病史使糖尿病的风险增加了 6.5 倍（2.8-15.2）。只有 3 名受试者发展为 1 型糖尿病，其他人在诊断后 1 年内表现为非胰岛素依赖型表型。GADA（+）和 GADA（-）受试者在基线时无临床差异，但在诊断为糖尿病后，他们更瘦，胰岛素抵抗程度更低。
GADA 阳性在 1 型糖尿病或成人隐匿性自身免疫性糖尿病家族中聚集。GADA 阳性独立于糖尿病家族史预测糖尿病，并且该风险随着 GADA 浓度的升高而进一步增加。
