Turner R, Stratton I, Horton V, Manley S, Zimmet P, Mackay I R, Shattock M, Bottazzo G F, Holman R
Diabetes Research Laboratories, Radcliffe Infirmary, Oxford, UK.
Lancet. 1997 Nov 1;350(9087):1288-93. doi: 10.1016/s0140-6736(97)03062-6.
Autoantibodies to islet-cell cytoplasm (ICA) and glutamic acid decarboxylase (GADA) can occur in apparently typical, non-insulin dependent diabetes mellitus (type 2). We investigated whether the presence of either or both antibodies characterises a subtype of diabetes and provides better prediction of requirement for insulin therapy by 6 years' follow-up than clinical variables.
We measured ICA and GADA at diagnosis of diabetes in a representative population of 3672 white patients with type 2 diabetes, aged between 25 and 65 years. The phenotype was assessed by age of onset, body-mass index, percentage haemoglobin A1c (HbA1c), and islet beta-cell function. We investigated the need for insulin therapy among 1538 patients not assigned insulin and followed up for 6 years from diagnosis.
The proportion of patients with ICA and GADA decreased with increasing age at diagnosis (from 33 [21%] of 157 patients aged 25-34 [corrected] to 66 [4%] of 1769 aged 55-65 for ICA; from 53 [34%] to 122 [7%] for GADA). Among patients younger than 35 at diagnosis, those with ICA or GADA had lower body-mass index than those without (mean 24.9 [SD 6.0] vs 31.7 [7.3] kg/m2; p < 0.0001 and had higher percentage of HbA1c (9.7 vs 8.7%, p < 0.05). 94% of patients with ICA and 84% of those with GADA required insulin therapy by 6 years, compared with 14% of those without the antibodies (p < 0.0001). Among patients older than 55 at diagnosis, the difference between those with and without antibodies in body-mass index was smaller (27.2 [5.4] vs 28.6 [4.8] kg/m2, p < 0.001); 44% of those with ICA, 34% of those with GADA, and 5% with neither antibody required insulin therapy by 6 years (p < 0.0001). Among patients older than 45 years, body-mass index and HbA1c provided little predictive information for insulin requirement, whereas the positive predictive values of GADA (> or = 60 U/L) alone, or both GADA (> or = 20 U/L) and ICA (> 5 U/L), for insulin therapy were 52% and 68%.
Among young adults with type 2 diabetes, the phenotype of those with ICA or GADA antibodies was similar to that of classic juvenile-onset insulin-dependent diabetes, and either phenotype or antibodies predicted insulin requirement. In older adults, the phenotype was closer to that of patients without antibodies and only the presence of antibodies predicted an increased likelihood of insulin requirement.
胰岛细胞质自身抗体（ICA）和谷氨酸脱羧酶自身抗体（GADA）可出现于明显典型的非胰岛素依赖型糖尿病（2型）患者中。我们研究了这两种抗体单独或同时存在是否可作为糖尿病的一个亚型特征，以及与临床变量相比，通过6年随访是否能更好地预测胰岛素治疗需求。
我们在3672例年龄在25至65岁之间的2型糖尿病白人患者的代表性人群中，于糖尿病诊断时检测了ICA和GADA。通过发病年龄、体重指数、糖化血红蛋白（HbA1c）百分比和胰岛β细胞功能评估表型。我们对1538例未分配胰岛素治疗的患者进行了随访，从诊断开始为期6年，研究其胰岛素治疗需求。
诊断时年龄越大，ICA和GADA阳性患者的比例越低（ICA：从25至34岁（校正后）的157例患者中的33例（21%）降至55至65岁的1769例患者中的66例（4%）；GADA：从53例（34%）降至122例（7%））。诊断时年龄小于35岁的患者中，ICA或GADA阳性者的体重指数低于阴性者（分别为24.9（标准差6.0）与31.7（7.3）kg/m2；p<0.0001），HbA1c百分比更高（分别为9.7%与8.7%，p<0.05）。6年后，94%的ICA阳性患者和84%的GADA阳性患者需要胰岛素治疗，而抗体阴性者为14%（p<0.0001）。诊断时年龄大于55岁的患者中，抗体阳性和阴性者在体重指数上的差异较小（分别为27.2（5.4）与28.6（4.8）kg/m2，p<0.001）；6年后，ICA阳性者中有44%、GADA阳性者中有34%以及两种抗体均阴性者中有5%需要胰岛素治疗（p<0.0001）。在年龄大于45岁的患者中，体重指数和HbA1c对胰岛素需求的预测价值不大，而单独GADA（≥60 U/L）或GADA（≥20 U/L）和ICA（>5 U/L）两者对胰岛素治疗的阳性预测值分别为52%和68%。
在患有2型糖尿病的年轻成年人中，ICA或GADA抗体阳性者的表型与经典的青少年起病的胰岛素依赖型糖尿病相似，表型或抗体均可预测胰岛素需求。在老年人中，表型更接近抗体阴性患者，只有抗体的存在可预测胰岛素需求增加的可能性。
