Department of Clinical and Biological Science, University of Exeter Medical School, Exeter, U.K.
School of Translational Sciences, Bristol Medical School, University of Bristol, Bristol, U.K.
Diabetes. 2024 Oct 1;73(10):1583-1591. doi: 10.2337/db23-0980.
We investigated whether characterization of full-length GAD (f-GADA) antibody (GADA) responses could identify early insulin requirement in adult-onset diabetes. In 179 f-GADA-positive participants diagnosed with type 2 diabetes, we assessed associations of truncated GADA (t-GADA) positivity, f-GADA IgG subclasses, and f-GADA affinity with early insulin requirement (<5 years), type 1 diabetes genetic risk score (T1D GRS), and C-peptide. t-GADA positivity was lower in f-GADA-positive without early insulin in comparison with f-GADA-positive type 2 diabetes requiring insulin within 5 years, and T1D (75% vs. 91% and 95% respectively, P < 0.0001). t-GADA positivity (in those f-GADA positive) identified a group with a higher T1D genetic susceptibility (mean T1D GRS 0.248 vs. 0.225, P = 0.003), lower C-peptide (1,156 pmol/L vs. 4,289 pmol/L, P = 1 × 10-7), and increased IA-2 antigen positivity (23% vs. 6%, P = 0.03). In survival analysis, t-GADA positivity was associated with early insulin requirement compared with those only positive for f-GADA, independently from age of diagnosis, f-GADA titer, and duration of diabetes (adjusted hazard ratio 5.7 [95% CI 1.4, 23.5], P = 0.017). The testing of t-GADA in f-GADA-positive individuals with type 2 diabetes identifies those who have genetic and clinical characteristics comparable to T1D and stratifies those at higher risk of early insulin requirement.
我们研究了全长谷氨酸脱羧酶（GAD）抗体（GADA）的特征是否可以识别成人发病型糖尿病的早期胰岛素需求。在 179 名 GAD 阳性的 2 型糖尿病患者中，我们评估了截断 GADA（t-GADA）阳性、GADA IgG 亚类和 GADA 亲和力与早期胰岛素需求（<5 年）、1 型糖尿病遗传风险评分（T1D GRS）和 C 肽之间的关联。与 5 年内需要胰岛素的 GADA 阳性 2 型糖尿病相比，无早期胰岛素的 GADA 阳性患者的 t-GADA 阳性率较低，而与 1 型糖尿病相比则更高（分别为 75%、91%和 95%，P < 0.0001）。在那些 GADA 阳性的患者中，t-GADA 阳性可识别出一组具有更高的 1 型糖尿病遗传易感性（平均 T1D GRS 为 0.248 比 0.225，P = 0.003）、更低的 C 肽（1,156 pmol/L 比 4,289 pmol/L，P = 1 × 10-7）和更高的 IA-2 抗原阳性率（23%比 6%，P = 0.03）。在生存分析中，与仅 GADA 阳性相比，t-GADA 阳性与早期胰岛素需求相关，与诊断年龄、GADA 滴度和糖尿病持续时间无关（调整后的危险比为 5.7[95%CI 1.4，23.5]，P = 0.017）。在 GADA 阳性的 2 型糖尿病患者中检测 t-GADA，可识别出具有与 1 型糖尿病相似的遗传和临床特征的患者，并对早期胰岛素需求风险较高的患者进行分层。
