Brooks-Worrell Barbara M, Boyko Edward J, Palmer Jerry P
VA Puget Sound Health Care System, Seattle, WA, and Department of Medicine, University of Washington, Seattle, WA
VA Puget Sound Health Care System, Seattle, WA, and Department of Medicine, University of Washington, Seattle, WA.
Diabetes Care. 2014 Dec;37(12):3286-93. doi: 10.2337/dc14-0961. Epub 2014 Sep 19.
Cross-sectional studies have suggested that islet autoimmunity may be more prevalent in type 2 diabetes (T2D) than previously appreciated and may contribute to the progressive decline in β-cell function. In this study, we longitudinally evaluated the effect of islet autoimmune development on the progressive β-cell dysfunction in T2D patients.
Twenty-three T2D patients negative for islet autoantibodies (GAD antibody and insulinoma-associated protein 2) and islet-specific T cells were evaluated prospectively for up to 36 months. We investigated the percentage of patients who developed islet autoantibodies (Ab+) and/or islet-reactive T cells (T+) and the effect of the islet autoimmunity on fasting and glucagon-stimulated C-peptide responses. We defined positive islet autoimmunity as Ab+ and/or T+ for at least two study visits.
Of the 23 patients, 6 (26%) remained negative for islet autoimmunity (Ab-T-), 14 (61%) developed Ab+ and/or T+, and 3 (13%) were unclassifiable because they developed islet autoimmunity at only one study visit. Islet Ab+ was observed to be less stable than islet-specific T-cell responses. Development of islet autoimmunity was significantly associated with a more rapid decline in fasting (P < 0.0001) and glucagon-stimulated (P < 0.05) C-peptide responses.
These pilot data suggest that the development of islet autoimmunity in T2D is associated with a significantly more rapid β-cell functional decline.
横断面研究表明，胰岛自身免疫在2型糖尿病（T2D）中可能比之前认为的更为普遍，并且可能导致β细胞功能的逐渐衰退。在本研究中，我们纵向评估了胰岛自身免疫发展对T2D患者β细胞功能逐渐衰退的影响。
对23例胰岛自身抗体（谷氨酸脱羧酶抗体和胰岛瘤相关蛋白2）及胰岛特异性T细胞均为阴性 的T2D患者进行了长达36个月的前瞻性评估。我们调查了出现胰岛自身抗体（Ab+）和/或胰岛反应性T细胞（T+）的患者百分比，以及胰岛自身免疫对空腹和胰高血糖素刺激后的C肽反应的影响。我们将至少两次研究访视时出现Ab+和/或T+定义为阳性胰岛自身免疫。
23例患者中，6例（26%）胰岛自身免疫保持阴性（Ab-T-），14例（61%）出现Ab+和/或T+，3例（13%）无法分类，因为他们仅在一次研究访视时出现了胰岛自身免疫。观察到胰岛Ab+不如胰岛特异性T细胞反应稳定。胰岛自身免疫的发展与空腹（P<0.0001）和胰高血糖素刺激后的（P<0.05）C肽反应更快下降显著相关。
这些初步数据表明，T2D中胰岛自身免疫的发展与β细胞功能明显更快衰退相关。
