Brooks-Worrell Barbara, Hampe Christiane S, Hattery Erica G, Palomino Brenda, Zangeneh Sahar Z, Utzschneider Kristina, Kahn Steven E, Larkin Mary E, Johnson Mary L, Mather Kieren J, Younes Naji, Rasouli Neda, Desouza Cyrus, Cohen Robert M, Park Jean Y, Florez Hermes J, Valencia Willy Marcos, Shojaie Ali, Palmer Jerry P, Balasubramanyam Ashok
VA Puget Sound Health Care System, Seattle, WA.
University of Washington, Seattle, WA.
Diabetes. 2022 Jan 21;71(6):1261-71. doi: 10.2337/db21-0590.
Islet autoimmunity may contribute to β-cell dysfunction in type 2 diabetes (T2D). Its prevalence and clinical significance have not been rigorously determined. In this ancillary study to the Glycemia Reduction Approaches in Diabetes-A Comparative Effectiveness (GRADE) Study, we investigated the prevalence of cellular and humoral islet autoimmunity in patients with T2D duration 4·0±3·0 y, HbA1c 7·5±0·5% on metformin alone. We measured T cell autoreactivity against islet proteins, islet autoantibodies against GAD65, IA2, ZnT8, and β-cell function. Cellular islet autoimmunity was present in 41·3%, humoral islet autoimmunity in 13·5%, and both in 5·3%. β-cell function calculated as iAUC-CG and ΔC-peptide(0- 30)/Δglucose(0-30) from an oral glucose tolerance test was lower among T cell-positives (T+) than T cell-negatives (T-) using two different adjustments for insulin sensitivity (iAUC-CG: 13·2% [95% CI 0·3, 24·4%] or 11·4% [95% CI 0·4, 21·2%] lower; ΔC-peptide(0-30)/Δglucose(0-30)) 19% [95% CI 3·1, 32·3%] or 17·7% [95% CI 2·6, 30·5%] lower). T+ patients had 17% higher HbA1c (95% CI 0·07, 0·28) and 7·7 mg/dL higher fasting plasma glucose levels (95% CI 0·2,15·3) than T- patients. We conclude that islet autoimmunity is much more prevalent in T2D patients than previously reported. T cell-mediated autoimmunity is associated with diminished β-cell function and worse glycemic control.
胰岛自身免疫可能导致2型糖尿病（T2D）患者的β细胞功能障碍。其患病率及临床意义尚未得到确切定论。在这项糖尿病血糖降低方法对比有效性（GRADE）研究的辅助研究中，我们调查了糖尿病病程为4.0±3.0年、仅使用二甲双胍治疗且糖化血红蛋白（HbA1c）为7.5±0.5%的T2D患者中细胞性和体液性胰岛自身免疫的患病率。我们检测了针对胰岛蛋白的T细胞自身反应性、针对谷氨酸脱羧酶65（GAD65）、胰岛抗原2（IA2）、锌转运体8（ZnT8）的胰岛自身抗体以及β细胞功能。细胞性胰岛自身免疫的患病率为41.3%，体液性胰岛自身免疫的患病率为13.5%，两者皆有的患病率为5.3%。在使用两种不同胰岛素敏感性校正方法后，口服葡萄糖耐量试验计算得出的以胰岛素分泌指数（iAUC-CG）和C肽变化量（0 - 30）/葡萄糖变化量（0 - 30）表示的β细胞功能，在T细胞阳性（T+）患者中低于T细胞阴性（T-）患者（iAUC-CG：低13.2% [95%置信区间0.3, 24.4%]或11.4% [95%置信区间0.4, 21.2%]；C肽变化量（0 - 30）/葡萄糖变化量（0 - 30）低19% [95%置信区间3.1, 32.3%]或17.7% [95%置信区间2.6, 30.5%]）。与T-患者相比，T+患者的HbA1c高17%（95%置信区间0.07, 0.28），空腹血糖水平高7.7mg/dL（95%置信区间0.2, 15.3）。我们得出结论，胰岛自身免疫在T2D患者中的患病率比之前报道的要高得多。T细胞介导的自身免疫与β细胞功能减退及血糖控制不佳有关。
