Islet Autoimmunity in Adults With Impaired Glucose Tolerance and Recently Diagnosed, Treatment Naïve Type 2 Diabetes in the Restoring Insulin SEcretion (RISE) Study.
Islet Autoimmunity in Adults With Impaired Glucose Tolerance and Recently Diagnosed, Treatment Naïve Type 2 Diabetes in the Restoring Insulin SEcretion (RISE) Study.
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DOI：
10.3389/fimmu.2021.640251
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发表时间：
2021
影响因子：
7.3
通讯作者：
RISE Consortium
中科院分区：
文献类型：
--
作者：
Brooks-Worrell BM;Tjaden AH;Edelstein SL;Palomino B;Utzschneider KM;Arslanian S;Mather KJ;Buchanan TA;Nadeau KJ;Atkinson K;Barengolts E;Kahn SE;Palmer JP;RISE Consortium
已证实患有2型糖尿病（T2 D）的成人中胰岛自身抗体和胰岛反应性T细胞（T+）的存在可识别出具有更严重β细胞功能障碍的患者。然而，在向临床T2 D进展的哪个阶段，胰岛自身免疫作为影响β细胞功能障碍的重要组成部分出现？在这项恢复胰岛素分泌（RISE）研究的辅助研究中，我们调查了患有糖耐量受损（IGT）和近期诊断为未经治疗（Ndx）T2 D的肥胖糖尿病前期成人中T+ β细胞功能障碍和65 kDa谷氨酸脱羧酶抗原（GADA）自身抗体的患病率及其相关性。我们进一步研究了12个月的RISE干预（二甲双胍或利拉鲁肽加二甲双胍，或甘精胰岛素治疗3个月，随后二甲双胍或安慰剂治疗9个月）对胰岛自身免疫反应性的影响。我们观察到基线时1.6%的NdxT 2D和4.6%的IGT患者GADA（+），12个月时1.6%的NdxT 2D和5.3%的IGT患者GADA（+），但GADA（+）与β细胞功能之间无显著相关性。在基线时50%的NdxT 2D和60.4%的IGT中观察到T（+），在12个月时68.4%的NdxT 2D和83.9%的IGT中观察到T（+）。与T（−）NdxT 2D相比，观察到T（+）NdxT 2D具有显著更高的空腹血糖（p = 0.004）和2小时血糖（p = 0.0032），但显著更低的稳态C肽（sscpep，p = 0.007）。与T（−）IGT相比，T（+）IGT参与者对葡萄糖的急性（第一阶段）C肽反应（ACPRg）较低，但不显著（p = 0.025）。二甲双胍治疗后，观察到T（+）受试者的血红蛋白A1 c（HbA 1c，p = 0.002）和空腹C肽（p = 0.002）显著低于T（−）受试者，而利拉鲁肽+二甲双胍治疗的T（+）受试者的sscpep（p = 0.010）显著低于T（−）受试者。在安慰剂组中，T（+）参与者的ACPRg显著低于T（-）参与者（p = 0.001）。总之，T（+）在很大比例的肥胖糖尿病前期成人IGT和最近诊断的T2 D中发现。T（+）与治疗效果和β细胞功能障碍显著相关。我们的研究结果表明，T（+）是T2 D的重要组成部分。
The presence of islet autoantibodies and islet reactive T cells (T+) in adults with established type 2 diabetes (T2D) have been shown to identify those patients with more severe β-cell dysfunction. However, at what stage in the progression toward clinical T2D does islet autoimmunity emerge as an important component influencing β-cell dysfunction? In this ancillary study to the Restoring Insulin SEcretion (RISE) Study, we investigated the prevalence of and association with β-cell dysfunction of T+ and autoantibodies to the 65 kDa glutamic acid decarboxylase antigen (GADA) in obese pre-diabetes adults with impaired glucose tolerance (IGT) and recently diagnosed treatment naïve (Ndx) T2D. We further investigated the effect of 12 months of RISE interventions (metformin or liraglutide plus metformin, or with 3 months of insulin glargine followed by 9 months of metformin or placebo) on islet autoimmune reactivity. We observed GADA(+) in 1.6% of NdxT2D and 4.6% of IGT at baseline, and in 1.6% of NdxT2D and 5.3% of IGT at 12 months, but no significant associations between GADA(+) and β-cell function. T(+) was observed in 50% of NdxT2D and 60.4% of IGT at baseline, and in 68.4% of NdxT2D and 83.9% of IGT at 12 months. T(+) NdxT2D were observed to have significantly higher fasting glucose (p = 0.004), and 2 h glucose (p = 0.0032), but significantly lower steady state C-peptide (sscpep, p = 0.007) compared to T(−) NdxT2D. T(+) IGT participants demonstrated lower but not significant (p = 0.025) acute (first phase) C-peptide response to glucose (ACPRg) compared to T(−) IGT. With metformin treatment, T(+) participants were observed to have a significantly lower Hemoglobin A1c (HbA1c, p = 0.002) and fasting C-peptide (p = 0.002) compared to T(−), whereas T(+) treated with liraglutide + metformin had significantly lower sscpep (p = 0.010) compared to T(−) participants. In the placebo group, T(+) participants demonstrated significantly lower ACPRg (p = 0.001) compared to T(−) participants. In summary, T(+) were found in a large percentage of obese pre-diabetes adults with IGT and in recently diagnosed T2D. Moreover, T(+) were significantly correlated with treatment effects and β-cell dysfunction. Our results demonstrate that T(+) are an important component in T2D.
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影响因子：
7.7
作者：
Ferraro A;Socci C;Stabilini A;Valle A;Monti P;Piemonti L;Nano R;Olek S;Maffi P;Scavini M;Secchi A;Staudacher C;Bonifacio E;Battaglia M
通讯作者：
Battaglia M
DOI：
10.4049/jimmunol.1002615
发表时间：
2011-01-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jagannathan-Bogdan M;McDonnell ME;Shin H;Rehman Q;Hasturk H;Apovian CM;Nikolajczyk BS
通讯作者：
Nikolajczyk BS
DOI：
10.1161/atvbaha.114.304636
发表时间：
2014-12
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
McLaughlin T;Liu LF;Lamendola C;Shen L;Morton J;Rivas H;Winer D;Tolentino L;Choi O;Zhang H;Hui Yen Chng M;Engleman E
通讯作者：
Engleman E
影响因子：
16.2
作者：
Brooks-Worrell, Barbara M.;Boyko, Edward J.;Palmer, Jerry P.
通讯作者：
Palmer, Jerry P.
影响因子：
3.8
作者：
Liang, Huiying;Cheng, Ying;Zhou, Zhiguang
通讯作者：
Zhou, Zhiguang