Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Diabetes Care. 2021 Feb;44(2):416-424. doi: 10.2337/dc20-1463. Epub 2020 Dec 10.
Islet autoimmunity is associated with diabetes incidence. We investigated whether there was an interaction between dietary fish intake or plasma phospholipid n-3 polyunsaturated fatty acid (PUFA) concentration with the 65-kDa isoform of GAD (GAD65) antibody positivity on the risk of developing adult-onset diabetes.
We used prospective data on 11,247 incident cases of adult-onset diabetes and 14,288 noncases from the EPIC-InterAct case-cohort study conducted in eight European countries. Baseline plasma samples were analyzed for GAD65 antibodies and phospholipid n-3 PUFAs. Adjusted hazard ratios (HRs) for incident diabetes in relation to GAD65 antibody status and tertiles of plasma phospholipid n-3 PUFA or fish intake were estimated using Prentice-weighted Cox regression. Additive (proportion attributable to interaction [AP]) and multiplicative interactions between GAD65 antibody positivity (≥65 units/mL) and low fish/n-3 PUFA were assessed.
The hazard of diabetes in antibody-positive individuals with low intake of total and fatty fish, respectively, was significantly elevated (HR 2.52 [95% CI 1.76-3.63] and 2.48 [1.79-3.45]) compared with people who were GAD65 antibody negative and had high fish intake, with evidence of additive (AP 0.44 [95% CI 0.16-0.72] and 0.48 [0.24-0.72]) and multiplicative ( = 0.0465 and 0.0103) interactions. Individuals with high GAD65 antibody levels (≥167.5 units/mL) and low total plasma phospholipid n-3 PUFAs had a more than fourfold higher hazard of diabetes (HR 4.26 [2.70-6.72]) and an AP of 0.46 (0.12-0.80) compared with antibody-negative individuals with high n-3 PUFAs.
High fish intake or relative plasma phospholipid n-3 PUFA concentrations may partially counteract the increased diabetes risk conferred by GAD65 antibody positivity.
胰岛自身免疫与糖尿病的发病有关。我们研究了饮食中鱼类摄入或血浆磷脂 n-3 多不饱和脂肪酸（PUFA）浓度与 65kDa 同工型谷氨酸脱羧酶（GAD65）抗体阳性是否与成人发病型糖尿病的发病风险存在交互作用。
我们使用了来自 EPIC-InterAct 病例对照研究的前瞻性数据，该研究在八个欧洲国家进行，共纳入了 11247 例成人发病型糖尿病新发病例和 14288 例非病例。基线时检测血浆 GAD65 抗体和磷脂 n-3PUFA。使用 Prentice 加权 Cox 回归估计 GAD65 抗体状态与血浆磷脂 n-3PUFA 三分位或鱼类摄入相关的新发糖尿病的调整后的危险比（HR）。评估 GAD65 抗体阳性（≥65 单位/ml）和低鱼/n-3PUFA 之间的相加（交互作用归因比例 [AP]）和相乘交互作用。
与 GAD65 抗体阴性且鱼类摄入量高的人相比，抗体阳性且总鱼和脂肪鱼摄入量低的人患糖尿病的风险显著升高（HR 分别为 2.52[95%CI 1.76-3.63]和 2.48[1.79-3.45]），存在相加（AP 分别为 0.44[95%CI 0.16-0.72]和 0.48[0.24-0.72]）和相乘（ = 0.0465 和 0.0103）交互作用。高 GAD65 抗体水平（≥167.5 单位/ml）和低总血浆磷脂 n-3PUFA 的个体患糖尿病的风险高出四倍以上（HR 4.26[2.70-6.72]），AP 为 0.46（0.12-0.80），与高 n-3PUFA 的抗体阴性个体相比。
高鱼类摄入或相对血浆磷脂 n-3PUFA 浓度可能部分抵消 GAD65 抗体阳性所带来的糖尿病风险增加。
