OBJECTIVE To investigate the longitudinal development of neurofilament light chain (NfL) levels in type 2 diabetes with and without diabetic polyneuropathy (+/−DPN) and to explore the predictive potential of NfL as a biomarker for DPN. RESEARCH DESIGN AND METHODS We performed retrospective longitudinal case-control analysis of data from 178 participants of the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care-Denmark (ADDITION-Denmark) cohort of people with screen-detected type 2 diabetes. Biobank samples acquired at the ADDITION-Denmark 5- and 10-year follow-ups were analyzed for serum NfL (s-NfL) using single-molecule array, and the results were compared with established reference material to obtain NfL z-scores. DPN was diagnosed according to Toronto criteria for confirmed DPN at the 10-year follow-up. RESULTS s-NfL increased over time in +DPN (N = 39) and −DPN participants (N = 139) at levels above normal age-induced s-NfL increase. Longitudinal s-NfL change was greater in +DPN than in −DPN participants (17.4% [95% CI 4.3; 32.2] or 0.31 SD [95% CI 0.03; 0.60] higher s-NfL or NfL z-score increase in +DPN compared with −DPN). s-NfL at the 5-year follow-up was positively associated with nerve conduction studies at the 10-year follow-up (P = 0.02 to <0.001), but not with DPN risk. Areas under the curve (AUCs) for s-NfL were not inferior to AUCs for the Michigan Neuropathy Screening Instrument questionnaire score or vibration detection thresholds. Higher yearly s-NfL increase was associated with higher DPN risk (odds ratio 1.36 [95% CI 1.08; 1.71] per 1 ng/L/year). CONCLUSIONS Our findings suggest that preceding s-NfL trajectories differ slightly between those with and without DPN and imply a possible biomarker value of s-NfL trajectories in DPN.

中文翻译：

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2 型糖尿病和早期糖尿病多发性神经病血清神经丝轻链的纵向变化：ADDITION-Denmark

目的 研究伴或不伴糖尿病性多发性神经病 (+/-DPN) 的 2 型糖尿病中神经丝轻链 (NfL) 水平的纵向发展，并探讨 NfL 作为 DPN 生物标志物的预测潜力。研究设计和方法 我们对丹麦初级保健筛查检测出的糖尿病患者（ADDITION-Denmark）筛查人群队列的英国-丹麦-荷兰强化治疗研究的 178 名参与者的数据进行了回顾性纵向病例对照分析。 - 检测出 2 型糖尿病。使用单分子阵列对在 ADDITION-Denmark 5 年和 10 年随访中获得的生物库样本进行血清 NfL (s-NfL) 分析，并将结果与​​已建立的参考材料进行比较以获得 NfL z 分数。 DPN 根据 10 年随访时确诊 DPN 的多伦多标准诊断。结果 +DPN (N = 39) 和 -DPN 参与者 (N = 139) 的 s-NfL 随着时间的推移而增加，其水平高于正常年龄引起的 s-NfL 增加。 +DPN 参与者的纵向 s-NfL 变化大于 -DPN 参与者（+DPN 中 s-NfL 或 NfL z 得分增加 17.4% [95% CI 4.3; 32.2] 或 0.31 SD [95% CI 0.03; 0.60]与−DPN 相比）。 5 年随访时的 s-NfL 与 10 年随访时的神经传导研究呈正相关（P = 0.02 至 <0.001），但与 DPN 风险无关。 s-NfL 的曲线下面积 (AUC) 不低于密歇根神经病筛查仪器问卷评分或振动检测阈值的 AUC。每年 s-NfL 增加较高与较高的 DPN 风险相关（比值比为 1.36 [95% CI 1.08; 1.71] 每 1 ng/L/年）。结论 我们的研究结果表明，有和没有 DPN 的人之前的 s-NfL 轨迹略有不同，这意味着 DPN 中 s-NfL 轨迹可能具有生物标志物价值。