Department of Neurology, University of Michigan, Ann Arbor, Michigan.
NeuroNetwork for Emerging Therapies, University of Michigan, Ann Arbor, Michigan.
Ann Clin Transl Neurol. 2021 Jun;8(6):1292-1307. doi: 10.1002/acn3.51367. Epub 2021 May 6.
The global rise in type 2 diabetes is associated with a concomitant increase in diabetic complications. Diabetic polyneuropathy is the most frequent type 2 diabetes complication and is associated with poor outcomes. The metabolic syndrome has emerged as a major risk factor for diabetic polyneuropathy; however, the metabolites associated with the metabolic syndrome that correlate with diabetic polyneuropathy are unknown.
We conducted a global metabolomics analysis on plasma samples from a subcohort of participants from the Danish arm of Anglo-Danish-Dutch study of Intensive Treatment of Diabetes in Primary Care (ADDITION-Denmark) with and without diabetic polyneuropathy versus lean control participants.
Compared to lean controls, type 2 diabetes participants had significantly higher HbA1c (p = 0.0028), BMI (p = 0.0004), and waist circumference (p = 0.0001), but lower total cholesterol (p = 0.0001). Out of 991 total metabolites, we identified 15 plasma metabolites that differed in type 2 diabetes participants by diabetic polyneuropathy status, including metabolites belonging to energy, lipid, and xenobiotic pathways, among others. Additionally, these metabolites correlated with alterations in plasma lipid metabolites in type 2 diabetes participants based on neuropathy status. Further evaluating all plasma lipid metabolites identified a shift in abundance, chain length, and saturation of free fatty acids in type 2 diabetes participants. Importantly, the presence of diabetic polyneuropathy impacted the abundance of plasma complex lipids, including acylcarnitines and sphingolipids.
Our explorative study suggests that diabetic polyneuropathy in type 2 diabetes is associated with novel alterations in plasma metabolites related to lipid metabolism.
2 型糖尿病的全球发病率上升与糖尿病并发症的相应增加有关。糖尿病多发性神经病是 2 型糖尿病最常见的并发症，与不良结局相关。代谢综合征已成为糖尿病多发性神经病的主要危险因素；然而，与糖尿病多发性神经病相关的代谢综合征相关代谢物尚不清楚。
我们对来自丹麦 Anglo-Danish-Dutch 研究中初级保健强化糖尿病治疗（ADDITION-Denmark）子队列的参与者的血浆样本进行了全球代谢组学分析，该子队列包括有和没有糖尿病多发性神经病的 2 型糖尿病患者与瘦对照参与者。
与瘦对照相比，2 型糖尿病患者的 HbA1c（p=0.0028）、BMI（p=0.0004）和腰围（p=0.0001）显著更高，但总胆固醇（p=0.0001）更低。在 991 种总代谢物中，我们确定了 15 种在 2 型糖尿病患者中根据糖尿病多发性神经病状态而有所不同的血浆代谢物，包括属于能量、脂质和异生物质途径的代谢物等。此外，这些代谢物与根据神经病变状态在 2 型糖尿病患者中血浆脂质代谢物的改变相关。进一步评估所有血浆脂质代谢物发现，2 型糖尿病患者的游离脂肪酸丰度、链长和饱和度发生了变化。重要的是，糖尿病多发性神经病的存在影响了包括酰基肉碱和神经酰胺在内的血浆复合脂质的丰度。
我们的探索性研究表明，2 型糖尿病中的糖尿病多发性神经病与与脂质代谢相关的血浆代谢物的新的改变有关。
