The significance of an impaired psychosocial stress response on therelease of reactive metabolites as a possible cause of diabeticcomplications

心理社会压力反应受损对反应性代谢物释放的重要性作为糖尿病并发症的可能原因

• 批准号: 396345954
• 负责人: Professorin Dr. Beate Wild
• 金额: --
• 依托单位: Klinik für Allgemeine Innere Medizin und Psychosomatik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/396345954?language=en
• 关键词: significance; impaired; psychosocial; stress; response

Previous research showed that in diabetes mellitus reactive metabolites such as methylglyoxal are elevated and accumulate. This can lead to long-term diabetic complications such as retinopathy, nephropathy, albminuria and/or neuropathy. There are also studies indicating that psychosocial stress leads to the accumulation of reactive metabolites. The goal of this proposed project is to examine and understand the association between psychological stress and the release of reactive metabolites with long-term complications in patients with diabetes mellitus. Accordingly, an experimental design will be undertaken with n=120 participants: 40 diabetic patients with complications, 40 without complications, and 40 healthy controls. Every participant will receive a thorough psychosomatic evaluation in the form of a questionnaire and the Structured Clinical Interview for DSM-IV (SCID). Stress levels and everyday stressors of the participants will be assessed using the Perceived Stress Scale (PSS), the Trier Inventory for the Assessment of Chronic Stress (TICS), and a Daily Stress Inventory (Alltagsbelastungsfragebogen, ABF). An experimental stress-provocation will be done in the form of the Trier Social Stress Tests (TSST). Both before and after the TSST, blood and saliva samples will be taken. The blood tests will be used to determine glucose, adrenalin, noradrenalin, and ACTH; as well as methylglyoxal and glyoxal and their glycation endproducts, and the total antioxidative capacity. In addition, the saliva tests will be used to measure cortisol activity.A prevalent hypothesis of this study is that the basal level of reactive metabolites is positively correlated with indicators of chronic stress (such as cortisol, heart rate, and subjective measurements). In addition, it is assumed that after acute stress episodes the dynamic change of reactive metabolites will be disturbed in a subgroup of diabetic patients. The central hypothesis is the assumption that the stress-induced dysbalance between production and decomposition of reactive metabolites will be more accentuated in patients with diabetic complications compared to those without complications. According to our understanding, this proposed project is the first three-group comparison design with repeated measurements, devised to examine the relationship between chronic stress, acute stress, methylglyoxal- and glyoxal- level (and changes), and diabetic complications. A close cooperation with the SFB 1118 'Reaktive Metabolite als Ursache diabetischer Folgeschäden' ('Reactive Metabolites as a Cause of Consequent Diabetic Complications') will be undertaken. In the context of a wider frame of reference, this study will serve as the basis for possible identification of the various stress-reactive patient groups that could benefit from stress-reduction therapy.

先前的研究表明，在糖尿病中，反应性代谢产物，如甲基乙二醛，会升高并积聚。这可能会导致长期的糖尿病并发症，如视网膜病变、肾病、白蛋白尿和/或神经病变。也有研究表明，心理社会压力会导致反应性代谢物的积累。这项拟议项目的目标是检查和了解糖尿病患者心理应激和反应性代谢产物的释放与长期并发症之间的联系。因此，将进行一项实验设计，n=120名参与者：40名有并发症的糖尿病患者，40名无并发症的糖尿病患者，以及40名健康对照。每个参与者都将接受以问卷和DSM-IV结构化临床访谈(SCID)的形式的全面心身评估。参与者的压力水平和日常应激源将使用感知压力量表(PSS)、Trier慢性压力评估问卷(TICS)和每日压力问卷(Alltag sbelastungsfragebogen，ABF)进行评估。实验压力激发将以Trier社会压力测试(TSST)的形式进行。在TSST之前和之后，都将采集血液和唾液样本。血液测试将用于测定葡萄糖、肾上腺素、去甲肾上腺素和ACTH；以及甲基乙二醛和乙二醛及其糖基化终产物，以及总抗氧化能力。此外，唾液测试将被用来测量皮质醇活性。这项研究的一个普遍假设是，反应性代谢物的基础水平与慢性应激指标(如皮质醇、心率和主观测量)呈正相关。此外，假设在急性应激发作后，糖尿病患者亚组的反应性代谢物的动态变化将受到干扰。中心假设是，与没有并发症的患者相比，有并发症的糖尿病患者应激诱导的反应代谢产物的产生和分解之间的失衡将更加突出。据我们了解，该项目是第一个重复测量的三组对照设计，旨在研究慢性应激、急性应激、甲基乙二醛和乙二醛水平(及其变化)与糖尿病并发症的关系。将与SFB 1118“反应性代谢物ALS Ursache糖尿病患者Folgeschäden”(“导致糖尿病并发症的反应性代谢物”)进行密切合作。在更广泛的参考框架下，这项研究将作为可能识别可能从减压治疗中受益的各种应激反应患者群体的基础。