Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital Tübingen, Tübingen, Germany.
Institute of Diabetes Research and Metabolic Diseases, Helmholtz Center Munich German Research Center for Environmental Health, Tübingen, Germany.
Cardiovasc Diabetol. 2024 Aug 22;23(1):306. doi: 10.1186/s12933-024-02402-z.
BACKGROUND: Metabolic clusters can stratify subgroups of individuals at risk for type 2 diabetes mellitus and related complications. Since obesity and insulin resistance are closely linked to alterations in hemostasis, we investigated the association between plasmatic coagulation and metabolic clusters including the impact on survival. METHODS: Utilizing data from the Ludwigshafen Risk and Cardiovascular Health (LURIC) study, we assigned 917 participants without diabetes to prediabetes clusters, using oGTT-derived glucose and insulin, high-density lipoprotein cholesterol, triglycerides, and anthropometric data. We performed a comprehensive analysis of plasmatic coagulation parameters and analyzed their associations with mortality using proportional hazards models. Mediation analysis was performed to assess the effect of coagulation factors on all-cause mortality in prediabetes clusters. RESULTS: Prediabetes clusters were assigned using published tools, and grouped into low-risk (clusters 1,2,4; n = 643) and high-risk (clusters 3,5,6; n = 274) clusters. Individuals in the high-risk clusters had a significantly increased risk of death (HR = 1.30; CI: 1.01 to 1.67) and showed significantly elevated levels of procoagulant factors (fibrinogen, FVII/VIII/IX), D-dimers, von-Willebrand factor, and PAI-1, compared to individuals in the low-risk clusters. In proportional hazards models adjusted for relevant confounders, elevated levels of fibrinogen, D-dimers, FVIII, and vWF were found to be associated with an increased risk of death. Multiple mediation analysis indicated that vWF significantly mediates the cluster-specific risk of death. CONCLUSIONS: High-risk prediabetes clusters are associated with prothrombotic changes in the coagulation system that likely contribute to the increased mortality in those individuals at cardiometabolic risk. The hypercoagulable state observed in the high-risk clusters indicates an increased risk for cardiovascular and thrombotic diseases that should be considered in future risk stratification and therapeutic strategies.
背景：代谢簇可将 2 型糖尿病及其相关并发症风险的个体亚组分层。由于肥胖和胰岛素抵抗与止血的改变密切相关，我们研究了包括对生存影响在内的血浆凝血与代谢簇之间的关系。
方法：利用来自路德维希港风险和心血管健康（LURIC）研究的数据，我们根据 OGTT 衍生的葡萄糖和胰岛素、高密度脂蛋白胆固醇、甘油三酯和人体测量数据，将 917 名无糖尿病的参与者分配到糖尿病前期簇中。我们对血浆凝血参数进行了全面分析，并使用比例风险模型分析了它们与死亡率的关系。进行中介分析以评估凝血因子对糖尿病前期簇中全因死亡率的影响。
结果：使用已发表的工具分配糖尿病前期簇，并将其分为低风险（簇 1、2、4；n=643）和高风险（簇 3、5、6；n=274）簇。高风险簇的个体死亡风险显著增加（HR=1.30；95%CI：1.01 至 1.67），并且与低风险簇相比，显示出显著升高的促凝因子（纤维蛋白原、FVII/VIII/IX）、D-二聚体、血管性血友病因子和 PAI-1 水平。在调整了相关混杂因素的比例风险模型中，发现纤维蛋白原、D-二聚体、VIII 和 vWF 水平升高与死亡风险增加相关。多重中介分析表明 vWF 显著介导簇特异性死亡风险。
结论：高风险糖尿病前期簇与凝血系统的促血栓形成变化相关，这可能导致处于代谢心血管风险的个体死亡风险增加。在高风险簇中观察到的高凝状态表明心血管和血栓性疾病的风险增加，这应在未来的风险分层和治疗策略中加以考虑。
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