Endothelial dysfunction markers syndecan-1 and thrombomodulin are associated with higher albuminuria levels in type 2 diabetes with no history of clinical cardiovascular disease.

Individuals with type 2 diabetes and increased albuminuria, a well-established marker of microvascular complications, are at a higher risk for cardiovascular disease (CVD) and premature mortality. Therefore, a better understanding of the underlying pathophysiology is needed to improve risk stratification and tailor prevention and intervention. We conducted a cross-sectional study including 463 individuals with type 2 diabetes, various degrees of albuminuria and without CVD. We analysed the association between albuminuria and markers of endothelial function (thrombomodulin and syndecan-1), thrombin generation (thrombin-antithrombin complex, prothrombin fragment 1 + 2), fibrinogen, platelet function (activation using soluble plasma selectin and aggregation using Multiplate® Analyzer) using regression models. In the study cohort 33 % were women, the mean ± SD age was 65 ± 9 years, and median [IQR] diabetes duration was 15 [9-20] years. In total, 344 (74 %) individuals had normal albuminuria, 87 (19 %) moderately- and 32 (7 %) severely increased albuminuria levels. Higher markers of endothelial function and fibrinogen were independently associated with higher albuminuria levels (p < 0.01). No association between albuminuria and markers of thrombin generation and platelet was demonstrated. We demonstrated an independent association between albuminuria and markers of endothelial function and fibrinogen in individuals with type 2 diabetes and no history of CVD.

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Declaration of competing interest LFFD, CGP, VRC, OBP, MFM, TWH and AMH report no conflicts of interest. NT is a full-time employee of Novo Nordisk Inc. PR has received grants for research to Steno Diabetes Center Copenhagen from Astra Zeneca, Bayer and Novo Nordisk, and has received honoraria to Steno Diabetes Center Copenhagen from Abbott, AstraZeneca, Bayer, Novo Nordisk, Boehringer Ingelheim, Eli Lilly, Sanofi and Gilead.