Ethnic differences in urinary monocyte chemoattractant protein-1 and heparanase-1 levels in individuals with type 2 diabetes: the HELIUS study

INTRODUCTION: We aimed to investigate ethnic differences in two urinary inflammatory markers in participants with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: We included 55 Dutch, 127 South-Asian Surinamese, 92 African Surinamese, 62 Ghanaian, 74 Turkish and 88 Moroccan origin participants with T2DM from the HEalthy LIfe in an Urban Setting study. Using linear regression analyses, we investigated differences in urinary monocyte chemoattractant protein-1 (MCP-1) and heparanase-1 (HPSE-1) levels across ethnic minorities compared with Dutch. Associations between the urinary markers and albuminuria (albumin:creatinine ratio (ACR)) was investigated per ethnicity. RESULTS: Urinary MCP-1 levels were higher in the Moroccan participants (0.15 log ng/mmol, 95% CI 0.05 to 0.26) compared with Dutch after multiple adjustments. Urinary HPSE-1 levels were lower in the African Surinamese and Ghanaian participants compared with the Dutch, with a difference of -0.16 log mU/mmol (95% CI -0.29 to -0.02) in African Surinamese and -0.16 log mU/mmol (95% CI -0.31 to -0.00) in Ghanaian after multiple adjustments. In all ethnic groups except the Dutch and Ghanaian participants, MCP-1 was associated with ACR. This association remained strongest after multiple adjustment in South-Asian and African Surinamese participants, with an increase in log ACR of 1.03% (95% CI 0.58 to 1.47) and 1.23% (95% CI 0.52 to 1.94) if log MCP-1 increased 1%. Only in the Dutch participants, an association between HPSE-1 and ACR was found, with increase in log ACR of 0.40% (95% CI 0.04 to 0.76) if log HPSE-1 increased 1%. CONCLUSIONS: We found ethnic differences in urinary MCP-1 and HPSE-1 levels, in a multi-ethnic cohort of participants with T2DM. In addition, we found ethnic differences in the association of MCP-1 and HPSE-1 levels with albuminuria. These findings suggest differences in renal inflammation across ethnic groups

Heparan sulfate mimetic fucoidan restores the endothelial glycocalyx and protects against dysfunction induced by serum of COVID-19 patients in the intensive care unit

Accumulating evidence proves that endothelial dysfunction is involved in COVID-19 progression. We previously demonstrated that the endothelial surface glycocalyx has a critical role in maintenance of vascular integrity. Here we hypothesised that serum factors of severe COVID-19 patients affect the glycocalyx and result into endothelial dysfunction. We included blood samples of 32 COVID-19 hospitalised patients at the Leiden University Medical Center: of which 26 from intensive care unit (ICU), 6 non-ICU, 18 convalescent samples 6 weeks after hospital discharge, and of 12 age-matched healthy donors (control) during the first period of the outbreak. First, we determined endothelial (angiopoietin 2, ANG2) and glycocalyx degradation (soluble thrombomodulin, sTM and syndecan-1, sSDC1) markers in plasma. In plasma of COVID-19 patients, circulating ANG2 and sTM were elevated in patients on the ICU. Primary lung microvascular endothelial cells (HPMEC) and human glomerular microvascular ECs (GEnCs) cultures in the presence of these sera led to EC glycocalyx degradation, barrier disruption, inflammation and increased coagulation on the endothelial surface, significantly different compared to healthy control and non-ICU patient sera. These changes all could be restored in the presence of fucoidan. In conclusion, our data highlight the link between endothelial glycocalyx degradation, barrier failure and induction of a procoagulant surface in COVID-19 patients on ICU which could be targeted earlier in disease by the presence of heparan sulfate (HS) mimetics

Ethnic differences in urinary monocyte chemoattractant protein-1 and heparanase-1 levels in individuals with type 2 diabetes: the HELIUS study

INTRODUCTION: We aimed to investigate ethnic differences in two urinary inflammatory markers in participants with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: We included 55 Dutch, 127 South-Asian Surinamese, 92 African Surinamese, 62 Ghanaian, 74 Turkish and 88 Moroccan origin participants with T2DM from the HEalthy LIfe in an Urban Setting study. Using linear regression analyses, we investigated differences in urinary monocyte chemoattractant protein-1 (MCP-1) and heparanase-1 (HPSE-1) levels across ethnic minorities compared with Dutch. Associations between the urinary markers and albuminuria (albumin:creatinine ratio (ACR)) was investigated per ethnicity. RESULTS: Urinary MCP-1 levels were higher in the Moroccan participants (0.15 log ng/mmol, 95% CI 0.05 to 0.26) compared with Dutch after multiple adjustments. Urinary HPSE-1 levels were lower in the African Surinamese and Ghanaian participants compared with the Dutch, with a difference of -0.16 log mU/mmol (95% CI -0.29 to -0.02) in African Surinamese and -0.16 log mU/mmol (95% CI -0.31 to -0.00) in Ghanaian after multiple adjustments. In all ethnic groups except the Dutch and Ghanaian participants, MCP-1 was associated with ACR. This association remained strongest after multiple adjustment in South-Asian and African Surinamese participants, with an increase in log ACR of 1.03% (95% CI 0.58 to 1.47) and 1.23% (95% CI 0.52 to 1.94) if log MCP-1 increased 1%. Only in the Dutch participants, an association between HPSE-1 and ACR was found, with increase in log ACR of 0.40% (95% CI 0.04 to 0.76) if log HPSE-1 increased 1%. CONCLUSIONS: We found ethnic differences in urinary MCP-1 and HPSE-1 levels, in a multi-ethnic cohort of participants with T2DM. In addition, we found ethnic differences in the association of MCP-1 and HPSE-1 levels with albuminuria. These findings suggest differences in renal inflammation across ethnic groups

Role of dietary interventions on microvascular health in South-Asian Surinamese people with type 2 diabetes in the Netherlands: A randomized controlled trial

Abstract Background/objectives We investigated whether dietary interventions, i.e. a fasting mimicking diet (FMD, Prolon®) or glycocalyx mimetic supplementation (EndocalyxTM) could stabilize microvascular function in Surinamese South-Asian patients with type 2 diabetes (SA-T2DM) in the Netherlands, a patient population more prone to develop vascular complications. Subjects/methods A randomized, placebo controlled, 3-arm intervention study was conducted in 56 SA-T2DM patients between 18 and 75 years old, for 3 consecutive months, with one additional follow up measurement 3 months after the last intervention. Sublingual microcirculation was assessed with SDF-imaging coupled to the GlycoCheckTM software, detecting red blood cell velocity, capillary density, static and dynamic perfused boundary region (PBR), and the overall microvascular health score (MVHS). Linear mixed models and interaction analysis were used to investigate the effects the interventions had on microvascular function. Results Despite a temporal improvement in BMI and HbA1c after FMD the major treatment effect on microvascular health was worsening for RBC-velocity independent PBRdynamic, especially at follow-up. Glycocalyx supplementation, however, reduced urinary MCP-1 presence and improved both PBRdynamic and MVHSdynamic, which persisted at follow-up. Conclusions We showed that despite temporal beneficial changes in BMI and HbA1c after FMD, this intervention is not able to preserve microvascular endothelial health in Dutch South-Asian patients with T2DM. In contrast, glycocalyx mimetics preserves the microvascular endothelial health and reduces the inflammatory cytokine MCP-1. Clinical study registration NCT03889236

Phosphatidylinositol metabolism of the renal proximal tubule S3 segment is disturbed in response to diabetes

Abstract Diabetes is a main risk factor for kidney disease, causing diabetic nephropathy in close to half of all patients with diabetes. Metabolism has recently been identified to be decisive in cell fate decisions and repair. Here we used mass spectrometry imaging (MSI) to identify tissue specific metabolic dysregulation, in order to better understand early diabetes-induced metabolic changes of renal cell types. In our experimental diabetes mouse model, early glomerular glycocalyx barrier loss and systemic metabolic changes were observed. In addition, MSI targeted at small molecule metabolites and glycero(phospho)lipids exposed distinct changes upon diabetes in downstream nephron segments. Interestingly, the outer stripe of the outer medullar proximal tubular segment (PT_S3) demonstrated the most distinct response compared to other segments. Furthermore, phosphatidylinositol lipid metabolism was altered specifically in PT_S3, with one of the phosphatidylinositol fatty acid tails being exchanged from longer unsaturated fatty acids to shorter, more saturated fatty acids. In acute kidney injury, the PT_S3 segment and its metabolism are already recognized as important factors in kidney repair processes. The current study exposes early diabetes-induced changes in membrane lipid composition in this PT_S3 segment as a hitherto unrecognized culprit in the early renal response to diabetes