Cardiovascular disease diabetes mellitus type 2
Conditions
Interventions
None listed
Sponsors
Universitair Medisch Centrum Groningen
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: • Men and women, age >= 18 years. • Written informed consent. • eGFR above 60 ml/min/1,73m2. • Using renin-angiotensin system (RAS) inhibitors. • Fulfils ADA criteria for diabetes. o Fasting plasma glucose >= 7.0 mmol/l. o Random plasma glucose >= 11.1 mmol/l. o HbA1C >= 6,5%.
Exclusion criteria
Exclusion criteria: • Patients who are mentally incompetent and cannot sign a Patient Informed Consent or are unwilling to sign a Patient Informed Consent. • Women who are currently pregnant, planning to become pregnant, breastfeeding women, or women with childbearing potential not using appropriate contraceptive measures. This will be discussed during the intake conversation and women who answer yes on any of the previous questions will be excluded. • Other causes for macroalbuminuria than nephropathy. • Systemic auto-immune disease or vasculitis. • Inflammation of unknown origin or sepsis. • Patients who use immunosuppressives or anti-inflammatory drugs that could interfere with the study results. • Recent (
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. The 99mTC-HSA clearance and urine albumin-creatinine ratio (uACR) as proxy for systemic vascular albumin leakage and albuminuria: This will be calculated via the transcapillary escape rate of 99mTC-HSA (TERalb). TERalb will be measured by the fractional disappearance rate of 99mTC-HSA from the total intravascular compartment in 1 hour after intravenous injection. Albuminuria will be defined as the amount of albumin found in the urine and will be calculated via the uACR. | — |
Secondary
| Measure | Time frame |
|---|---|
| 2. Arterial [18F]-FDG uptake as proxy for arterial inflammation. Arterial inflammation will be quantified as the FDG uptake maximal standardized uptake value (SUVmax). SUVmax will be corrected for the prescan glucose level. A target-to-background ratio (TBR) will be calculated by dividing the SUVmax of the arteries by the SUVmean of the caval veins (bloodpool). TBRs will be calculated for four individual segments (carotid arteries, ascending aorta and aortic arch, descending and abdominal aorta, and iliac and femoral arteries) and averaged for the total aortic tree (meanTBR). 3. Measuring the endothelial glycocalyx as proxy for systemic vascular damage. The perfused boundary region (PBR), a marker of the glycocalyx barrier function, will be measured non-invasively in sublingual microvessels with a diameter of 5-25*µm using a Sidestream Dark Field camera (GlycoCheck BV, Maastricht, The Netherlands). Increased PBR indicates reduced glycocalyx thickness. 4. The amount of heparanase, heperan sulfate (HS) and metalloproteinase (MMP) 2 and 9 as proxy for endothelial glycocalyx damage: The amount of heparanase will be measured via the human heparanase ELISA kit. Plasma will be used and the amount will be noted as pg/ml. HS will be measured via the human HS ELISA kit and the amount of HS will be noted as pg/ml. The amount of MMP 2 and 9 will be tested via a urinary activity assay and will be noted as mg/mmol creatinine. HS, MMP 2 and 9 will be measured by a single urinary morning void. 5. Brachial arterial blood pressure, central arterial blood pressure and carotid to femoral pulse wave velocity (PWV) will be measured as proxy for arterial stiffness. The PWV will be calculated by dividing travelled distance by transit time (PWV = distance [meters]/transit time [seconds]). 6. Nailfold capillaroscopy will be performed as a method to examine a patient*s microcirculation and assess pathological changes. Nailfold capillary images will be collected wit | — |
Countries
Netherlands
Outcome results
None listed