Increased Urinary Albumin Excretion, Endothelial Dysfunction, and Chronic Low-Grade Inflammation in Type 2 Diabetes
Open accessAbstract
In 328 type 2 diabetic patients followed for 9.0 years (mean), we investigated whether endothelial dysfunction and chronic inflammation (estimated from plasma markers) can explain the association between (micro)albuminuria and mortality. Of the patients, 113 died. Mortality was increased in patients with baseline microalbuminuria or macroalbuminuria (odds ratios as compared with normoalbuminuria, 1.78 [P < 0.05] and 2.86 [P < 0.01]) and in patients with soluble vascular cell adhesion molecule 1 in the third tertile and C-reactive protein in the second and third tertiles (odds ratios as compared with the first tertile, 2.05 [ P < 0.01], and 1.80 [P < 0.05] and 2.92 [ P < 0.01]). These associations were mutually independent. The mean yearly change in urinary albumin excretion was 9.4%; in von Willebrand factor, 8.1%; in tissue-type plasminogen activator, 2.8%; in soluble vascular cell adhesion molecule 1, 5.2%; in soluble E-selectin, −2.3%; in C-reactive protein, 3.8%; and in fibrinogen, 2.3%. The longitudinal development of urinary albumin excretion was significantly and independently determined by baseline levels of and the longitudinal development of BMI, systolic blood pressure, serum creatinine, glycated hemoglobin and plasma von Willebrand factor (baseline only), soluble E-selectin (baseline only), tissue-type plasminogen activator, C-reactive protein, and fibrinogen. The longitudinal developments of markers of endothelial function and inflammation were interrelated. In type 2 diabetes, increased urinary albumin excretion, endothelial dysfunction, and chronic inflammation are interrelated processes that develop in parallel, progress with time, and are strongly and independently associated with risk of death.
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Diabetic nephropathy is associated with a state of low-grade inflammation in the microvasculature of the kidney's glomeruli.
“Diabetic nephropathy is associated with a state of low-grade inflammation in the microvasculature of the kidney's glomeruli [99, 100].”
From Anti-Inflammatory Effects of GLP-1-Based Therapies beyond Glucose Control (2016) · cites this paper as [100]
The Introduction (page not available) associates microalbuminuria in diabetic patients with low-grade inflammation, and the Discussion (page not available) links inflammatory markers to increasing urinary albumin excretion in type 2 diabetes. The paper does not establish that the inflammation is located in the glomerular microvasculature; its findings concern circulating markers and albumin excretion. (LLM, conf=0.84)
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- Authors
- Stehouwer, C. D. A., Gall, M.-A., Twisk, J. W. R., Knudsen, E., Emeis, J. J., & Parving, H.-H.
- Affiliations
- Amsterdam Cardiovascular Sciences (NL)
- Steno Diabetes Center, Gentofte, Denmark
- Amsterdam Public Health (NL)
- Netherlands Organisation for Applied Scientific Research (NL)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2002-04-01
- Volume
- 51
- Issue
- 4
- Pages
- 1157-1165
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2171285048
- Cited by
- 652
- References
- 28
- Citations by year
- 2026: 9 · 2025: 5 · 2024: 12 · 2023: 10 · 2022: 15 · 2021: 13 · 2020: 25 · 2019: 16 · 2018: 25 · 2017: 20 · 2016: 24 · 2015: 28 · 2014: 27 · 2013: 37 · 2012: 30
- FWCI
- 32.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- TNO Repository (submittedVersion)
- Funders
- Nierstichting
- Topics
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- type 2 diabetes, urinary albumin excretion, microalbuminuria, macroalbuminuria, endothelial dysfunction, low-grade inflammation, mortality, soluble vascular cell adhesion molecule-1, C-reactive protein, von Willebrand factor, tissue plasminogen activator, soluble E-selectin, fibrinogen, cardiovascular risk
- MeSH terms
- Albuminuria, Blood Pressure, C-Reactive Protein, Cholesterol, Creatinine, Diabetes Mellitus, Type 2, Endothelium, Vascular, Female, Glycated Hemoglobin, Humans, Inflammation, Cholesterol, HDL, Male, Middle Aged, Tissue Plasminogen Activator, Predictive Value of Tests, Reference Values, Risk Factors, Smoking, von Willebrand Factor, Biomarkers, Odds Ratio, Vascular Cell Adhesion Molecule-1, E-Selectin
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