Biomarkers of inflammation and endothelial dysfunction as predictors of pulse pressure and incident hypertension in type 1 diabetes: a 20 year life-course study in an inception cohort

Aims/hypothesis Vascular inflammation and endothelial dysfunction are thought to contribute to arterial stiffening and hypertension. This study aims to test this hypothesis with longitudinal data in the context of type 1 diabetes. Methods We investigated, in an inception cohort of 277 individuals wi...

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Bibliographic Details
Published in:Diabetologia 2018-01, Vol.61 (1), p.231-241
Main Authors: Ferreira, Isabel, Hovind, Peter, Schalkwijk, Casper G., Parving, Hans-Henrik, Stehouwer, Coen D. A., Rossing, Peter
Format: Article
Language:English
Subjects:
Biomarkers
Biomarkers - blood
Blood pressure
Blood Pressure - physiology
C-reactive protein
C-Reactive Protein - metabolism
Cholesterol
Creatinine
Data processing
Diabetes
Diabetes mellitus
Diabetes Mellitus, Type 1 - blood
E-selectin
E-Selectin - blood
Human Physiology
Humans
Hypertension
Hypertension - blood
Hypertension - metabolism
Hypotheses
Inflammation
Inflammation - blood
Insulin
Intercellular adhesion molecule 1
Intercellular Adhesion Molecule-1 - blood
Internal Medicine
Longitudinal studies
Mathematical models
Medicine
Medicine & Public Health
Metabolic Diseases
Risk factors
Smoking
Vascular Stiffness - drug effects
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Summary:Aims/hypothesis Vascular inflammation and endothelial dysfunction are thought to contribute to arterial stiffening and hypertension. This study aims to test this hypothesis with longitudinal data in the context of type 1 diabetes. Methods We investigated, in an inception cohort of 277 individuals with type 1 diabetes, the course, tracking and temporal inter-relationships of BP, specifically pulse pressure (a marker of arterial stiffening) and hypertension, and the following biomarkers of systemic and vascular inflammation/endothelial dysfunction: C-reactive protein (CRP), soluble intracellular adhesion molecule-1 (sICAM-1), soluble vascular cellular adhesion molecule-1 (sVCAM-1) and soluble E-selectin (sE-selectin). These biomarkers and other risk factors were measured at baseline and repeatedly up to 20 years after the onset of type 1 diabetes. Data were analysed with generalised estimating equations including adjustments for age, sex, smoking status, BMI, HbA 1c , serum creatinine, total cholesterol, urinary AER, insulin treatment dose and mean arterial pressure. Results Increases were noted in all biomarkers except sE-selectin, which decreased over time. Levels differed from baseline at 2–4 years and preceded the increase in pulse pressure, which occurred at 8–10 years after the onset of type 1 diabetes. Higher levels of sICAM-1 and sVCAM-1, but not CRP or sE-selectin, at baseline and throughout the 20 year follow-up, were significantly associated with higher (changes in) pulse pressure at subsequent time points. Higher levels of sVCAM-1 at baseline and during follow-up were also significantly associated with the prevalence (OR 3.60 [95% CI 1.36, 9.53] and OR 2.28 [1.03, 5.25], respectively) and incidence (OR 2.89 [1.08, 7.75] and OR 3.06 [1.01, 9.26], respectively) of hypertension. We also investigated the longitudinal associations between BP or hypertension as determinants of subsequent (changes in) levels of CRP, sICAM-1, sVCAM-1 and sE-selectin, but did not find evidence to support a reverse causality hypothesis. Conclusions/interpretation These findings support the involvement of vascular endothelial dysfunction and inflammation in the development of premature arterial stiffening and hypertension in type 1 diabetes.
ISSN:0012-186X
1432-0428
DOI:10.1007/s00125-017-4470-5