Endothelial Glycocalyx Damage Coincides With Microalbuminuria in Type 1 Diabetes
- Max Nieuwdorp1,
- Hans L. Mooij1,
- Jojanneke Kroon1,
- Bektas Atasever2,
- Jos A.E. Spaan3,
- Can Ince2,
- Frits Holleman4,
- Michaela Diamant5,
- Robert J. Heine5,
- Joost B.L. Hoekstra4,
- John J.P. Kastelein1,
- Erik S.G. Stroes1 and
- Hans Vink3
- 1Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands
- 2Department of Clinical Physiology, Academic Medical Center, Amsterdam, the Netherlands
- 3Department of Medical Physics, Academic Medical Center, Amsterdam, the Netherlands
- 4Department of Internal Medicine, Academic Medical Center, Amsterdam, the Netherlands
- 5Department of Endocrinology, Diabetes Center, VU University Medical Center, Amsterdam, the Netherlands
- Address correspondence and reprint requests to Erik Stroes, MD, PhD, Department of Vascular Medicine, Room F4.275, Academic Medical Center University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, Netherlands. E-mail: e.s.stroes{at}amc.uva.nl
Abstract
Chronic hyperglycemia underlies microvascular complications in patients with type 1 diabetes. The mechanisms leading to these vascular complications are not fully understood. Recently, we observed that acute hyperglycemia results in endothelial glycocalyx damage. To establish whether glycocalyx is associated with microvascular damage, we performed glycocalyx perturbation volume measurements in type 1 diabetic patients with microalbuminuria (DM1-MA group; n = 7), without microalbuminuria (DM1-NA group; n = 7), and in age-matched control subjects (CON; n = 7). Systemic glycocalyx volume was determined comparing intravascular distribution volume of a glycocalyx-permeable tracer (dextran 40) to that of a glycocalyx-impermeable tracer (labeled erythrocytes). Sublingual capillaries were visualized using orthogonal polarization spectral microscopy to estimate microvascular glycocalyx. Patients and control subjects were matched according to age and BMI. Glycocalyx volume decreased in a stepwise fashion from CON, DM1-NA, and finally DM1-MA subjects (1.5 ± 0.1, 0.8 ± 0.4, and 0.2 ± 0.1 l, respectively, P < 0.05). Microvascular glycocalyx in sublingual capillaries was also decreased in type 1 diabetes versus the control group (0.5 ± 0.1 vs. 0.9 ± 0.1 μm, P < 0.05). Plasma hyaluronan, a principal glycocalyx constituent, and hyaluronidase were increased in type 1 diabetes. In conclusion, type 1 diabetic patients are characterized by endothelial glycocalyx damage, the severity of which is increased in presence of microalbuminuria.
Footnotes
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Accepted January 9, 2006.
- Received December 14, 2005.
- DIABETES
