Increased functional and structural skin capillary density in type 1 diabetes patients with vascular complications
© Tibiriçá et al; licensee BioMed Central Ltd. 2009
Received: 26 March 2009
Accepted: 3 December 2009
Published: 3 December 2009
The present study was designed to study skin capillary density and recruitment of the upper and lower extremities in patients with type 1 diabetes with vascular complications, when compared to patients without complications and healthy subjects. We used intravital video-microscopy to measure basal and maximal (during venous congestion) skin capillary densities as well as capillary recruitment using post-occlusive reactive hyperemia (PORH) in the dorsum of the fingers and toes.
Our results showed that besides microvascular vasodilation and loss of autoregulatory capacity, patients with type 1 diabetes with vascular complications present increased skin capillary density in both extremities.
Diabetes is one of the major risk factors for development of micro- and macrovascular disorders. Microangiopathy in type 1 diabetes is characterized by a generalized precapillary vasodilation and increased microvascular blood flow , resulting in capillary hypertension and endothelial dysfunction, which in turn lead to vascular complications . Using intravital videomicroscopy, we recently demonstrated that capillary recruitment is impaired in patients with type 1 diabetes who do not display clinical complications . The present study was designed to study skin capillary density and recruitment in patients with type 1 diabetes with vascular complications.
Baseline characteristics of study subjects.
(n = 47)
(n = 62)
Diabetes with complications
(n = 26)
25.1 ± 4.6
24.6 ± 10.4
34.8 ± 9.9*§
Male, n (%)
Smokers, n (%)
Body mass index, kg/m2
23.5 ± 4.2
22.8 ± 3.4
23.4 ± 2.8
Diabetes duration, years
10.2 ± 8.4
18.0 ± 8.0§
5.2 ± 0.3
9.9 ± 2.6*
10.6 ± 2.6*
(0.5 - 17.2)
(1.6 - 20.0)*
(13.4 - 1608.5)*§
Intravital video microscopy was carried out in the morning using a standardized and well-validated technique [4–7] in a temperature-controlled room (21-24°C). Subjects were seated and the skin of the dorsum of the middle phalanx of the left hand and proximal phalanx of the great toe was examined. Capillary density was defined as the total number of spontaneously perfused capillaries per mm2 of skin. Percentage capillary recruitment was assessed by post-occlusive reactive hyperemia (PORH) after stopping arterial blood flow to the forearm and hand or to the foot by inflating a sphygmomanometer cuff over 3 min to 200 mmHg. Ten minutes after PORH, maximization of skin capillaries was obtained with 2 minutes of venous occlusion inflating the cuff to 60 mmHg (upper limb) or 90 mmHg (lower limb).
Data were analyzed by SPSS 13.0 and the Student's t test, Mann-Whitney, Wilcoxon and X2 tests were used when indicated. p values < 0.05 were considered statistically significant.
Microvascular disease is a major feature of type 1 diabetes that results from chronic functional and structural alterations . Patients display generalized microvascular vasodilation, mainly due to altered levels of vasoactive substances, chronic plasma volume expansion and tissue hypoxia . The absence of capillary recruitment in both extremities during PORH, which is related to endothelium-dependent vasodilation at the pre-capillary level, in the nutritive skin microcirculation of diabetic patients without complications has been demonstrated previously by our group  and was confirmed in the present study. Patients either with or without vascular complications were not able to increase capillary density during reactive hyperemia. Microvascular endothelial dysfunction associated with blunted myogenic responsiveness in type 1 diabetes may account for the pressure-induced glomerular damage in the renal pre-glomerular arterioles .
The new finding of the present study is that increased functional as well as structural capillary density in both extremities is observed only in diabetic patients presenting with vascular complications. Not surprisingly, capillary density was positively correlated with age and disease duration, which were significantly higher in patients with complications. Functional density corresponds to values obtained during PORH, while maximal skin capillary density (structural density) was evaluated using venous congestion, which is known to increase the red blood cell content inside capillaries and expose capillaries non-perfused at resting conditions . The absence of capillary recruitment in these patients suggests that diabetic capillaries at rest are already recruited maximally as well as a loss of microvascular autoregulatory capacity. Increased capillary density at baseline (spontaneously perfused capillaries) was observed in the feet, but not in the hands of patients without complications, suggesting that microvascular alterations in type 1 diabetes initiate in the lower extremities and could contribute to complications such as chronic foot ulcers . Accordingly, these microvascular alterations in lower extremities observed in our study could be considered as an early marker for foot complications. It is also worth noting that different growth factors, including vascular endothelial growth factor, are involved in the pathophysiology of diabetic kidney microvascular disease . For that reason, the increased structural skin capillary density observed in our patients presenting with vascular complications could have resulted from increased levels of circulating growth factors. Taken together, our results suggest that besides microvascular vasodilation and loss of autoregulatory capacity, patients with type 1 diabetes with vascular complications present microvascular growth, probably angiogenesis, as a compensatory response to the disease process.
This investigation was supported by grants of FAPERJ (Fundação de Amparo à Pesquisa, Rio de Janeiro, Brazil) and CNPq (Conselho Nacional de Desenvolvimento Tecnológico, Brasília, Brazil).
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