Microvascular Response to Tissue Injury and Capillary Ultrastructure in the Foot Skin of Type I Diabetic Patients

1995 ◽  
Vol 89 (5) ◽  
pp. 467-474 ◽  
Author(s):  
G. Rayman ◽  
R. A. Malik ◽  
A. K. Sharma ◽  
J. L. Day

1. Microvascular blood flow responses to injury and capillary ultrastructure were assessed by laser Doppler flowmetry and detailed light and electron microscopy respectively in skin biopsied from 28 patients with insulin-dependent diabetes and 17 control subjects. 2. The hyperaemic response induced by biopsy (P < 0.001) and heating to 44°C (P < 0.001) was significantly lower in the diabetic patients and showed progressive impairment with the severity of complications (P < 0.001). 3. Skin capillary basement membrane thickness was significantly increased in the diabetic patients (P < 0.001) and also increased with the severity of complications (P < 0.002). Both the luminal area (P < 0.001) and the endothelial cell outer perimeter (P < 0.002), measures of luminal and capillary size, respectively, were significantly reduced in all diabetic patients. 4. Basement membrane thickness was related significantly to the impaired hyperaemic response to both biopsy (P < 0.01) and thermal injury (P < 0.01). 5. Our findings support the hypothesis that structural abnormalities, which are characterized by an early reduction in capillary size and later thickening of basement membrane, form an important mechanism for the impaired hyperaemic response in diabetic patients.

Author(s):  
A.R. Diani ◽  
G.A. Sawada ◽  
T. Peterson ◽  
B.M. Wyse ◽  
M.C. Blanks ◽  
...  

Microangiopathy has been recognized as a critical complication which afflicts the human diabetic population and magnifies the risk for permanent injury and/or mortality. One of the major manifestations of diabetic microvascular disease in man appears to be capillary basement membrane thickening (CBMT) which has been termed the “hallmark of diabetic microangiopathy”. CBMT of diabetic patients seems to be a product of vascular injury imposed by the interaction of metabolic derangement, environmental factors and genetics (1). Although the degree of thickening varies with age, duration of diabetes, severity of metabolic impairment and location in the body, capillary basement membranes from the kidney, skeletal muscle and heart are usually expanded in diabetic man. However, due to the sparsity of systematic studies and inherent problems with human experimentation, the pathogenesis of CBMT remains controversial. In an attempt to achieve a better understanding of the etiology and progression of CBMT, diabetic animal models have recently been the focal point of intensive research (2).


1992 ◽  
Vol 68 (06) ◽  
pp. 628-633 ◽  
Author(s):  
Isobel Ford ◽  
Rayaz A Malik ◽  
Paul G Newrick ◽  
F Eric Preston ◽  
John D Ward ◽  
...  

SummaryWe have examined haemostatic factors in 15 diabetic patients with peripheral neuropathy and 10 diabetic patients without clinical complications. Plasma and blood viscosity, fibrinogen, factor VIIIc, von Willebrand factor activity, spontaneous platelet aggregation and fibrinolytic activity were not significantly different between diabetic patients without clinical complications and diabetic patients with peripheral neuropathy. Platelet aggregation was enhanced in diabetic patients with neuropathy compared with those without complications. In the 15 patients with neuropathy and 3 without complications, who underwent biopsy of sural nerve, skin and muscle, associations were found between haemostatic variables and measures of nerve capillary pathology, notably: plasma fibrinogen and nerve capillary basement membrane thickness (r = 0.70, p <0.001); thromboxane B2 production and nerve capillary basement membrane thickness (r = –0.61, p <0.01); plasma fibrinolytic activity and endoneurial capillary lumen size (r = 0.60, p <0.01) and endothelial cell outer perimeter (r = 0.65, p <0.01). The main associations of skin and muscle capillary abnormalities were with measures of in vitro platelet aggregation, and the correlations found with nerve capillary measurements were not echoed in the overlying muscle and skin. The results are supportive of the involvement of haemostatic abnormalities in the pathogenesis of diabetic neuropathy.


1987 ◽  
Author(s):  
I Ford ◽  
P G Newrick ◽  
R Malik ◽  
F E Preston ◽  
J D Ward ◽  
...  

We have examined coagulation parameters in 15 neuropathic (Group A) and 10 complication-free diabetic patients (Group B). Venesection and sample testing were performed under standard conditions. Group A underwent sural nerve biopsy and 14 also had measurements of endoneurial oxygen tension. Factor VIII related antigen was higher in Group A (l-617u/ml ± 0.67) compared to Group B (0.944u/ml ± 0.26); (mean ± SD; p<.0.05) perhaps suggesting endothelial cell damage, although this did not correlate with capillary basement membrane thickness or endothelial cell number nor with endoneurial oxygen levels. Platelets from Group A were more sensitive to arachidonate than those of Group B, showing aggregation thresholds in platelet rich plasma of 0.36 ± 0.17mM and 0.57 ± 0.9mM respectively compared with 0.65 ± 0.37mM in non-diabetic controls.Platelets from Group A subjects also produced more thromboxane B2 in response to arachidonate than Group B or normal controls (37.95 ± 27.5; 25.5 ± 13.0; 16.55 ± 15-5pmol/107 platelets). Blood fibrinolytic capacity measured by euglobulin clot lysis time, was diminished in NIDDs (post-occlusion ECLT 165.7 mins ± 116.0), compared to IDDs (55.5 ± 34.5) (p<0.05) due at least in part to excess of tissue plasminogen-activator inhibitor, although we found no significant difference in ECLT between Group A and Group B. Interaction between haemostatic and microvascular abnormalities in diabetes may contribute to the pathogenesis of diabetic neuropathy.


2002 ◽  
Vol 166 (12) ◽  
pp. 1590-1595 ◽  
Author(s):  
Alan L. James ◽  
Peta S. Maxwell ◽  
Gladys Pearce-Pinto ◽  
John G. Elliot ◽  
Neil G. Carroll

Diabetes Care ◽  
1979 ◽  
Vol 2 (6) ◽  
pp. 472-478 ◽  
Author(s):  
E. A. Siess ◽  
H. E. Nathke ◽  
T. Dexel ◽  
M. Haslbeck ◽  
H. Mehnert ◽  
...  

1978 ◽  
Vol 45 (4) ◽  
pp. 619-625 ◽  
Author(s):  
H. L. Wyatt ◽  
J. Mitchell

To investigate the effects of physical conditioning and deconditioning on the coronary vasculature, eight dogs were exercised by treadmill running. Five dogs were deconditioned by confinement in cages following the conditioning period. A technique was developed and validated for measuring circumflex coronary artery diameter from magnified projections of standardized coronary angiograms. Myocardial capillary density, perimeter, and basement membrane thickness were determined from electron microscopy of serial ventricular septal biopsy samples. Physical conditioning caused a small but statistically significant increase in cross-sectional area of the circumflex artery. Although physical conditioning caused no statistically significant changes in the myocardial capillaries, trends were apparent for increases in density and perimeter of myocardial capillaries and a decrease in basement membrane thickness. Physical deconditioning caused statistically significant reductions in cross-sectional area of the circumflex artery and in myocardial capillary density but little change in perimeter or basement membrane thickness of myocardial capillaries. The results suggest that physical conditioning may be associated with an improvement in coronary vascular capacity which may regress rapidly with deconditioning.


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