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Plantar skin in type II diabetes: an investigation of protein glycation and biomechanical properties of plantar epidermis. Eur J Dermatol. 2006 Jan-Feb;16(1):23-32
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The generation of thickened plantar stratum corneum (SC) in response to elevated pressures, places individuals with diabetes at risk of ulceration. Such a response may culminate from altered biochemical and physical states of the epidermis as a result of non-enzymatic glycation (NEG). The objective of this study was to quantify specific glycation products generated in plantar epidermal proteins in individuals with Type 2 Diabetes Mellitus (T2DM) and age-matched controls (n = 103 and n = 87, respectively) and to compare these data with the viscoelastic properties (in vivo) of the epidermis. Plantar SC and venous blood samples were collected from all participants for the quantification of furosine and pentosidine using high performance liquid chromatography (HPLC). The viscoelastic properties of plantar epidermis were measured by the application of negative pressure on the surface of the skin. Plantar epidermal thickness was measured using high frequency (20 MHz) ultrasonography. There was a significantly greater concentration of pentosidine in the SC samples from people with T2DM (p = 0.001). There was no correlation between the concentration of glycated proteins in the epidermal proteins and serum proteins (furosine r = - 0.115, pentosidine r = - 0.023). The plasticity of the epidermis was significantly lower in the T2DM group than the control group (p = 0.007). The results suggest that alterations in the glycation of plantar epidermal proteins may constitute additional aggravators of ulceration in people with T2DM.
BACKGROUND:
Diabetic foot ulceration has a complex and multifactorial etiology and can involve changes in the pathophysiology of the plantar soft tissue. In the current study, histomorphological analyses of diabetic and non-diabetic plantar tissue were performed. It was hypothesized that the diabetic tissue would have thicker skin (epidermis and dermis), less interdigitation between the dermis and epidermis, thicker elastic septa and decreased adipose cell size.
MATERIALS AND METHODS:
Two locations of the foot (the heel and the first metatarsal) were examined, both of which have been reported to be locations with a high incidence of ulceration. Stereological methods and quantitative morphological techniques were used to evaluate the skin thickness, interdigitation index, elastic septae thickness and adipocyte cell size.
RESULTS:
The diabetic donors had a greater body mass index (BMI) than the non-diabetic donors. The diabetic tissue had significantly thicker elastic septae and dermis. However, no significant difference was observed in the interdigitation index or adipocyte size.
CONCLUSION:
These findings demonstrate that morphological changes can be evaluated histologically to give a better understanding of the pathological changes in the plantar soft tissue with diabetes. These evaluations can then be associated with biomechanical changes that occur in diabetes to provide new insight into how microstructural changes can alter macroscopic properties.
CLINICAL RELEVANCE:
An understanding of the histomorphological changes in the soft tissue in relationship to the location on the foot could help to explain the biomechanical changes that occur in diabetes and the subsequent increase in susceptibility to breakdown.
Cutaneous Structural and Biochemical Correlates of Foot Complications in High-Risk Diabetes.
Tahrani AA, Zeng W, Shakher J, Piya MK, Hughes S, Dubb K, Stevens MJ. Diabetes Care. 2012 Jun 29.
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OBJECTIVEImpairment of skin quality may contribute to diabetic foot ulceration (DFU). Our goal was to determine whether high-risk patients exhibited specific skin structural and metabolic deficits that could predispose to foot complications.
RESEARCH DESIGN AND METHODSA total of 46 patients comprising 9 diabetic control subjects, 16 with diabetic peripheral neuropathy (DPN) alone, and 21 with recurrent DFUs (including 9 with Charcot neuroarthropathy [CNA]) were recruited and compared with 14 nondiabetic control (NDC) subjects. DPN was assessed using the Michigan Neuropathy Screening Instrument (MNSI). Skin punch biopsies (3 mm) were performed on upper and lower leg skin for measurements of intraepidermal nerve fiber density (IENFD), structural analysis, type 1 procollagen abundance, tissue degrading matrix metalloproteinases (MMPs), and poly(ADP-ribose) (PAR) immunoreactivity.
RESULTSMNSI scores were comparable across DPN groups. IENFD was decreased by diabetes and DPN but did not differ between neuropathic groups. Skin structural deficit scores were elevated in all neuropathic subjects, particularly in the DFU group. Type 1 procollagen abundance was reduced in DFU subjects 387 ± 256 units (mean ± 1 SD) compared with NDC subjects (715 ± 100, P < 0.001). MMP-1 and MMP-2 were activated by diabetes. PAR immunoreactivity was increased in DFU (particularly in the CNA group; P < 0.01) compared with other DPN subjects.
CONCLUSIONSIncreased PAR, reduced type 1 procollagen abundance, and impaired skin structure are associated with foot complications in diabetes. The potential of therapies that improve skin quality to reduce DFU needs to be investigated.
Mechanical properties of lower limb dermis following static and cyclic compression.
Evans DW, Scott AT, Teasdall RD, Smith BP, Howlett A, Connor-Kerr T, Sparks JL. Biomed Sci Instrum. 2012;48:104-11.
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Lower extremity amputations and foot ulcers are complications associated with diabetes, and have been shown to affect diabetic African Americans (AA) three times as often as diabetic non-Hispanic Whites (NHW). Possible causes for the increased risk include ethnic differences in structure and function within the dermis of the lower extremity. Testing this hypothesis requires studying the mechanical properties of skin from different ethnic groups with and without the diagnosis of noninsulin-dependent diabetes. The purpose of this study was to develop a testing method to investigate changes in tensile mechanical properties resulting from static and cyclic compression of dermis harvested from patients undergoing lower extremity amputations. Full thickness dermal samples were obtained from 15 patients undergoing below-knee amputations. Sections of each sample were conditioned with a compressive static pressure (170 mmHg) or cyclic pressures (110-170 mmHg) for 4 hours to elicit collagen bundle remodeling. Skin samples were then tested in tension to obtain sub-plastic stress vs. strain mechanical behavior. Length of the stress-strain toe-region was examined to quantify the effect of collagen bundle remodeling. Toe-region mean lengths were 0.141±0.041, 0.146±0.034, and 0.164±0.064 strains for the control, cyclic, and statically compressed samples respectively (p>.05). These results suggest that the preconditioning regimes did not produce sufficient collagen remodeling to affect the tensile properties of full-thickness dermis. Future work will examine histology from each specimen to identify microstructural features associated with this trend.
Effect of viscoelastic properties of plantar soft tissues on plantar pressures at the first metatarsal head in diabetics with peripheral neuropathy.
Jan YK, Lung CW, Cuaderes E, Rong D, Boyce K. Physiol Meas. 2012 Dec 18;34(1):53-66.
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Diabetic foot ulcers are one of the most serious complications associated with diabetes mellitus. Current research studies have demonstrated that biomechanical alterations of the diabetic foot contribute to the development of foot ulcers. However, the changes of soft tissue biomechanical properties associated with diabetes and its influences on the development of diabetic foot ulcers have not been investigated. The purpose of this study was to investigate the effect of diabetes on the biomechanical properties of plantar soft tissues and the relationship between biomechanical properties and plantar pressure distributions. We used the ultrasound indentation tests to measure force-deformation relationships of plantar soft tissues and calculate the effective Young's modulus and quasi-linear viscoelastic parameters to quantify biomechanical properties of plantar soft tissues. We also measured plantar pressures to calculate peak plantar pressure and plantar pressure gradient. Our results showed that diabetics had a significantly greater effective Young's modulus and initial modulus of quasi-linear viscoelasticity compared to non-diabetics. The plantar pressure gradient and biomechanical properties were significantly correlated. Our findings indicate that diabetes is linked to an increase in viscoelasticity of plantar soft tissues that may contribute to a higher peak plantar pressure and plantar pressure gradient in the diabetic foot.
Background: Accumulation of advanced glycation end products (AGEs) may contribute to diabetic foot ulceration (DFU). Our goal was to determine whether AGEs measurement by skin autofluorescence (SAF) would be an additional marker for DFU management.
Patients and Methods: We performed SAF analysis in 66 patients with a history of DFU prospectively included and compared the results with those of 84 control patients with diabetic peripheral neuropathy without DFU. We then assessed the prognostic value of SAF levels on the healing rate in the DFU group.
Results: Mean SAF value was significantly higher in the DFU group in comparison with the control group, even after adjustment for other diabetes complications (3.2±0.6 arbitrary units vs. 2.9±0.6 arbitrary units; P=0.001). In the DFU group, 58 (88%) patients had an active wound at inclusion. The mean DFU duration was 14±13 weeks. The healing rate was 47% after 2 months of appropriate foot care. A trend for a correlation between SAF levels and healing time in DFU subjects was observed but was not statistically significant (P=0.06).
Conclusions: Increased SAF levels are associated with neuropathic foot complications in diabetes. Use of SAF measurement to assess foot vulnerability and to predict DFU events in high-risk patients appears to be promising.
Plantar skin properties in diabetes
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