The association between mechanical and biochemical/histological characteristics in diabetic and non-diabetic plantar soft tissue

Abstract

Diabetes, and the subsequent complication of lower limb ulcers leading to potential amputation, remains an important health care problem in United States, even with declining amputation rates. It has been well documented that diabetes can alter the mechanical properties (i.e., increased stiffness) of the plantar soft tissue, although this finding is not universal. Similarly, biochemical and histological changes have been found in the plantar soft tissue, but, as with the mechanical changes, these findings are not consistent across all studies. Our group’s work has demonstrated that diabetes increases plantar soft tissue modulus and increases elastic septal thickness. The purpose of the current study was to explore the association between mechanical, biochemical and histological properties. Using previously collected data, a linear mixed effects regression was conducted. The correlations were weak; of the 32 that were tested, only 3 (modulus to septal thickness when location was accounted for, energy loss to total collagen, and energy loss to collagen/elastin ratio) were statistically significant, none with an R2 greater than 0.10. The main differences in the means were increase tissue stiffness and increase septal wall thickness, both trends were supported in the literature. However, as the correlations were weak, it is likely that another unexamined biochemical factor (perhaps collagen crosslinking) is associated with the mechanical tissue changes.

Diabetes Status is Associated With Plantar Soft Tissue Stiffness Measured Using Ultrasound Reverberant Shear Wave Elastography Approach

“…. The results of the current study in which shear wave speed is correlated with the fasting blood sugar level is in line with the In-vitro studies of cadaveric diabetic feet in which a thicker fibrous septa with an increase in elastin concentrations [35] was linked to the increased stiffness in the mechanical properties of plantar soft tissue in diabetes [36].…”

Histomorphological and biochemical properties of plantar soft tissue in diabetes

“…This could translate to changes in the mechanical properties of the tissues and a greater susceptibility to breakdown. Future studies would involve correlating these biochemical and histomorphological metrics with the mechanical properties of the tissue [23, 47]. This could lead to an understanding of how the structural changes result in an increase in susceptibility of tissue to breakdown with load.…”

Changes in sub-calcaneal fat pad composition and their association with dynamic plantar foot pressure in people with diabetic neuropathy

“…Another possible mechanism is through non-enzymatic glycosylation of proteins which originates from continuously high levels of blood glucose in long-standing diabetes (Delbridge et al, 1985;Kao et al, 1999). The fat pad of the foot in people with diabetes shows increased fragmentation and thickening of fibrous or collagenous septa that separate the fat, which results in smaller adipose cells than in normal tissue (Brash et al, 1996;Buschmann et al, 1995;Ledoux et al, 2016;Wang et al, 2017). Collagen attracts water and even though the composition of fat is not known to change with diabetes, the total amount of fat may change.…”

“…Thinning of the fat pads underneath the metatarsal heads in association with displacement of these fat pads has been shown in MRI studies (Bus et al, 2004), while biomechanical studies have shown increased metatarsal head plantar pressures in these cases . The mechanical properties of fat pad tissue are different in people with diabetes, with increased tissue stiffness mostly reported (Klaesner et al, 2002;Ledoux et al, 2016;Sun et al, 2011;Williams et al, 2017). The septal walls of plantar foot adipose tissue have shown to be thicker and elastin content higher in diabetic versus non-diabetic cadaver feet (Wang et al, 2017).…”