Changes in the Characteristics of Plantar Soft Tissue with Diabetes

描述（由申请人提供）：糖尿病可能是一种毁灭性的疾病，特别是考虑到足部溃疡和截肢的并发症。有了这个建议，我们将更好地了解糖尿病的疾病过程如何改变足底软组织的细胞和基质水平特性，从而影响组织的力学特性。我们还将探讨由于组织位置（即脚掌与脚后跟）和标本年龄（即年轻与年老）而导致的足底软组织特征的差异。本研究的长期目标是通过使用改进的足部矫形器来改变糖尿病足下的应力分布，或者可能启动细胞/基质水平的治疗来改变组织力学特性，从而减少下肢溃疡和截肢的发生率。我们将通过完成本研究的具体目标来实现这一目标，其中包括：[1]评估1)老年糖尿病患者、2)老年非糖尿病患者和3)年轻非糖尿病患者足下六个不同部位足底软组织的力学特性，[2]评估1)老年糖尿病患者、2)老年非糖尿病患者和3)年轻非糖尿病患者足下六个不同部位足底软组织的细胞/基质特性，[3]确定足底软组织的力学和细胞/基质特性是如何相关的。这项研究将增加我们对疾病过程的基本了解，并实施所获得的知识将减少糖尿病患者溃疡和截肢的负担。本研究设计了一个组间组件，检查糖尿病和年龄对组织的影响，以及一个重复测量组件，解决组织位置的影响。先前的研究支持糖尿病、组织位置或年龄导致的机械（刚度增加）和细胞/基质（胶原蛋白和胶原交联增加）特性变化的假设，但尚未对这些特性如何相互作用进行系统研究。我们将使用最先进的材料测试机器进行机械测试，而所有细胞/基质测试将采用完善的协议。美国有超过1800万糖尿病患者，在1996年至2002年间，每年有超过8万例非创伤性截肢。因此，美国不仅有大量的糖尿病患者（60%），而且在所有非创伤性下肢截肢中，糖尿病患者的数量也不成比例（60%）。

DESCRIPTION (provided by applicant): Diabetes mellitus can be a devastating disease, particularly when considering the complications of foot ulceration and amputation. With this proposal we will better understand how the disease process of diabetes alters the cellular and matrix level properties of the plantar soft tissue, which in turn affects the mechanical properties of the tissue. We will also explore differences in the plantar soft tissue characteristics due to tissue location (i.e., the ball of the foot versus the heel) and specimen age (i.e., young versus old). The long- term goal of this research is to reduce the incidence of lower extremity ulceration and amputation by using the knowledge gained to alter the stress distribution beneath diabetic feet with improved foot orthoses, or perhaps to initiate a cellular/matrix level treatment that alters the tissue mechanical properties. We will work towards this goal by completing the specific aims of this study, which include: [1] assess the mechanical properties of 1) older diabetic, 2) older non-diabetic, and 3) younger non-diabetic plantar soft tissue at six different locations beneath the foot, [2] assess the cellular/matrix properties of 1) older diabetic, 2) older non- diabetic, and 3) younger non-diabetic plantar soft tissue at six different locations beneath the foot and [3] determine how the mechanical and cellular/matrix properties of the plantar soft tissue are related. This research will increase our fundamental understanding of the disease process and implementing the knowledge gained will reduce the burden of ulceration and amputation on diabetic patients. This study is designed with a between-group component examining the effect of diabetes and age on the tissues and a repeated measures component addressing the effect of tissue location. Previous research supports the hypothesized changes in the mechanical (increased stiffness) and cellular/matrix (increased collagen and collagen cross-linking) properties due to diabetes, tissue location or age, however there has not been a systematic study of how these properties interact. We will conduct mechanical testing, using state-of-the-art materials testing machines, while all cellular/matrix testing will employ well-established protocols. There are over 18 million Americans with diabetes, accounting for over 80,000 non-traumatic amputations each year between 1996 and 2002. Thus, not only is there a large diabetic population in the United States (> 6%), but they also account for a disproportional amount (>60%) of all non-traumatic lower extremity amputations.