Wound Healing, Tissue Repair, and Regeneration in Diabetes

Debasis Bagchi, Amitava Das, Sashwati Roy

• Publisher: Academic Press
• Year: 2020
• ISBN:
  9780128164143
• Topic: Technology & Engineering
• Subtopic: Food Science
• Index: Technology & Engineering

Wound Healing, Tissue Repair and Regeneration in Diabetes explores a wide range of topics related to wound healing, tissue repair and regeneration, putting a special focus on diabetes and obesity. The book addresses the molecular and cellular pathways involved in the process of wound repair and regeneration. Other sections explore a wide spectrum of nutritional supplements and novel therapeutic approaches, provide a comprehensive overview, present various types of clinical aspects related to diabetic wounds, including infection, neuropathy, and vasculopathy, provide an exhaustive review of various foods, minerals, supplements and phytochemicals that have been proven beneficial, and assess future directions.

This book is sure to be a welcome resource for nutritionists, practitioners, surgeons, nurses, wound researchers and other health professionals.

• Explains diabetic wounds and their complications
• Assesses the role of nutraceuticals, herbal supplements and other modalities for use in treating diabetic wounds
• Provides protocols for diabetic wound management

Part 1

Background and overview

Chapter 1

The diabetic foot

Shomita S. Mathew-Steiner; Dolly Khona; Chandan K. Sen Indiana Center for Regenerative Medicine and Engineering, Department of Surgery, Indiana University Health Comprehensive Wound Center, Indiana University School of Medicine, Indianapolis, IN, United States

Abstract

Diabetes is an ongoing global epidemic associated with pathologies such as foot ulcers, which are a leading cause of hospitalization. Ulceration, infection, gangrene, and amputation are outcomes of underlying vascular, neurological, and immunological dysfunction, leading to an estimated burden of billions of dollars every year in health care costs. Improving the treatment of ulcers together with prevention are key facets in foot ulcer control and they require integrated, multidisciplinary approaches.

Keywords

Diabetes; Foot ulcers; Vascular; Neurological and immunological dysfunctions; Multidisciplinary approaches

1 Introduction

Diabetic foot ulcers (DFU) are a common reason for hospitalization of diabetic patients and frequently result in amputation of lower limbs. Of the one million people who undergo nontraumatic leg amputations annually worldwide, 75% are performed on people who have type 2 diabetes mellitus (T2DM) [1,2]. The risk of death at 10 years for a diabetic with DFU is twice as high as the risk for a patient without a DFU [3]. The amputation rate in patients with DFU is 38.4% [4]. Infection is a common (> 50%) complication of DFU [1,5–13]. Emerging evidence underscores the importance of biofilm infection in the progression of nonhealing DFU [12,14]. Eighty-five percent of amputations in diabetic patients is attributed to DFUs made chronic by infections [15]. DFUs occur due to a combination of mechanical changes in the foot, peripheral neuropathy and peripheral arterial disease [16,17]. In the United States, DFU management alone is estimated to cost somewhere between $9 and $13 billion [18]. DFU management includes the use of therapeutic footwear to offload the wound [19,20] together with maintenance of a moist wound environment [21]. Debridement together with aggressive antibiotic therapy is necessitated for infected wounds [22,23]. Additionally, the maintenance of optimal blood glucose and treatment of vascular insufficiencies are key elements of wound management.

This chapter provides a brief overview of the pathology of the diabetic foot. Details of the component elements are presented in other chapters within this book.

2 Clinical classification

2.1 Definition

A diabetic foot is characterized by ulceration that is driven by neuropathy and/or peripheral artery disease of the lower limb and is a complex, frequent, and expensive complication in diabetic patients.

2.2 Risk factors

Several direct and indirect risk factors are associated with the development of a DFU. These include (a) lifestyle factors such as smoking, uncontrolled diabetes, poor nutrition, immobility, age, etc.; (b) physiological factors such as neuropathy (loss of sensation), vasculopathy (insufficient oxygen availability), shear stress and trauma, and bone deformities (c) genetic and ethnic factors have been implicated in the development of diabetes and diabetic complications [24,25]. DFU is of particular concern among Latinos African Americans, and in Native Americans, who have the highest risk for diabetes worldwide [26].

2.3 Etiology

DFUs develop due to a combination of neuropathy [27], arterial disease [28], pressure [19], and plantar deformity [6]. Diabetic neuropathy is found in 80% of diabetic persons with foot ulcers and is a key factor in development of DFUs.

Biomechanical factors, such as tissue stiffness and thickness, may contribute to DFUs. In a study involving 39 subjects, the heel pad of the foot without an ulcer was found to be stiffer than that with an ulcer [29]. In patients with neuropathy, the plantar soft tissue is thicker and less stiff in specific parts of the foot that are more prone to developing into ulcers. Therefore, mechanical properties of plantar soft tissue could have predictive value for DFU prognosis [30].

2.4 Epidemiology

According to the Centers for Disease Control, 30 million Americans are estimated to have diabetes [31]. DFUs, in particular, are associated with increased hospitalizations [18]. Fifteen percent of diabetic patients develop a foot ulcer, and 38.4% of these require amputation. Indeed, in the United States, most nontraumatic lower-extremity amputations are associated with diabetes [32].

Diabetes and complications such DFUs have been reported globally and are indicators of the growing and profound impact of this pervasive disease [8,33–41].

3 The complicated diabetic foot

The diabetic foot develops as a consequence of several independent and interdependent complications discussed briefly below.

3.1 Vascular

Diabetes is associated with microvascular and macrovascular etiologies, including cerebrovascular, cardiovascular, and peripheral arterial disease. DFU patients have higher premature mortality due to cardiovascular complications [42,43]. Diabetic adults are 2–4 times more at risk for heart disease and stroke than their nondiabetic counterparts. In fact, 65% of deaths in diabetics are associated with vascular complications [31]. In addition to the association of ischemic heart disease and mortality, chronic ulceration could induce chronic inflammation, which could promote the development of atherosclerosis [44]. Furthermore, the ischemia caused by poor blood flow promotes nonhealing ulceration of the foot, leading to amputation. The key impact from this complication is the lack of oxygen supply to the foot and wound and therefore, aggressive treatment of limb ischemia is vital to managing the wound and preventing amputation [45,46].

3.2 Neural

It is believed that 45%–60% of all DFUs are purely neuropathic, while up to 45% have neuropathy combined with ischemia [47,48]. Peripheral sensory neuropathy (PSN) is a major factor leading to DFUs [27,47,49,50]. PSN, even with adequate arterial perfusion, will often promote infection progression primarily due to a lack of sensation in the foot [51,52]. Unnoticed excessive temperature exposures, pressure from ill-fitting shoes, or trauma may cause blistering and ulceration. Motor neuropathy results in muscle atrophy causing foot deformities such as hammertoe, foot drop, etc. [53,54]. Neuropathy induced muscular atrophy together with vascular deficiencies are significant risk factors for limb loss in diabetic patients. Autonomic neuropathy leads to skin breakdown creating a portal for entry of microbes that cause infection [55,56]. In diabetic people with neuropathy [57], the wound recurrence rate is 66% with an associated increase in amputation rate by 12%. Cardiovascular autonomic neuropathy (CAN) is another complication of diabetes that is associated with increased mortality and silent myocardial ischemia [58]. Somatic neuropathy has been implicated in the calcification of the arterial wall leading to cardiovascular mortality [59].

Sensory and motor neuropathy in the foot together with bone and joint deformities and associated vascular changes cause a progressive condition called Charcot foot (neuropathic osteoarthropathy), which physically manifests as a convex foot with a rocker-bottom appearance [60–62]. It is thought to affect about 2% of diabetic persons. Excessive inflammation and vascular calcification common in diabetic patients are implicated in...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Dedication
• Contributors
• About the authors
• Preface
• Part 1: Background and overview
• Part 2: Molecular mechanisms in diabetic wounds
• Part 3: Emerging therapeutics in diabetic wound care
• Part 4: Nanotechnology and nanocarriers in wound healing
• Part 5: Biomarkers in wound healing
• Part 6: Novel concepts in diabetic wound healing
• Index