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Helping Diabetic Foot Ulcer Patients Through Collaborative Team Care

May 9, 2022

Patients with diabetes are at high risk for diabetic foot ulcer (DFU), with an annual incidence of 6% in the diabetic population. The annual cost of diabetes is estimated to be around 250 billion dollars, and, alarmingly, patients who develop a diabetic foot ulcer have a five-year mortality approaching 50%. Throughout the state of Pennsylvania, and in particular the southwestern region of the state, diabetes is endemic. Moreover, many of the patients are members of underserved populations. Amputation rates and major mortality are much more likely in DFU patients that are underserved. 

An exciting collaboration between the UPMC Division of Endocrinology and Metabolism and the UPMC Wound Healing Services is working to improve clinical outcomes for diabetic foot ulcer patients within the UPMC health system. UPMC Wound Healing Services, led by J. Peter Rubin, MD, FACS, professor and chair of the Department of Plastic Surgery, is a multidisciplinary service line encompassing 19 outpatient centers throughout Pennsylvania and western Maryland. Fourteen of these sites offer hyperbaric oxygen therapy. UPMC wound healing centers, collectively, have more than 70,000 patient visits annually. The multidisciplinary nature of the service line is a key factor in optimizing care for patients with diabetic foot ulcers and other chronic wounds. Specialties involved with the wound centers include plastic surgeons, vascular surgeons, general surgeons, orthopaedic surgeons, dermatologists, podiatrists, infectious disease experts, internists, family practice physicians, nephrologists, rheumatologists, gerontologists, and, of course, diabetes experts within the UPMC Division of Endocrinology and Metabolism. 

A keystone project in the service line has been the development of a standardized and integrated clinical pathway for diabetic foot ulcer management. Because evaluation and management of medical comorbidities play such an important role in the care of the diabetic foot ulcer patient, the entry point of the pathway includes evaluation and optimization of glycemic control, renal function, nutritional status, blood pressure, coronary artery disease, obstructive sleep apnea, and other significant morbidities. Lifestyle optimization, including smoking cessation and management of obesity, are also included in the early phases of the pathway. This is an area where the collaboration between the Division of Endocrinology and Metabolism and the UPMC Wound Healing Services has been particularly important and impactful. 

A direct link with Diabetes Education Services has been established throughout all our wound care centers so that glycemic control can be optimized in these patients. Notably, the collaboration has been deepened to include the UPMC Health Plan, which ensures more than 3 million people. Esra Karslioglu-French, MD, MBA, ECNU, who works across the UPMC Health Plan and the UPMC health system, and is herself a diabetes expert, has coordinated a data analysis project with the Wound Healing Service. Through this collaboration, we are now able to identify a subset of patients with poor glycemic control (A1C >8%) who also have a diabetic foot ulcer. This leverages the database capacity across the UPMC system to the benefit of our patients. The Division of Endocrinology and Metabolism and the UPMC Wound Healing Services will be piloting specific health coaching strategies to ensure greater attention and access to care for these patients who are at high risk for limb loss.

Basic Science Research to Support Innovation 

Given the cost, complexity, and comorbidity associated with diabetic ulcers, it is imperative we generate reliable preclinical models which can accurately replicate key biochemical and architectural components of chronic wounds. Lauren Kokai, PhD, who is an assistant professor of Plastic Surgery, and Shawn Loder, MD, a Burroughs-Welcome Fellow, are spearheading pioneering work. Large animal porcine models, commonly referred to as gold-standard for their similarity to human skin, are costly, limited by logistical barriers to training and husbandry, and critically lack the genetic tractability needed to easily dissect out biochemical pathways involved in wound pathology. Murine models, which are more affordable, accessible, and biologically versatile, remain critical. However, murine skin healing is typically dissimilar to the clinical reality of human diabetic wounds. While humans heal through slow stages of granulation and reepithelization, mice primarily heal by rapid contracture, often achieving epithelialization in under seven days. Radiation, infection, and genetic knockout of the wound healing cascade can more readily induce chronicity; however, model-specific side effects limit their broader applicability to diabetic wounds. Manipulation of the model to better replicate clinical conditions, a process referred to as “humanization,” is thus critical to this effect. 

In their laboratory, they have capitalized on prior efforts to develop “humanized” murine wounds, including “oxidative stress” models, which manipulate the wound environment to delay healing. In this vein, they have developed a surgical model of wounding which reliably extends wound closure in diabetic animals past the seven-week mark with predictable delays in closure and a quasi-nonhealing state achievable between four and six weeks. The team has focused on the optimization of surgical models, specifically because of their replicability, ease of training and dissemination of technique, and applicability to the wide range of genetic backgrounds and systemic insults available in the murine space which allows us to better address the range of pathologies present in the human chronic diabetic wound.

Clinical Research to Define Future Care

UPMC Wound Healing Services is part of the NIH NIDDK Consortium for research in diabetic foot ulcer biomarkers. UPMC is one of six sites nationally on the steering committee. This research team, including the chief of the Division of Endocrinology and Metabolism, Erin Kershaw, MD, seeks to investigate and validate clinically useful biomarkers that can be employed for diagnosis, prognosis, risk stratification, and treatment decisions. Additionally, basic science research in diabetic wound healing has yielded innovative new rodent models that better simulate the chronic state and inflammatory microenvironment of human diabetic wounds. 

UPMC has a rich tradition of clinical excellence and research in diabetic wound healing. David Steed, MD, professor emeritus of Vascular Surgery, laid the groundwork for many current clinical algorithms. The UPMC Orthopaedic Foot and Ankle Division, led by MaCalus Hogan, MD, MBA, brings extensive expertise in managing boney deformities associated with higher risk of ulceration. Podiatric experts such as Jarrett Cain, DPM, MSc, also within the UPMC Orthopaedic Foot and Ankle Division, brings additional multidisciplinary expertise. The UPMC Division of Endocrinology and Metabolism plays a central role in the multidisciplinary landscape, and this team care approach is rapidly evolving to meet changing patient needs. Meaningful datasets enable detailed analysis across large diabetic patient populations and fuels innovation in this program.