What Are Diabetic Foot Ulcers?

Diabetic foot ulcers (DFUs) are wounds that develop on the feet of people with diabetes. Over time, they can be life-threatening. Unsightly and difficult to heal, they can get infected and sometimes lead to disability and amputations.

For decades, healthcare experts have been trying to figure out a way to predict which of these wounds will heal and which will fester in order to treat them more effectively and avoid serious consequences.

A new study, led by Marjana Tomic-Canic Ph.D., a professor of dermatology at the University of Miami Miller School of Medicine, investigated two specific biomarkers found in wound tissue — c-myc and phosphorylated-glucocorticoid receptor (p-GR) — to determine if these molecules could help predict healing.

The results were inconclusive, but this first-of its-kind investigation was successful in other ways. It was a valuable “stepping stone” in the field’s effort to identify biomarkers that might identify, in the early stage of infection, wounds that will not heal.

In other words, Dr. Tomic-Canic and her team opened the door to the analysis of wound tissue samples in diabetic foot ulcer research. By collecting wound tissue samples for this study, they helped create a national biorepository of samples that can be used by scientists to continue searching for biomarkers or other reliable ways to predict healing and improve treatment for people with DFUs.

The study, published in Wound Repair and Regeneration, was the first conducted by the national Diabetic Foot Consortium (DFC).

The DFC is a research network supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Established in October 2018, it began with six clinical sites (called “clinical research units”) around the country that sought to study diabetic foot ulcers through biomarker research, clinical trials and data collection. The goal was for no DFU to go unstudied. The University of Miami Phillip Frost Department of Dermatology and Cutaneous Surgery was a founding member. Since then, the network has grown and expanded to more clinical sites and is developing testing and validating diverse potential biomarkers.

“The study showed the value of tissue sample analysis and set up a collection of potential information that other researchers can use in the future,” says Dr. Tomic-Canic, who is also director of the Wound Healing and Regenerative Medicine Research Program.

“This is just the beginning, but it laid the groundwork for more biomarker discovery and for advancing DFU science and clinical practice. It is an impressive team effort.”

According to the American Diabetes Association, 38.4 million Americans, or 11.6% of the population, had diabetes in 2021, and about 1.2 million Americans are diagnosed with the condition every year. Another 97.6 million Americans ages 18 and older had prediabetes. Prevalence continues to rise because of obesity, a sedentary lifestyle, an aging population and other lifestyle factors. Studies estimate that as many as a third of people with diabetes will develop a DFU in their lifetime. 

More than 18.6 million people worldwide, and 1.6 million in the U.S. alone, suffer from diabetic foot ulcers, which impair physical function and reduce quality of life.

Left untreated, these wounds can lead to infection and gangrene requiring hospitalization. About 20% of serious infections end in amputation. Even more concerning, those with DFU have a 5-year mortality rate of 30%, with a mortality rate greater than 70% for people with an above-foot amputation.

Yet, “there are no diagnostic tools in the field of chronic wounds that can guide treatment, unlike in the cancer field, where special markers from a biopsy can help with diagnosis and treatment” Dr. Tomic-Canic says.

In other words, physicians and scientists have no way to predict what wounds will not heal.

This is what precision medicine is all about, she says. Learning this early can provide guidance for advanced interventions to be applied.

Further complicating the diagnosis and treatment of DFUs is the effects of diabetes on the body, particularly as the body tries to heal itself. In people with diabetes, a simple wound can worsen because of poor circulation, weaker immune response and nerve damage. Diabetes tends to impair blood flow to the feet, which, in turn, inhibits healing. Also, high blood sugar levels damage nerves, leading to a loss of sensation in the feet, making it difficult for a diabetic patient to even notice an injury or feel pain.

 “By the time a person discovers [the wound], it can be well advanced,” Dr. Tomic-Canic says.

Dr. Tomic-Canic’s search for potential diagnostic tools began about 25 years ago.

She became “fascinated” by the skin’s ability to heal and regenerate throughout lifetime. Knowing that this capability is compromised by diabetes, she focused her research on understanding the molecular mechanisms of wound healing and its inhibition in patients. In 2005, her team discovered two molecules that are “super active” in the tissue of wounds that have not healed.

Those two molecules, c-myc and p-GR, were the object of this most recent study, which evaluated wound tissue collected from 107 participants with active DFUs and assessed the nuclear presence of the two molecules. And while biomarker levels were similar between ulcers that healed by the 12-week mark and those that did not, the discovery of elevated p-GR levels in wounds that did not heal suggested “possible avenues for further investigation.”  

In the meantime, “raising awareness of this complex and devastating disease is equally important,” she adds.

Written by Ana Veciana-Suárez, a regular contributor to the University of Miami Health System. She is an acclaimed author and journalist who has worked for The Miami Herald, The Miami News, and The Palm Beach Post.

Tags: chronic wound diagnostics, diabetes-related amputation risk, precision wound care, University of Miami wound study