MAYWOOD, IL – Men with diabetes are 2.4 times more likely than non-diabetics to suffer heart failure and women are five times more likely.

A new Loyola University Chicago Stritch School of Medicine study reveals how, on a cellular level, diabetes can cause heart failure. The findings could lead to medications to treat and perhaps prevent heart failure in diabetes patients, researchers said.

The study from the lab of Jonathan A. Kirk, PhD, is published in the American Society for Clinical Investigation journal JCI Insight. Dr. Kirk is an assistant professor in the Department of Cell and Molecular Physiology of Loyola University Chicago Stritch School of Medicine.

In a healthy heart, microscopic lattice-like structures called myofilaments cause heart muscle cells to contract. The cells work in concert to make the heart contract and relax with each beat. In patients suffering from heart failure, heart muscle cells become weaker, and consequently, the heart does not pump enough blood to meet the body's needs. The patient experiences symptoms such as shortness of breath, fatigue and swelling in the legs. Heart failure ultimately can be fatal.

In the Loyola study, researchers focused on a molecule called methylglyoxal. When the body transforms food into chemical energy, waste products are generated, including methylglyoxal. Normally, the body does an efficient job clearing out methylglyoxal. But the cleansing process does not work as well in diabetics, allowing methylglyoxal to accumulate. Methylglyoxal attaches to key building blocks of proteins, which can affect how the proteins function.

Researchers examined heart tissue from three groups: people without heart failure, people with heart failure who also had diabetes and people with heart failure who did not have diabetes. The study found that methylglyoxal modifies the cardiac myofilament more in diabetic heart failure patients than it does in people who either don't have heart failure or have heart failure without diabetes. Researchers further found that the modifications caused by methylglyoxal weakened heart muscle cells by interfering with how the molecular motor works.

“This little molecule, methylglyoxal, builds up in heart cells during diabetes and gums up the myofilaments so they cannot contract as well,” said lead author Maria Papadaki, PhD, a post-doctoral fellow at Loyola University Chicago Stritch School of Medicine.

The findings suggest a new approach to treating patients with diabetes who are at risk of developing heart failure. This approach involves developing drugs that would counter the effects of methylglyoxal by fine-tuning the myofilament motors.

Dr. Kirk speculates that the effects of methylglyoxal, as identified in the study, may be a key early step in how diabetes induces heart failure. This discovery could provide an effective therapeutic target for preventing heart failure in the growing population of diabetics.

The study is titled, "Diabetes with heart failure increases methylglyoxal modifications in the sarcomere, which inhibit function" (sarcomere is the technical term for the molecular motor unit in heart muscle). The study was funded by grants from the National Institutes of Health and American Heart Association.

In addition to Drs. Kirk and Papadaki, other co-authors are Thomas G. Martin and Marisa J. Stachowski of Loyola University Chicago's Department of Cell and Molecular Physiology; Ronald J. Holewinski, PhD, and Jennifer E. Van Eyk, PhD, of Cedars-Sinai Medical Center; Samantha Beck Previs, Amy Li, PhD, and David M. Warshaw, PhD, of the University of Vermont; Cheavar A. Blair, PhD, and Ken Campbell, PhD, of the University of Kentucky; and Christine S. Moravec, PhD, of the Cleveland Clinic.

About Loyola Medicine

Loyola Medicine, a member of Trinity Health, is a nationally ranked academic, quaternary care system based in Chicago's western suburbs. The three-hospital system includes Loyola University Medical Center (LUMC), Gottlieb Memorial HospitalMacNeal Hospital, as well as convenient locations offering primary care, specialty care and immediate care services from nearly 2,000 physicians throughout Cook, Will and DuPage counties. LUMC is a 547-licensed-bed hospital in Maywood that includes the William G. and Mary A. Ryan Center for Heart & Vascular Medicine, the Cardinal Bernardin Cancer Center, the John L. Keeley, MD, Emergency Department, a Level 1 trauma center, Illinois's largest burn center, the Nancy W. Knowles Orthopaedic Institute, a certified comprehensive stroke centertransplant center and a children’s hospital. Having delivered compassionate care for over 50 years, Loyola also trains the next generation of caregivers through its academic affiliation with Loyola University Chicago’s Stritch School of Medicine and Marcella Niehoff School of Nursing.   

For more information, visit loyolamedicine.org. You can also follow Loyola Medicine on LinkedIn, Facebook, Instagram or X (formerly known as Twitter).

About Trinity Health

Trinity Health is one of the largest not-for-profit, faith-based health care systems in the nation. It is a family of 127,000 colleagues and more than 38,300 physicians and clinicians caring for diverse communities across 26 states. Nationally recognized for care and experience, the Trinity Health system includes 93 hospitals, 107 continuing care locations, the second largest PACE program in the country, 142 urgent care locations and many other health and well-being services. In fiscal year 2024, the Livonia, Michigan-based health system invested $1.3 billion in its communities in the form of charity care and other community benefit programs. For more information, visit us at www.trinity-health.org, or follow us on LinkedIn, Facebook, and X (formerly known as Twitter).