Main Line Health scientists receive federal grant to study molecule that may be key to preventing life-threatening diabetes complications

Controlling 3DG may do what lowering glucose has not for diabetes-related kidney and heart disease, stroke

Diabetes can lead to a variety of potentially life-threatening complications, putting patients at increased risk of kidney disease, heart disease, stroke, and other serious conditions. Lankenau Institute for Medical Research (LIMR), part of Main Line Health, will study unexplored pathways that may cause these complications and seek to develop new treatments after being awarded a three-year, $1.67 million federal grant.

The causes of diabetes complications have remained elusive despite decades of research. Supported by a National Institute of Diabetes and Digestive and Kidney Disease grant, the research team will study the effects of a glucose-derived molecule called 3-deoxyglucosone (3DG) that has seen relatively little investigation to date.

“While there are numerous drugs to lower glucose in the bloodstream, they do not directly target 3DG as a bad actor in diabetes,” said George Prendergast, PhD, President and CEO of LIMR and principal investigator for the program. “Indeed, recent research has shown that intensive glucose control does little to reduce complications for most diabetic patients. Innovative drugs that safely lower 3DG may hold the key to preventing diabetes complications, such as heart attacks, kidney failure, liver disease, and wound healing that proceeds slowly or not at all.”

LIMR scientists will seek to identify new drug candidates that can block production of the disease-causing molecule. They also will investigate a source of 3DG production that might explain its elevation in diabetic patients. Research into 3DG and its source might lead to its use to predict the course of disease and prevent complications, much like the discovery of cholesterol did in the 20th century for heart attacks.

“The grant supports establishing how 3DG is produced within cells and the effect of this production on diabetic complications,” said Melvin Reichman, PhD, senior investigator at LIMR and principal investigator for the project. “It also supports learning how certain food components may increase 3DG production and identifying new drug candidates that lower levels of 3DG as an innovative therapeutic strategy.”

More than 34 million Americans overall—just over 1 in 10—have diabetes. An estimated one-third of them have chronic kidney disease, according to the U.S. Centers for Disease Control.

Lisa Laury-Kleintop, PhD, a LIMR associate professor and expert in preclinical models of diabetes and heart disease, is another key investigator for the project. The LIMR team will be joined by renowned scientists at three other academic institutions for this multidisciplinary project. The research program is 100% federally funded.