The Link Between High Blood Glucose and High Infection Risk

High blood sugar levels increase the chances of a dangerous infection in those with diabetes, experts have long known. Infections in the feet and hands of those with diabetes that can't be brought under control with antibiotics can result in amputation.

diabetes amputationNow, scientists say they may have discovered the mechanism that sets this into motion on the molecular level. What appears to happen, say researchers, is that the high glucose levels associated with type 1 and type 2 diabetes unleash destructive molecules that hamper the body's natural immune defenses that fight infections.

When blood sugar is out of control, ''you have the production of these bad molecules that can attach to certain proteins, and at least in the laboratory we have shown there is a significant effect on immune function," says Wesley Williams, PhD, a research scientist who conducted the study while at Case Western Reserve University School of Dental Medicine.

Eventually, he says, the discovery may lead to the development of better antimicrobials to fight infection. First, however, he says, ''we have to confirm that the high degree of function loss that we see against bacterial and immune cell attacks in the laboratory is going to be as dramatic in a living diabetic."

The study was published in PLOS One on Aug. 5.

In the study, Williams and his team took a close look at the harmful molecules, known as dicarbonyls. They found that two types of dicarbonyls changed the structure of infection-fighting peptides known as human beta-defensin-2. In the process of changing that structure, the harmful molecules hampered the ability of the peptides to fight off bacteria and infection.

The destructive molecule, when exposed to the infection-fighting molecules, also reduced their ability to be ''on the lookout,'' so to speak, for destructive microbes, an important task of the immune system. When they exposed the infection-fighting peptides in the lab to the harmful molecule, it slashed the ability of the peptides to inhibit the bacteria by about half, Williams found.

The research was entirely lab-based, so studies in animal models and human tissues must be done next to verify the findings, Williams says. It's possible, the scientists say, that additional human peptides other than those they studied in the lab could be affected negatively by the harmful molecules.

As the bad molecules accumulate, the infection-fighting peptides could be overwhelmed, Williams says.

The eventual hope, he says, is to develop medicines that would neutralize the pathway of the bad molecules, eliminating their effect. 

"It's certainly interesting," says Aaron Glatt, MD, an infectious disease specialist and spokesman for the Infectious Diseases Society of America. He is also the hospital epidemiologist for the South Nassau Communities Hospital, Oceanside, NY.  He reviewed the study findings. However, he adds that the finding ''doesn't prove anything." More research, he agrees, is needed.

"We've known for a long time that diabetics are at greater risk for infections," Dr.  Glatt says. The more out of control the blood glucose, the higher the risk, he says.

For better blood sugar control, the American Diabetes Association suggests paying attention to diet and exercise, measuring your blood sugar more frequently and perhaps changing your insulin dose and schedule. Guidance from your healthcare practitioner and diabetes support team is needed for all those measures.

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