What drives inflammation in type 2 diabetes? Not glucose, says new research

To date, the underlying causes of inflammation in obesity and type 2 diabetes mellitus (T2DM) have been poorly understood, which has been hampered efforts to develop treatments to prevent complications from being the third leading cause of death in the United States.

Purpose New research at the University of Kentucky shows that changes to mitochondria-the powerhouse of cells-drive chronic inflammation of cells exposed to certain types of fats, which assumes that glucose is the culprit.

Chronic inflammation fuels many of the devastating complications of type 2 diabetes, including cardiovascular, kidney, and periodontal diseases, and is thus one of the key targets for therapy development. This new data can be used to treat people with diabetes.

The research was recently published in Cell Metabolism Barbara Nikolajczyk (UK Barnstable Brown Diabetes Center, Department of Pharmacology and Nutritional Sciences) and Douglas Lauffenberger (MIT Department of Biological Engineering).

Nikolajczyk and Lauffenberger did not set out to disprove glucose-inflammation causation theory. Based on the importance of glycolysis-a 10-reaction sequence that produces energy-in other types of inflammation, the team hypothesized that immune cells from type 2 diabetes would produce energy by burning glucose. "We were wrong," Nikolajczyk said.

"We have used this method to explain the role of diabetes," said Nikolajczyk, "Noting that humans, but not animal models of diabetes, have the specific pro-inflammatory T cell profile her team had identified in earlier research.

The team was surprised to find that glycolysis was not driving chronic inflammation. Instead, a combination of defects in mitochondria and elevated fat derivatives were responsible.

Nikolajczyk said she sees applications for this research in both basic and clinical sciences. One of the most important lipid types in the world, and one of the key features of this study is to identify lipid types and explore two types of diabetes. She is also interested in contributing to the development of new analytical approaches, spearheaded by Dr. Lauffenburger's team, which suggests ongoing lipid-related findings in a new understanding of pathology in type 2 diabetes.

"Aggressive blood glucose control to lower the risk of diabetic complications," said Nikolajczyk. "Our data provide an explanation for why people with tight glucose control can not have disease progression."