Type 2 diabetes strains people’s lives and the U.S. health care system. More than an estimated 29 million people in the country have the disease.

In addition, currently 86 million people in the U.S. have an early stage of type 2 diabetes, known as prediabetes. This is a state in which the body’s blood sugar levels are elevated, indicating the possibility that the body could progress to the full state of the disease. However, roughly 9 out of 10 people in this early stage don’t know it.

In the last few years, the Centers for Disease Control and Prevention and the American Medical Association developed the Prevent Diabetes STAT (Screen, Test, Act Today) campaign to increase awareness of prediabetes so people with elevated blood sugar can begin remedying their health to reduce further health risks.

“These organizations called the whole nation to be aware of prediabetes screening because we don’t have a cure for type 2 diabetes,” said Zhiyong Cheng, an assistant professor of human nutrition, foods and exercise in the College of Agriculture and Life Sciences.

“Since we don’t have a cure, we have to diagnose those with prediabetes as early as possible to prevent more people from having the disease.”

As a nutrition scientist, Cheng works to develop a diagnostic system for early risk factors, such as certain molecular and cellular changes, which could ultimately help identify risk sooner.

Recently, he and a team of collaborators at Virginia Tech, Carilion Clinic, and the University of Nebraska Medical Center found that changes in mitochondria, the main energy producer in cells, may be a better biomarker of early prediabetes than other diagnostic tools currently in use.

Their results were recently published in the open access journal Oxidative Medicine and Cellular Longevity.

Nutrition researchers have found that changes in mitochondria, the main energy producer in cells, may be an effective biomarker for early stage prediabetes. Red arrows point out the mitochondria; the yellow arrow points to the cell's nucleus. Image courtesy Zhiyong Cheng.
Nutrition researchers have found that changes in mitochondria, the main energy producer in cells, may be an effective biomarker for early stage prediabetes. Red arrows point out the mitochondria; the yellow arrow points to the cell’s nucleus. Image courtesy Zhiyong Cheng.

They recruited 87 participants across three health conditions: healthy, prediabetic, and those diagnosed with type 2 diabetes.

Using blood samples from the participants, they evaluated the levels of fasting glucose and glycated hemoglobin (also known as A1c), which are two parameters recommended by the American Diabetes Association to determine whether a person has type 2 diabetes or prediabetes.

Overall, they found that these measures inconsistently represent the diagnosed health conditions.

“When we used the two major parameters, we found a wide variation between how they represent the health of patients,” said Cheng, who is an affiliated researcher with the Fralin Life Science Institute and the Fralin Translational Obesity Research Center.

“These two variables tell different stories, so there’s something missing. The goal to pursue a consistent diagnosis prompts us to identify a new biomarker for people with higher risk.”

The body relies on mitochondria – tiny organelles that produce energy and underpin cellular functions. Healthy people have 800-1200 mitochondria in their cells, but this number is significantly reduced for obese people with prediabetes, according to a 2015 study by Cheng and collaborators.

Since then, Cheng and his team have been exploring why prediabetic individuals had fewer mitochondria. In doing so, they found the molecular process of making mitochondria changes as people become resistant to insulin. This process is known as mitochondrial DNA methylation, which takes place in a region of the mitochondrial genome that mediates mitochondrial duplication.

In this new study, the researchers identified changes in the DNA methylation in another region of the mitochondrial genome, the region which controls the production of a mitochondrial protein that affects how mitochondria function.

The researchers found that these mitochondrial changes were poorly linked to fasting glucose and hemoglobin A1c levels, which tend to predict risk of type 2 diabetes only one to two and a half years before its onset. Instead, these changes were strongly associated with impaired insulin sensitivity, which can be tracked up to five years before disease onset.

Since these changes in mitochondrial DNA methylation are significantly correlated with insulin resistance – an early stage predictor – they may be a potential indicator or biomarker of early stage prediabetes.

“If we have a more effective diagnostic system, we would be able to help people better understand their risks,” said Fabio Almeida, a former Virginia Tech investigator who is now in the College of Public Health at the University of Nebraska Medical Center.

“Increasing evidence shows that epigenetic changes such as DNA methylation can reflect the human-environment interaction and risks of disease. The good news for people who have higher risk for developing diabetes is there’s a very good chance to reverse the disease risks if we can identify the individuals as early as possible and implement lifestyle interventions.”

This project was part of a larger parent study in the diaBEAT-it program, which is designed to raise awareness and help prevent onset of type 2 diabetes. The study was supported in part by the USDA National Institute of Food and Agriculture Hatch Project (1007334) and by a grant from the National Institutes of Health (5R18DK091811-02).