OKLAHOMA CITY – The epidemic of Type 2 diabetes has taken a toll on thousands of Oklahomans who often don’t know they have the disease until it has irreparably damaged their bodies. A researcher at Harold Hamm Diabetes Center at OU Medicine is studying ways to predict who will get diabetes, so that physicians can intervene earlier.
Dharambir Sanghera, Ph.D., recently received a $2.5 million grant from the National Institutes of Health to further her diabetes research, which aims to understand how a person’s genetic makeup interacts with lifestyle factors like poor diet and lack of exercise to lead to diabetes.
Unlike diseases like cystic fibrosis, which is caused by a defect in one major gene, diabetes is caused by multiple genetic defects in combination with a person’s lifestyle, Sanghera said. Although people who are obese face a higher risk for diabetes, some people who are overweight never get the disease. Understanding why could hold the key to predicting, at an early stage, who is likely to get diabetes. “Diabetes is a devastating disease,” she said. “It can cause heart disease, stroke, hypertension, kidney failure, blindness and more. Our intent is to identify biomarkers that can be used to predict diabetes, then we can begin treating individuals who are at the highest risk.”
Since the human genome was sequenced in the early 2000s, researchers have identified more than 100 genes that likely contribute in some way to diabetes, Sanghera said. However, very little is known about which of those genes play a role and to what extent. To illuminate that process, Sanghera is using a new approach called metabolomics. State-of-the-art technology will be used to create a snapshot of a person’s metabolomics profile, which will be combined with their lifestyle factors, to see if patterns come to light.
“In the human body, genes are the chemicals that produce proteins, and proteins determine whether a person has a disease like diabetes,” she said. “However, in diabetes, researchers are still trying to understand what happens in the process of genes creating proteins. With metabolomics, we can bridge the gap between genes and proteins and gain functional readouts of what is going on in our bodies.”
In her research, Sanghera will profile more than 4,600 people, looking for genetic and metabolomics patterns that emerge, such as a chemical compound that consistently increases its response to insulin resistance. Because Sanghera’s team also knows each person’s lifestyle profile – what they eat, how much they exercise, stressors they face – the research is highly personalized. Sanghera’s research project is also unique because of the technology used, called mass spectrometry and gas chromatography. The technologies themselves are not new, but only in more recent years have they been able to read more than one sample at a time. A large number of samples is necessary to work toward a meaningful solution. “This technology is considered high throughput – they can read thousands of metabolites in one single sample,” she said. “If you’re looking at only 50 or 100 patients, you might find something interesting, but you have to have large data sets to discover something that might be applicable to patient care.”
Sanghera predicts that in the future, physicians will order a genetic risk score test just as they order lab tests to check their patients’ cholesterol panel. She hopes her research helps to pave the way toward that reality and its potential to help people at risk for diabetes. “We are tackling this problem in multiple ways – we know that it’s not only genetics that causes diabetes, and it’s not only lifestyle. It’s their interaction, and that’s why it’s complicated,” she said. “Metabolomics is enabling us to sort it out and find solutions.”
Research reported in this press release was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under the award number 1R01DK118427-01A1. Sanghera leads the grant, working with collaborators Ravindranath Duggirala, Ph.D., and Harald Goring, Ph.D., at the University of Texas Rio Grande Valley.
Sanghera’s research is also supported by the Presbyterian Health Foundation in Oklahoma City, which awarded a bridge grant that allowed her to earn the current NIH grant.