Geneticist Michael Snyder, PhD, has almost no privacy. For more than two years, he and his lab members at the Stanford University School of Medicine pored over his body’s most intimate secrets: the sequence of his DNA, the RNA and proteins produced by his cells, the metabolites and signaling molecules wafting through his blood. They spied on his immune system as it battled viral infections.
Finally, to his shock, they discovered that he was predisposed to type-2 diabetes and then watched his blood sugar shoot upward (hyperglycemia) as he developed the condition during the study. It’s the first eyewitness account — viewed on a molecular level — of the birth of a disease that affects millions of Americans. It’s also an important milestone in the realization of the promise of truly personalized medicine, or tailoring health care to each individual’s unique circumstances.
The researchers call the unprecedented analysis, which relies on collecting and analyzing billions of individual bits of data, an integrative Personal “Omics” Profile, or iPOP. The word “omics” indicates the study of a body of information, such as the genome (which is all DNA in a cell), or the proteome (which is all the proteins). Snyder’s iPOP also included his metabolome (metabolites), his transcriptome (RNA transcripts) and autoantibody profiles, among other things.
“I was not aware of any type-2 diabetes in my family and had no significant risk factors,” said Snyder, “but we learned through genomic sequencing that I have a genetic predisposition to the condition. Therefore, we measured my blood glucose levels and were able to watch them shoot up after a nasty viral infection during the course of the study.”
As a result, he was able to immediately modify his diet and exercise to gradually bring his levels back into the normal range and prevent the ongoing tissue damage that would have occurred had the disease gone undiagnosed.
For Snyder, one set of measurements was particularly telling. On day 301, about 12 days after a viral infection, his glucose regulation appeared to be abnormal. Shortly thereafter his glucose levels became elevated, prompting him to visit his primary care physician. On day 369, he was diagnosed with type-2 diabetes.
“We are all responsible for our own health,” said Snyder, who is also the director of the Stanford Center for Genomics and Personalized Medicine. “Normally, I go for a physical exam about once every two or three years. So, under normal circumstances, my diabetes wouldn’t have been diagnosed for one or two years. But with this real-time information, I was able to make diet and exercise changes that brought my blood sugar down and allowed me to avoid diabetes medication.”
A number of molecular cues led to the discovery of Snyder’s diabetes. His genomic sequence suggested he had an increased risk for high cholesterol, coronary artery disease (which he knew already), as well as basal cell carcinoma and type-2 diabetes, which was unexpected. Conversely, the sequence predicts his risk for hypertension, obesity and prostate cancer is lower than that of other men his age (54 when the study started). Based on the type-2 diabetes prediction, the team decided to also monitor Snyder’s blood sugar levels, which were normal when the study began.
Snyder, who has two small children, experienced two viral infections during the course of the study: one with rhinovirus (at day 0), and one with respiratory syncytial virus (beginning at day 289). Each time, his immune system reacted by increasing the blood levels of pro-inflammatory cytokines — secreted proteins that cells use to communicate and coordinate their responses to external events such as an infection.
Snyder also exhibited increased levels of auto-antibodies, or antibodies that reacted with his own proteins, after viral infection. Although auto-antibody production can be a normal, temporary reaction to illness, the researchers were interested to note that one in particular targeted an insulin receptor binding protein.
In Snyder’s case, the researchers observed unexpected relationships and pathways between viral infection and type-2 diabetes by comparing the results of a variety of “omics” studies. “This study opens the door to better understanding this concerted regulation, how our bodies interact with the environment and how we can best target treatment for many other complex diseases at a truly personal level.”
The researchers identified about 2,000 genes that were expressed at higher levels during infection, including some involved in immune processes and the engulfment of infected cells, and about 2,200 genes that were expressed at lower levels, including some involved in insulin signaling and response.
“In the future, we may not need to follow 40,000 variables,” said Snyder. “It’s possible that only a subset of them will be truly predictive of future health. But studies like these are important to know which are important and which don’t add much to our understanding.
Health-e-Solutions comment: The complexity of our bodies’ response to a simple viral infection demonstrates the difficulty in finding a drug that will cure diabetes, any type of diabetes, including type 1 and type 2. Snyder’s dietary changes and exercise were the best medicine he could have taken in his efforts to prevent, even reverse type 2 diabetes. We think the diabetic-alkaline lifestyle is a great tool for managing diabetes, even type 1 diabetes, with the priority on food and exercise rather than on drugs. Drugs are good when you require them, but we believe lifestyle changes should be the first priority with chronic diseases.