Nutrition scientists have been working to understand the relationship between Type 2 diabetes and genes that express a salivary enzyme that breaks down starch, but many conflicting studies have led to few clear answers.
Now, a new study published July 2 in PLOS One brings some clarity to the association. It was previously known that people with more copies of the genes that express salivary amylase (called AMY1) produce more salivary amylase enzyme. The new paper supports the idea that having more copies of the AMY1 gene may be protective against Type 2 diabetes, though additional long-term studies are needed to prove the theory. If researchers do eventually prove a clear association between AMY1 copy number and diabetes, it could lead to genetically testing people at birth to predict their susceptibility.
"If you knew you had an increased risk of diabetes from day one, it may affect your daily choices, your life choices earlier on where you could prevent it from developing later in life," said Angela Poole, assistant professor of molecular nutrition in the Division of Nutritional Science in the College of Agriculture and Life Sciences.
"This is a big deal because diabetes is very prevalent and its prevalence is increasing," Poole said.
AMY1 genes have duplicated over time, and people can have between two and twenty copies. Salivary amylase breaks down starches into sugars, to start the digestion process, but some have questioned whether more efficient starch breakdown would exacerbate Type 2 diabetes. The disease is a chronic condition in which the body has trouble producing insulin or cells fail to properly respond to it, causing high blood sugar levels.
Prior studies by other researchers had tried to examine the association between the number of AMY1 copies and diabetes risk, but results have been conflicting. Some studies used an analog lab technique called qPCR (quantitative polymerase chain reaction) while others used a more modern technique called digital PCR. These techniques amplify and quantify specific DNA sequences. Many scientists believe that the qPCR technique leads to inaccurate findings, which accounts for the differing results.
In Poole's current study, the researchers genotyped - identified a person's unique genetic make-up - more than 100 patient samples, each belonging to one of two groups: individuals who self-reported having Type 2 diabetes or prediabetes, and those who self-reported being without Type 2 diabetes or prediabetes. They found that when the qPCR protocol was properly run, there was a little more variability compared to digital PCR, but the two techniques matched up very well, giving comparable values for AMY1 copy numbers.
"You shouldn't assume a finding is wrong because they used qPCR," Poole said.
Also, the researchers collected measurements from each participant of amylase activity very early in the morning after fasting and in the evening. They found that morning readings were much lower than they were in the evenings. "We looked into the literature and there is a diurnal effect," Poole said. "Regardless of copy number, amylase activity differs throughout the day." That means when researchers conduct studies, they should collect samples at the same time of day and not mix morning and evening readings.
When they compared participants, they found that salivary amylase activity was higher for each additional copy of AMY1 in those with Type 2 diabetes or prediabetes, compared to those without either. "If you have two people with a copy number of 10, and one of them has diabetes and one of them doesn't, the person with diabetes will have higher readings, even with the same copy number," Poole said.
The findings have led Poole to suspect that a higher copy number of AMY1 genes may be protective, though more study is needed to verify it.
Since amylase breaks down starch into sugars, common sense would suggest that a higher AMY1 copy number would increase blood glucose and be detrimental to people with Type 2 diabetes. Poole suspects that during chewing of starch, the body senses the glucose, and it causes people with a higher AMY1 copy number to release insulin (which regulates blood glucose and is lacking in diabetics) sooner, leading to a protective effect. Gut microbes may also play a role.
"I suspect that people with a lower copy number are at higher risk for Type 2 diabetes," Poole said. But she added, it also depends on how much starch they eat. To fully answer these questions, future studies will need to control diet, follow people over a long time and have a large number of participants, she said.
Sri Lakshmi Sravani Devarakonda, Ph.D. '23, is the paper's first author; and Jennifer Ren '19, former Poole lab manager, is a co-author.
