What is it about?

Our saliva contains an enzyme called amylase, which starts breaking down starches as soon as we eat. The amount of this enzyme varies between people because of differences in a gene called AMY1. This gene can appear in the human genome anywhere from 2 to 20 times, depending on the individual. This study explored how variations in the number of AMY1 gene copies—and the resulting salivary amylase activity—relate to type 2 diabetes (T2D). Researchers collected saliva from people with and without diabetes and measured both their gene copy number and enzyme activity. They found that more copies of the gene generally led to higher enzyme activity, but that people with diabetes showed a steeper increase in enzyme levels for each extra gene copy. Enzyme levels also tended to rise over the course of the day. The findings suggest that people with T2D may experience an increase in salivary amylase activity as a way to help regulate blood sugar. Understanding these relationships could lead to better ways to predict or manage diabetes, using non-invasive saliva tests.

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Why is it important?

This study is unique because it investigates genetic, physiological, and environmental factors (i.e., AMY1 copy number, amylase activity, and time of day) in relation to type 2 diabetes status, while also addressing the accuracy of different lab methods used to measure gene copy number. While accounting for these variables, it shows that the relationship between AMY1 copy number and salivary amylase activity is not static—it is stronger in individuals with T2D or prediabetes. This introduces the idea that higher amylase activity may be a compensatory response to impaired glucose regulation. The article is timely because it contributes clarity to an ongoing debate about the role of AMY1 in metabolic health, and addresses concerns about inconsistent findings due to differences in measurement methods. By confirming the reliability of qPCR versus ddPCR depending on the PCR protocol, it opens the door for more accessible research on gene copy number in broader population studies. As interest in precision nutrition and non-invasive metabolic markers grows, this work has the potential to influence clinical strategies and research design.

Perspectives

Research on the AMY1 gene has been fraught with contradictions—some studies link higher copy numbers to lower T2D risk and higher glucose response to digestible starch, while others link lower copy numbers to obesity or no effect at all. Much of the confusion stems from methodological differences and a tendency to treat gene copy number as the sole relevant variable. This article makes a meaningful contribution by examining the interplay between AMY1 copy number, salivary amylase activity, and disease state. Another critical factor that other studies have considered is carbohydrate intake. Habitual intake of digestible starch versus whole grains likely has a tremendous impact directly in the small intestine and indirectly via pathways modulated by the gut microbiome. By showing that salivary amylase activity scales more dramatically with gene copy number in people with T2D or prediabetes, the study reframes AMY1 as not just a fixed genetic risk factor, but a gene whose effects can be modulated by health status. It also underscores the need to measure enzyme activity directly, not just gene dosage, especially in metabolic studies. The study reinforces that metabolic health is influenced by both inherited genetic architecture and adaptive physiological responses. It also suggests that salivary amylase activity could serve as a non-invasive biomarker for early metabolic dysfunction—a valuable insight as researchers seek low-cost screening tools and personalized dietary interventions. Going forward, the field may shift from solely genotyping AMY1 to incorporating real-time biomarker measurements to better understand—and perhaps predict—the onset of metabolic disease.

Angela Poole
Cornell University

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This page is a summary of: The association between salivary amylase gene copy number and enzyme activity with type 2 diabetes status, PLOS One, July 2025, PLOS,
DOI: 10.1371/journal.pone.0324660.
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