The association between salivary amylase gene (AMY1) copy number (CN) and metabolic health parameters, such as insulin resistance, has been studied but with conflicting results. The cause of these inconsistencies is multifaceted and confounded by differences in genotyping methods. In this study, we investigated the factors that affect the association between AMY1 CN, salivary amylase activity (SAA), and type 2 diabetes (T2D) status. We collected up to four saliva samples from two cohorts: individuals with self-reported T2D or prediabetes (n = 18) and individuals who self-reported as being without T2D or prediabetes (controls, n = 178). We genotyped individuals for AMY1 CN using both quantitative PCR and droplet digital PCR and measured SAA in the saliva samples. We demonstrated that these two commonly used methods give comparable values for AMY1 CN. We showed a positive association between the time of saliva collection and SAA throughout the day. We also observed that AMY1 CN and SAA are positively associated in individuals with and without T2D or prediabetes. With increasing AMY1 CN, SAA was higher for each additional copy of AMY1 CN in individuals with T2D or prediabetes compared to controls. Our findings support the premise that increased SAA in T2D patients is a compensatory mechanism related to the long-term protective effect of high AMY1 CN on glucose metabolism.

The authors have declared no competing interest.

This study did not receive any funding.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The Institutional Review Board of Cornell University gave ethical approval for this work (Approval Number: 1902008575 [starch study] and 1808008178 [T2D microbiome study]).

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All data produced in the present study will be publicly available upon publication of the manuscript in a peer-reviewed journal.