Abstract

Type 2 diabetes mellitus (T2DM) is an increasing global public health concern, but its impact on the salivary proteome is still unclear. To evaluate the effect of glycemic levels in middle-aged and elderly individuals with T2DM on salivary proteomics, we compared the differences by liquid chromatography tandem mass spectrometry (LC–MS/MS). Unstimulated whole saliva samples from 8 T2DM patients with good glycemic control (G group, HbA1c <6.5%) and 16 patients with poor control (P group, HbA1c ≥6.5%) were analyzed by LC–MS/MS in the data-independent acquisition mode (Clinical register number: ChiCTR1900023582.). After functional annotation, cluster analysis and receiver operating characteristic (ROC) curve analysis were carried out to screen and evaluate candidate proteins. A total of 5,721 proteins were quantified, while 40 proteins differed significantly. In the P group, proteins involved in oxidative stress-related processes were upregulated, whereas proteins related to salivary secretion were downregulated. The combination of thioredoxin domain-containing protein 17, zymogen granule protein 16B, and FAM3 metabolism regulating signaling molecule D yielded an area under the curve of 0.917 which showed a robust ability to distinguish the P and G groups. In conclusion, poorly controlled hyperglycemia may affect salivary proteins through various pathways, including oxidative stress and glandular secretion. Furthermore, the differentially expressed proteins, especially the three proteins with the best differentiation, might serve as an anchor point for the further study of hyperglycemia and oral diseases.

Highlights

  • Diabetes mellitus (DM) is a common metabolic disease manifesting as defects in insulin secretion, insulin action or both, which results in a type of hyperglycemic status

  • We investigated the proteomic profile of whole saliva by LC-MS/MS with the Data-independent acquisition (DIA) mode in Type 2 diabetes mellitus (T2DM) patients with satisfactory glycemic control in comparison with the poorlycontrolled individuals

  • From April 2019 to July 2019, we recruited 24 subjects, and they all signed written informed consent forms. After matching their periodontal condition and other indicators, they were divided into two groups according to their glycosylated hemoglobin A1c (HbA1c) levels: a well-controlled group (n 8; one male and seven females; HbA1c

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Summary

Introduction

Diabetes mellitus (DM) is a common metabolic disease manifesting as defects in insulin secretion, insulin action or both, which results in a type of hyperglycemic status. Type 2 diabetes mellitus (T2DM) accounts for over 90% of cases of DM worldwide and Glycemic Levels and Salivary Proteomics has become an increasing global public health concern. In addition to the complications of diabetes mentioned above, there are many oral manifestations associated, including periodontitis, dental caries, oral candidiasis, and salivary dysfunction (Mauri-Obradors et al, 2017). Diabetic patients suffer from vascular endothelial damage due to specific vascular diseases and are vulnerable to invasion and injury, coupled with an increased systemic inflammatory response in hyperglycemia (Graves et al, 2020). All of these factors promote the occurrence and development of oral complications

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