Salivary protein glycosylation as a noninvasive biomarker for assessment of glycemia.

Assessment of short-term glycemic control can facilitate monitoring of diabetes development in at-risk individuals and monitoring response to lifestyle modification or medication. We evaluated salivary protein glycosylation levels as a novel, noninvasive, short-term glycemic index in comparison to hemoglobin A1c (HbA1c), fructosamine, 1,5-anhydroglucitol (1,5-AG), and continuous glucose monitoring (CGM). Ten subjects with type 2 diabetes were monitored by CGM and saliva and blood were collected at baseline and days 1, 7, 14, 21, and 28 for determination of salivary protein glycosylation, serum fructosamine, and serum 1,5-anhydroglucitol (1,5-AG) levels, as well as HbA1c (baseline and day 28). Weekly, 14-day, 21-day, and 28-day summary blood glucose measures from CGM were computed and matched to the time of each study visit. Salivary protein glycosylation exhibited a moderate correlation with fructosamine (r = .65) and 1,5-AG (r = -.48) at baseline, and weak correlation with HbA1c (r = .3). Salivary protein glycosylation exhibited a stronger correlation than fructosamine and 1,5-AG with 7-, 14-, and 21-day average BG (r = .84, .84, and .69, respectively, vs -.37, -.28, and .00 [fructosamine] and .00, -.21, and -.57 [1,5-AG]), maximum BG (r = .79, .76, and .53 vs -.09, -.21, and -.05 [fructosamine] and -.32, -.27, and -.52 [1,5-AG]), and percentage of time over 140 mg/dL (r = .87, .79, and .59 vs -.26, -.32, and .07 [fructosamine] and -.04, -.10, and -.50 [1,5-AG]). Salivary protein glycosylation represents a promising noninvasive technology for monitoring short-term glycemic control.

Proteomic identification of salivary biomarkers of type-2 diabetes.

The identification of biomarkers to noninvasively detect prediabetes/diabetes will facilitate interventions designed to prevent or delay progression to frank diabetes and its attendant complications. The purpose of this study was to characterize the human salivary proteome in type-2 diabetes to identify potential biomarkers of diabetes. Whole saliva from control and type-2 diabetic individuals was characterized by multidimensional liquid chromatography/tandem mass spectrometry (2D-LC-MS/MS). Label-free quantification was used to identify differentially abundant protein biomarkers. Selected potential biomarkers were then independently validated in saliva from control, diabetic, and prediabetic subjects by Western immunoblotting and ELISA. Characterization of the salivary proteome identified a total of 487 unique proteins. Approximately 33% of these have not been previously reported in human saliva. Of these, 65 demonstrated a greater than 2-fold difference in abundance between control and type-2 diabetes samples. A majority of the differentially abundant proteins belong to pathways regulating metabolism and immune response. Independent validation of a subset of potential biomarkers utilizing immunodetection confirmed their differential expression in type-2 diabetes, and analysis of prediabetic samples demonstrated a trend of relative increase in their abundance with progression from the prediabetic to the diabetic state. This comprehensive proteomic analysis of the human salivary proteome in type-2 diabetes provides the first global view of potential mechanisms perturbed in diabetic saliva and their utility in detection and monitoring of diabetes. Further characterization of these markers in a larger cohort of subjects may provide the basis for new, noninvasive tests for diabetes screening, detection, and monitoring.