1,5-Anhydroglucitol in Saliva Is a Noninvasive Marker of Short-Term Glycemic Control

Context: In most ethnicities at least a quarter of all cases with diabetes is assumed to be undiagnosed. Screening for diabetes using saliva has been suggested as an effective approach to identify affected individuals. Objective: The objective of the study was to identify a noninvasive metabolic marker of type 2 diabetes in saliva. Design and Setting: In a case-control study of type 2 diabetes, we used a clinical metabolomics discovery study to screen for diabetes-relevant metabolic readouts in saliva, using blood and urine as a reference. With a combination of three metabolomics platforms based on nontargeted mass spectrometry, we examined 2178 metabolites in saliva, blood plasma, and urine samples from 188 subjects with type 2 diabetes and 181 controls of Arab and Asian ethnicities. Results: We found a strong association of type 2 diabetes with 1,5-anhydroglucitol (1,5-AG) in saliva (P = 3.6 × 10−13). Levels of 1,5-AG in saliva highly correlated with 1,5-AG levels in blood and inversely correlated with blood glucose and glycosylated hemoglobin levels. These findings were robust across three different non-Caucasian ethnicities (Arabs, South Asians, and Filipinos), irrespective of body mass index, age, and gender. Conclusions: Clinical studies have already established 1,5-AG in blood as a reliable marker of short-term glycemic control. Our study suggests that 1,5-AG in saliva can be used in national screening programs for undiagnosed diabetes, which are of particular interest for Middle Eastern countries with young populations and exceptionally high diabetes rates.