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Nothing to spit at: the salivary proteome of type 2 diabetes
ingly, the levels of some proteins, such as alpha-1-antitrypsin (A1AT) and alpha-2-macroglobulin, correlated with With the incidence of type 2 diabetes disease progression. For example, the mellitus reaching near-epidemic prolevel of A1AT in saliva increased proportions, reliable, noninvasive diagnosgressively in the following order: contic tests are more important than ever. trol < IGT < IGT + IFG < type 2 diaMany patients, especially children, betes. Nagalla says, “These results dread the inevitable needle prick show that the process of becoming needed to obtain blood for diagnostic diabetic is not like flipping a switchsa testing, as well as the requirement for significant number of profasting or glucose ingestion. teomic changes occur over a Wouldn’t simply spitting into a period of time before we clascup be a much more appealsify the subject as diabetic.” ing alternative? To identify poThe potential salivary biotential biomarkers of type 2 markers could improve the diagdiabetes and prediabetes that nosis of diabetes and prediabecould be detected by a saliva tes, allow doctors to tailor test, Charles Roberts, Srinivasa interventions to specific disease Nagalla, Paturi V. Rao, and colstages, and assist in monitoring leagues at DiabetOmics, LLC, therapy and complications. Roband Nizam’s Institute of Medierts notes that all current tests cal Sciences University (India) for type 2 diabetes involve glucompared the salivary procose levels. “We’re basically preteomes of individuals with and dicting, monitoring, and assesswithout type 2 diabetes. Reing diabetes with glucose levels, sults from their study were in one way or another, and published in JPR (DOI that’s pretty one-dimensional; 10.1021/pr8003776). To avoid complications of maybe we’re missing a lot,” he diabetes such as cardiovascusays. “By looking at a whole lar disease and renal dysfunchost of proteins in the salivary tion, early diagnosis and treatproteome, we’re trying to be Possible salivary biomarkers. With MS identification strategies, ment are critical. Researchers much more multidimensional, researchers have found candidate biomarkers that could help in the now recognize a continuum of and potentially much more acdiagnosis of diabetes and prediabetic conditions. diabetic disorders that ranges curate and informative, with from various prediabetic conthese diagnostic approaches.” fieds33% for the first time in human ditions to full-blown type 2 diabetes. The research team is further characterizsaliva. The amounts of the identified “Several studies have reported that ing the potential biomarkers of type 2 proteins in normal and diabetic saliva early intervention delays the onset of diabetes and prediabetes in a larger were compared by spectral counting. type 2 diabetes,” says Nagalla. “If you cohort. Sixty-five proteins were differentially could delay the onset, you could poThe researchers also plan to investiabundant in the saliva of control subtentially delay the unwanted complicagate whether salivary biomarkers could jects and patients with type 2 diabetes, tions associated with diabetes. But for provide an alternative to the daily and most of these proteins were inus to intervene, we have to establish monitoring of blood glucose levels. “The volved in metabolism or immune rethat an individual is in a prediabetic biggest noncompliance issue with diasponse. Many of the potential biomarstate.” betics is that they have to check their In addition to being relatively invakers had been linked with diabetes in blood glucose by pricking their fingers sive, current diagnostic proceduress analyses of other body fluids. numerous times throughout the day,” including the impaired fasting glucose The relative abundances of some of says Nagalla. “If we can find other ways (IFG), impaired glucose tolerance the 65 potential biomarkers in normal to do that, for example, with the salivary (IGT), and hemoglobin A1C testssall and diabetic saliva samples were veriproteome, it will have immense utility rely on glucose levels. According to Nafied by western blotting and ELISA. In because the patients are going to be galla, “There’s some debate over addition, the investigators examined more adherent to what you ask them to whether glucose is the best parameter the levels of these proteins in saliva do.” to assess the metabolic state for prefrom individuals with two types of pre—Laura Cassiday diabetes or diabetes complications. So diabetes (IGT or IGT + IFG). InterestJULIE FARRAR
we wanted to look in an unbiased way at the spectrum of diabetic states to see if there are other markers of metabolic changes.” To characterize salivary proteomes, whole-saliva samples from five normal controls and five patients with type 2 diabetes were pooled separately and subjected to 2D-LC/MS/MS. A total of 487 unique proteins were identi-
10.1021/pr8008397
© 2009 American Chemical Society
Journal of Proteome Research • Vol. 8, No. 1, 2009 3
