Diabetes Subphenotypes and Metabolomics: The Key to Discovering Laboratory Markers for Personalized Medicine?

Abstract

For decades, glucose, hemoglobin A 1c , insulin, and C peptide have been the laboratory tests of choice to detect and monitor diabetes (1 ). However, these tests do not identify individuals at risk for developing type 2 diabetes (T2Dm) 4 (so-called prediabetic individuals and the subphenotypes therein), which would be a prerequisite for individualized prevention. Nor are these parameters suitable to identify T2Dm subphenotypes, a prerequisite for individualized therapeutic interventions. The oral glucose tolerance test (oGTT) is still the only means for the early and reliable identification of people in the prediabetic phase with impaired glucose tolerance (IGT). This procedure, however, is very timeconsuming and expensive and is unsuitable as a screening method in a doctorЈs office. Hence, there is an urgent need for innovative laboratory tests to simplify the early detection of alterations in glucose metabolism.The search for diabetic risk genes was the first and most intensively pursued approach for individualized diabetes prevention and treatment. Over the last 20 years cohorts of tens of thousands of people have been analyzed, and more than 70 susceptibility loci associated with T2Dm and related metabolic traits have been identified (2 ). But despite extensive replication, no susceptibility loci or combinations of loci have proven suitable for diagnostic purposes.Why did the genomic studies fail? One reason might be that T2Dm is a polygenetic disease, but there is another more important reason. The large diabetes cohorts investigated in these studies were very heterogeneous, consisting of poorly characterized individuals who were usually selected because they had an increase in blood glucose. Subsequently it has become clear that many different subphenotypes already exist in the prediabetic phase (3, 4 ).Metabolomics represents a new potential approach to move the diagnosis of diabetes beyond the application of the classical diabetic laboratory tests. This strategy means the profiling of hundreds (targeted metabolomics) or thousands (nontargeted metabolomics) of metabolites (5 ).In the current issue of Clinical Chemistry, Liu and coworkers (6 ) present data on the nontargeted metabolomic investigation of fasting serum samples of a T2Dm subtype with IGT as demonstrated by an oGTT [2-h glucose concentration Ն200 mg/dL (11.1 mmol/L)] but fasting glucose concentrations within reference intervals. Following the nomenclature of Liu and coworkers, this T2Dm subtype will henceforth be referred to as isolated postchallenge diabetes (IPD). Of note, IPD remains undetected when only fasting glucose is measured. Fifteen IPD-specific metabolites were identified. Concentrations of these metabolites were significantly different not only between healthy controls and patients with IPD, but also between patients with IPD and individuals with newly diagnosed T2Dm and impaired fasting glucose. Linoleic acid, oleic acid, and dehydroepiandrosterone sulfate were the most powerful markers. In a replication study (n ϭ 400), the area...

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Detección de la alteración del metabolismo glucídico y resistencia a la insulina en una muestra piloto infantil: Aproximación metabolómica

“…Durante décadas, la glucosa, la hemoglobina A1c, la insulina y el péptido C han sido las pruebas de laboratorio de elección para detectar y vigilar la diabetes. Sin embargo, estas pruebas no identifican a los individuos prediabéticos o sus subfenotipos que están en riesgo de desarrollar DM tipo 2, este sería un requisito para la prevención individualizada (17) .…”

“…Este procedimiento, sin embargo, es muy largo y costoso y no es recomendable como método de cribado en una consulta médica. Por lo tanto, existe la necesidad de pruebas de laboratorio innovadoras para simplificar la detección precoz de las alteraciones en el metabolismo de la glucosa (17) . Las nuevas tecnologías para el diagnóstico, como la metabolómica, son herramientas sensibles, específicas y de gran utilidad frente a otras técnicas modernas, como la genómica.…”