Components of the Purine Metabolism Pathways as Biomarkers for the Early Diagnosis of Diabetes

Abstract

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder characterized by persistent hyperglycemia and often hyperlipidemia. T2DM is usually accompanied with obesity, insulin resistance (IR), inflammation, and oxidative stress. Development of T2DM usually starts from IR and metabolic impairment (prediabetes), which may exist for years before the clinical manifestation of the disease and T2DM diagnosis.Purinosome is an intricate system composed of numerous transporters, receptors, mediators, and catabolic and synthetic enzymes involved in the de novo biosynthesis of purines. This biological system is linked with glucose and lipid metabolic pathways. It is believed that purinosome system enzymes and metabolites regulate insulin secretion and glucose metabolism and consequently are involved in the pathological mechanisms of T2DM development. Numerous studies have reported altered levels of purinsome-based metabolites and enzymes or their catabolic products in obese, prediabetic, and metabolic syndrome subjects. These components of the purine metabolism pathways can be considered early biomarkers for the screening, early diagnosis, and monitoring of diabetes and related complications. Some of them (e.g., isopentenyladenosine-5-monophosphate, uric acid, xanthine, and xanthine oxidase) were reported as T2DM predictive biomarkers. The altered level of key purine enzymes and related metabolites in relation to T2DM, prediabetes, and obesity is discussed in this chapter.KeywordsDiabetesPrediabetesMetabolic diseasesInsulin resistanceObesityPurine metabolismXanthine oxidaseAdenosineInosineUric acidBiomarkers