Eur J Clin Invest 2012; 42 (6): 579-588 ABSTRACT: Glucose-based methods are currently gold standards for identifying individuals at risk of type 2 diabetes. Obviously, these methods only consider one of many pathologies of impaired glucose metabolism and they all suffer from a poor specificity as type 2 diabetes risk assessment tools. Recently, however, panels of multiple biomarkers reflecting several pre-diabetic pathologies have been developed. Their specificity and potentials for future risk stratification are discussed. As a multifactorial disorder type 2 diabetes calls for a multifactorial treatment approach targeting multiple but modifiable vascular risk factors. The same holds for pre-diabetic states and prevention hereof. In addition, type 2 diabetes and pre-diabetes show major heterogeneity between affected individuals in pathology, risk of organ damages, progression rate and responsiveness to treatment or prevention. Despite the heterogeneity and uniqueness of type 2 diabetes and pre-diabetes most affected individuals are currently offered interventions as if they all have the same disease or risk of disease and will respond similarly. The complex origin and course of type 2 diabetes combined with uniformity and non-specificity of current interventions may explain the high rate of treatment failures and the relative poor prognosis of many diabetes patients. Given this situation, the present review also explores the perspectives of selected examples within applied genomics and metagenomics for improving patient care by facilitating interventions tailored to specific subpopulations.