KKG Nutrigenomics and Type 2 Diabetes mellitus

Medical Background

Type 2 diabetes mellitus is a heterogeneous metabolic disease which results from a complex and poorly understood interaction between genetic factors and lifestyle components. Several genome-wide association (GWA) studies have led to the discovery of a still growing number of SNPs associated with the risk of developing diabetes. Most of the identified gene loci are of unknown biological function. Much research effort is still required to identify the responsible genomic variants in the identified loci and to understand the precise functional role of the risk alleles on the molecular level.

Furthermore, at present little is known about the metabolic and other phenotypic consequences in the carriers of these gene variants. Comprehensive lifestyle modification is extremely effective to prevent diabetes in subjects at risk. However, the individual responses to interventions are rather variable, indicating that new concepts are needed for a more individualized and effective prevention and treatment of this disease. It was also reported that some SNPs can be involved in the individual variation of response.

Only a few clinical predictors of type 2 diabetes are known which can be used to disentangle the heterogeneous forms of the disease. Therefore, there is an urgent need for the identification and validation of novel disease biomarkers or biomarker signatures to allow a more precise prediction, besides the different established glucose measures. Hence, it is tempting to develop new provocation tests to achieve a better discrimination in the prediabetic state for early characterization of subjects at risk. To meet this challenge, additional work in terms of standardization and interpretation of novel test methods is required. Furthermore, the current development of novel technologies for a rapid and comprehensive analysis of the human ‘metabolome’ opens new perspectives for the identification of novel, more specific biomarkers. This process depends on the careful clinical phenotyping of human subjects and the precise definition and standardization of the operation procedures.

We use an approach which includes a functional characterization of SNPs as the prerequisite for understanding their effects on diabetes development. In vivo nutrition challenges will help to understand SNP functions and will be explored for their potential as diagnostic tools. Using similar analysis in subjects at risk for diabetes combined with metabolomic approaches, we aim to identify new biomarkers for prediction. Besides the planned projects, the CCG is aiming to serve as a core unit to develop and provide necessary translational methods for the elucidation of the interaction between diabetes gene variants and lifystyle factors, in particular dietary factors.

Project Aim

We aim to understand the molecular mechanisms which account for the biological effects of SNPs, the interaction between diabetes risk SNPs/nutrition/metabolism using a translational research approach and to identify new diabetes biomarkers.