Diabetes MUltiplex Family STudy

Study Objective

Primary outcomes

• Detailed genomic and metagenomic assessment of the host genome and gut microbial communities in intensively phenotyped and genotyped human subjects from diabetic families.

• Genomic differences between disconcordant siblings and between generations using next generation sequencing and integration of this genomic information with the gut microbiota specifics to generate a network that allows the functional deregulation patterns to be identified compared with known cellular pathways, processes and complexes in order to visualize potential disease modifiers on either host genomic or microbiotic site.

• Metagenomics in selected multiplex diabetes families, based on the outcome of deep microbial community profiling (using a 16S/23S rRNA gene sequencing approach).

• Enterotypes to be compared with existing data bases (Danish, Spanish, US), using systems biomedicine approach (i.e. high-throughput methodologies).

Secondary outcomes

• Extend the generated network by the input of routinely measured parameters and metabolomics from host blood/urine and from gut flora as well as transcriptomics (second phase: proteomics).

• Metagenomics in multiplex families in comparison with Genomic background.

• Metagenomics in relationship with metabolomics, transcriptomics and proteomics.

• Metagenomics in relationship with metabolic status.

• Metagenomics in relationship with lifestyle.

• Prioritize genetic markers for distinct biological situations and deregulations from the systematic analyses and verification of those markers by means of common clinical and laboratory tools or by proof of concept approaches

Patient population

- 4-6 multiplex families with T2DM, at least in two generations, 1 person with and one sibling without T2DM.

- 4-6 multiplex families withT1DM at least in two generations, 1 person with and one without T1DM.

- 4-6 obese families without diabetes at least in two generations, 1 person with (BMI >30 kg/m2) and one without obesity (BMI<25 kg/m2).

- Healthy controls (whole genome screen; microbiome data sets, as present in public domain, open source databases) (20 individuals).
Maximum number of patients to be included (assuming 10 subjects per multiplex family + 20 healthy controls): 200.
 

Centre Hospitalier de Luxembourg