PROTON: Personalising Treatment of Diabetic Nephropathy

Outcome of diabetic nephropathy has improved with treatment of blood pressure with agents blocking renin angiotensin system, but the prognosis is still poor. A more detailed understanding of the diversity of diabetic renal complications is crucial to advance the field. Therefore, new targets for better interventions and markers for risk of side effects are urgently needed.


Proton is a cross-sectional study with 160 patients with type 1 diabetes and different stages of diabetic nephropathy (50 with normoalbuminuria; 50 with microalbuminuria; and 60 with macroalbuminuria - compared to 50 healthy non-diabetic controls). A detailed phenotyping of this cohort will provide information on differences in phenotype associated with renal disase and thus will enable an increased understanding of what determines individual development and progression of diabetic renal complications.


In general, single marker strategies have pointed towards potential new candidates related to e.g. inflammation or growth factors, but only added very little to the already applied phenotypic characteristics of diabetic nephropathy including urinary albumin excretion, whereas an emerging interest in multimarker strategies have shown promising results, but still at an early stage.

Therefore, a deep multidimensional phenotypic characterisation, including glycocalyx thickness in relation to gut microbiota and potential pathological biomarkers associated with initiation and progression of diabetic renal disease may allow for new intervention strategies and personalised treatment in the future based on specific disease mechanisms and biomarkers of the individual person.


Aim

By using a multidimensional ‘omics’ approach and a deep multidimensional phenotypic characterisation, we aim to search for novel proteins, metabolites and pathways that will point to the putative new mechanisms which underlie the early renal decline related to diabetic nephropathy.

Collaborators

The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of metabolic Genetics, University of Copenhagen  
Department of system medicine, SDCC

Novo Nordisk, Måløv

Folkhälsan Research Center/FinnDiane Biomedicum, Helsinki, Finland

Genetics and Epidemiology, Joslin Diabetes Center, Boston, US

Universitair Medisch Centrum Groningen, The Nederlands


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