PeRsOnalising Treatment Of Diabetic Nephropathy:

Study Overview
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Brief Summary
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Background: Today diabetic nephropathy is a frequent, and the most lethal and costly complication of diabetes. Although treating blood pressure with agents blocking renin angiotensin system has improved outcome, the prognosis is still poor and no new interventions have been successful during the past decade. There is an urgent need for discovery of new pathways behind the development and progression of diabetic nephropathy as well as of biomarkers which can identify subjects at risk of developing adverse events. Objective: By using a multidimensional 'omics' approach, we aim to search for novel proteins, metabolites and pathways that will point to the putative new mechanisms which underlie the early renal decline. Design: Cross-sectional study, with long-term register-based follow-up. Study population: 160 patients with type 1 diabetes recruited from Steno Diabetes Center Copenhagen stratified based on stage of diabetic kidney disease, and 50 healthy non-diabetic controls. Endpoints: Primary endpoint: Glycocalyx thickness, assessed as perfused boundary region. Secondary endpoints: Gut microbiome characterisation and markers of gastrointestinal inflammation, autonomic and periphery neuropathy, urine and plasma Flow Cytometry Analysis (FACS), metabolomics and proteomics in plasma and urine, and other potential biomarkers.

Detailed Description
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Design: Cross-sectional study, with long-term register-based follow-up. Study population: 160 patients with type 1 diabetes recruited from Steno Diabetes Center Copenhagen stratified based on stage of diabetic kidney disease, and 50 healthy non-diabetic controls. Endpoints: Primary endpoint: Glycocalyx thickness, assessed as perfused boundary region. Secondary endpoints: Gut microbiome characterisation and markers of gastrointestinal inflammation, autonomic and periphery neuropathy, urine and plasma Flow Cytometry Analysis (FACS), metabolomics and proteomics in plasma and urine, and other potential biomarkers.

Official Title
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PeRsOnalising Treatment Of Diabetic Nephropathy: From Albuminuria to Multidimensional Characterisation of Diabetic Nephropathy - a Cross-sectional Study

Conditions
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Diabetes Mellitus, Type 1, Diabetes Complications, Diabetic Nephropathies

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with type 1 diabetes Written informed consent must be provided before participation Male or female patients >18 years of age with a diagnosis of type 1 diabetes (WHO criteria) Persistent urinary albumin creatinine ratio (UACR) assessed from EPJ (Electronic Patient Journal): < 30 mg/g in 2 out of 3 consecutive samples (normoalbuminuria) 30 - 299 mg/g in 2 out of 3 consecutive samples (microalbuminuria) ≥ 300 mg/g in 2 out of 3 consecutive samples (macroalbuminuria) - at least 30 with concurrent eGFR < 60 ml/min/1.73m2 2. Control subjects without diabetes Written informed consent must be provided before participation. Male or female patients >18 years of age without a diagnosis of diabetes (assessed by Hb1Ac, haemoglobin and creatinine) Exclusion Criteria: (Both subjects with and without diabetes) Non-diabetic kidney disease as indicated by medical history and/or laboratory findings Renal failure (eGFR<15 ml/min/1.73m2), dialysis or kidney transplantation Change in RAAS blocking treatment during the last month Treatment with antibiotics during the last 2 month Pregnancy or breastfeeding (urine HCG is performed on all fertile women) Patients who, in the judgement of the investigator, is incapable to participate For controls: Other diseases or intake of medicine which in the judgement of the investigator could affect the results, specifically renal, cardiovascular or inflammatory/infectious diseases should be considered for exclusion

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Type 1 DM, Normo albuminuric<br>Type 1 diabetics with no history of albumnuria (UACR < 30 mg/g in 2 out of 3 consecutive samples) | |
| Type 1 DM, Micro albuminuric<br>Type 1 diabetics with history of micro albumnuria (UACR 30-299 mg/g in 2 out of 3 consecutive samples) | |
| Type 1 DM, Macro albuminuric<br>Type 1 diabetics with history of macro albumnuria (UACR 30-299 mg/g in 2 out of 3 consecutive samples) | |
| Healthy subjects<br>Subjects with no history of diabetes, other diseases or intake of medicine which in the judgement of the investigator could affect the results, specifically renal, cardiovascular or inflammatory/infectious diseases should be considered for exclusion. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The microvascular function by estimating the glycocalyx thickness | Glycocalyx thickness assessed as perfused boundary region by a hand-hold camera (GlycoCheck) | 2019 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gut microbiome | Characterisation of the gut microbiota and markers of gastrointestinal inflammation | 2019 | 
| Urine and plasma Flow Cytometry Analysis (FACS) | cell types related to inflammation | 2019 | 
| Metabolomics in plasma | metabolite risk score in plasma | 2019 | 
| Metabolomics in urine | metabolite risk score in urine | 2019 | 
| proteomics in urine | proteomic risk score in urine | 2019 | 
| proteomics in plasma | proteomic risk score in plasma | 2019 | 
| Autonomic neuropathy | beat to beat variation (R-R test) upon Deep breathing | 2019 | 
| peripheral neuropathy | vibration perception threshold | 2019 |