The Arterial Wall in Patients With Diabetes: Do Changes in Arterial Basement Membrane Proteins Predict Future Arterial Disease? Are Remodeling Processes Altered?

1. People living with type 2 diabetes are told that they have a significantly higher risk of developing a disease related to the heart or blood vessels. These diseases can play a major role for the overall health of the patient and can even cause death due to a blood clot in the heart, brain or other parts of the body. Understandibly, this information can cause a great deal of stress and anxiety for the patient.

As of today a doctor can not determine which patient has a higher risk of disease in the Heart and blood vessels. Therefore, we see a great need for further exploration of the mechanisms that could help identify diabetic patients with a particularly high risk of developing these diseases.

In this PhD project we aim at identifying diabetic patients with a specific pattern in the amount of proteins in the blood, tissue and genetic material who are at high risk of death or disease related to the heart and blood vessels. We explore this problem from two angles.

In the first part of the PhD study, we identify and measure proteins, which are related to high risk of disease in the heart and blood vessels. These proteins come from the blood vessels (a specific part called the basement membrane) and are believed to be present in a higher concentration, when people have diabetes. At the same time, we measure the same proteins in a blood sample from the patients, and we also examine their genetic properties with a focus on specific genetic areas.

All the tissue and blood samples have already been collected from patients, who have undergone a by-pass operation in the Heart at Odense University Hospital since 2008. All of the material is stored in a biobank (Odense Artery Biobank).

We also collect data from Statictics Denmark about each individual. These data are used to categorize people into risk categories.

We then hope to see a pattern in the measurements from the laboratory that match the risk profile of the patient.

In the second part of the study we use a different approach. Data from a large study done on the population of Malmö, Sweden, can be used to examine the Development of blood vessels in diabetic patients.

In this study healthy people from Malmö have undergone a number of examinations in the early 1990'ies and again 15 years later. One of the tests was an ultrasound of the large blood vessel on the neck, the carotid artery. With this ultrasound we are able to measure the thickness of the wall of the blood vessel and the diameter in which the blood can pass through.

We think that there is a connection between diabetes and the diameter of the blood vessel and that, over time, diabetes can cause the blood vessel to become narrower. This idea links the two studies because the same proteins that can be found in the first study are important in determining the risk of having a narrow blood Vessel when the patient has diabetes.

This project can contribute with a deeper knowledge about the linking mechanisms between diabetes and disease in the heart and blood vessels: which proteins are present in higher concentration? How does this relate to a higher risk? How do diabetic blood vessels change over time? We will aim at answering these questions.

With regards to clinical practice, we see several perspectives:

• deeper knowledge and understanding of the mechanisms behind the diasease in the heart and blood vessels that follows diabetes
• development of a new blood test. Over time, the proteins measured in this study could be developed to a new blood test that gives information about a patients risk of developing a diasease in the heart or blood vessels
• better treatment for patients with diabetes because aptient with high risk can be treated more intensely

In order to achieve the goals of this project there are several overall tasks:

• select patients form the biobank, that are suitable for the project (the correct type of tissue and blood sample available)
• do work in the laboratory. This includes cutting and preparing tissue, analyzing the tissue and blood samples, implementing new methods for analysis etc.
• collect clinical data form Statistics Denmark. This process can be quite detailed and time consuming.
• obtain data from 'The Diet and Cancer Study' in Sweden, Malmö
• analyze data from study 1
• analyze data from study 2
• write articles
• collect all parts of the projects in the final thesis