Research Internal Medicine
Vascular complications of diabetes and the metabolic syndrome
A major aim of the program is to deliver specific and sensitive diagnostic biomarkers for the identification of patients developing insulin resistance and type 2 diabetes and to identify patients with high risk of micro- and macrovascular complications. A second aim of our program is to obtain insight in the pathophysiology of vascular complications in patients with the metabolic syndrome and diabetes at the molecular level. In the past years we have directed our research towards the development of insulin resistance, insulin-resistance-associated adverse large artery changes (atherosclerosis and stiffening), impaired capillary recruitment and vascular complications. These existing research programs are continued and extended with the integration of findings obtained from epidemiological studies in the different cohorts within in vitro experiments (especially cultures of endothelial cells, adipocytes and hepatocytes), animal models and in man. Current studies focus mainly on the relationships between insulin resistance and microvascular function both in man and in animal models and on the importance of specific advanced glycation endproducts, complement activation and the immune system and the relation between these phenomena for the development of diabetic complications.
Our research program is organized in different lines of research and is performed by means of epidemiological, clinical-physiological, clinical, experimental research and analytical research.
Background:
Epidemiological research
There is a large number of sera by active participation in a number of long-term studies (Hoorn study (type 2 diabetes); EURODIAB (type 1 diabetes); and Steno cohorts (type 1 and type 2 diabetes). In addition, we have three large own cohorts:
- CoDaM I and II (NGT/IGT/type 2 diabetes) (link)
- Familiar Combined Hyperlipidemia (FGH) cohort (link)
- Maastricht-study (type 2 diabetes)
Clinical-physiological research
We have the infrastructure for investigating the structure and function of large and small blood vessels and for investigating metabolic processes. The clinical-physiological research is mainly carried out in the circulation laboratory in which we are accurately measuring metabolic processes (for example, insulin sensitivity) and structure and function of microcirculation and large arteries in small groups of healthy volunteers and patients. The premise is that metabolic disorders lead to dysfunction of both large and small blood vessels, while at the same time it has been found that dysfunction of the microcirculation can lead to insulin resistance and thus to metabolic disorders, including diabetes.
Patient-bound research
This (intervention) research concerns both pathophysiological investigations in selected but relatively small groups, building on the above clinical-physiological research.
Experimental research
Experimental research is carried out in cultured cells in vitro, especially endothelial cells, adipocytes and liver cells and in animal models. Factors including AGEs and complement are studied that may affect the functioning of these cells and as such are involved in insulin resistance and vascular complications. The experimental and analytical research is being conducted in the laboratory of metabolism and vascular medicine.
Analytical research
There is an analytical unit in which analyses are carried out which are used in the above research. Analyses are carried out with HPLC, LC-MSMS and with immunoassays and multiarrays. Also SNP analyses are housed in this unit.
Lines of research are:
- Advanced glycation endproducts
- Complement activation
- Immune system