Key words: overweight, diabetes, cardiovascular diseases, insulin resistance, beta cell function, weight reduction

"Unraveling Obesity’s Road to Diabetes and Cardiovascular Disease: Contributors to Insulin Resistance, Beta-cell Dysfunction and Vascular Dysfunction"

Worldwide, more and more people are overweight. Overweight people develop insensitivity to the hormone insulin (insulin resistance), the pancreas works less well (beta cell dysfunction) and large and small blood vessels function less well (vascular dysfunction). Later, this causes diabetes and cardiovascular disease.

This dissertation identified various mechanisms that cause the above processes to originate in overweight people. This was done in a study in which overweight people underwent an energy-restricted diet. It was discovered that various mechanisms independently contribute to insulin resistance, beta cell dysfunction and vascular dysfunction. This independence is essential, because if there are different ways to get sick, then different treatments are also possible as well as necessary. Moreover, some mechanisms were never before described in humans, such as the contribution of so-called NK cells. The findings of this thesis can therefore lead to targeted prevention and treatment strategies for diabetes and cardiovascular diseases.