DIRECT - Innovative Medicines Initiative:
DIabetes REsearCh on patient straTification

Acute beta-cell secretagogues (3.4)

This study combines two existing sets of study data from Copenhagen, Denmark and Leiden, The Netherlands.

In the Danish study, two studies called the “family study” and the “UNG92” study had been performed previously quite a long time ago. All the participants were given an intravenous glucose tolerance test followed by a glucose infusion and tolbutamide (sulphonylurea) infusion. The purpose of the tests (or stimuli) was to cause the production of insulin to see how well the beta cells in the pancreas were working. Some of the patients were studied again after many years had passed, allowing the comparison between their samples from the different visits to see how age had affected the function of the beta cells in the pancreas. In the UNG92 study, at the time of the second test all the participants were young individuals aged 18-32 years. They were not diabetics. In the family study though, the participants were diabetics. Their children and wives/husbands were studied as well. Some of the children had diabetes and some did not. This allowed the researchers to look at what genes might influence whether or not the children developed diabetes.

In the Dutch study, called the “hyperglycaemic clamp study”, the participants were firstly given an infusion of glucose to stabilise the level of blood sugars and then given an infusion of an enzyme called GLP-1 followed by an infusion of arginine. Again, the purpose of the tests was to stimulate the production of insulin. The GLP-1 is a hormone released from the stomach after eating that tells the pancreas to produce insulin. Since it is released into the blood from the stomach (i.e. secreted), it is called a “secretagogue”. The arginine response is a measure of near maximal insulin secretion so it measures what the pancreas in that person is capable of if it was working at its absolute hardest. The participants included different types of twins (identical and non-identical twins) and also their brothers and sisters. The majority of the participants showed no signs of diabetes at the time they were tested.

The DNA from the participants in both these studies has been examined to see if there are any particular genes that might influence insulin response to the stimuli that were used, as well as to study the inheritance of diabetes.

Also the blood from the participants was studied to see if any biomarkers could be found that either predicted the response to stimuli or were changed after the stimuli were added.

By combining the data from these 2 studies we have been able to ask a number of important questions and to study why some people’s beta cells in their pancreas work very well and others do not. We have also been able to study why diabetes passes down in families between parent and child.

For more information take a look at the Patient Information Sheet from the previous studies contributing to the DIRECT project: