Early Detection of DNA Methylation in Pancreas Could Help Identify Diabetes

Type 2 diabetes (T2D) is an extremely common chronic disease that affects the way the body uses insulin to regulate glucose levels. Specifically, the body either resists the effects of insulin, or it doesn’t produce enough of it to properly metabolize glucose. This could lead to nerve damage, heart and blood vessel complications, and other adverse health effects down the line.

There are several factors that could lead to developing T2D, including obesity, lack of exercise, and poor diet. There is currently no cure for T2D, but improving diet and weight loss seem to help get the disease under control.

Scientists from the DZD- German Center for Diabetes Research wanted to determine the changes that occur on a molecular level in patients that are susceptible to developing T2D with the hope of improving diagnostic and prevention abilities.

Insulin is produced and secreted in the area of the pancreas called the Islets of Langerhans.  To determine the effect that T2D has on this area, the research team decided to examine DNA methylation patterns in the pancreata of obese mice, as well as from human blood samples. It turns out that epigenetic changes in the islets of Langerhans may help to detect T2D before it can fully develop.

“Our aim was to identify early changes in DNA methylation and the expression pattern in the islets of Langerhans in a diabetes-prone mouse and then to test which of these can also be detected in the blood of humans before diabetes is diagnosed,” said Prof. Dr. Annette Schürmann, lead author of the study. Previous studies have indicated that it may be possible to detect T2D by blood test by measuring DNA methylation of 4 specific genes, which demonstrates some promise for this particular study.

The research team began by feeding 10 week old obese mice a high calorie diet for five weeks.  After the five week period, the mice were divided into 2 different groups: diabetes-prone and diabetes-resistant animals, based on liver fat content and other factors, and isolated the Islets from both groups.

Upon examining DNA methylation patterns of both groups, they were able to determine 497 different methylated genes that were related to insulin production and secretion pathways in the mice that later developed diabetes.

They wanted to see if their findings in the mice group were parallel to human subjects. They obtained blood samples from the EPIC Potsdam Study cohort, and examined them for similar epigenetic changes. These samples were submitted between the years 1994-1998 by men and women aged 35-65.

In total, they examined 540 blood cell samples: 270 control and 270 new-onset diabetes cases.  Their analysis revealed that 105 genes experienced altered DNA methylation levels in the subjects that went on to develop T2D.

Dr. Schürmann highlighted the importance of their discovery: “Our broad and translational research approach has identified a number of interesting genes whose expression and altered DNA methylation are associated with the later diagnosis of diabetes,” said Schürmann. “In humans, 105 such differences can be detected in blood cells a few years prior to the diabetes diagnosis. This may open up the possibility of using some of these changes as diagnostic markers for type 2 diabetes in the future. “

The findings in this study are significant, because while there is no cure for T2D, improving early detection and prevention methods would be the next best thing. Further research is needed to determine ways to correct abnormal DNA methylation levels in the pancreas.

Source:

Ouni, M. et al.(2020). Epigenetic Changes in Islets of Langerhans Preceding the Onset of Diabetes. Diabetes 2020;69:1–15

Reference:

DZD- German Center for Diabetes Research. “Epigenetic changes precede onset of diabetes.” DZD News, 10 September 2020.