Epigenetic changes precede onset of diabetes

Date:
September 10, 2020
Source:
Deutsches Zentrum fuer Diabetesforschung DZD
Summary:
Epigenetic changes in the islets of Langerhans of the pancreas
can be detected in patients several years before the diagnosis of
type 2 diabetes. These changes are responsible for the altered
methylation activity of specific genes which differs from that
in healthy individuals. In humans, 105 such changes have been
discovered in blood cells.



FULL STORY ========================================================================== Epigenetic* changes in the islets of Langerhans of the pancreas can be
detected in patients several years before the diagnosis of type 2 diabetes (T2D). These changes are responsible for the altered methylation activity
of specific genes which differs from that in healthy individuals. In
humans, 105 such changes have been discovered in blood cells. This was
shown in a study by researchers from the DZD/DIfE, which has now been
published in the journal Diabetes. These findings could help to develop diagnostic markers for type 2 diabetes.


========================================================================== Several causes play a role in the development of type 2 diabetes. These
include a genetic predisposition, epigenetic factors as well as a diet
high in fat and sugar, overweight and lack of exercise. In order to
prevent the development of the metabolic disease, it is important to
identify people with an increased risk for the metabolic disease at an
early stage. Since the development of diabetes can also lead to functional disorders in the islets of Langerhans in the pancreas, researchers from
the German Institute of Human Nutrition (DIfE) and the German Center for Diabetes Research (DZD) have investigated whether there are epigenetic
changes in the islets of Langerhans that are related to the development
of diabetes. Lund University also participated in the study.

"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 Schu"rmann, spokesperson of the DZD and head of the Department of Experimental
Diabetology at DIfE, explaining the translational research approach. For
this purpose, obese mice were fed a high- calorie diet for five weeks and divided into diabetes-prone and diabetes- resistant animals on the basis
of certain criteria (e.g. the liver fat content). The DNA methylations
and expression patterns in the islets of Langerhans were determined for
both groups. "We were able to identify 497 candidates which differed
both in terms of their expression and their DNA methylation," said first
author Dr. Meriem Ouni.

The next step was to search for similar epigenetic changes in blood
cells of participants in the EPIC-Potsdam study** (270 controls and
270 incident T2D cases on average 3.8 years before diagnosis). The
researchers found altered levels of DNA methylation in 105 genes that
were associated with the later diagnosis of diabetes. Most of these
changes were also found in the islets of Langerhans in type 2 diabetes patients. The researchers assume that most of the alterations in DNA methylation that can be detected in the blood before diagnosis are still present in the islets of Langerhans later in the course of the disease.

"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 Schu"rmann. "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. " Next, the researchers want to investigate whether diets
or certain drugs can correct unfavorable DNA methylation patterns. They
also want to determine whether the identified markers differ in the
various diabetes clusters.

Notes: * Epigenetics investigates those characteristics of genes that
are not revealed by the DNA itself, but by its readability. Epigenetic information is mediated by methyl groups or other biomolecules. Epigenetic marks change the way genes are expressed.They act like a kind of switch
in the genome that turns a gene on or off. Current research results
suggest that lifestyle can also lead to epigenetic changes.

** EPIC-Potsdam: The European Prospective Investigation into Cancer and Nutrition(EPIC) Potsdam Study is a prospective cohort study. Between
1994 and 1998, 27,548 women and men between the ages of 35 and 65 were recruited. The EPIC Potsdam Study is part of one of the largest long-term studies in the world with a total of around 521,000 study participants
from ten European countries.

The aim of the study is to investigate the effect of nutrition on the development of cancer and other chronic diseases.


========================================================================== Story Source: Materials provided by Deutsches_Zentrum_fuer_Diabetesforschung_DZD. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Meriem Ouni, Sophie Saussenthaler, Fabian Eichelmann, Markus
Ja"hnert,
Mandy Stadion, Clemens Wittenbecher, Tina Ro"nn, Lisa Zellner,
Pascal Gottmann, Charlotte Ling, Matthias B. Schulze, Annette
Schu"rmann.

Epigenetic Changes in Islets of Langerhans Preceding the Onset of
Diabetes. Diabetes, 2020; db200204 DOI: 10.2337/db20-0204 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200910110843.htm

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