Genetic variations increase risk of type II diabetes and affect body weight
Likened to a lock and key, insulin is the key that opens up the door so that glucose can pass into the cell. In type 2 diabetes, the door won't open fully even with the right key.
An international team of researchers has identified a genetic variation that increases the risk of type II diabetes mellitus. Type II diabetes is a disease affecting the metabolism of sugar. The body is initially able to generate enough of the hormone insulin, but it is unable to work properly on the target cells. The consequence is that the cells do not open up to take sugar out of the bloodstream. The blood is ‘over-sugared’. As the disease progresses, the pancreas produces less and less insulin so that the status of the condition deteriorates further. Previously, this form of diabetes was also known as age-related diabetes. Nowadays, however, more and more young patients are suffering from this metabolic disorder, which is not least due to the fact that more and more young people are overweight or even obese.
In an analysis of patient groups from Denmark, West Africa and Iceland, the scientists identified several genetic variations of the TCF7L2 gene. The HapBT2D variation brings with it the highest risk of developing type II diabetes mellitus. People with one copy of this variation have a 45% increased risk of developing the condition. If they have two copies, the risk increases by 100 per cent.
Over the course of this international cooperation project, scientists at the National Genome Research Network (NGFN) demonstrated a relationship between the different variations of the TCF7L2 gene and body weight. Initial findings by the scientists show that the TCF7L2 gene is involved in regulating hormones that control the balance between the feeling of fullness and appetite.
Depending on which variation of the TCF7L2 gene is found in the DNA, there is a greater or lesser genetic risk of becoming overweight. This effect is more pronounced in men than in women.Men with the HapBT2D variation weigh on average a little less in relation to their body size, so they have a lower Body Mass Index (BMI).By contrast, men with the genetic variation HapA have a higher BMI, so they weigh more.“People with the HapA gene variation were at an advantage in centuries gone by,” says Dr. Anke Hinney of the University of Duisburg-Essen.This is because people able to form sufficient fat reserves were also able to survive periods of famine.
Hormones regulate the balance between the feeling of fullness and appetite.
Of interest is the fact that although the HapA gene variation increases the risk of becoming overweight, it plays only an auxiliary role in the development of type II diabetes mellitus. Conversely, the HapBT2D gene variation makes people weigh less in relation to their body size, but is associated with a particularly high risk of developing type II diabetes. “This finding confused us,” says Professor Johannes Hebebrand, coordinator of the NGFN neuronetwork on obesity.
“Since type II diabetes is frequently associated with being overweight, we expected something different. At the same time, however, this result shows us how complex this disease is and leads us to assume that people with a HapBT2D variation are suffering from a different form of type II diabetes than people who develop it as a result of being overweight."
Being overweight and obese (extremely overweight) are conditions that have spread in almost epidemic fashion over the past few decades. In order to discover the genetic causes for this health problem, the German Ministry for Education and Research (BMBF) has been promoting the investigation of genetic mechanisms involved with body weight regulation in the National Genome Research Network since 2001.
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