Type 2 diabetes and obesity

 

Social and economic factors have led to a dramatic rise in type 2 diabetes and obesity around the world. In a review in Science, Mark McCarthy, professor at the University of Oxford, UK, and Paul Franks, professor at Lund University, Sweden, examine the knowledge of the actual causes and the interplay between genetics and lifestyle factors.

By studying how our genes express themselves in response to environmental factors and changes in lifestyle, we will better understand how health recommendations and treatments can be tailored to each individual.
"Environmental factors that disturb cellular and physiological processes and have an effect on the individual's predisposition to diseases, such as type 2 diabetes, are likely to do so through active, and reactive, modulation of genome function. There is a compelling rationale behind this concept, but the details about how these processes work remain poorly defined," says Paul Franks.
"However, there is emerging evidence that epigenomic changes such as DNA methylation and histone modifications, which affect the ways in which genes are transcribed and translated into proteins, are important features of these processes," he continues.
Previous research has largely focused on dietary components and which diet would be best to lower the risk of obesity and type 2 diabetes, but so far there is no clear evidence from epidemiological or clinical trial data that a specific diet is optimal for long-term weight-loss or lowering the risk of diabetes. Some types of dietary fat may be harmful while others may in fact be protective. The researchers also concluded that the widely established view that vitamin D supplementation lowers blood sugar levels and the risk of type 2 diabetes is unlikely to be accurate.
In recent years, there has been an explosion of interest in the role of the gut microbiome in the development of type 2 diabetes and obesity.
"Several studies have detected differences in the composition of the gut microbiome between healthy people and those with obesity and type 2 diabetes, but the cause and effect remain unclear," says Mark McCarthy, and continues:
"In addition, both high and low birth weight have been linked to type 2 diabetes later in life. It seems as if these associations reflect the complex interplay of genetic variation in both the foetus and the mother, along with the impact of the intrauterine environment."
The major challenge is getting closer to a mechanistic understanding of why type 2 diabetes and obesity occur and why they have become so much more common in the last 40-50 years.
"We have only a superficial understanding of that. It often gets blamed on our western lifestyle but the specific components of modern life that are most damaging remain unclear. We also know that this occurs on the background of hundreds of genetic differences that influence predisposition. The genetic findings are increasingly allowing us to understand the mechanisms involved, and to start to connect the genetic and environmental contributions," says Mark McCarthy.

---

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

---

Journal Reference:

1. P. W. Franks, M. I. McCarthy. Exposing the exposures responsible for type 2 diabetes and obesity. Science, 2016; 354 (6308): 69 DOI: 10.1126/science.aaf5094 

 

Diabetes is a serious condition that affects over 29 million Americans. Obesity also affects a large part of the United States population. A new scientific breakthrough may have found a way to prevent both of these disorders.

Researchers have isolated a protein that in the future may stop the development of diabetes.

According to the Centers for Disease Control and Prevention (CDC), over 36.5 percent of the American population are obese.
Obesity has been associated with a variety of serious conditions, such as heart disease, stroke, certain types of cancer, and type 2 diabetes.
Type 2 diabetes is also widespread, with the CDC reporting that more than 29 million Americans are living with the condition, and an additional 86 million have prediabetes.
Diabetes can lead to severe complications, and the illness is the seventh leading cause of death in the U.S.
While there is currently no cure for diabetes, scientists are investigating several possibilities, including pancreas transplantation and genetic manipulation.
Researchers at the Catholic University of Louvain in Belgium may have made a breakthrough by discovering a protein that could soon halt the development of diabetes and obesity in humans.

Researching the bacteria Akkermansia in mice

For the past 10 years, researchers led by Patrice Cani, a WELBIO researcher at the Louvain Drug Research Institute of the University of Louvain, and Willem de Vos, professor at the University of Wageningen in the Netherlands, have been working on a bacterium called Akkermansia muciniphila.
Akkermansia are one of the most common bacteria, accounting for 1-5 percent of the gut microbiota.
Cani and team have shown, for the first time, that Akkermansia muciniphila may be crucial in the fight against obesity and type 2 diabetes.
Researchers hypothesized about the key role of Akkermansia in 2007 and confirmed their hypothesis in 2013. Until then, it was known that type 2 diabetes and obesity are characterized by altered gut microbiota, inflammation, and gut barrier disruption, but the exact mechanism responsible for this was unknown.
In their 2013 study, Cani and team isolated Akkermansia muciniphila - a mucin-degrading bacterium that resides in the mucus layer. They noticed that levels of this bacterium were lower in obese rodents. They also administered an Akkermansia-based treatment to mice, which reversed several metabolic disorders.

Studying pasteurized Akkermansia in humans

Now, the researchers have decided to produce Akkermansia and test it on humans. The trials have been ongoing since December 2015 at the Saint-Luc clinics of the University of Louvain.
For now, researchers have shown that using the bacterium on humans is safe. However, the scientists still need to prove that the positive effects demonstrated in mice in 2013 also apply to humans.
During their research, Cani and team accidentally discovered that pasteurization has positive effects on Akkermansia:

"Unexpectedly, we discovered that pasteurization of A. muciniphila enhanced its capacity to reduce fat mass development, insulin resistance and dyslipidemia in mice."

Scientists were trying to facilitate the production of Akkermansia by finding a way to make it inactive without destroying its properties. Pasteurization was one such way, as it makes the bacterium stable and easier to administer.
However, after pasteurizing it, researchers found that its efficacy had doubled. Akkermansia became so effective that it prevented the development of the obesity and type 2 diabetes mice.
This is the first time that scientists have shown pasteurized Akkermansia effective against these metabolic conditions in mice.
Results were published in the journal Nature Medicine.

The benefits of the purified protein Amuc_1100*

In an attempt to understand why the bacterium was made so effective by pasteurization, researchers isolated a protein that can be found on the outer membrane of the bacterium.
Since pasteurization kills off everything in the bacterium except the protein, researchers hypothesized that this protein might be the reason for its effectiveness.
With the help of genetic engineering, scientists produced the protein Amuc_1100* and tested it on rodents.

Results showed the protein Amuc_1100* was as effective in stopping diabetes and obesity as pasteurized Akkermansia.
As the authors note, their study demonstrates that Akkermansia muciniphila "retains its efficacy when grown on a synthetic medium" and is "compatible with human administration."
Amuc_1100* is known to be good for the immune system, as it blocks toxins from reaching the bloodstream and strengthens the immunity of the intestines.
In the near future, the protein Amuc_1100* could help prevent diabetes and obesity in humans, and later on it might also treat other conditions, such as inflammation of the intestine caused by stress, alcoholism, liver disease, or cancer.
Read how viagra may benefit heart health for men with type 2 diabetes.

Written by Ana Sandoiu