Can Strong Beta Cells Protect Against Diabetes?
By Helen Gao, Alexander Wolf, and Emily Regier
Could type 1 and type 2 diabetes share a common genetic link? A recent Nature Genetics article suggests yes. According to the article, a genetic predisposition to beta cell “fragility” – put simply, having “weaker” beta cells – may contribute to the development of both type 1 and type 2 diabetes. This major discovery not only sheds further light on the causes of these conditions but also opens the door for new avenues of research to potentially prevent and cure type 1 and type 2 diabetes.
In this study, mice with beta cells that were better at repairing DNA and preventing cell death (“apoptosis”) in response to stress were less likely to develop either type 1 or type 2 diabetes. The researchers identified two genes in particular – “Glis3” and “Xrcc4” – that can increase the risk of developing the two conditions. Moreover, the researchers found that a similar genetic predisposition was found in humans with diabetes – providing support that this research in mice may have clinical implications.
As the study’s authors have stated:
"Our research finds that genetics is critical for the survival of beta cells – the cells that make insulin. Thanks to our genetic make-up, some of us have beta cells that are tough and robust, while others have beta cells that are fragile and can't handle stress. It is these people who develop diabetes, either type 1 or type 2, while others with tougher beta cells will remain healthy even in if they suffer from autoimmunity or metabolic disorder"
What do these results mean for people with diabetes?
For type 1 diabetes, these results suggest a new avenue for prevention and cure research. Thus far, much of that research has focused on preventing the immune attack on beta cells or on beta cell replacement (such as with stem cells), rather than on “strengthening” the beta cell itself. Theoretically, this research could help lead to development of therapies to help the beta cells defend against an autoimmune attack.
For type 2 diabetes, the authors suggest that this data could help researchers better understand the progression of the disease, particularly later stages involving beta cell death (at which point patients must transition to taking insulin). The authors believe this study could lay the groundwork for type 2 therapies aimed at preserving beta cell resilience, which could be especially useful for people who have had type 2 diabetes for many years. Indeed, aside from insulin and new insulin/GLP-1 agonist combination drugs, there are no diabetes therapies targeted specifically at late-stage type 2 diabetes. The mice with the genetic predisposition toward beta cell fragility can also serve as models to test new therapies that target more advanced type 2 diabetes.
While the results of this study reflect potential for a new therapeutic approach to treating or preventing diabetes, this work remains far from reaching patients. More research will be needed to better understand the genetics of the two conditions – particularly in humans – and to actually translate this work into medical therapies.