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Clinical trials to stop the progression of type 2 diabetes

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Type 2 diabetes progresses over time

Type 2 diabetes is a chronic, progressive disease. Blood glucose levels may initially return to normal in people who are fairly recently diagnosed with diabetes who are taking a first-line medication (for example, metformin). Unfortunately, blood glucose generally rise again over the course of time, leading people to require a second medication. Again, while blood glucose levels improve with extra medication, they typically creep up again over time, leading to the addition of more medications.

 

Why does type 2 diabetes progress over time?

Type 2 diabetes is caused when the beta-cells in the pancreas cannot make enough insulin to keep blood glucose levels in the normal range. This is known as beta-cell dysfunction, and this dysfunction gets worse with the passage of time, resulting in rising blood glucose levels. Most importantly, none of the currently available diabetes medications can stop this progressive deterioration of the beta-cells. This is why more and more medications need to be added over time, to try to keep a person’s blood glucose levels at target.

 

Can the worsening of beta-cells be stopped or reversed?

In the first few years after the diagnosis of type 2 diabetes, there is a reversible component to beta-cell dysfunction. In fact, in early type 2 diabetes, intensive insulin therapy for as little as two to four weeks can improve the function of the beta-cells and cause diabetes to go into remission, which means that people can maintain blood glucose levels in the target range for up to a year without needing any medication. While this is encouraging news, this remission is not permanent. Eventually, blood glucose levels rise over time and return to the diabetes range. Nevertheless, this reversibility early in the course of the disease speaks to an opportunity to potentially stop the progression of type 2 diabetes.

 

Clinical studies aiming to stop the progression of type 2 diabetes

The Leadership Sinai Centre for Diabetes at Mount Sinai Hospital in Toronto recognizes this potential opportunity, and researchers there are thus studying strategies to stop the progression of type 2 diabetes.

The RESET IT study is testing the strategy of whether short-term intensive insulin therapy for two weeks every three months can actually “reset” the beta-cells early in the course of type 2 diabetes, and halt progression of the disease. Since this therapy works on reversible beta-cell dysfunction, this trial is only for patients who have had diabetes for a maximum of 5 years, and who are being treated with either metformin or lifestyle therapy only.

For people who have had diabetes for a maximum of seven years, and who are being treated with up to 2 medications, the PREVAIL study is being conducted, which is testing different insulin-based strategies for reversing beta-cell dysfunction.

Ultimately, the goal of these trials is to preserve the function of the beta-cells and thereby halt the progression of type 2 diabetes.

For more information about these studies, please contact Ms. Haysook Choi at Mount Sinai Hospital via email (haysook.choi@sinaihealthsystem.ca) or telephone (416-586-8778).

To learn more about managing complications, click here.

About Ravi Retnakaran MD MSc FRCPC and Haysook Choi

Dr. Ravi Retnakaran is a Professor of Medicine at the University of Toronto and an endocrinologist and clinician-scientist at Mount Sinai Hospital in Toronto, Canada. His research program focuses on the pathophysiology and treatment of type 2 diabetes (T2DM), with a particular interest in the potential reversibility of pancreatic beta-cell dysfunction early in the course of diabetes. In this context, his research group is conducting a series of innovative clinical trials evaluating novel therapeutic strategies for the preservation of beta-cell function in early T2DM, including the CIHR-funded RESET IT Trial and PREVAIL Trial. Haysook Choi is a Registered Nurse and Certified Diabetes Educator with over 25 years of experience in the field of diabetes management. She is presently working as a clinical research nurse coordinator at the Leadership Sinai Centre for Diabetes in Toronto. Currently her focus is on the RESET IT trial that is evaluating novel strategies for preservation of beta-cell function and thereby maintaining remission of Type 2 Diabetes.

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