Since the first clinical trials aiming to cure Type 1 diabetes began approximately 30 years ago, a cure has been the mission of investigators worldwide. However, despite several advances, a cure still seems just out of reach. That point was made frustratingly clear for investigators worldwide earlier this year, when many clinical trials that had held great hope based on laboratory investigation studies produced unsatisfactory results.

Mark A. Atkinson, Ph.D., an eminent scholar in the University of Florida College of Medicines department of pathology, immunology and laboratory medicine and co-director of the UF Diabetes Center of Excellences explained,

“A lack of universal standards for defining diabetes and reversal of the disease in animal studies makes it difficult to translate laboratory successes into human trials.”

In a report appearing Wednesday, Aug. 17, in the journal Science Translational Medicine, Atkinson recommends criteria on which the scientific community can base discussions aimed at building an agreement and constructing a base for more successful human trials.

Atkinson said,

“We haven’t given up, we need to keep moving forward with as much passion as ever.

It’s halftime and we have to go to the locker room and figure out what we have to do better to win the game.”

According to the Centers for Disease Control and Prevention, over 1 million people in the U.S. live with Type 1 diabetes, and more than 30,000 new cases are diagnosed every year.

Type 1 diabetes is caused because the immune system attacks insulin-producing cells in the pancreas, whose job is to move glucose out of the blood so it can be converted to energy. Glucose then accumulates in the blood, causing organ damage. Those with the disease must take insulin injections to survive. However, insulin does not cure or prevent complications, such as blindness, kidney disease and heart disease.

There is an opportunity for study early in the progress of the disease. Individuals who are newly diagnosed have residual insulin-producing cells that may still be functional. Investigators have focused on trying to save those cells and coax them to produce enough insulin. The development of new molecular-based therapies has proven attractive to researchers over the years.

A host of laboratory investigations has prepared the way for clinical trials in humans. However, without better animal models and a standardized way to outline the disease or its reversal in those models it has been hard to create an effective clinical strategy. Individual scientists have been free to decide in their own animal studies what blood sugar levels over what time frame indicate diabetes, how long to administer therapies being tested, how many animals to treat, what represents a cure, and other variables. A few have tested new treatments in conjunction with insulin standard therapy in newly diagnosed Type 1 diabetes in humans while other scientists did not use insulin. Currently there are approximately 50 published ways to reverse diabetes and more than 300 ways to prevent it in mice.

In contrast, in clinical practice, there is a specific definition of diabetes that all physicians use to diagnose Type 1 diabetes. Furthermore, they have worked carefully over the last 10 years to develop standards for quality trial design, which includes techniques that allow comparison or results acquired using different drugs.

Richard A. Insel, M.D., chief scientific officer of the Juvenile Diabetes Research Foundation, who was not involved in the current analysis, explained,

“If we can do that for humans I think we can do this for animals and yet we haven’t done it.

People use the words cure and reversal very loosely we should never be talking about curing mice unless we have a strict definition of what a cure represents.”

Implementing standards may help progress research efforts, because laboratory investigations could be compared more effectively. Which would allow only the most promising techniques to proceed to human trial, and in doing so, reduce emotional turmoil and stress for patients, families and investigators, reduce the number of animals used in laboratory investigations, and cut costs. Type 1 diabetes reversal trials, on average, cost $20,000 to $40,000 per patient.

Atkinsons recommendations for standardizing diabetes reversal studies include:

  • establishing a minimum number of animals uses
  • defining control groups
  • limiting the age of specimens uses
  • standardizing the time from the onset of high blood sugar to the start of treatment.

He also asks for the definition of diabetes to be based on blood rather than urine measurements, establishment of a specific blood glucose concentration as the threshold for diabetes onset, and agreement on whether insulin therapy should be used after diagnosis.

Atkinson lastly proposes that all investigations report blood glucose level at the time treatment begins, adopt a universal definition of reversal of diabetes, and determine a standard length of time that animals must be observed in order to make sure there is true disease reversal.

Neutral bodies such as the National Institutes of Health and funding organizations such as the Juvenile Diabetes Research Foundation can help to guide the standardization process.

Atkinson said, “Im hopeful that within six months to a year from now that the field moves toward this.”

Written by Grace Rattue