One of the most exciting recent breakthroughs in diabetes treatment research, involving cell therapy, was achieved by an international team including researchers from Germany, Israel, the United Kingdom, and VA investigators at the Miami VAMC led by 1977 Nobel Laureate Dr. Andrew Schally. Publishing in the online Proceedings of the National Academy of Sciences last fall, the team reported that it had devised a way to transplant healthy beta cells – the pancreatic cells that store and release insulin – into a human body without the usual risk of rejection. The development has profound implications for the treatment of type 1 diabetes, the form of the disease caused by autoimmune destruction of beta cells.

Using artificial compounds that mimic growth hormone-releasing hormone (GHRH), they found they could increase both the viability of transplanted beta cells and their ability to make insulin.

In the “artificial pancreas” developed by Israeli researchers, explained Dr. Zafar Iqbal, the portfolio manager for VA’s Diabetes Research program, donor beta cells “are packed in a gel that seals them from attack by the host’s immune system. The whole assembly is housed in a biocompatible plastic shell, and the chamber, which is about 2.5 inches in diameter and a half-inch thick, can be surgically implanted and linked to ports that the patient himself can use to inject fresh oxygen, until new blood vessels develop around the graft.” The 63-year-old patient who was given the implant was followed for 10 months, without taking any drugs for immunosuppression, after which the artificial pancreas was removed.

The Miami VA team played a crucial role in developing and testing the system in animal models, said Iqbal. Using artificial compounds that mimic growth hormone-releasing hormone (GHRH), they found they could increase both the viability of transplanted beta cells and their ability to make insulin. “Using this knowledge,” he said, “they have shown recently the stimulatory effect of new chemical compounds they designed themselves, GHRH agonists, which enhance the production of insulin. These pancreatic cells were treated in vitro with GHRH agonists and then transplanted into mice with diabetic symptoms. They’ve found that this treatment of diabetic mice with GHRH agonists normalizes glucose levels, in contrast to untreated mice in which the glucose levels are very high.”

The discovery suggests the potential for using these agonists in a future version of the bioartificial pancreas, Iqbal said, or perhaps even for direct subcutaneous injection, in order to stimulate the secretion of endogenous insulin – but no studies of such applications have yet been proposed.

Learning – and Unlearning – Methods of Care

One of the most important outcome determinants for diabetic patients is the way in which health care is organized, administered, and delivered. VA’s Health Services Research and Development (HSR&D) Service and its Quality Enhancement Research Initiative (QUERI) conduct and fund research devoted to improving access to and quality of care.

A newer approach to treating diabetic veterans is group treatment or shared medical appointments, which has been shown to benefit patients with similar medical issues. According to William Yancy, associate professor of medicine at Duke University and senior investigator for the Center for Health Services Research in Primary Care at the Durham VAMC, teaching more than one patient at a time how to manage diabetes has proven more efficient, and allowed a multidisciplinary team of specialists – a physician, PA, or nurse practitioner, perhaps accompanied by a behaviorist or dietician – to deliver care, rather than an individual. The approach has also benefited patients. “You still are able to monitor their disease individually with very brief one-on-one sessions,” he said. “You can adjust their medications if needed. And they also benefit from the social support they receive – not only from the members of the team involved in delivering the treatments, but also from each other.”

At the Durham VAMC, Yancy said, researchers are evaluating a refinement to this group treatment approach, combining diabetes education with weight-management counseling. “Those two problems go hand in hand,” he said, “but typically the group visits, in the past, have not really impacted the patients’ weight. So we’re trying to combine an intensive weight-management program with the medical group visits. Now we’ll see how that works.”

Dr. David Aron, associate director of the VA’s QUERI Center for Implementation Practice and Research Support at the Cleveland VAMC, has been participating in group care for eight years, and says studies continue to provide evidence that they remain a useful tool both for glycemic control and for broadening the expertise applied to individual patients. Another method for bringing the knowledge of diabetes specialists to primary care doctors, currently being evaluated jointly by HSR&D/QUERI and the VA’s Office of Specialty Care Transformation, is the use of the agency’s teleconferencing program, SCAN-ECHO, to conduct consultations through a patient’s electronic medical record.

The Cleveland VAMC is one of the centers simultaneously rolling out and studying the diabetes SCAN-ECHO, said Aron. “This is an example of research and operations informing each other,” he said. “Research can be adjusted to meet the operations needs, and operations can be adjusted based on the research findings. This kind of partnered research has become of great interest to VA HSR&D.”

When research and interprofessional clinical care are conducted alongside each other, informing real-time adjustments, the knowledge base evolves rapidly. In some settings, said Aron, clinical practice is slow to catch up. “I think one of the most critical research questions, in medical practice in general and in diabetes specifically, is: How do you stop doing what was previously accepted as correct, when it is shown no longer to be correct?”

For example, the clinical care guidelines developed by the VA and other organizations have, for more than 15 years, emphasized the importance of establishing individualized targets for glycemic control – and yet research led by Aron and Pogach has revealed many practitioners continuing to work with a fixed target, in the common A1c blood test, of less than 7 percent glycated hemoglobin. This target isn’t appropriate for many patients, such as those at risk for low blood sugar. “[Seven percent] has been the mantra for many years,” Aron said, “but for many patients, that degree of glycemic control is not appropriate. It will provide little, if any, benefit, but comes with risks.”

Based on the findings of Aron, Pogach, and others, the VA and the Department of Health and Human Services (HHS) will soon roll out a nationwide Hypoglycemia Safety Initiative to encourage individualized targets for glycemic control. Aron has been funded to evaluate the efficacy of the initiative. “There will be a number of research questions coming out of that,” he said. “Specifically, how do you get people to de-implement outdated practices?”

In terms of the number of patients who have a stake in such questions, there may be no more important research program at the VA than the portfolio of studies designed to attack diabetes, prevent it from occurring, and optimize the care delivered to diabetic veterans. VA investigators and clinicians are helping lead the way in learning which interventions will optimize outcomes for these patients – and, if necessary, in unlearning those that won’t.

This article first appeared in The Year in Veterans Affairs & Military Medicine 2014-2015 Edition.