Spotlight

Spotlight on Francine Kaufman

EMBC’ 18 speaker discusses Medtronic’s work on an artificial pancreas

In 2009, I left my position as a Distinguished Professor at the Keck School of Medicine and the Annenberg School of Communications at the University of Southern California to become the Chief Medical Officer and Vice President of Clinical, Medical and Health Affairs at Medtronic Diabetes. I was drawn to Medtronic to work on the “artificial pancreas” project that was going to combine an insulin pump, a continuous glucose monitor, and a control algorithm to automatically deliver basal insulin to people with type 1 diabetes. As a pediatric endocrinologist, I had seen the medical consequences of uncontrolled diabetes and done research on the benefit of exquisite glycemic control for children with type 1 diabetes. I wanted to be part of the team that was positioned to deliver this major leap forward in diabetes management, and which promised to improve health and reduce the burden of managing diabetes.

When I began my career in pediatrics more than 40 years ago, developing diabetes as a child negatively impacted health and well-being, and reduced life expectancy by many years. Children had episodes of very high and very low glucose levels that required hospitalization and could result in coma, seizures and death. After 15 or so years of diabetes, patients were at risk of long-term severe complications that included blindness, amputation, kidney failure and cardiovascular disease (heart attacks and stroke).

It wasn’t until 1992—with the completion of the National Institute of Health (NIH)-funded Diabetes Control and Complications Trial (DCCT)—that we finally had hard scientific evidence that controlling glucose was key in the management of diabetes. After the DCCT, there were tremendous breakthroughs in the development of diabetes management tools. New insulins were bioengineered (human insulin first, then a variety of analogue insulins), blood glucose monitoring equipment and continuous glucose monitoring systems advanced, and insulin pumps added new features and advantages. Using these new therapies allowed the children I cared for at the Children’s Hospital of Los Angeles to achieve markedly improved glucose control, and for the most part avoid the short and long-term complications of this disease.

By 2009—when I became the Chief Medical Officer of Medtronic Diabetes—it was obvious that Medtronic was likely going to be the first company to commercialize an “artificial pancreas” because it had already integrated the continuous glucose sensor and the insulin pump. After that—and in rapid succession—Medtronic released devices that were capable of stopping insulin delivery, first at a preset low glucose threshold to mitigate hypoglycemic exposure, and then with a predictive algorithm, to prevent hypoglycemia. But the real challenge was not in stopping insulin delivery to diminish low glucose levels, but the ability to give insulin through a control algorithm that responded to a number of inputs at five-minute intervals. Continuous glucose monitoring data allowed for the determination of the trajectory of the glucose level—and when this was combined with the amount of insulin delivered and the sensitivity to insulin—the pump could be directed to deliver micro-boluses of insulin to drive more glucose values in the target range (70-180 mg/dL) and reduce time spent in hypoglycemia and hyperglycemia.

After the development of constraints on insulin delivery to assure safety—and a number of early in silico modeling studies and in clinic feasibility studies to test edge cases—negotiations with the FDA allowed Medtronic to begin its pivotal trial in 2015. The study was a pre-post study in 124 subjects, aged 14-75 years, who used the first device to automate basal insulin delivery for three months at home. When the data were analyzed, the Medtronic MiniMed 670G system was determined to be safe, and it was soon approved for commercialization. We received FDA approval for the first hybrid closed loop device to automate basal insulin delivery for people with type 1 diabetes in early summer 2017 and launched the therapy commercially in early fall 2017.

Throughout my career in medicine, I have looked to develop strategies to improve the outcomes of people with diabetes. I have investigated diabetes technologies, diabetes prevention strategies and long-term diabetes outcomes. I have had the chance to influence diabetes practice guidelines. While early in my career, type 2 diabetes was not an issue in the pediatric age range, unfortunately, by the beginning of the 2000s, type 2 diabetes associated with childhood obesity was considered an epidemic.

Over the following years, I led the NIH effort to understand, prevent and treat type 2 diabetes in youth by chairing the HEALTHY program, a school-based diabetes risk prevention effort aimed at adolescents in middle-school, and the TODAY Studies, a multicenter randomized treatment trial in youth with type 2 diabetes. I also wrote Diabesity (Random House), which attempted to characterize the global diabetes/obesity epidemic for the public. I traveled the world with a Discovery Health film crew to make an acclaimed documentary titled, Diabetes: A Global Epidemic, and I helped ban the sale of sodas in the Los Angeles Unified School District. In 2003, I became the President of the American Diabetes Association, a three-year commitment as a lay leader, and I was particularly excited to be the second woman to hold that position since the beginning of the ADA in 1940. Being elected to the National Academy of Medicine (the former Institute of Medicine) and having the opportunity to interact with the greatest medical professionals from around the world has perhaps been my greatest honor and what I am most proud of.

My career has spanned basic, clinical and public health research. I have authored more than 250 scientific articles, 40 books and book chapters, and—most importantly—I have mentored hundreds of students, trainees and junior faculty. I have also had the most incredible opportunity to use my skills as a pediatric endocrinologist in philanthropy efforts around the world. Since joining Medtronic, I have established diabetes camps in Haiti, which have run at full capacity for seven years. This April, I traveled to Ethiopia with the non-profit group, Life for a Child, where I taught diabetes management in multiple clinics in the north of the country where diabetes in children is becoming more and more prevalent.

Leaving academics for industry was a significant change in my focus, but one I am glad for. I have learned many of the intricacies of business, I have come to understand how complex an endeavor product development can be, and I have become quite familiar with many engineering and regulatory processes. But the most important thing I have come to appreciate as a core principle at Medtronic—and similar to what I saw in academic medicine—is that the patient must always come first.