Lois Jovanovič, MD, MACE: Pioneer in the Field of Diabetes and Pregnancy and Beyond

Lois Gretchen Blaustone was born 2 May 1947 in Minneapolis, Minnesota. She grew up in a working-class Orthodox Jewish neighborhood. After losing her father at a young age to the ravages of type 1 diabetes, she was raised by her single mother.

Early on, Lois showed her determination: she honed her legendary memorization skills as a young girl to ensure that she would always be prepared. Lois could always memorize anything and would remember it always!

Her dream was to be a ballerina, and she was classically trained at the American Ballet Theatre. Her diminutive height was a barrier, so she moved on to medicine, her second-choice career, while maintaining a lifelong love of ballet.

Lois earned a bachelor of science degree in biology from Columbia University in 1969, while simultaneously earning a bachelor’s degree in Hebrew literature from The Jewish Theological Seminary. The following year, she began and completed a master’s degree in Hebrew literature, also from The Jewish Theological Seminary, while simultaneously enrolled in the Albert Einstein College of Medicine. She earned her doctor of medicine degree in 1973.

Dr. Jovanovič then trained at the New York Hospital–Cornell University Medical College, completing her internal medicine residency in 1975. She stayed on for a senior resident year and then an endocrinology fellowship, which she completed in 1978.

During this time, she became a mother, hiding her pregnancies as long as possible because motherhood was not readily accommodated for doctors-in-training in those days. She would tell stories of tucking her babies under the nursing station while she conducted rounds.

Lois’s interest in finding a cure for diabetes began with watching her father suffer, but after she developed type 1 diabetes herself as a young woman she focused on treating diabetes in women during pregnancy. Her groundbreaking work began with the premise that a woman with diabetes should have the same chance of having a healthy baby as a healthy woman without diabetes, as long as she could achieve normoglycemia prior to and throughout pregnancy. During her fellowship at the New York Hospital–Cornell University Medical College, she conducted a study showing that strict monitoring and absolute normalization of blood glucose could yield healthy babies (4). A year later, she published a larger trial of 52 women that showed conclusively that women with diabetes, even those with severe disease, could have healthy babies (5).

Dr. Jovanovič served as the original principal investigator for the New York Hospital–Cornell University Medical College site of the Diabetes in Early Pregnancy Study (DIEP) (6). This landmark study, which enrolled women after they became pregnant, showed that even without prepregnancy stabilization, intervention early in pregnancy reduced the rate of malformations (7). It also demonstrated that, among the changes in insulin requirement during the course of pregnancy, there was a decreased need for insulin in the late first trimester (8).

She was also the original principal investigator for the New York Hospital–Cornell University Medical College center of the Diabetes Control and Complications Trial (DCCT), a decade-long multicenter clinical trial that showed that strict glucose control could reduce the risk of long-term complications (9–11).

Dr. Jovanovič was interested early on in automating insulin delivery. While in New York, she pioneered the use of the original Glucose-Controlled Insulin Infusion System (Biostator) in labor and delivery (12), a prototype for her later work on the artificial pancreas. She was also one of the creators of the Pocket Doc insulin dosage calculator (13).

In 1984, Dr. Jovanovič joined what is now Sansum Diabetes Research Institute in Santa Barbara, California. In 1996, she was appointed Chief Executive Officer and Chief Scientific Officer, a post she held until 2013. During her tenure, Sansum Diabetes Research Institute became known worldwide as a center of excellence, thanks to her tireless work to improve the lives of people with diabetes through research, education, and care.

Although the rapid-acting insulin analogs had only been tested in nonpregnant individuals when first approved for use, Dr. Jovanovič was convinced that they would be safe for use during pregnancy. Her first studies, randomized trials of the analog versus standard recombinant insulin, were conducted in women with gestational diabetes mellitus. As expected, outcomes with the analogs were just as good as with standard insulins, and the women enjoyed the flexibility of use (14,15). Working with other investigators in a multicenter retrospective study of women who had used a rapid-acting insulin analog before pregnancy and throughout the first trimester, she helped demonstrate that rates of congenital anomalies were not increased (16).

She was also one of the principal investigators on a trial using a long-acting basal insulin analog during pregnancy. This study again demonstrated the safety of the analog for use during pregnancy and, because of the greater stability of the analog, women experienced fewer hypoglycemic events (17). Because of this work, many pregnant women with diabetes now enjoy the convenience and improved control that comes with the use of these analogs.

Dr. Jovanovič and two of her close international colleagues drafted a study design to test the impact of continuous glucose monitoring (CGM) on outcomes of pregnancies in women with type 1 diabetes, which became the basis for the Continuous Glucose Monitoring in Women with Type 1 Diabetes in Pregnancy Trial (CONCEPTT) (18). This multicenter international study randomized women with type 1 diabetes to either CGM along with capillary glucose monitoring or to capillary glucose monitoring alone and demonstrated that with CGM women spent more time within their glucose target range and had fewer hyperglycemic episodes. This resulted in a modest but significant improvement in A1C and, importantly, was associated with better neonatal outcomes. The newborns of the CGM group were less likely to be large for gestational age, spent less time in the neonatal intensive care unit, had fewer hypoglycemic episodes, and left the hospital an average of 1 day earlier (19). Once again, Dr. Jovanovič was at the forefront of demonstrating that better diabetes control results in better pregnancy outcomes.

Dr. Jovanovič also advocated for and treated pregnant women with type 2 diabetes or with gestational diabetes mellitus. Throughout her career in Santa Barbara, she attended the weekly diabetes-in-pregnancy clinic at the Santa Barbara County health facility. Many of her patients spoke only Spanish, and although Dr. Jovanovič always said that her Spanish was rudimentary, she was clearly fluent enough to run the clinic. Like her patients with type 1 diabetes, these women with type 2 diabetes or gestational diabetes mellitus, many of whom were low-income minority women, had improved pregnancy results (20).

Dr. Jovanovič’s dream, short of a cure, was to be able to automate insulin delivery. She participated in numerous industry trials that tested various methods of continuous glucose sensing and automated insulin delivery, including early versions of an implantable pump. She tested run-to-run control algorithms as a potential key in automating insulin delivery in type 1 diabetes (21,22). She was principal investigator and later coinvestigator at the Santa Barbara site of the JDRF- and National Institutes of Health–funded Artificial Pancreas Project (23–29). She was named in nine U.S. patent submissions related to insulin dosage algorithms and automated insulin delivery devices, of which four were granted (30–33).

Dr. Jovanovič was the recipient of multiple awards and tributes (Table 1). Of all her awards, the ones she cherished the most were her honorary membership in the Diabetic Pregnancy Study Group of the European Association for the Study of Diabetes and all the awards that acknowledged her as a teacher. In addition to keeping a very busy clinical and research schedule, Dr. Jovanovič made time to serve on the Diabetes Care editorial board from 1982 to 1990 as well as from 2000 to 2002, and she served as an associate editor for Diabetes Care from 2002 to 2008.

Always committed to her role as mentor/teacher, Dr. Jovanovič helped train generations of medical students, residents, and endocrine fellows. She was especially proud of her young protégées who chose to specialize in diabetes and pregnancy, whom she fondly referred to as “Little Loises.” She was sought after as a lecturer at symposia and grand rounds throughout the world. At the time of her death, she had commitments to speak in the coming months.

Dr. Jovanovič’s legacy also includes generations of babies, many of whom were named Lois by their grateful parents.

Both of her children, Kevin Jovanovic, MD, and Larisa Taylor, MD, entered the medical field in obstetrics and gynecology. She left behind four cherished grandchildren, one of whom, following in his grandmother’s footsteps, enrolled in the School of American Ballet.

Acknowledgments. The authors wish to acknowledge the assistance of Dr. Jovanovič’s daughter Larisa Taylor, MD, private practice, and Jeannine Glockler, Sansum Diabetes Research Institute.