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Giants in Obstetrics and Gynecology: A profile of Donald R. Coustan, MD

  • Roberto Romero
    Correspondence
    Corresponding author: Roberto Romero, MD, DMedSci.
    Affiliations
    Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institutes of Health/Department of Health and Human Services, Bethesda, MD, and Detroit, MI
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      Click Supplemental Materials under article title in Contents at ajog.org
      Donald R. Coustan, MD, Professor and past Chair of the Department of Obstetrics and Gynecology at the Warren Alpert Medical School of Brown University, and Chief of Obstetrics and Gynecology of the Women & Infants Hospital of Rhode Island for 17 years, is being recognized as a “Giant in Obstetrics and Gynecology” for his major contributions to understanding the metabolism of glucose and insulin regulation during pregnancy, introducing criteria for the diagnosis of gestational diabetes, his advocacy for tight glucose control to improve pregnancy outcome, and his role in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study.
      • Coustan D.R.
      • Lowe L.P.
      • Metzger B.E.
      • Dyer A.R.
      International Association of Diabetes and Pregnancy Study Groups Consensus Panel. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study: paving the way for new diagnostic criteria for gestational diabetes mellitus.
      Of the galaxy of stars to emerge from the Department of Obstetrics and Gynecology at Yale, Don was perhaps the one with the most “blue.” He was an undergraduate at Yale; went to Yale Medical School; did his internship in internal medicine and his residency in obstetrics and gynecology there; and, after two years as Lieutenant Commander and Chief of Obstetrics at the Naval Regional Medical Center in Oakland, California, returned to Yale as an assistant professor, where he was Director of the Diabetes in Pregnancy Program and Co-director of the Residency Program for seven years before moving to Brown as Director of the Division of Maternal-Fetal Medicine.
      Don does not ascribe his success to careful planning. Two principles he claims decided which forks in the road of his own life he would take are: “kismet,” a Turkish word meaning fate, and “serendipity,” fortunate happenstance or making discoveries you were not in quest of. Being self-effacing, Don likes to say that it is more important to be lucky than smart, but he graduated magna cum laude from Yale, so no one believes that luck explains his success. In an unguarded moment, even Don will concede that, as Louis Pasteur said, “Discovery comes to the prepared mind.”

      Why obstetrics and gynecology?

      When asked why he chose our discipline, Don said that “the internal medicine department was trying to figure out the structure of the digitalis receptor; the obstetrics and gynecology department was trying to discern how to deliver a breech–and that seemed, to me, to have more potential.”

      Choosing between obstetrics and gynecology

      Upon arrival at the Naval Regional Medical Center in Oakland in 1973 with Bill Stallone, another obstetrician/gynecologist on the “Berry Plan” (which allowed deferment of those doing a residency), the chief of the service called both of them into his office and asked which one liked obstetrics and which one liked gynecology. Bill said he liked gynecology, whereupon the chief said, “OK, Stallone, you’re chief of gynecology; Coustan, you’re chief of obstetrics.”
      “It could have gone either way,” Don explained, “but Bill spoke first.”

      A pregnant patient with diabetes started it all

      During his first week as Chief of Obstetrics, Don saw a laboring woman with diabetes whose blood sugar level measured 100-120 milligrams per deciliter (mg/dL). Having been taught in New Haven to keep the urine of pregnant diabetics at 1+ for glucose to prevent hypoglycemia, which roughly corresponds to a blood sugar level of about 150 mg/dL, Don exclaimed, “Who’s taking care of this patient? She is going to become hypoglycemic!”
      A voice behind him replied, “Haven’t you read anything?” It was Dr Steve Lewis, who would become Don’s friend and collaborator.
      Steve showed Don the report by Karlsson and Kjellmer
      • Karlsson K.
      • Kjellmer I.
      The outcome of diabetic pregnancies in relation to the mother's blood sugar level.
      from Sweden indicating that perinatal mortality in pregnant diabetic women correlated with mean glucose in the third trimester and was lowest when the mean was less than 100 mg/dL. At the naval hospital, there was a well-equipped clinical research unit, so the two of them decided to study normal pregnant women in the third trimester. They admitted seven women to the metabolic research unit for 24 hours, gave them a standard diet, and measured several parameters, including glucose and insulin every hour as well as C-peptide. They described the glucose and insulin changes through the day in an article published in Diabetologia.
      • Lewis S.B.
      • Wallin J.D.
      • Kuzuya H.
      • et al.
      Circadian variation of serum glucose, C-peptide immunoreactivity and free insulin in normal and insulin-treated diabetic pregnant subjects.
      Fasting glucose was slightly lower than in nonpregnant women, peaked at about 120 mg/dL after breakfast, and then stayed between 70-110 mg/dL pretty much throughout the day. They showed their results to a mathematician who came up with a formula to describe the insulin curve: from this, they calculated the dose and ratio of intermediate to short-acting insulin that many pregnant diabetic women still use today: 2:1 in the morning, 1:1 in the evening, and total morning dose twice the total evening dose.

      A randomized clinical trial of insulin administration in gestational diabetes

      Aware of the randomized trial by O’Sullivan and Mahan
      • O'Sullivan J.B.
      • Mahan C.M.
      Insulin treatment and high risk groups.
      of prophylactic insulin in gestational diabetes, Don and Steve conducted their own randomized trial in 72 pregnant women with gestational diabetes that compared the effect of treatment with insulin and diet, diet alone, or neither to the frequency of macrosomia, defined as a birthweight greater than 8.5 pounds. The insulin dose was 20 units of NPH (isophane insulin) and 10 units of regular insulin derived from the mathematician’s formula, and the result of the trial was positive: treatment of gestational diabetics with insulin reduced the rate of large babies. This report was published in Obstetrics and Gynecology.
      • Coustan D.R.
      • Lewis S.B.
      Insulin therapy for gestational diabetes.
      After he returned to New Haven, Don and another colleague published an observational study of 445 women with gestational diabetes that showed that not only did prophylactic treatment with insulin reduce the frequency of fetal macrosomia, but it also reduced the rate of operative deliveries and birth trauma.
      • Coustan D.R.
      • Imarah J.
      Prophylactic insulin treatment of gestational diabetes reduces the incidence of macrosomia, operative delivery, and birth trauma.

      The Diabetes in Pregnancy Program: New Haven

      Upon returning to Yale, where he ran the Diabetes in Pregnancy Program, Don and his colleagues published a case series, “Tight metabolic control of overt diabetes in pregnancy”
      • Coustan D.R.
      • Berkowitz R.L.
      • Hobbins J.C.
      Tight metabolic control of overt diabetes in pregnancy.
      of 73 patients.
      At the time, estrogen production was considered to be a test for placental function, and patients in their third trimester were monitored with daily 24-hour total urinary estriol. A sudden drop in total estriol was an indication for induction. Don’s commitment to the care of diabetic patients went so far as to volunteer to bring the 24-hour collection personally from Guilford, Connecticut, to New Haven: he would meet patients from surrounding areas at 6:30 am in a parking lot on the Connecticut Turnpike and bring the containers to the hospital. Fortunately, for everyone involved, this fetal-placental function test has been replaced by considerably more convenient approaches.
      Tight glucose control depended on serial monitoring of blood sugar, and the advent of portable glucometers, which patients could take home, was an advance that facilitated this goal. Don recalls that Langer and Mazze
      • Langer O.
      • Mazze R.
      The relationship between large-for-gestational-age infants and glycemic control in women with gestational diabetes.
      were the first to use glucometers with a memory chip, which would allow precise recording of blood sugars in pregnant women with diabetes. One of the challenges of tight glucose control in patients with type 1 diabetes was the episodes of hypoglycemia brought on by treatment. Don taught patients and residents that the optimal treatment was crackers and peanut butter or cheese, rather than sugar, to avoid wide swings in glucose concentration.
      Another of Don’s contributions was a feasibility study demonstrating the outpatient use of an insulin pump by pregnant diabetics.
      • Rudolf M.C.
      • Coustan D.R.
      • Sherwin R.S.
      • et al.
      Efficacy of the insulin pump in the home treatment of pregnant diabetics.
      The idea for the study was born in a casual conversation at lunch at the coffee shop of the hospital, when Drs Robert Sherwin and William Tamborlane of the Department of Medicine's Endocrine Division told Don that they were working on an insulin pump. The next step was to do a randomized clinical trial in pregnancy: the insulin pump had comparable results to the conventional tight control of blood sugar.
      • Coustan D.R.
      • Reece E.A.
      • Sherwin R.S.
      • et al.
      A randomized clinical trial of the insulin pump vs intensive conventional therapy in diabetic pregnancies.
      The studies were done in collaboration with Dr Mary C. J. Rudolf (a fellow in medical endocrinology), the faculty of the Endocrine Division, and Dr E. Albert Reece, who led the Diabetes in Pregnancy Program after Don went to Brown. Together, Don and Al have published important books about the care of pregnant patients with diabetes.
      • Reece E.A.

      The story behind the Carpenter and Coustan criteria for the diagnosis of gestational diabetes

      Marshall Carpenter and Don
      • Carpenter M.W.
      • Coustan D.R.
      Criteria for screening tests for gestational diabetes.
      published a study in the American Journal of Obstetrics and Gynecology that would became a citation classic, defining the criteria for diagnosing gestational diabetes and bringing clarity to that area of the field.
      Marshall was a Robert Wood Johnson scholar doing a combined clinical epidemiology and maternal-fetal medicine fellowship at Yale. When working on his thesis, he and Don were wrestling with what they should use as the diagnostic criteria for gestational diabetes. Everyone was using criteria O’Sullivan published in 1964
      • O'Sullivan J.B.
      • Mahan C.M.
      Criteria for the oral glucose tolerance test in pregnancy.
      and revised in 1973,
      • O'Sullivan J.B.
      • Mahan C.M.
      • Charles D.
      • Dandrow R.V.
      Screening criteria for high-risk gestational diabetic patients.
      but they were based on whole blood using the Somogyi-Nelson method for measuring glucose, which measures not only glucose but also other reducing sugars as well.
      Over time, clinical laboratories had switched to using plasma (rather than whole blood) and an enzymatic method, glucose oxidase, which was much more specific for glucose. After consulting with laboratory medicine experts and the literature, Marshall and Don concluded that the Somogyi-Nelson method measured about 5 mg of reducing sugars not measured by the enzymatic method, and that plasma glucose was about 14% higher than whole-blood glucose because the added red-cell volume in whole blood effectively diluted the plasma glucose concentration; therefore, the O’Sullivan criteria were converted to the Carpenter and Coustan criteria by subtracting 5 mg and adding 14% to the whole-blood glucose and by reducing the one-hour value above which a three-hour glucose tolerance test was indicated from 143 to 135 mg/dL to improve the sensitivity of the test (Figure 1).
      • Carpenter M.W.
      • Coustan D.R.
      Criteria for screening tests for gestational diabetes.
      They later showed that the one-hour glucose screen could be used in women who were not fasting if the threshold was reduced from 135 to 130 mg/dL (Figure 2).
      • Coustan D.R.
      • Widness J.A.
      • Carpenter M.W.
      • Rotondo L.
      • Pratt D.C.
      • Oh W.
      Should the fifty-gram, one-hour plasma glucose screening test for gestational diabetes be administered in the fasting or fed state?.
      This was followed by the concept of the breakfast tolerance test to screen for gestational diabetes with a standardized, mixed-nutrient meal.
      • Coustan D.R.
      • Widness J.A.
      • Carpenter M.W.
      • Rotondo L.
      • Pratt D.C.
      The “breakfast tolerance test”: screening for gestational diabetes with a standardized mixed nutrient meal.
      Figure thumbnail gr2
      Figure 1Improving patient care for gestational diabetics
      • Carpenter M.W.
      • Coustan D.R.
      Criteria for screening tests for gestational diabetes.
      Romero. Profile of Donald R. Coustan, MD. Am J Obstet Gynecol 2017.
      Figure thumbnail gr3
      Figure 2Enriched screening techniques for the detection of gestational diabetes
      • Coustan D.R.
      • Widness J.A.
      • Carpenter M.W.
      • Rotondo L.
      • Pratt D.C.
      • Oh W.
      Should the fifty-gram, one-hour plasma glucose screening test for gestational diabetes be administered in the fasting or fed state?.
      Romero. Profile of Donald R. Coustan, MD. Am J Obstet Gynecol 2017.

      The HAPO study

      In the 1980s, there was increasing awareness about the lack of international consistency regarding the diagnosis of gestational diabetes. In 1990, at the Third International Workshop-Conference on Gestational Diabetes, a series of recommendations were made for the diagnosis, summarized by Boyd Metzger
      • Metzger B.E.
      Summary and recommendations of the Third International Workshop-Conference on Gestational Diabetes Mellitus.
      in Diabetes. One of the recommendations was the universal use of the 75-g glucose challenge during pregnancy; however, physicians were using different sets of diagnostic criteria. Some, such as those recommended by the World Health Organization (WHO), were based on criteria for nonpregnant individuals and did not take into account changes in carbohydrate metabolism for pregnant women. Others were using the criteria proposed by O’Sullivan, which were based on pregnant women, but were derived by adding 2 SD to the mean glucose concentration and were predictive of future diabetes in the mother rather than pregnancy outcomes. The organizers of the meeting recognized the need for international agreement on all aspects of diagnostic testing and for the development of criteria based on pregnancy outcomes. Investigators from North America, Europe, Asia, and the Middle East met to plan a study to examine the relationship between maternal glucose and adverse neonatal outcome; this led to a Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)- and National Institute of Diabetes and Digestive and Kidney Diseases-sponsored meeting about the effects of gestational diabetes on perinatal mortality. Don and Boyd were key in this effort, as was Dr Gilman Grave of NICHD.
      • Blank A.
      • Grave G.D.
      • Metzger B.E.
      Effects of gestational diabetes on perinatal morbidity reassessed. Report of the International Workshop on Adverse Perinatal Outcomes of Gestational Diabetes Mellitus, December 3-4, 1992.
      Among others, the protagonists of the initial efforts of the HAPO trial included Don, Boyd, Jeremy Oats, David Hadden, Moshe Hod, and David Sacks. Other contributors from the steering committee included Lynn Lowe, Alan Dyer, Liz Trimble, and Bengt Persson as well as those from centers in Thailand and Hong Kong. While not ultimately involved in the study, Professor Yasue Omori of Tokyo also played an important role in planning the project.
      Boyd and Don, along with other members of the steering committee, designed the international HAPO study to determine the relationship among glucose, insulin, and adverse pregnancy outcomes. Boyd had run the Northwestern University site of the Diabetes Control and Complications Trial and a number of other large multi-institutional studies, so he had considerable experience with field centers. While data analyses were conducted at Northwestern, the central laboratory for chemical analysis was located in Belfast, Northern Ireland.
      The study enrolled approximately 25,000 women at 15 field centers in nine countries. The original results were published in the New England Journal of Medicine,
      • Metzger B.E.
      • Lowe L.P.
      • Dyer A.R.
      • et al.
      HAPO Study Cooperative Research Group
      Hyperglycemia and Adverse Pregnancy Outcomes.
      and a full description of the background of the HAPO study and its role in paving the way for new diagnostic criteria for gestational diabetes was published in the American Journal of Obstetrics and Gynecology in 2010 (Figure 3).
      • Coustan D.R.
      • Lowe L.P.
      • Metzger B.E.
      • Dyer A.R.
      International Association of Diabetes and Pregnancy Study Groups Consensus Panel. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study: paving the way for new diagnostic criteria for gestational diabetes mellitus.
      The “main conclusions were that: (1) the relationship between maternal glucose levels and fetal growth and fetal outcome appears to be a basic biological phenomenon and not a clearly demarcated disease state; and (2) the construction of diagnostic criteria for a condition called ‘gestational diabetes’ was not going to be easily accomplished directly from the configuration of significant associations between maternal glycemia and outcomes. It was clear that the HAPO results were applicable to all the involved field centers, since the associations did not vary significantly across field centers, even though the prevalence of adverse outcomes differed among them. Thus, the HAPO results should be applicable globally to develop outcome-based criteria for classifying glucose metabolism in pregnancy.”
      • Metzger B.E.
      • Lowe L.P.
      • Dyer A.R.
      • et al.
      HAPO Study Cooperative Research Group
      Hyperglycemia and Adverse Pregnancy Outcomes.
      Figure thumbnail gr4
      Figure 3A seminal study to further benefit pregnant women with gestational diabetes mellitus
      • Coustan D.R.
      • Lowe L.P.
      • Metzger B.E.
      • Dyer A.R.
      International Association of Diabetes and Pregnancy Study Groups Consensus Panel. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study: paving the way for new diagnostic criteria for gestational diabetes mellitus.
      Romero. Profile of Donald R. Coustan, MD. Am J Obstet Gynecol 2017.
      How the data from the HAPO study could be used to formulate recommendations for the diagnosis of gestational diabetes was described by Don, Lynn Lowe, Boyd Metzger, and Alan Dyer,
      • Coustan D.R.
      • Lowe L.P.
      • Metzger B.E.
      • Dyer A.R.
      International Association of Diabetes and Pregnancy Study Groups Consensus Panel. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study: paving the way for new diagnostic criteria for gestational diabetes mellitus.
      in their 2010 article. Because there were no clear inflection points in the data, the HAPO investigators asked the International Association of Diabetes and Pregnancy Study Groups (IADPSG) to convene an international panel of experts to consider the available information and make recommendations. The process took more than two years and eventuated in the publication of the IADPSG recommendations,
      • Metzger B.E.
      • Gabbe S.G.
      • Persson B.
      • et al.
      International Association of Diabetes and Pregnancy Study Groups Consensus Panel
      International Association of Diabetes and Pregnancy Study Groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy.
      which have been endorsed by the International Federation of Gynecology and Obstetrics in a working group chaired by Moshe Hod as well as by the WHO, American Diabetes Association, and International Diabetes Federation.

      Leadership at Women & Infants Hospital of Rhode Island and Brown University

      People trained and inspired are the most lasting contributions medical leaders can make to their field. The educational opportunities built at the department at Brown stand as Don’s greatest and most enduring contributions to our specialty.
      When Don arrived at Brown, it was a small department with no reproductive endocrinology faculty or fellowships. When he stepped down in 2008, there were 40 faculty members as well as divisions and fellowships in every subspecialty of obstetrics and gynecology. Under Don’s leadership, the department became part of the Maternal-Fetal Medicine and Stillbirth Network of NICHD as well as urogynecology and reproductive endocrinology and infertility networks, and now has secured funding for the training of physician/scientists. Now, under the leadership of Dr Maureen Phipps, one of Don’s former residents, Brown has continued as the site of a major training grant: Women’s Reproductive Health Research. Katharine Wenstrom was recruited by Joanna Cain to lead the division of maternal-fetal medicine, Sandra Carson to lead reproductive endocrinology and infertility, and Cornelius “Skip” Granai to head gynecologic oncology.
      It speaks volumes about Don that he has been at Brown for 35 years, during which time a new maternity hospital for Providence was built. Don became Chair of Obstetrics and Gynecology at Brown in 1982 after nine years as Division Director of Maternal-Fetal Medicine, taking the place of renowned vaginal surgeon Dr David Nichols. Don held the post of Chair for 17 years before stepping down, and he continues to be active clinically as Professor and Director of the Diabetes in Pregnancy Program at the medical school, now the Warren Alpert Medical School of Brown University.

      A doctor’s doctor

      Don is, at heart, a clinician: a doctor’s doctor to whom you would entrust the care of your family and loved ones because he is a person who cares, not sentimentally, but seriously–about life, about others. This caring is reflected in everything he does: in his tastes and hobbies, and in his keen sense of humor, which is always either situational or at his own expense, never at the expense of others. Like the story he likes to tell of the first command he issued as Chief of Obstetrics in the Navy on finding a diabetic patient he had delivered by cesarean the previous night in tears during morning rounds because she was not allowed to wear her underwear.
      After being informed by the head nurse that it was a standing policy not to allow underwear because it allowed episiotomies to heal better, Don noted that women who have cesarean deliveries don’t have episiotomies, and then issued his first command: “I am hereby commanding you that, from now on, women who have cesarean sections may wear their underwear.”
      “Aye, aye, sir,” the head nurse replied.

      Mentors and friends

      To Don, an important thing to have in life is a mentor, but he is quick to add that this is something that just happens, and it is not something that can be arranged or assigned to you. Don has had a number of mentors in his life: the first was Professor of Physiological Psychology Fred Gault,
      • Gault F.P.
      • Coustan D.R.
      Nasal air flow and rhinenecephalic activity.
      with whom Don conducted his first research project about the effect of nasal air flow on evoked potentials in the rhinencephalon. They studied the effect of chemical esters on the sense of smell.
      Don also credits Robert Resnik, who was a senior resident, as a friend and advisor throughout his career. Bob was always there when they were residents, when Don was considering a move to Brown, and when he was reflecting on becoming President of the American Gynecological and Obstetrical Society and the Society for Maternal-Fetal Medicine (formerly the Society for Perinatal Obstetricians). Don also considers Boyd Metzger, Peter Van Dorsten, Nathan Kase, John Hobbins, Alan DeCherney, Richard Berkowitz, and Jeremy Oats as his mentors and friends.

      Outside of medicine

      Don was born on the south side of Chicago to parents with Russian-Jewish heritage. His relatives left during the pogroms and moved to the Milwaukee-Chicago area. The name “Coustan” was thought to have been shortened from “Coustanovic” and was given to his grandfather upon arrival to Ellis Island. Don’s father was a certified public accountant, and his mother was a nurse who passed away from breast cancer when Don was eight years old.
      During high school in Illinois, Don was enrolled in a special science program and was awarded a summer scholarship in Connecticut, which included a short visit to Yale: he fell in love with the campus and atmosphere of the university. As an undergraduate, Don was a resident at Branford College (one of the Yale colleges), majoring in physiological psychology, where he met Professor Fred Gault, with whom he did his first experimental work in animals. Fred advised him that “if you want to study humans, you need to become a physician.”
      Don then applied to 2 medical schools: McGill and Yale. He never heard from Yale, so he called the admissions office one day to ask if his application had arrived and whether he was being considered. He could hear the conversation between the dean and his assistant: they found the application in a pile, and he was told he had been accepted. Don believes that the moral of this story is that had he not made the call, he may not have attended medical school in New Haven. He says that this is a theme of many things in his life: “things just happen.”

      Don and Terri

      Don and his wife, Terri, originally met in high school, but they didn’t date until she was a senior at the University of Michigan in Ann Arbor. Don had written Terri a letter from New Haven telling her he wanted to come and visit. She wrote back indicating he shouldn’t bother, as she already had a boyfriend and wasn’t interested in another one. Despite this, Don hitchhiked from New Haven to Ann Arbor. Seven weeks after their first date, Don and Terri were married and have been, happily, for 52 years.
      In their home in Guilford, and then in both Providence and Jamestown, Rhode Island, Don and Terri hosted residents and fellows, often the first to welcome newcomers in the training program to the home of a faculty member. Terri’s warmth, elegance, and interest in literature have made her an admirable companion of Don throughout their lives and careers. They have three children: Rebecca, Rachel, and David. Becky has a law degree and an interest in education; Rachel practices veterinary medicine; and David is a digital marketing strategist. Among them, they have provided Don and Terri with six grandchildren and two “grand-dogs.”
      Terri has been a teacher for 50 years, was New Haven’s first Head Start teacher (a program established by President Lyndon Johnson), and taught preschool children from the inner city as well as refugees, who she has helped settle in the United States. More recently, Terri taught English as a second language. She has a broad range of interests–she enjoys drawing and reading and has a gift for gardening. While in Providence, Don and Terri lived in a historic Victorian home with an exceptional garden.
      Don and Terri enjoy traveling all over the world, have special memories of their visits to Normandy, and are passionate about letting young people know about the sacrifices and contributions that past generations have made for this country. They enjoy attending Broadway musicals and have put down roots in a new home of their own design in Jamestown, where they make wine from grapes picked from their vineyard. One of Don’s other hobbies is photography and, when explaining his love of the art, Don is characteristically self-deprecatory: “It’s because I can’t draw;” however, the variety and mood of his photographs tell a different story, for they speak of a man interested in capturing the essence of what he is looking at, which he always manages to do. I believe that this gift he has is the source of his common sense and soundness of judgment, which makes him such a good physician and friend; it is reflected in the steadfastness and authenticity that characterize every facet of Don’s life.

      Appendix

      Figure thumbnail fx1
      Supplemental Figure 1The harbinger of a successful career in medicine
      Don’s Yale Medical School admissions notification, March 1964.
      Romero. Profile of Donald R. Coustan, MD. Am J Obstet Gynecol 2017.
      Figure thumbnail fx2
      Supplemental Figure 2Don's early experimental research in animals
      Article by Arthur Kling and Donald Coustan on electrical stimulation of amygdala and hypothalamus. Experimental Neurology, 1964.
      • Kling A.
      • Couston D.
      Electrical Stimulation of the amygdala and hypothalamus in the kitten.
      Romero. Profile of Donald R. Coustan, MD. Am J Obstet Gynecol 2017.
      Figure thumbnail fx3
      Supplemental Figure 3A champion on and off the football field
      Oak Leaf: Oak Knoll flag football champions, 1973.
      Romero. Profile of Donald R. Coustan, MD. Am J Obstet Gynecol 2017.
      Figure thumbnail fx4
      Supplemental Figure 4Leading the naval medical community
      Don Coustan speaking on diabetes in pregnancy at Naval Regional Medical Center, Oakland, CA; 1974.
      Romero. Profile of Donald R. Coustan, MD. Am J Obstet Gynecol 2017.
      Figure thumbnail fx5
      Supplemental Figure 5The first study of carbohydrates and insulin in pregnancy
      “Circadian variation of serum glucose, C-peptide immunoreactivity and free insulin in normal and insulin-treated diabetic pregnant subjects.”
      • Lewis S.B.
      • Wallin J.D.
      • Kuzuya H.
      • et al.
      Circadian variation of serum glucose, C-peptide immunoreactivity and free insulin in normal and insulin-treated diabetic pregnant subjects.
      Romero. Profile of Donald R. Coustan, MD. Am J Obstet Gynecol 2017.
      Figure thumbnail fx6
      Supplemental Figure 6Traveling abroad and working on the HAPO study in Europe
      In Graz, Austria, 1992: beginnings of the Hyperglycemia and Adverse Pregnancy Outcome Study. Left to right: Terri Coustan, Don Coustan, Yasue Omori, Lois Metzger, Boyd Metzger, Moshe Hod, Tsipi Hod.
      Romero. Profile of Donald R. Coustan, MD. Am J Obstet Gynecol 2017.
      Figure thumbnail fx7
      Supplemental Figure 7The Coustan family in 2015
      Left to right, front row: Sarah Asherov, Rami Asherov, Becky Coustan, Kai Paine, Terri Coustan, Molly Coustan, David Coustan. Back row: Zoe Paine, Rachel Coustan, Jonathon Paine, Jacob Grossman, Milly Asherov, Noah Grossman, Don Coustan.
      Romero. Profile of Donald R. Coustan, MD. Am J Obstet Gynecol 2017.
      Figure thumbnail fx8
      Supplemental Figure 8Roberto Romero and Don Coustan attending an annual meeting of the Yale Obstetrical and Gynecological Society
      Romero. Profile of Donald R. Coustan, MD. Am J Obstet Gynecol 2017.

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