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Diabetes Research and Care Through the Ages Diabetes Care Volume 40, October 2017

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Diabetes Research and Care Through the Ages Diabetes Care Volume 40, October 2017 1302 Diabetes Care Volume 40, October 2017 SYMPOSIUM Bernard Zinman,1 Jay S. Skyler,2 Diabetes Research and Care Matthew C. Riddle,3 and Ele Ferrannini 4 DIABETES CARE Through the Ages Diabetes Care 2017;40:1302–1313 | https://doi.org/10.2337/dci17-0042 As has been well established, the Diabetes Care journal’s most visible signature event is the Diabetes Care Symposium held each year during the American Diabetes Association’s Scientific Sessions. Held this past year on 10 June 2017 in San Diego, California, at the 77th Scientific Sessions, this event has become one of the most attended sessions during the Scientific Sessions. Each year, in order to continue to have the symposium generate interest, we revise the format and content of this event. For this past year, our 6th annual symposium, I felt it was time to provide a compre- hensive overview of our efforts in diabetes care to determine, first and foremost, how we arrived at our current state of management. I also felt the narrative needed to include the current status of management, especially with a focus toward cardiovas- cular disease, and finally, we wanted to ask what the future holds. Toward this goal, I asked four of the most noted experts in the world to provide their opinion on this topic. The symposium started with a very thoughtful presentation by Dr. Jay Skyler entitled “A Look Back as to How We Got Here.” That was followed by two lectures on current concepts by Dr. Bernard Zinman entitled “Current Treatment Paradigms TodaydHow Well Are We Doing?” and by Dr. Matthew Riddle entitled “Evolving Concepts and Future Directions for Cardiovascular Outcomes Trials.” The final lecture for the symposium was delivered by Dr. Ele Ferrannini and was entitled “What Does the Future Hold?” As always, a well-attended and well-received symposium is now the norm for our signature event and our efforts were rewarded by the enthusiasm of the attendees. This narrative summarizes the lectures held at the symposium. dWilliam T. Cefalu Chief Scientific, Medical & Mission Officer, American Diabetes Association 1Lunenfeld-Tanenbaum Research Institute, I. A LOOK BACK AS TO HOW WE GOT HERE Mount Sinai Hospital, University of Toronto, A polyuric state, presumably diabetes, was described more than 3,500 years ago, being Toronto, Ontario, Canada 2Diabetes Research Institute, University of Mi- noted by the physician Hesy-Ra in an Egyptian papyrus (from approximately 1500 B.C.) ami, Miami, FL found by George Ebers. The sweetness of urine was noted by the Hindu physicians 3Division of Endocrinology, Diabetes & Clinical Charaka and Sushruta around 400–500 B.C. (1). Apollonius of Memphis (around Nutrition, Oregon Health & Science University, 250 B.C.) used the term “diabetes” (from the Greek for siphon), and Aretaeus of Portland, OR 4 Cappadocia (A.D. 30–90) described what is likely type 1 diabetes (T1D) as a melting CNR Institute of Clinical Physiology, and the fl Department of Clinical and Experimental Medicine, down of esh into urine, with short survival (2). The sugary nature of the urine also was University of Pisa, Pisa, Italy noted by Zhen Li-Yan in China in the 7th century A.D., by the Arabian Avicenna (A.D. Corresponding author: Matthew C. Riddle, 980–1037), and in detail by Thomas Willis in 1675, who labeled it the “pissing evil” (1,3). [email protected]. “ ” John Rollo in 1797 applied the descriptor mellitus (from the Latin for honey) (4,5). Received 26 July 2017 and accepted 26 July 2017. Dietary Manipulations © 2017 by the American Diabetes Association. As elegantly catalogued in the classic 1919 monograph “Total Dietary Regulation in the Readers may use this article as long as the work ” is properly cited, the use is educational and not Treatment of Diabetes (6), the treatment of diabetes for centuries was empiric and for profit, and the work is not altered. More infor- fundamentally one of dietary restrictions and manipulations, with the addition of various mationisavailableathttp://www.diabetesjournals substances, some of which might be considered drugs. Aretaeus recommended a .org/content/license. care.diabetesjournals.org Zinman and Associates 1303 “non-irritating diet” of milk and carbohy- resulting,” but he used the Bouchardat fruits and garden stuff.” He also proposed drates and hiera, nardum, mastix, and theriak plan with the addition of vegetables and to “avoid worry and lead an even, quiet as drugs. Aetius¨ of Amida (A.D. 550) intro- restriction of fluid intake as well as exer- life” in an equitable climate, use flannel or duced bleeding, emetics, and narcotics, cise, warm clothing, and baths (6). silk near the skin, take a cold bath daily which were used long after. Avicenna Arnoldo Cantani established a new and a Turkish bath occasionally, and get used a treatment consisting of powders strict level of treatment (9). He isolated moderate exercise or massage. He noted of fenugreek, lupin, and wormseed in his patients “under lock and key, and al- that “no one drug has directly curative dosages up to 45 g/day (6). lowed them absolutely no food but lean influence” but that “opium alone stands Thomas Willis said that “treatment meat and various fats. In the less severe the test of experience as a remedy should aim to thicken the blood and sup- cases, eggs, liver, and shell-fish were per- capable of limiting the progress of the ply salts” and recommended “milk, rice, mitted. For drink the patients received disease.” He wrote that other “effective” and starchy and gummy foods” (6). He water, plain or carbonated, and dilute al- agents included potassium bromide, lac- limited patients to a diet of milk and bar- cohol for those accustomed to liquors, tic acid, arsenicals, creosote, and lithium ley water boiled with bread and thus be- the total fluid intake being limited to salts. came the author of the first carbohydrate one and one-half to two and one-half li- or undernutrition care (6). He also initi- ters per day” (6). Insulin Era ated opium treatment (3). Bernhard Naunyn encouraged a strict In 1889, Josef von Mering and Oskar Thomas Sydenham prescribed narcotics carbohydrate-free diet (6,10). He locked Minkowski reported that total pancrea- andtheriakandsaid,“Let the patient eat patients in their rooms for 5 months tectomy in dogs resulted in severe diabe- food easy of digestion, such as veal, mut- when necessary for “sugar-freedom” (6). tes in the dog (14,15). In 1893, Gustave ton, and the like, and abstain from all When sugar-freedom was not attained Edouard Laguesse (16) deduced that the sorts of fruits and garden stuff” (6). through the withdrawal of carbohydrate, pancreatic islands described by Paul John Rollo began treatment with protein was reduced as low as 40–50 g/day Langerhans in 1869 (17) as a “little heap bleeding. He ordered “confinement . and the calories were also diminished. of cells” produced an internal secretion preferably to one room, with the utmost Occasional fast days were advised as that regulated glucose metabolism. In possible quiet and avoidance of exercise” necessary. 1901, Eugene L. Opie reported that de- (6). A diet of animal food, as rancid as KarlvonNoordenused1or2fastdays, generation of the “islets of Langerhans” possible, was also proposed. Drugs were with the only food being alcohol (up to was associated with diabetes (18,19). All chosen to produce anorexia and nausea, 200–250 mL cognac). As soon as gly- of these events contributed to the search including ammonium sulfide, wine of an- cosuria and acidosis were partially con- for the hypothetical hormone that Jean timony, tincture of opium, digitalis, and trolled, he quickly provided an “oat-cure” De Meyer in 1909 dubbed “insuline” tobacco (4–6). (6). (20). Edward Sharpey-Shafer in 1916 Apollinaire Bouchardat in France resur- Frederick M. Allen of the hospital of coined “insulin” as a single substance rected and transformed the Rollo treat- The Rockefeller Institute for Medical Re- from the pancreas responsible for diabetes. ment (7,8). Some consider him the father search was one of the first to appreciate Meanwhile, multiple people (Table 1) of diabetology. He was the first to insist that diabetes involves total metabolism around the world were attempting the on individualized treatment for patients. rather than carbohydrate metabolism extraction of insulin. These are chronicled He disapproved the rancid character of alone (6,11). He studied a detailed regi- in detail in Michael Bliss’sbookThe Dis- the fats in the Rollo diet but substituted men that involved fasting 2–10 days to covery of Insulin and will not be reviewed fat and alcohol for carbohydrate in the clear glycosuria, followed by a restricted- here (21). diet (6). He forbade milk because of its calorie diet that provided mainly fat and It was in 1921 that Frederick Banting carbohydrate content, and he “urged protein (especially eggs) with the smallest and Charles Best, working in the laboratory of that patients eat as little as possible, amount of carbohydrates (mostly vegeta- J.J.R. Macleod at the University of Toronto, and masticate carefully” (6). He introduced bles) necessary to sustain life. If glycosuria successfully extracted insulin. It was first used fasting to control glycosuria and recom- appeared, fasting was resumed for 1–2 as treatment in January 1922 (22) and was a mended green vegetables to provide days. The regimen essentially starved truly life-saving achievement. Unselfishly, “little sugar, a little protein and fat, but people with severe diabetes in order to the University of Toronto made their especially potassium, organic acids, and control the disease. achievement available to companies various salts” (6). He also first introduced Elliot P. Joslin embraced the Allen ap- around the world so that insulin could the intelligent use of exercise in the treat- proach but also used a treatment that be widely used.
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