History of diabetology

from Wikipedia, the free encyclopedia

The history of insulin and insulin preparations is an important part of medical history , not least because the results of this research have made diabetes mellitus a deadly disease that has lost its horror.

Antiquity

In the 6th century BC The Indian surgeon Sushruta found sticky-sweet urine in one of his patients. ... In the 2nd century AD his compatriot described Charaka the disease in the Charaka Samhita eventually follows: "You have a patient that urine can be like a rutting elephant, is the urine Honigharn or Zuckerruhrharn and its urine tastes sweet and the Ants and attracts insects. "

.. 100 AD used Aretaios first time the word diabetes (διαβήτης; originally, siphon ', only later - at Galen  - "Harndurchfall" and "thirst disease") as a disease name for a disease in which the body supplied liquid flows out immediately and he wrote: “Diabetes is a puzzling disease.” He described the symptoms and the course: “Diabetes is a terrible condition, not very common in humans, a melting of the flesh and limbs into urine ... Life is short, uncomfortable and painful, the thirst insatiable, ... and death inevitable. "

middle Ages

In the first half of the 13th century, the Arab scholar Abd al-Latif al-Baghdadi wrote a treatise on diabetes.

17th century

Thomas Willis

In 1675, Thomas Willis described the taste of urine in diabetes as "honey-sweet": "... tasted as if it has been mixed with honey". The term “mellitus” goes back to him; Diabetes mellitus was also called Willis' desease for some time . Willis also described the symptoms of diabetic neuropathy in his patients: “stinging and other (…) frequent contractions or convulsions, twinging of the tendons and other disturbancies”. He couldn't cure the diabetes: "It seems a most hard thing in this disease to draw propositions for curing, for that its cause lies so deeply hid, and hath its origin so deep and remote." Although he observed that patients on an extremely hypocaloric diet temporarily felt better, he did not yet recognize the connections. In contrast to his colleagues, who viewed diabetes as a pure kidney disease, he already suspected that the cause must be in the blood.

In 1683 Johann Konrad Brunner Hunden removed the pancreas and observed extreme thirst and polyuria as a result ; he is therefore considered to be the discoverer of pancreatic diabetes mellitus .

18th century

In 1776, the British doctor and natural philosopher Matthew Dobson (1732–1784) made a kind of sugar in the urine responsible for its sweet taste. A connection between diabetes and diseases of the pancreas was first described in 1788 by Thomas Cowley . In 1794 Johann Peter Frank was the first to differentiate between diabetes mellitus and diabetes insipidus .

19th century

Paul Langerhans

In 1860 Joseph Alexander Fles (1819–1905) treated a diabetic with extracts from calf pancreas, four years later he published these experiments. Paul Langerhans described the islet cells in the tissue of the pancreas in his dissertation in 1869, although he did not investigate their function. In the same year Langdon Down reported on a treatment attempt with pancreatin (extract from ground pork pancreas, obtained from slaughterhouse waste).

In 1875, the French doctor Apollinaire Bouchardat published his work “De la glycosurie ou Diabète sucré son traitement hygiénique” in Paris, in which he sets out basic principles of diabetes treatment that are important to the present day, including a special diet and the importance of weight reduction, physical Activity, metabolic control and patient education. His compatriot Étienne Lancereaux coined the terms diabete maigre (“lean diabetes”) and diabete gras (“fat diabetes”) in a publication in 1880 , thus establishing the distinction between different forms of diabetes.

In 1889 Wilhelm von Leube described the frequent connection between pancreatic diseases and diabetes mellitus. The German doctors Oskar Minkowski (1858–1931) and Josef von Mering (1849–1908) removed the pancreas from dogs in the same year in order to observe the effect on lipid metabolism. In doing so, however, they discovered that they caused the disease diabetes mellitus.

In honor of Paul Langerhans, the French pathologist Édouard Laguesse (1861-1927) called the cell clusters "Ilots de Langerhans", " Langerhans islands " in 1893 . He also postulated its function as an endocrine (hormone-producing) tissue with a regulatory effect on the metabolism.

In the same year, Minkowski tried to supply a pancreatic extract by subcutaneous injection. Minkowski, Hédon and Thiroloix discovered that after removal of the pancreas, diabetes does not occur if pancreatic substance is transplanted somewhere under the skin. In 1898, Carl von Noorden published the second edition of The Diabetic Disease and Its Treatment .

First half of the 20th century

Nicolae Paulescu
Frederick Banting (right) and Charles Best with one of their test dogs; note the container on the dog's belly
Insulin crystals, grown in weightlessness

In 1900 Leonid PoP Sobolew (1876–1919) recognized the "islands" as production facilities for blood sugar-lowering substances.

In 1902 Carl von Noorden developed a diet oat cure that lowers blood sugar levels. In 1903, the German internist Georg Ludwig Zülzer (1870–1949) examined a therapeutic pancreatic extract that can lower blood sugar and is the first approach to treating diabetes mellitus. However, because of serious side effects that were possibly allergic in nature , the preparation known as “Zülzer extract” could not be used in humans.

For the still unknown substance, the Belgian Jean de Meyer suggested the name insulin , derived from the Latin insula ("island"). In 1910 the English physiologist Edward Albert Sharpey-Schafer called the substance from the pancreas lacking in diabetics “insulin”. It is not clear from the available sources who coined the name first.

Around 1905, the clinical chemist Ivar Christian Bang (1869–1918) in Lund had developed a reliable and inexpensive method for determining blood sugar.

In 1916 Nicolae Paulescu succeeded for the first time in obtaining insulin from pancreatic tissue. He named the preparation Pankrein , it was effective on a diabetic dog. In 1921 Paulescu published his findings, and the following year he patented the manufacturing process for Pankrein in Romania.

Even Frederick G. Banting and Charles H. Best managed the extraction of insulin from pancreatic animal 1,921 fetuses , they called it isletin . They also carried out their experiments on dogs whose pancreas had been surgically removed. In their publications they confirm the work of Paulescu. Previous attempts by other scientists had not been successful because other digestive juices of the pancreas destroyed the insulin because they had used the whole ground pancreas. The biochemist James Collip was hired by John James Rickard Macleod to support Banting and Best. Collip succeeded in obtaining a much purer extract by means of fractionated protein precipitation with high percentage alcohol.

In 1922, the team led by Banting and Best succeeded in rescuing a diabetic for the first time . 13-year-old Leonard Thompson, who had had the disease for a year and a half, was treated with beef insulin by them at Toronto General Hospital. After just three days, his urine is free of sugar and acetone . Banting, Best, Collip, Campbell, and Fletcher reported on it in the Canadian Medical Association Journal. Thompson survived for 14 years until he died of pneumonia unrelated to his diabetes. Theodore Ryder , who was treated in July 1922, was five years old at the time, and even survived for 70 years and thus achieved what is probably the longest documented survival time of a diabetes patient in medical history.

In 1922, the Senate of the University of Toronto formed a committee to control the industrial production of insulin using the patented process. First, a contract was signed with the Lilly company.

Banting and MacLeod received the 1923 Nobel Prize in Physiology or Medicine "for the discovery of insulin"; they later voluntarily shared the award with Best and Collip. In the same year, Eli Lilly and Company , who had worked with Banting and Best, launched the first insulin preparation "Iletin" in Toronto. Insulin production in Europe also began in 1923. On October 31, the Hoechst company presented “Insulin Hoechst”, made from calf and cattle pancreas. Further production facilities were set up in Denmark (Hagedorn) and Austria.

In the decades that followed, insulin was extracted from the pancreas of cattle and pigs. Although animal insulin is also effective in humans, attempts have nevertheless been made to produce human insulin, as treatment with unmodified animal insulin often led to serious immunological side reactions.

In 1926 John Jacob Abel (1857–1938) at the Johns Hopkins University in Baltimore succeeded in producing insulin in a pure, crystalline form. Two years later, Oskar Wintersteiner (1898–1971) demonstrated that insulin is a protein .

In 1930 Gerhardt Katsch opened the first diabetic home in Europe in Garz auf Rügen, where patients were cared for and trained in how to deal with the disease. The second home in Karlsburg followed in 1947.

In 1931 Sjögren and The Svedberg determined the molar mass of insulin, and a year later Dorothy Crowfoot Hodgkin began the chemical analysis of insulin in Oxford. It would take 35 years to decipher the entire structure.

David Aylmer Scott developed the first zinc insulin in 1934 after he had shown that insulin contains zinc and that its effects are thereby slowed down. The long-acting insulin preparation Neutral Protamine Hagedorn (NPH insulin) was first produced by Hans Christian Hagedorn in 1936.

A year later, Gerhardt Katsch coined the term "conditionally healthy" for diabetics in his Garz theses . The differentiation of diabetes mellitus into different forms based on differences in insulin sensitivity was described by Harold Percival Himsworth in 1939.

The couple Carl Ferdinand and Gerty Cori received the 1947 Nobel Prize in Physiology or Medicine "for their discovery of the course of catalytic glycogen metabolism". The Cori cycle is an important part of the sugar metabolism. The second part of the Nobel Prize for Medicine went to Bernardo Alberto Houssay “for his discovery of the importance of the hormones in the anterior pituitary for sugar metabolism”. In 1950 the International Diabetes Federation was founded.

Second half of the 20th century

Frederick Sanger
Insulin pens

In 1955 Frederick Sanger published the complete amino acid sequence of insulin after twelve years of work, in which Hans Tuppy was also involved. For this he was awarded the second Nobel Prize in the history of insulin in 1958 , this time in the field of chemistry, “for his work on the structure of proteins, especially insulin”.

The era of radioimmunoassay , developed by Rosalyn Sussman Yalow and Solomon Aaron Berson , began in 1959. This made it possible to determine the level of insulin in the blood. In 1960 Nicol and Smith described the structure of human insulin . 1963 succeeded Helmut Zahn and his team at the German Wool Research Institute in Aachen, the world's first chemical synthesis of insulin. However, due to the more than 200 synthesis steps, this insulin synthesis could not yet be used industrially. However, she did away with the prejudice that proteins cannot be synthesized. A year later, Konrad Bloch and Feodor Lynen received the Nobel Prize in Medicine “for their discoveries about the mechanism and regulation of the metabolism of cholesterol and fatty acids” . They created important foundations for the treatment of lipid metabolism disorders, which play an important role in type 2 diabetes.

Based on a 1958 publication by the American pathologist Philip Medford LeCompte , the Belgian pathologist Willy Gepts described in 1965 an infiltration of cells of the immune system into the islets of Langerhans called insulitis as characteristic of type 1 diabetes and thus made an important contribution to understanding this form of diabetes as an autoimmune disease . In the same year, Donald F. Steiner discovered that the two-chain insulin is not "composed", but rather arises from a single chain, the proinsulin . In 1969, Dorothy Crowfoot Hodgkin's group in the Laboratory of molecular biophysics in Oxford clarified the three-dimensional protein structure of insulin. In 1970, several research teams discovered the fact that insulin is bound to the surface of cells.

Electronic blood glucose meters have been around since the early 1970s. The training of the patients in the use of the devices was entrusted to diabetes advisors. Corresponding training and further education have been available since 1983. Since the 1990s, ever smaller and more precise devices have come onto the market, which have since been widely used and are part of the standard therapy for diabetes mellitus.

In 1972 the German Diabetes Society (DDG) awarded the Paul Langerhans Medal for the first time for research in the field of diabetology. Rosalyn Sussman Yalow was awarded the Nobel Prize in Physiology or Medicine in 1977 for the development of radioimmunological methods for the determination of peptide hormones .

In 1976, Rainer Obermaier and Rolf Geiger at Hoechst created the enzymatic synthesis of human insulin from pig insulin, which differs from human insulin in only one amino acid unit. The product was launched in 1983.

The genetic engineering of insulin was first achieved in 1979 at Genentech . For this purpose, corresponding genes were introduced into E. coli bacteria. Two years later it was possible for the first time to produce this synthetic insulin in large quantities by genetically modified bacteria, and the product was launched on the American market in 1982. In the meantime, yeasts have also taken on this task. In Germany, the production of human insulin by genetically modified bacteria was only allowed in 1998.

Joan Massagué Solé discovered in 1980 a. a. the insulin receptor .

The first report on the successful treatment of a diabetic with an infusion device "Infusaid" that can be implanted in the abdominal cavity, a forerunner of the insulin pump , dates back to 1984.

In 1985 the first insulin pen , Novo Nordisk's NovoPen , was launched. The birthday of Frederick Banting in 1991 by the IDF and WHO for World Diabetes Day determined. This year Zygmunt S. Derewenda , Urszula Derewenda u. a. that the insulin molecule changes when it binds to the insulin receptor ( conformational change ). What exactly happens is still the subject of research to this day. In addition, in 1991, Steven P. Smeekens and Donald F. Steiner determined after many years of work the enzymes that produce insulin in the body from proinsulin.

1996 comes with lispro from Lilly , the first fast-acting insulin analogue on the market; the second was Insulin aspart from Novo Nordisk in 1998 . Both proteins differ from human insulin in only a few amino acid residues and are produced by genetically modified bacteria.

21st century

The first long-acting analog insulin was sold by Aventis in 2000 with insulin glargine . Four years after that insulin detemir of Novo exposed as the second long-term insulin analogue. In 2005 the FDA approved Symlin®, an analogue of the amylin hormone , the first drug since insulin for the treatment of type 1 diabetes. The third fast-acting analog insulin was made available by Sanofi-Aventis in 2000 with insulin glulisin .

In 2006 McKern u. a. In a work for the first time the structure of the entire extracellular domain of the insulin receptor (over 1800 amino acids) by X-ray crystallographic. In 2007 World Diabetes Day was declared a UN Day of Action by the UN .

Insulin pumps have been in use since the early 1990s and increasingly after the turn of the century . An insulin pump contains a reservoir for insulin and delivers a continuous basal rate that can be set individually for the patient for 24 hours. A bolus is delivered manually for each meal. The insulin pump is connected to an injection needle via a catheter on the body for subcutaneous insulin delivery. The pump technology was improved by the continuous measurement of tissue sugar ( continuous glucose monitoring ). Here a second catheter is attached to the body next to the pump. A sensor continuously measures the level of tissue sugar and transmits the values ​​to the pump or to your own device. This can trigger an alarm if the blood sugar is below or above a tolerance value. If the result measured in this way is below a critical value, the pump can also be switched off automatically in order to avoid hypoglycaemia . The latest insulin pump technology is the production of a closed control loop in which the pump independently releases glucagon in addition to the insulin to counteract dangerous hypoglycaemia.

See also

literature

  • Colin W. Ward, Michael C. Lawrence: Landmarks in Insulin Research. In: Frontiers in Endocrinology. 2, 2011, S., doi: 10.3389 / fendo.2011.00076 .
  • Peter Dilg: Insulin. In: Werner E. Gerabek, Bernhard D. Haage, Gundolf Keil, Wolfgang Wegner (eds.): Enzyklopädie Medizingeschichte . De Gruyter, Berlin 2005, ISBN 3-11-015714-4 , p. 680.
  • P. De Meyts: Insulin and its receptor: structure, function and evolution. In: BioEssays: news and reviews in molecular, cellular and developmental biology. Volume 26, Number 12, December 2004, pp. 1351-1362, ISSN  0265-9247 . doi: 10.1002 / bies.20151 . PMID 15551269 . (Review).
  • Dietrich von Engelhardt (Ed.): Diabetes: Its Medical and Cultural History. Outlines - Texts - Bibliography. Springer-Verlag, Berlin / Heidelberg / New York 1989, ISBN 3-540-50950-X , 491 pages.
  • Johannes Steudel : The History of Diabetes. In: Diabetiker 3, 1953, pp. 45 f., 61 f. and 71 f.
  • N. Sp. Papaspyros: The history of Diabetes mellitus. London 1952.

Web links

Individual evidence

  1. ↑ Stern.de: The Secret of Honey Urine ( Memento from February 17, 2015 in the Internet Archive ), accessed on February 17, 2015
  2. ↑ Thomas Schlich: Diabetes. In: Werner E. Gerabek , Bernhard D. Haage, Gundolf Keil , Wolfgang Wegner (eds.): Enzyklopädie Medizingeschichte. De Gruyter, Berlin / New York 2005, ISBN 3-11-015714-4 , p. 298 f .; here: p. 298.
  3. ^ A b Gerhard-Walter Schmeisl: Training book for diabetics . Elsevier, Munich 2005, ISBN 3-437-47271-2
  4. ↑ Peter Fasching: Insulin analogues - more quality of life for diabetics who need insulin . Lecture at the ÖDG annual conference, Innsbruck 2007
  5. ↑ Hans-Jürgen Thies: The diabetes tractate ʿAbd al-Latīf al-Bagdādīs. Investigations on the history of the disease in Arabic medicine. (Medical dissertation Bonn: Oriental seminar of the university) Bonn 1971 (= Bonn oriental studies, new series. Ed. By Otto Spies , volume 21).
  6. ↑ a b c d Elizabeth Lane Furdell: Fatal thirst: diabetes in Britain until insulin . ISBN 90-04-17250-5 , p. 89
  7. ↑ Thomas Willis: Pharmaceutice rationalis. Sive Diatriba de medicamentorum operationibus in humano corpore. 1674/1675 Scan from Google Books (PDF) p. 217, in PDF 274
  8. ↑ a b c Insulin - a success story in modern medicine . (PDF) Research for Life: Biofocus No. 69
  9. ↑ a b M. Dobson: Nature of the urine in diabetes . In: Medical Observations and Inquiries . 5, 1776, pp. 298-310.
  10. ^ Heinz Schott and co-workers: The Chronicle of Medicine . Chronik-Verlag, 1993, ISBN 3-611-00273-9 .
  11. ^ A b c Bernhard Meyer: Hope of diabetics, victims of tuberculosis . In: Berlin monthly magazine ( Luisenstädtischer Bildungsverein ) . Issue 7, 1997, ISSN  0944-5560 , p. 56–60 ( luise-berlin.de - portrait of Paul Langerhans).
  12. ↑ Biography of G.-E. Laguesse. ( Memento of the original from October 24, 2007 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. (French) @1@ 2Template: Webachiv / IABot / www.chru-lille.fr
  13. ↑ NASA picture gallery
  14. ↑ Quoted from the Wikipedia article
  15. ^ History of Diabetes Timeline. ( Memento of the original from December 31, 2006 in the Internet Archive ) Info: The archive link was automatically inserted and not yet checked. Please check the original and archive link according to the instructions and then remove this notice. University of Massachusetts @1@ 2Template: Webachiv / IABot / www-unix.oit.umass.edu
  16. ↑ expasy.org
  17. ^ Ivar Christian Bang: Methods for micro-determination of some blood components. Wiesbaden 1916.
  18. ^ Christoph Gradmann : Bang, Ivar Christian. In: Werner E. Gerabek , Bernhard D. Haage, Gundolf Keil , Wolfgang Wegner (eds.): Enzyklopädie Medizingeschichte. De Gruyter, Berlin / New York 2005, ISBN 3-11-015714-4 , p. 137.
  19. ^ History of the discovery of insulin by Banting, Best, Collip, and MacLeod . ( Memento of the original from March 26, 2012 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. Austrian Diabetes Society @1@ 2Template: Webachiv / IABot / 216.71.46.171
  20. ^ Charles Wassermann: Insulin. The struggle for a discovery . Ullstein 1991, ISBN 3-548-34769-X
  21. ↑ FG Banting, CH Best, JB Collip, WR Campbell, AA Fletcher: Pancreatic extracts in the treatment of diabetes mellitus . In: Canadian Medical Association Journal , 12, 1922, pp. 141-146.
  22. ↑ Peter Dilg: On the early history of industrial insulin production in Germany . In: Pharmacy in our time , no one 2,001th
  23. ↑ 80 years of insulin - How two Canadian researchers wrote medical history. July 27, 2001, accessed on December 29, 2018 (including a photo of the preparation).
  24. ↑ Sanofi-Aventis: Insuline yesterday and today  ( page no longer available , search in web archives )  Info: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice.@1@ 2Template: Dead Link / www.diabetesportal.at  
  25. ↑ DF Steiner, r PE Oye: The Biosynthesis of Insulin and a Probable Precursor of Insulin by a Human Islet Cell Adenoma . In: Proc. Natl. Acad. Sci. USA , 1967, 57, pp. 473-480. DF Steiner, D. Cunningham, L. Spigelman, B. Aten: Insulin Biosynthesis: Evidence for a Precursor . In: Science , 1967, 157, pp. 697-700.
  26. ↑ MJ Adams, TL Blundell, EJ Dodson, GG Dodson, M. Vijayan, EN Baker, MM Harding, DC Hodgkin, B. Rimmer, S. Sheat: Structure of Rhombohedral 2 Zinc Insulin Crystals . In: Nature , 224, 1969, pp. 491-495, doi: 10.1038 / 224491a0 .
  27. ^ Dorothy Crowfoot Hodgkin: X Rays and the Structure of Insulin . In: British Medical Journal , 1971, 4, 447–451, PMC 1799667 (free full text)
  28. ↑ TL Blundell, JF Cutfield, SM Cutfield et al .: Atomic positions in rhombohedral 2-zinc insulin crystals . In: Nature . 231, No. 5304, June 1971, pp. 506-11. PMID 4932997 .
  29. ↑ Aaron Pfaff: The metabolic self-control - from the determination of urine sugar to digital blood sugar measurement . In: Anna Palm, Sabine Wöhlke (ed.): Human-technology interaction in medicalized everyday life . Universitätsverlag Göttingen, Göttingen 2018, ISBN 978-3-86395-358-4 , p. 129-143, 129-134, 137-139, 140 ( oapen.org [accessed March 15, 2019]).
  30. ↑ a b c Beate Meichsner, Uwe Wirth: Insulin - protein with a long history. The key to diabetes therapy . In: Chemistry in Our Time . tape 43 , no. 5 , October 2009, ISSN  0009-2851 , p. 340–346 , doi : 10.1002 / ciuz.200900486 ( wiley.com [accessed May 14, 2018]).
  31. ^ J. Massagué, PF Pilch, MP Czech: Electrophoretic resolution of three major insulin receptor structures with unique subunit stoichiometries. In: PNAS. Volume 77, Number 12, December 1980, pp. 7137-7141. PMID 6938960 . PMC 350456 (free full text).
  32. ^ IW Campbell, H. Kritz, C. Najemnik, G. Hagmueller, K. Irsigler: Treatment of type I diabetic with subcutaneous insulin resistance by a totally implantable insulin infusion device ("Infusaid") . In: Diabetes Research (Edinburgh, Scotland) . tape 1 , no. 2 , July 1, 1984, ISSN  0265-5985 , p. 83-88 , PMID 6442226 .
  33. ↑ FDA Approves New Drug to Treat Type 1 and Type 2 Diabetes
  34. ↑ NM McKern, MC Lawrence et al. a .: Structure of the insulin receptor ectodomain reveals a folded-over conformation . (PDF; 239 kB) In: Nature , Volume 443, Number 7108, September 2006, pp. 218-221. doi: 10.1038 / nature05106 . PMID 16957736 .
  35. ↑ Artificial pancreas treats type 1 diabetes with iPhone support. In: Deutsches Ärzteblatt online. June 16, 2014, accessed May 17, 2019 .