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Susruta (5th century B.C.) described a condition 'Madhurneha' in which a person passes
urine which resembles honey. He also knew that carbuncle occurred in such patients.
The Egyptian Papyrus Ebers (1500 BC) described the illness of diabetes. Aretaeus of
Cappadocia (2nd century AD) gave the name diabetes. He lived in Alexandria (about 2nd century AD). Polyuria, sticky urine and sweet urine were described in 3rd and 4th centuries AD by scholars of China and Japan. It was Avicenna, an ancient Arab physician who observed that gangrene complicates the disease and it has got a hereditary tendency.
Willis in 1674 added his observation that urine is honey-or sugar-like in diabetes. The
name diabetes mellitus (mellitus means honey) was thus established. After 200 years of Willis' observation, Mathew Dobson (1784) of America demonstrated that sweetness of urine in diabetes is due to sugar which is excreted from blood stream. Claude Bernard showed that glucose absorbed is stored in liver as glycogen and secreted directly into the blood stream according to metabolic demands.
Islet tissue of pancreas was first noted by Brockmann in 19th century. But in 1869
Langerhans described them in mammals and since then islets of Langerhans was established. Two German Scientists Joseph Von Mehring and Oskar Minkowski (1889) found that surgical removal of pancreas produced diabetes in dogs. Eugene Lindsay Opie (1901) found that beta cells in the islets are damaged in humans dying of diabetes. The term Insulin (Latin Word-Insula means island) was proposed by Sir Edward Sharper. He suggested that diabetes is due to failure of islets to produce internal secretion.
Diabetic coma was described for the first time by Adolf Kussmaul (1882-1902) of
Germany. Bernard Naunyn (1839-1925) of Berlin published the results of his work in 1898 in a monograph "Der Diabets Mellitus". Formation of acids in diabetic coma was first noted by Bernard Naunyn. He coined the term acidosis. John Rollo described the ketotic odour of decaying apple.
Carl Von Noorden (1858-1945) of Vienna devoted mainly to study of diabetes and the
influence of diet on the disease.
The most famous contribution to endocrinology came on 30th July 1921 when a young
surgeon, Frederik Banting and his graduate student assistant Charles Best working in Toronto in the Physiology Laboratory of Prof.JJ.R. Macleod, prepared active extract of pancreas, which lowered the elevated level of glucose in diabetic dogs. The first patient who received the active extract prepared by Banting and Best was Leonard Thompson, a boy aged 14 yrs. He came to Toronto General Hospital with a blood sugar of 500 mg%. On 11/01/1922 he received pancreatic extract. He improved and became stronger. This was truly a dramatic interruption of metabolic disorder recorded in history of medicine. Thompson lived for 11 yrs. and died of bronchopneumonia following a motor cycle accident.
Dr. Banting and his associates published their finding on 50 cases in Jan. 1923 issue of
B.M.J. In May 1923 US investigators reported m Journal of Metabolic Research their findings on the use of insulin in diabetic patients. Use of pork and beef pancreas glands came about largely because, they came from most plentiful slaughtered animals and could therefore assure a supply of glands for insulin production. Geerfe Walden produced isoelectric precipitate of insulin. In 1926-John Abel prepared crystalline insulin. Zinc insulin crystal was prepared by Dr. David Scoott and Dr. Albert Fisher of John Hopkins University. In June 1935 Dr. H.C. Hagedorn described N.P.H. In 1949 PZI was introduced. In 1950 Novolas Copenhagen described ultralente, semilente and lente insulins. In 1955 Sanger first described the structure of insulin. Pro insulin was discovered by Steiner and Oyer in 1967 at University of Chicago. Givol and his colleagues in 1965 for first time attempted to bio synthesise, insulin by transformation of single chain to A and B. In 1972 Gel filtration chromatography to purify insulin was introduced by Lilly pharmaceutical industry. By July 1980 Human Insulin of recombinant DNA origin was available for human studies. U 100 concentrates of insulin was introduced in USA in early 1974. By late 1978 almost 80% of insulin sold in USA was U 100.
In 1979 portable insulin pumps for continuous subcutaneous infusion of insulin for
ambulatory diabetics became available. Dr. G.H.A. Claves, Director ELI LILLY offered the services of his company for large scale production of insulin for commercial use. In 1923 large scale production of insulin for the needs of approximately 10, 000 diabetics was commenced.
In 1942 Jenson and coworkers discovered P-Amino benzene sulfonamide
isopropylhiadiazole (a sulforsamide) which reduced blood glucose but it was later found that this effect was not seen in pancreatecotomised animals. He therefore suggested that the hypoglycemic effect was the result of stimulation of pancreas to secrete insulin. In 1956 tolbutamide came in market and in 1957 chlorpropamide became available. Acetohexamide was marketed in 1963 and in 1969 glyburide (Glibenclamide) was introduced which was followed by glipizide in 1973.
History of metformin may be traced from medieval times when the plant Galega officinalis
(Goat's rue or French Lilacia) was used in Europe. This substance is rich in guanidine which reduced blood glucose concentration in animals. Toxicity disfavoured its clinical use. In 1950 there was a renewed interest in these compounds. This led to development of Biguanides - Metformin, Phenformin and Buformin. In 1970 phenformin went into disrepute because of lactic acidosis and phenformin was withdrawn in several countries. Latter it was found if metformin is used judiciously lactic acidosis is less common.
In 1959 rebound hyperglycemia or Somogyi's effect was described. In 1976 glucose
oxidase membrane sensor was developed by Soeldner's group in Boston and Bessman's group in Los Angeles, of USA. They developed a fine cell glucose sensor which was used in artificial pancreas. In 1957 Sament and Schwartz described first time hyperosmolar non ketotic coma. French physician Bouchard, described planned diet, advocated boiling vegetables to remove starch. He also introduced exercise in therapy of diabetes. Frederick M. Alien and Elliot P. Joslin at Boston USA introduced balanced diet therapy consisting of carbohydrates, fat and protein in diabetes. Careful weighing of foods was introduced. Joslin's view was that in diabetic diet management, one has to take care of total calories and it should be appropriate to the individual patients. With the advent of insulin and oral hypoglycemic agents there was a tendency for liberal diet from previous starvation diet. IN 1950 low carbohydrate (Only 35% of total calories) was used. With this diet it was not palatable and high fat contents led to increased atherogenesis and CAD. Hence in 1959 high carbohydrate diet and low fat diet was introduced and the concept of isocaloric diet was used. High fibres (3-5 grms%) was prescribed.
Laser Photo Coagulation therapy was first started in 1959 by Meyer,In 1970 vitrectomy
surgery for organized haemorrhage secondary to proliferative retinopathy was done by Machemer.
The UGDP study controversy : (1970) In this study it was found that over 8 yrs. 30
deaths among 204 insulin independent diabetics taking l.Sgm of tolbutamide on fixed dose. 26 deaths out of 30 were cardiovascular. In placebo group only 10 deaths out of 205 occurred. In phenformin group 26 deaths out of 31 occurred. UGDP study served a valuable purpose. It reminded physicians of dietary treatment in diabetes mellitus and to avoid abuse of oral hypoglycemic drugs. It emphasizes switch over to insulin when diet and OHA fail to achieve euglycemia in diabetes.
Islet cell transplantation : In 1892 MInkowski attempted pedicle transplant of pancreatic
lobe into abdominal wall. Same year, Hedan reported that transplantation of partially rejected pancreas prevented diabetes mellitus. In 1902 S. Soboleu suggested pancreatic transplantation as a treatment for diabetes mellitus. Since 1971 pancreatic duodenal allotransplantation in terminal diabetes mellitus with nephropathy has been tried.
References:
1. Recombinant DNA and Human Insulin, A Sark Book: LILLY Diabetes Care.
2. Diabetes and metformiri - A research and clinical update published by the royal
society of medicine. Wintrobe street London No 79.1984 Page 17.
3. Diabetes - A brief Historical aspect. Page 1-5, A hand book of diabetes mellitus. New
Mediwave publication - LUPIN.
4. Current concepts of diabetes. Page 1-2, by Alexander Marble joslin's Diabetes
mellitus - llth Edn.Lea and Febiger Publishers, Philadelphia, 1971.
LAND MARKS IN THE HISTORY OF DIABETES MELLITUS
1) 1500 BC : Ebers Papyrus (EGYPT) -Polyuria & Honey Urine described.
2) 400 BC : Sushruta in India-Described Sweetness of urine in diabetes.
3) 1674 : Thomas Willes - Rediscovered sweet taste of diabetic urirxe.
4) 180Q : Dietary Regieme for diabetes outlined by Rollo
5) 1867 : Paul Langherhans described Islets ofLanghehands in Pancreas.
6) 1869 : Dog was made diabetic by removal of pancreas by MINKOWSKI.
7) 1921 : Fred Banting Orthopaedic surgeon and medical student CHARLES Best
Isolated insulin & got Nobel Prize.
 1922 : 14 yrs. old boy Leonard Thompson in Toronto on 11.01.1922 received first
insulin injection.
9) 1926 : Abel-Prepared insulin in crystalline form.
10) 1936 : Houssay - Hypophysectomoy ameliorated diabetes in the dog.
11) 1948 : Diabetic detection drive, First done by American Diabetic association.
12) 1950 : NPH Insulin Introduced.
13) 1955 : First Tablet for Diabetes introduced. Structure of Insulin discovered-
FREDERICK.
14) 1956 : Biguanide - (DBI) was introduced.
15) 1959 : Immune Assay for Insulin first done by Berson & Yalow.
16) 1960 : Sanger Established the amino acid sequence of Insulin,
17) 1969 : STEINER discovered Pro Insulin.
18) 1890 : Human Insulin prepared by genetic engineering.
5 Nobel Prices awarded for work in connection with insulin for diabetes.
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1922 : 14 yrs. old boy Leonard Thompson in Toronto on 11.01.1922 received first