Recently, diabetes has been linked to hearing loss. Thus, audiologists need to become familiar with this disorder and how it affects the auditory mechanism. This week Hearing International looks at the history of diabetes (click the link for a History of Diabetes Video) and how we came to know the disease.
Diabetes is one of the first diseases described in written history. An Egyptian manuscript from 1500 BC (right) mentions “too great emptying of the urine.” The first described cases are believed to be of Type 1 diabetes. Indian physicians around the same time identified the disease and classified it as madhumeha or honey urine noting that the urine would attract ants. The term “diabetes” or “to pass through” was first used in 230 BC by the Greek Apollonius Of Memphis.
Type 1 and Type 2 diabetes were identified as separate conditions for the first time by the Indian physicians Sushruta and Charaka in 400-500 AD with Type 1 associated with youth and type 2 with being overweight. The term “mellitus” or “from honey” was added by Thomas Willis in the late 1600s to separate the condition from diabetes insipidus which is also associated with frequent urination.
The first complete clinical description of diabetes was given by the Ancient Greek physician Aretaeus of Cappadocia in the first century AD, who also noted the excessive amount of urine which passed through the kidneys. Diabetes mellitus appears to have been a death sentence in the ancient era. Hippocrates makes no mention of it, which may indicate that he felt the disease was incurable. Aretaeus did attempt to treat it but could not give a good prognosis; he commented that “life (with diabetes) is short, disgusting and painful”.
The disease must have been rare during the time of the Roman Empire with Galen commenting that he had only see two cases during his career. In the medieval Persia, Avicenna (980–1037) provided a detailed account on diabetes mellitus in The Canon of Medicine, describing the “abnormal appetite and the collapse of sexual functions,” and he documented the sweet taste of diabetic urine.
Like Aretaeus before him, Avicenna recognized a primary and secondary diabetes. He also described diabetic gangrene, and treated diabetes using a mixture of lupine, trigonella (fenugreek), and zedoary seed, which produces a considerable reduction in the excretion of sugar, a treatment which is still prescribed in modern times. Avicenna also described diabetes insipidus very precisely for the first time, though it was much later that Thomas Willis differentiated it from diabetes mellitus in a chapter of his book Pharmaceutice rationalis (1674).
Although diabetes has been recognized since antiquity, and treatments of various efficacy have been known in various regions since the Middle Ages, and in legend for much longer, pathogenesis of diabetes has only been understood experimentally since about 1900. An effective treatment was only developed after the Canadians Frederick Banting and Charles Best first used insulin in 1921 and 1922. The discovery of a role for the pancreas in diabetes is generally ascribed to Joseph von Mering and Oskar Minkowski, who in 1889 found that dogs whose pancreas were removed developed all the signs and symptoms of diabetes and died shortly afterwards.
In 1910, Sir Edward Albert Sharpey-Schafer suggested that people with diabetes were deficient in a single chemical that was normally produced by the pancreas. He proposed calling this substance insulin, from the Latin insula, meaning island, in reference to the insulin-producing islets of Langerhans in the pancreas.
The endocrine role of the pancreas in metabolism, and indeed the existence of insulin, was further clarified in 1921, when Sir Frederick Grant Banting and Charles Herbert Best repeated the work of Von Mering and Minkowski, and went further to demonstrate they could reverse induced diabetes in dogs by giving them an extract from the pancreatic islets of Langerhans of healthy dogs.
The islets of Langerhans was discovered in 1869 by an anatomist named Paul Langerhans. He identified the keys cells in the pancreas which produce the main substance that controls glucose levels in the body. Banting, Best, and colleagues (especially the chemist Collip) went on to purify the hormone insulin from bovine pancreases at the University of Toronto. This led to the availability of an effective treatment—insulin injections—and the first patient was treated in 1922. For this, Banting and laboratory director John MacLeod received the Nobel Prize in Physiology or Medicine in 1923; both shared their prize money with others in the team who were not recognized, in particular Best and Collip. Banting and Best made the patent available without charge and did not attempt to control commercial production. Insulin production and therapy rapidly spread around the world, largely as a result of this decision. Banting is honored by World Diabetes Day which is held on his birthday, November 14.
The distinction between what is now known as Type 1 diabetes and Type 2 diabetes was first clearly made by Sir Harold Percival (Harry) Himsworth, and published in January 1936.
- Development of the long acting insulin NPH in the 1940s by Novo-Nordisk.
- Identification of the first of the sulfonylureas in 1942
- Reintroduction of the use of biguanides for Type 2 diabetes in the late 1950s. Metformin was first marketed in France in 1979, but not until 1994 in the US.
- The determination of the amino acid sequence of insulin (by Sir Frederick Sanger, for which he received a Nobel Prize)
- The radioimmunoassay for insulin, as discovered by Rosalyn Yalow and Solomon Berson (gaining Yalow the 1977 Nobel Prize in Physiology or Medicine)
- The three-dimensional structure of insulin (PDB 2INS)
- Dr Gerald Reaven‘s identification of the constellation of symptoms now called metabolic syndrome in 1988
- Demonstration that intensive glycemic control in type 1 diabetes reduces chronic side effects more as glucose levels approach ‘normal’ in a large longitudinal study, and also in type 2 diabetics in other large studies
- Identification of the first thiazolidinedione as an effective insulin sensitizer during the 1990s
In 1980, U.S. biotech company Genentech developed biosynthetic human insulin. The insulin was isolated from genetically altered bacteria (the bacteria contain the human gene for synthesizing synthetic human insulin), which produce large quantities of insulin. The purified insulin is distributed to pharmacies for use by diabetes patients. Initially, this development was not regarded by the medical profession as a clinically meaningful development. However, by 1996, the advent of insulin analogues which had vastly improved absorption, distribution, metabolism, and excretion (ADME) characteristics which were clinically meaningful based on this early biotechnology development.
The first portable glucose meter was created in 1969 by Ames Diagnostics. They were very expensive, $650 at first, but as the invention progressed the cost went down and the amount of blood required to analyze and give results changed substantially over time. Some meters are now about $10 and extremely helpful to patients in the management of their diabetes.
Next week in Part II of this Hearing international series we will look at the disorder of diabetes on our way to understanding how the disease effects the auditory mechanism as it creates hearing loss.