Diabetes mellitus is a metabolic disorder characterized by
hyperglycemia (high blood sugar) and other signs, as distinct from a single
disease or condition. The World Health Organization recognizes three main forms
of diabetes: type 1, type 2, and gestational diabetes (occurring during
pregnancy),[1] which have similar signs, symptoms, and consequences, but
different causes and population distributions. Type 1 is usually due to
autoimmune destruction of the pancreatic beta cells which produce insulin. Type
2 is characterized by tissue-wide insulin resistance and varies widely; it
sometimes progresses to loss of beta cell function. Gestational diabetes is
similar to type 2 diabetes, in that it involves insulin resistance. The hormones
of pregnancy cause insulin resistance in those women genetically predisposed to
developing this condition. Types 1 and 2 are incurable chronic conditions, but
have been treatable since insulin became medically available in 1921.
Gestational diabetes typically resolves with delivery.
Diabetes can cause many complications. Acute glucose level abnormalities may
occur if insulin level is not well-controlled. Serious long-term complications
include cardiovascular disease (doubled risk), chronic renal failure (the main
cause of dialysis in developed world adults), retinal damage (which can lead to
blindness and is the most significant cause of adult blindness in the
non-elderly in the developed world), nerve damage (of several kinds), and
microvascular damage, which may cause erectile dysfunction (impotence) and poor
healing. Poor healing of wounds, particularly of the feet, can lead to gangrene
which can require amputation — the leading cause of non-traumatic amputation in
adults in the developed world.
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.[4] 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 was removed developed all the signs and
symptoms of diabetes and died shortly afterwards.[5] 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.[4]
The endocrine role of the pancreas in metabolism, and indeed the existence of
insulin, was not further clarified until 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.[6]
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
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.
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.[7]
Despite the availability of treatment, diabetes has remained a major cause of
death. For instance, statistics reveal that the cause-specific mortality rate
during 1927 amounted to about 47.7 per 100,000 population in Malta.[8]
Other landmark discoveries include:[4]
identification of the first of the sulfonylureas in 1942
the determination of the amino acid order 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)[9]
the three-dimensional structure of insulin
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,[10] and also in type 2 diabetics in other large studies
identification of the first thiazolidinedione as an effective insulin sensitizer
during the 1990s
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