Insulin (medication)
   HOME

TheInfoList



OR:

As a
medication A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and re ...
, insulin is any
pharmaceutical A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and re ...
preparation of the protein hormone
insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
that is used to treat high blood glucose. Such conditions include
type 1 diabetes Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin (beta cells) are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar for ...
,
type 2 diabetes Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, ...
,
gestational diabetes Gestational diabetes is a condition in which a woman without diabetes develops high blood sugar levels during pregnancy. Gestational diabetes generally results in few symptoms; however, it increases the risk of pre-eclampsia, depression, and of ...
, and complications of
diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
such as
diabetic ketoacidosis Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of diabetes mellitus. Signs and symptoms may include vomiting, abdominal pain, deep gasping breathing, increased urination, weakness, confusion and occasionally loss of ...
and hyperosmolar hyperglycemic states. Insulin is also used along with
glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using ...
to treat
hyperkalemia Hyperkalemia is an elevated level of potassium (K+) in the blood. Normal potassium levels are between 3.5 and 5.0mmol/L (3.5 and 5.0mEq/L) with levels above 5.5mmol/L defined as hyperkalemia. Typically hyperkalemia does not cause symptoms. Occasi ...
(high blood potassium levels). Typically it is given by
injection under the skin Subcutaneous administration is the insertion of medications beneath the skin either by injection or infusion. A subcutaneous injection is administered as a bolus into the subcutis, the layer of skin directly below the dermis and epidermis, col ...
, but some forms may also be used by
injection into a vein Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...
or
muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...
. There are various types of insulin, suitable for various time spans. The types are often all called ''insulin'' in the broad
sense A sense is a biological system used by an organism for sensation, the process of gathering information about the world through the detection of Stimulus (physiology), stimuli. (For example, in the human body, the brain which is part of the cen ...
, although in a more precise sense, insulin is identical to the naturally occurring molecule whereas
insulin analog An insulin analog ( also called an insulin analogue) is any of several types of medical insulin that are altered forms of the hormone insulin, different from any occurring in nature, but still available to the human body for performing the same a ...
ues have slightly different molecules that allow for modified time of action. It is on the
World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health ...
. In 2020, regular human insulin was the 307th most commonly prescribed medication in the United States, with more than 1million prescriptions. Insulin can be made from the
pancreas The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an end ...
of pigs or cows. Human versions can be made either by modifying pig versions or
recombinant technology Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be foun ...
. It comes in three main types: short–acting (such as
regular insulin Regular insulin, also known as neutral insulin and soluble insulin, is a type of short-acting medical insulin. It is used to treat type 1 diabetes, type 2 diabetes, gestational diabetes, and complications of diabetes such as diabetic ketoacid ...
), intermediate-acting (such as neutral protamine Hagedorn (NPH) insulin), and longer-acting (such as
insulin glargine Insulin glargine, sold under the brand name Lantus among others, is a long-acting modified form of medical insulin, used in the management of type I and type II diabetes. It is typically the recommended long acting insulin in the United King ...
).


History

Insulin was first used as a medication in Canada by Charles Best and
Frederick Banting Sir Frederick Grant Banting (November 14, 1891 – February 21, 1941) was a Canadian medical scientist, physician, painter, and Nobel laureate noted as the co-discoverer of insulin and its therapeutic potential. In 1923, Banting and J ...
in 1922. ''This is a chronology of key milestones in the history of the medical use of insulin. For more details on the discovery, extraction, purification, clinical use, and synthesis of insulin, see
Insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
'' * 1921 Research on the role of pancreas in the nutritive assimilation * 1922
Frederick Banting Sir Frederick Grant Banting (November 14, 1891 – February 21, 1941) was a Canadian medical scientist, physician, painter, and Nobel laureate noted as the co-discoverer of insulin and its therapeutic potential. In 1923, Banting and J ...
, Charles Best and
James Collip James Bertram Collip (November 20, 1892 – June 19, 1965) was a Canadian biochemist who was part of the Toronto group which isolated insulin. He served as the Chair of the Department of Biochemistry at McGill University from 1928–1941 an ...
use bovine insulin extract in humans at
Connaught Laboratories The Connaught Medical Research Laboratories was a non-commercial public health entity established by Dr. John G. FitzGerald in 1914 in Toronto to produce the diphtheria antitoxin. Contemporaneously, the institution was likened to the Pasteur Inst ...
in Toronto, Canada. * 1922 Leonard Thompson becomes the first human to be treated with insulin. * 1922
James D. Havens James Dexter Havens (1900–1960) was a printmaker and painter in Rochester, New York, who is considered part of the color woodblock printing, woodblock revival in America.Watrous, James: "The American Color Woodcuts: Bounty from the Block, 1890s-1 ...
, son of former congressman
James S. Havens James Smith Havens (May 28, 1859 – February 27, 1927) was an American lawyer and politician who served part of one term as a United States House of Representatives, U.S. Representative from New York (state), New York from April 1910 to Ma ...
, becomes the first American to be treated with insulin. * 1922
Elizabeth Hughes Gossett Elizabeth Evans Hughes Gossett (August 19, 1907 April 21, 1981), the daughter of U.S. statesman Charles Evans Hughes, was the first American, and one of the first people in the world, treated with insulin for type 1 diabetes. She received over 42 ...
, daughter of the U.S. Secretary of State, becomes the first American to be (officially) treated in Toronto. * 1923
Eli Lilly Eli Lilly (July 8, 1838 – June 6, 1898) was an American soldier, pharmacist, chemist, and businessman who founded the Eli Lilly and Company pharmaceutical corporation. Lilly enlisted in the Union Army during the American Civil War and r ...
produces commercial quantities of much purer bovine insulin than Banting et al. had used * 1923 Farbwerke
Hoechst Hoechst, Hochst, or Höchst may refer to: * Hoechst AG, a former German life-sciences company * Hoechst stain, one of a family of fluorescent DNA-binding compounds * Höchst (Frankfurt am Main), a city district of Frankfurt am Main, Germany ** Fra ...
, one of the forerunners of today's
Sanofi Aventis Sanofi S.A. is a French multinational pharmaceutical and healthcare company headquartered in Paris, France. Originally, the corporation was established in 1973 and merged with Synthélabo in 1999 to form Sanofi-Synthélabo. In 2004, Sanofi-Syn ...
, produces commercial quantities of bovine insulin in Germany * 1923
Hans Christian Hagedorn Hans Christian Hagedorn (6 March 1888 – 6 October 1971) was the creator of NPH insulin and the founder of Nordisk Insulinlaboratorium, which is known today as Novo Nordisk. Biography Hagedorn and August Krogh (1874–1949) obtained the rights fo ...
founds the Nordisk Insulinlaboratorium in Denmark – forerunner of today's
Novo Nordisk Novo Nordisk A/S is a Danish multinational pharmaceutical company headquartered in Bagsværd, Denmark, with production facilities in nine countries, and affiliates or offices in five countries. Novo Nordisk is controlled by majority shareholder ...
* 1923
Constance Collier Constance Collier (born Laura Constance Hardie; 22 January 1878 – 25 April 1955) was an English stage and film actress and acting coach. She wrote hit plays and films with Ivor Novello and she was the first person to be treated with insu ...
returns to health after being successfully treated with insulin in Strasbourg * 1926 Nordisk receives a Danish charter to produce insulin as a non-profit * 1936 Canadians David M. Scott and Albert M. Fisher formulate a zinc insulin mixture at
Connaught Laboratories The Connaught Medical Research Laboratories was a non-commercial public health entity established by Dr. John G. FitzGerald in 1914 in Toronto to produce the diphtheria antitoxin. Contemporaneously, the institution was likened to the Pasteur Inst ...
in Toronto and license it to
Novo ''Novo'' is a 2002 French romantic comedy film directed by Jean-Pierre Limosin and starring Eduardo Noriega. The film tells the story of a man who suffers from amnesia. It screened at the Locarno Film Festival. Plot Graham suffers from severe am ...
* 1936 Hagedorn discovers that adding protamine to insulin prolongs the duration of action of insulin * 1946 Nordisk formulates Isophane porcine insulin aka Neutral Protamine Hagedorn or
NPH insulin Neutral Protamine Hagedorn (NPH) insulin, also known as isophane insulin, is an intermediate-acting insulin given to help control blood sugar levels in people with diabetes. It is used by injection under the skin once to twice a day. Onset of ...
* 1946 Nordisk crystallizes a protamine and insulin mixture * 1950 Nordisk markets
NPH insulin Neutral Protamine Hagedorn (NPH) insulin, also known as isophane insulin, is an intermediate-acting insulin given to help control blood sugar levels in people with diabetes. It is used by injection under the skin once to twice a day. Onset of ...
* 1953 Novo formulates Lente porcine and bovine insulins by adding zinc for longer lasting insulin * 1955
Frederick Sanger Frederick Sanger (; 13 August 1918 – 19 November 2013) was an English biochemist who received the Nobel Prize in Chemistry twice. He won the 1958 Chemistry Prize for determining the amino acid sequence of insulin and numerous other p ...
determines the
amino acid sequence Protein primary structure is the linear sequence of amino acids in a peptide or protein. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end. Protein biosynthes ...
of insulin * 1965 Synthesized by total synthesis by
Wang Yinglai Wang Yinglai (; 13 November 1907 – 5 May 2001), also known as Ying-Lai Wang, was a Chinese biochemist recognized as the first person to create synthetic insulin, a major scientific breakthrough that produced a biologically active compound fr ...
, Chen-Lu Tsou, et al. * 1969
Dorothy Crowfoot Hodgkin Dorothy Mary Crowfoot Hodgkin (née Crowfoot; 12 May 1910 – 29 July 1994) was a Nobel Prize-winning British chemist who advanced the technique of X-ray crystallography to determine the structure of biomolecules, which became essential fo ...
solves the crystal structure of insulin by
X-ray crystallography X-ray crystallography is the experimental science determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to diffract into many specific directions. By measuring the angles ...
* 1973 Purified monocomponent (MC) insulin is introduced * 1973 The U.S. officially "standardized" insulin sold for human use in the U.S. to U-100 (100 units per milliliter). Prior to that, insulin was sold in different strengths, including U-80 (80 units per milliliter) and U-40 formulations (40 units per milliliter), so the effort to "standardize" the potency aimed to reduce dosage errors and ease doctors' job of prescribing insulin for people. Other countries also followed suit. * 1978
Genentech Genentech, Inc., is an American biotechnology corporation headquartered in South San Francisco, California. It became an independent subsidiary of Roche in 2009. Genentech Research and Early Development operates as an independent center within R ...
produces biosynthetic human insulin in ''Escherichia coli'' bacteria using recombinant DNA techniques, licenses to Eli Lilly * 1981
Novo Nordisk Novo Nordisk A/S is a Danish multinational pharmaceutical company headquartered in Bagsværd, Denmark, with production facilities in nine countries, and affiliates or offices in five countries. Novo Nordisk is controlled by majority shareholder ...
chemically and enzymatically converts porcine to human insulin * 1982
Genentech Genentech, Inc., is an American biotechnology corporation headquartered in South San Francisco, California. It became an independent subsidiary of Roche in 2009. Genentech Research and Early Development operates as an independent center within R ...
synthetic human insulin (above) approved * 1983
Eli Lilly and Company Eli Lilly and Company is an American pharmaceutical company headquartered in Indianapolis, Indiana, with offices in 18 countries. Its products are sold in approximately 125 countries. The company was founded in 1876 by, and named after, Colonel ...
produces biosynthetic human insulin with
recombinant DNA Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be foun ...
technology, Humulin * 1985
Axel Ullrich Axel Ullrich (born 19 October 1943) is a German cancer researcher and has been the director of the molecular biology department at the Max Planck Institute of Biochemistry in Martinsried, Germany since 1988. This department's research has primar ...
sequences a human cell membrane insulin receptor. * 1988
Novo Nordisk Novo Nordisk A/S is a Danish multinational pharmaceutical company headquartered in Bagsværd, Denmark, with production facilities in nine countries, and affiliates or offices in five countries. Novo Nordisk is controlled by majority shareholder ...
produces recombinant biosynthetic human insulin * 1996 Lilly Humalog "lispro" insulin analogue approved. * 2000
Sanofi Aventis Sanofi S.A. is a French multinational pharmaceutical and healthcare company headquartered in Paris, France. Originally, the corporation was established in 1973 and merged with Synthélabo in 1999 to form Sanofi-Synthélabo. In 2004, Sanofi-Syn ...
Lantus insulin "glargine" analogue approved for clinical use in the US and Europe. * 2004
Sanofi Aventis Sanofi S.A. is a French multinational pharmaceutical and healthcare company headquartered in Paris, France. Originally, the corporation was established in 1973 and merged with Synthélabo in 1999 to form Sanofi-Synthélabo. In 2004, Sanofi-Syn ...
Apidra insulin "glulisine" insulin analogue approved for clinical use in the US. * 2006
Novo Nordisk Novo Nordisk A/S is a Danish multinational pharmaceutical company headquartered in Bagsværd, Denmark, with production facilities in nine countries, and affiliates or offices in five countries. Novo Nordisk is controlled by majority shareholder ...
Levemir Insulin detemir, sold under the brand name Levemir among others, is a long-acting modified form of medical insulin used to treat both type 1 and type 2 diabetes. It is used by injection under the skin. It is effective for up to 24 hours. ...
"detemir" insulin analogue approved for clinical use in the US.


Medical uses

Insulin is used to treat a number of diseases including
diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
and its acute complications such as
diabetic ketoacidosis Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of diabetes mellitus. Signs and symptoms may include vomiting, abdominal pain, deep gasping breathing, increased urination, weakness, confusion and occasionally loss of ...
and hyperosmolar hyperglycemic states. It is also used along with
glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using ...
to treat high blood potassium levels. Use during
pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...
is relatively safe for the baby. Insulin was formerly used in a psychiatric treatment called
insulin shock therapy Insulin shock therapy or insulin coma therapy was a form of psychiatric treatment in which patients were repeatedly injected with large doses of insulin in order to produce daily comas over several weeks.Neustatter WL (1948) ''Modern psychiatry ...
.


Side effects

Some side effects are
hypoglycemia Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose belo ...
(low blood sugar),
hypokalemia Hypokalemia is a low level of potassium (K+) in the blood serum. Mild low potassium does not typically cause symptoms. Symptoms may include feeling tired, leg cramps, weakness, and constipation. Low potassium also increases the risk of an abno ...
(low blood potassium), and
allergic reactions Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derma ...
. Allergy to insulin affected about 2% of people, of which most reactions are not due to the insulin itself but to preservatives added to insulin such as zinc,
protamine Protamines are small, arginine-rich, cell nucleus, nuclear proteins that replace histones late in the haploid phase of spermatogenesis and are believed essential for sperm head condensation and DNA stabilization. They may allow for denser packagin ...
, and
meta-cresol ''meta''-Cresol, also 3-methylphenol, is an organic compound with the formula CH3C6H4(OH). It is a colourless, viscous liquid that is used as an intermediate in the production of other chemicals. It is a derivative of phenol and is an isomer of ...
. Most reactions are
Type I hypersensitivity Type I hypersensitivity (or immediate hypersensitivity), in the Gell and Coombs classification of allergic reactions, is an allergic reaction provoked by re-exposure to a specific type of antigen referred to as an allergen. Type I is distinct fro ...
reactions and rarely cause
anaphylaxis Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the follow ...
. A suspected allergy to insulin can be confirmed by skin prick testing, patch testing and occasionally
skin biopsy Skin biopsy is a biopsy technique in which a skin lesion is removed to be sent to a pathologist to render a microscopic diagnosis. It is usually done under local anesthetic in a physician's office, and results are often available in 4 to 10 days. ...
. First line therapy against insulin hypersensitivity reactions include symptomatic therapy with antihistamines. The affected persons are then switched to a preparation that does not contain the specific agent they are reacting to or undergo desensitization. Cutaneous adverse effects Other side effects may include pain or skin changes at the sites of injection. Repeated subcutaneous injection without site rotation can lead to
lipohypertrophy Lipohypertrophy is a lump under the skin caused by accumulation of extra fat at the site of many subcutaneous injections of insulin. It may be unsightly, mildly painful, and may change the timing or completeness of insulin action. It is a common, ...
and amyloidomas, which manifest as firm palpable nodules under the skin.


Principles

Insulin is an
endogenous Endogenous substances and processes are those that originate from within a living system such as an organism, tissue, or cell. In contrast, exogenous substances and processes are those that originate from outside of an organism. For example, es ...
hormone A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...
, which is produced by the
pancreas The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an end ...
. The insulin
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
has been highly conserved across evolutionary time, and is present in both
mammals Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...
and
invertebrates Invertebrates are a paraphyletic group of animals that neither possess nor develop a vertebral column (commonly known as a ''backbone'' or ''spine''), derived from the notochord. This is a grouping including all animals apart from the chordate ...
. The insulin/
insulin-like growth factor The insulin-like growth factors (IGFs) are proteins with high sequence similarity to insulin. IGFs are part of a complex system that cells use to communicate with their physiologic environment. This complex system (often referred to as the IGF "a ...
signalling pathway (IIS) has been extensively studied in species including nematode worms (e.g.''
C. elegans ''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' (r ...
''), flies (''
Drosophila melanogaster ''Drosophila melanogaster'' is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the "vinegar fly" or "pomace fly". Starting with Ch ...
'') and mice (''
Mus musculus Mus or MUS may refer to: Abbreviations * MUS, the NATO country code for Mauritius * MUS, the IATA airport code for Minami Torishima Airport * MUS, abbreviation for the Centre for Modern Urban Studies on Campus The Hague, Leiden University, Neth ...
''). Its mechanisms of action are highly similar across species. Both
type 1 diabetes Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin (beta cells) are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar for ...
and
type 2 diabetes Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, ...
are marked by a loss of pancreatic function, though to differing degrees. People who are affected with diabetes are referred to as diabetics. Many diabetics require an exogenous source of insulin to keep their blood sugar levels within a safe target range. In 1916, Nicolae C. Paulescu (1869–1931) succeeded in developing an aqueous pancreatic extract that normalized a diabetic dog. In 1921, he published 4 papers in the Society of Biology in Paris centering on the successful effects of the pancreatic extract in diabetic dogs. Research on the Role of the Pancreas in Food Assimilation by Paulescu was published in August 1921 in the Archives Internationales de Physiologie, Liège, Belgium. Initially, the only way to obtain insulin for clinical use was to extract it from the pancreas of another creature. Animal glands were obtainable as a waste product of the meatpacking industry. Insulin was derived primarily from
cows Cattle (''Bos taurus'') are large, domesticated, cloven-hooved, herbivores. They are a prominent modern member of the subfamily Bovinae and the most widespread species of the genus ''Bos''. Adult females are referred to as cows and adult ma ...
(
Eli Lilly and Company Eli Lilly and Company is an American pharmaceutical company headquartered in Indianapolis, Indiana, with offices in 18 countries. Its products are sold in approximately 125 countries. The company was founded in 1876 by, and named after, Colonel ...
) and
pigs The pig (''Sus domesticus''), often called swine, hog, or domestic pig when distinguishing from other members of the genus '' Sus'', is an omnivorous, domesticated, even-toed, hoofed mammal. It is variously considered a subspecies of ''Sus s ...
(
Nordisk Insulinlaboratorium Novo Nordisk A/S is a Danish multinational pharmaceutical company headquartered in Bagsværd, Denmark, with production facilities in nine countries, and affiliates or offices in five countries. Novo Nordisk is controlled by majority shareholder ...
). The making of eight ounces of purified insulin could require as much as two tons of pig parts. Insulin from these sources is effective in humans as it is highly similar to human insulin (three amino acid difference in bovine insulin, one amino acid difference in porcine). Initially, lower preparation purity resulted in allergic reactions to the presence of non-insulin substances. Purity has improved steadily since the 1920s ultimately reaching purity of 99% by the mid-1970s thanks to
high-pressure liquid chromatography High-performance liquid chromatography (HPLC), formerly referred to as high-pressure liquid chromatography, is a technique in analytical chemistry used to separate, identify, and quantify each component in a mixture. It relies on pumps to pa ...
(HPLC) methods. Minor allergic reactions still occur occasionally, even to synthetic "human" insulin varieties. Beginning in 1982, biosynthetic "human" insulin has been manufactured for clinical use through genetic engineering techniques using
recombinant DNA Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be foun ...
technology.
Genentech Genentech, Inc., is an American biotechnology corporation headquartered in South San Francisco, California. It became an independent subsidiary of Roche in 2009. Genentech Research and Early Development operates as an independent center within R ...
developed the technique used to produce the first such insulin, Humulin, but did not commercially market the product themselves.
Eli Lilly Eli Lilly (July 8, 1838 – June 6, 1898) was an American soldier, pharmacist, chemist, and businessman who founded the Eli Lilly and Company pharmaceutical corporation. Lilly enlisted in the Union Army during the American Civil War and r ...
marketed Humulin in 1982. Humulin was the first medication produced using modern genetic engineering techniques in which actual human DNA is inserted into a host cell (''
E. coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...
'' in this case). The host cells are then allowed to grow and reproduce normally, and due to the inserted human DNA, they produce a synthetic version of human insulin. Manufacturers claim this reduces the presence of many impurities. However, the clinical preparations prepared from such insulins differ from endogenous human insulin in several important respects; an example is the absence of
C-peptide The connecting peptide, or C-peptide, is a short 31-amino-acid polypeptide that connects insulin, insulin's A-chain to its B-chain in the proinsulin molecule. In the context of diabetes or hypoglycemia, a measurement of C-peptide blood serum lev ...
which has in recent years been shown to have systemic effects itself.
Novo Nordisk Novo Nordisk A/S is a Danish multinational pharmaceutical company headquartered in Bagsværd, Denmark, with production facilities in nine countries, and affiliates or offices in five countries. Novo Nordisk is controlled by majority shareholder ...
has also developed a genetically engineered insulin independently using a yeast process. According to a survey that the International Diabetes Federation conducted in 2002 on the access to and availability of insulin in its member countries, approximately 70% of the insulin that is currently sold in the world is recombinant, biosynthetic 'human' insulin. A majority of insulin used clinically today is produced this way, although clinical experience has provided conflicting evidence on whether these insulins are any less likely to produce an allergic reaction. Adverse reactions have been reported; these include loss of warning signs that patients may slip into a coma through
hypoglycemia Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose belo ...
, convulsions, memory lapse and loss of concentration. However, the International Diabetes Federation's position statement from 2005 is very clear in stating that "there is NO overwhelming evidence to prefer one species of insulin over another" and " odern, highly purifiedanimal insulins remain a perfectly acceptable alternative." Since January 2006, all insulins distributed in the U.S. and some other countries are synthetic "human" insulins or their analogues. A specia
FDA importation process
is required to obtain bovine or porcine derived insulin for use in the U.S., although there may be some remaining stocks of porcine insulin made by Lilly in 2005 or earlier, and porcine lente insulin is also sold and marketed under the brand name Vetsulin(SM) in the U.S. for veterinary usage in the treatment of companion animals with diabetes.


Basal insulin

In type 1 diabetes, insulin production is extremely low, and as such the body requires
exogenous In a variety of contexts, exogeny or exogeneity () is the fact of an action or object originating externally. It contrasts with endogeneity or endogeny, the fact of being influenced within a system. Economics In an economic model, an exogeno ...
insulin. Some people with type 2 diabetes, particularly those with very high
hemoglobin A1c Glycated hemoglobin, also known as HbA1c, glycohemoglobin, hemoglobin A1c, A1C, is a form of hemoglobin (Hb) that is chemically linked to a sugar. Most monosaccharides, including glucose, galactose and fructose, spontaneously (i.e. non-enzymat ...
values, may also require a baseline rate of insulin, as their body is desensitized to the level of insulin being produced. Basal insulin regulates the body's blood glucose between mealtimes, as well as overnight. This basal rate of insulin action is generally achieved via the use of an intermediate-acting insulin (such as NPH) or a long-acting insulin analog. In type 1 diabetics, it may also be achieved via continuous infusion of rapid-acting insulin using an
insulin pump An insulin pump is a medical device used for the administration of insulin in the treatment of diabetes mellitus, also known as continuous subcutaneous insulin therapy. The device configuration may vary depending on design. A traditional pump ...
. Approximately half of a person's daily insulin requirement is administered as a basal insulin, usually administered once per day at night.


Prandial insulin

When a person eats food containing carbohydrates and glucose, insulin helps regulate the body's metabolism of the food. Prandial insulin, also called mealtime or bolus insulin, is designed as a bolus dose of insulin prior to a meal to regulate the spike in blood glucose that occurs following a meal. The dose of prandial insulin may be static, or may be calculated by the patient using either their current blood sugar, planned carbohydrate intake, or both. This calculation may also be performed by an insulin pump in patients using a pump. Insulin regiments that consist of doses calculated in this manner are considered intensive insulin regimens. Prandial insulin is usually administered no more than 15–30 minutes prior to a meal using a rapid-acting insulin or a regular insulin. In some patients, a combination insulin may be used that contains both NPH (long acting) insulin and a rapid/regular insulin to provide both a basal insulin and prandial insulin.


Challenges in treatment

There are several challenges involved in the use of insulin as a clinical treatment for diabetes: * Mode of administration. * Selecting the 'right' dose and timing. The amount of carbohydrates one unit of insulin handles varies widely between persons and over the day but values between 7 and 20 grams per 1 IE is typical. * Selecting an appropriate insulin preparation (typically on 'speed of onset and duration of action' grounds). * Adjusting dosage and timing to fit food intake timing, amounts, and types. * Adjusting dosage and timing to fit exercise undertaken. * Adjusting dosage, type, and timing to fit other conditions, for instance the increased stress of illness. * Variability in absorption into the bloodstream via subcutaneous delivery * The dosage is non-physiological in that a subcutaneous bolus dose of insulin alone is administered instead of combination of insulin and
C-peptide The connecting peptide, or C-peptide, is a short 31-amino-acid polypeptide that connects insulin, insulin's A-chain to its B-chain in the proinsulin molecule. In the context of diabetes or hypoglycemia, a measurement of C-peptide blood serum lev ...
being released gradually and directly into the
portal vein The portal vein or hepatic portal vein (HPV) is a blood vessel that carries blood from the gastrointestinal tract, gallbladder, pancreas and spleen to the liver. This blood contains nutrients and toxins extracted from digested contents. Approxima ...
. * It is simply a nuisance for people to inject whenever they eat carbohydrate or have a high blood glucose reading. * It is dangerous in case of mistake (most especially 'too much' insulin).


Types

Medical preparations of insulin are never just insulin in water (with nothing else). Clinical insulins are mixtures of insulin plus other substances including preservatives. These prevent the protein from spoiling or denaturing too rapidly, delay absorption of the insulin, adjust the pH of the solution to reduce reactions at the injection site, and so on. Slight variations of the human insulin molecule are called
insulin analog An insulin analog ( also called an insulin analogue) is any of several types of medical insulin that are altered forms of the hormone insulin, different from any occurring in nature, but still available to the human body for performing the same a ...
ues, (technically "insulin receptor
ligand In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electr ...
s") so named because they are not technically insulin, rather they are analogues which retain the hormone's glucose management functionality. They have absorption and activity characteristics not currently possible with subcutaneously injected insulin proper. They are either absorbed rapidly in an attempt to mimic real beta cell insulin (as with
insulin lispro Insulin lispro, sold under the brand name Humalog among others, is a modified type of medical insulin used to treat type 1 and type 2 diabetes. It is used by injection under the skin or within an insulin pump. Onset of effects typically occu ...
,
insulin aspart Insulin aspart, sold under the brand name NovoLog and Fiasp, among others, is a insulin analog, modified type of Insulin (medication), medical insulin used to treat type I diabetes, type 1 and type 2 diabetes. It is generally used by injection ...
, and
insulin glulisine Insulin glulisine is a rapid-acting modified form of medical insulin that differs from human insulin in that the amino acid asparagine at position B3 is replaced by lysine and the lysine in position B29 is replaced by glutamic acid. It was devel ...
), or steadily absorbed after injection instead of having a 'peak' followed by a more or less rapid decline in insulin action (as with
insulin detemir Insulin detemir, sold under the brand name Levemir among others, is a long-acting modified form of medical insulin used to treat both type 1 and type 2 diabetes. It is used by injection under the skin. It is effective for up to 24 hours. ...
and
insulin glargine Insulin glargine, sold under the brand name Lantus among others, is a long-acting modified form of medical insulin, used in the management of type I and type II diabetes. It is typically the recommended long acting insulin in the United King ...
), all while retaining insulin's glucose-lowering action in the human body. However, a number of
meta-analyses A meta-analysis is a statistical analysis that combines the results of multiple scientific studies. Meta-analyses can be performed when there are multiple scientific studies addressing the same question, with each individual study reporting me ...
, including those done by the
Cochrane Collaboration Cochrane (previously known as the Cochrane Collaboration) is a British international charitable organisation formed to organise medical research findings to facilitate evidence-based choices about health interventions involving health profess ...
in 2005, Germany's Institute for Quality and Cost Effectiveness in the Health Care Sector QWiGreleased in 2007, and the Canadian Agency for Drugs and Technology in Health (CADTH) also released in 2007 have shown no unequivocal advantages in clinical use of insulin analogues over more conventional insulin types. Choosing insulin type and dosage/timing should be done by an experienced medical professional working closely with people who are diabetic . The commonly used types of insulin are as follows.


Fast-acting (Rapid-acting)

Includes the insulin analogues ''aspart'', ''lispro'', and ''glulisine''. These begin to work within 5 to 15 minutes and are active for 3 to 4 hours. Most insulins form
hexamer In chemistry and biochemistry, an oligomer () is a molecule that consists of a few repeating units which could be derived, actually or conceptually, from smaller molecules, monomers.Quote: ''Oligomer molecule: A molecule of intermediate relative ...
s, which delay entry into the blood in active form; these analog insulins do not but have normal insulin activity. Newer varieties are now pending regulatory approval in the U.S. which are designed to work rapidly, but retain the same genetic structure as regular human insulin.


Short-acting

Includes ''
regular insulin Regular insulin, also known as neutral insulin and soluble insulin, is a type of short-acting medical insulin. It is used to treat type 1 diabetes, type 2 diabetes, gestational diabetes, and complications of diabetes such as diabetic ketoacid ...
'', which begins working within 30 minutes and is active about 5 to 8 hours.


Intermediate-acting

Includes ''
NPH insulin Neutral Protamine Hagedorn (NPH) insulin, also known as isophane insulin, is an intermediate-acting insulin given to help control blood sugar levels in people with diabetes. It is used by injection under the skin once to twice a day. Onset of ...
'', which begins working in 1 to 3 hours and is active for 16 to 24 hours.


Long-acting

Includes the analogues ''
glargine Insulin glargine, sold under the brand name Lantus among others, is a long-acting modified form of medical insulin, used in the management of type I and type II diabetes. It is typically the recommended long acting insulin in the United Kingd ...
'' U100 and ''
detemir Insulin detemir, sold under the brand name Levemir among others, is a long-acting modified form of medical insulin used to treat both type 1 and type 2 diabetes. It is used by injection under the skin. It is effective for up to 24 hours. ...
'', each of which begins working within 1 to 2 hours and continues to be active, without major peaks or dips, for about 24 hours, although this varies in many individuals.


Ultra-long acting

Includes the analogues ''
insulin glargine Insulin glargine, sold under the brand name Lantus among others, is a long-acting modified form of medical insulin, used in the management of type I and type II diabetes. It is typically the recommended long acting insulin in the United King ...
'' U300 and '' degludec'', which begin working within 30 to 90 minutes and continues to be active for greater than 24 hours.


Combination insulin products

Includes a combination of either fast-acting or short-acting insulin with a longer acting insulin, typically an ''
NPH insulin Neutral Protamine Hagedorn (NPH) insulin, also known as isophane insulin, is an intermediate-acting insulin given to help control blood sugar levels in people with diabetes. It is used by injection under the skin once to twice a day. Onset of ...
''. The combination products begin to work with the shorter acting insulin (5–15 minutes for fast-acting, and 30 minutes for short acting), and remain active for 16 to 24 hours. There are several variations with different proportions of the mixed insulins (e.g. Novolog Mix 70/30 contains 70% aspart protamine
kin to NPH __NOTOC__ Kin usually refers to kinship and family. Kin or KIN may also refer to: Culture and religion *Otherkin, people who identify as not entirely human *Kinism, a white supremacist religious movement * Kinh, the majority ethnic group of V ...
and 30% aspart.)


Methods of administration

Unlike many medicines, insulin cannot be taken orally at the present time. Like nearly all other proteins introduced into the
gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organ (biology), organs of the digestive syste ...
, it is reduced to fragments (single amino acid components), whereupon all activity is lost. There has been some research into ways to protect insulin from the digestive tract, so that it can be administered in a pill. So far this is entirely experimental.


Subcutaneous

Insulin is usually taken as
subcutaneous injection Subcutaneous administration is the insertion of medications beneath the skin either by injection or infusion. A subcutaneous injection is administered as a bolus into the subcutis, the layer of skin directly below the dermis and epidermis, ...
s by single-use
syringe A syringe is a simple reciprocating pump consisting of a plunger (though in modern syringes, it is actually a piston) that fits tightly within a cylindrical tube called a barrel. The plunger can be linearly pulled and pushed along the inside ...
s with needles, an
insulin pump An insulin pump is a medical device used for the administration of insulin in the treatment of diabetes mellitus, also known as continuous subcutaneous insulin therapy. The device configuration may vary depending on design. A traditional pump ...
, or by repeated-use
insulin pen An injector pen (also called a medication pen) is a device used for injecting medication under the skin. First introduced in the 1980s, injector pens are designed to make injectable medication easier and more convenient to use, thus increasing ...
s with needles. People who wish to reduce repeated skin puncture of insulin injections often use an
injection port An injection port is a medical device used for the administration of insulin or other physician approved medicine into the subcutaneous tissue (the tissue layer just below the skin). The device is similar to infusion sets used by insulin pumps, ex ...
in conjunction with syringes. The use of subcutaneous injections of insulin is designed to mimic the natural physiological cycle of insulin secretion, while taking into account the various properties of the formulations used such as half-life, onset of action, and duration of action. In many people, both a rapid- or short-acting insulin product as well as an intermediate- or long-acting product are used to decrease the amount of injections per day. In some, insulin injections may be combined with other injection therapy such as
GLP-1 agonist Glucagon-like peptide-1 receptor agonists, also known as GLP-1 receptor agonists (GLP-1-RA) or incretin mimetics, are agonists of the GLP-1 receptor. This class of medications is used for the treatment of type 2 diabetes Some drugs are also approve ...
s. Cleansing of the injection site and injection technique are required to ensure effective insulin therapy.


Insulin pump

Insulin pump An insulin pump is a medical device used for the administration of insulin in the treatment of diabetes mellitus, also known as continuous subcutaneous insulin therapy. The device configuration may vary depending on design. A traditional pump ...
s are a reasonable solution for some. Advantages to the person are better control over background or basal insulin dosage, bolus doses calculated to fractions of a unit, and calculators in the pump that may help with determining bolus infusion dosages. The limitations are cost, the potential for hypoglycemic and hyperglycemic episodes, catheter problems, and no "closed loop" means of controlling insulin delivery based on current blood glucose levels. Insulin pumps may be like 'electrical injectors' attached to a temporarily implanted
catheter In medicine, a catheter (/ˈkæθətər/) is a thin tube made from medical grade materials serving a broad range of functions. Catheters are medical devices that can be inserted in the body to treat diseases or perform a surgical procedure. Cath ...
or
cannula A cannula (; Latin meaning 'little reed'; plural or ) is a tube that can be inserted into the body, often for the delivery or removal of fluid or for the gathering of samples. In simple terms, a cannula can surround the inner or outer surfaces ...
. Some who cannot achieve adequate glucose control by conventional (or jet) injection are able to do so with the appropriate pump. Indwelling catheters pose the risk of infection and ulceration, and some peoples may also develop
lipodystrophy Lipodystrophy syndromes are a group of genetic or acquired disorders in which the body is unable to produce and maintain healthy fat tissue. The medical condition is characterized by abnormal or degenerative conditions of the body's adipose tissue. ...
due to the infusion sets. These risks can often be minimized by keeping infusion sites clean. Insulin pumps require care and effort to use correctly.


Dosage and timing


Dosage units

One
international unit In pharmacology, the international unit (IU) is a unit of measurement for the effect, not mass of a substance; the variance is based on the biological activity or effect, for the purpose of easier comparison across similar ''forms'' of substance ...
of insulin (1 IU) is defined as the "biological equivalent" of 34.7 μg pure crystalline insulin. The first definition of a unit of insulin was the amount required to induce
hypoglycemia Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose belo ...
in a rabbit. This was set by
James Collip James Bertram Collip (November 20, 1892 – June 19, 1965) was a Canadian biochemist who was part of the Toronto group which isolated insulin. He served as the Chair of the Department of Biochemistry at McGill University from 1928–1941 an ...
at the University of Toronto in 1922. Of course, this was dependent on the size and diet of the rabbits. The unit of insulin was set by the insulin committee at the University of Toronto. The unit evolved eventually to the old USP insulin unit, where one unit (U) of insulin was set equal to the amount of insulin required to reduce the concentration of
blood glucose Glycaemia, also known as blood sugar level, blood sugar concentration, or blood glucose level is the measure of glucose concentrated in the blood of humans or other animals. Approximately 4 grams of glucose, a simple sugar, is present in the blo ...
in a
fasting Fasting is the abstention from eating and sometimes drinking. From a purely physiological context, "fasting" may refer to the metabolic status of a person who has not eaten overnight (see " Breakfast"), or to the metabolic state achieved after ...
rabbit Rabbits, also known as bunnies or bunny rabbits, are small mammals in the family Leporidae (which also contains the hares) of the order Lagomorpha (which also contains the pikas). ''Oryctolagus cuniculus'' includes the European rabbit speci ...
to 45 m g/ d l (2.5 m mol/ L). Once the chemical structure and mass of insulin was known, the unit of insulin was defined by the mass of pure crystalline insulin required to obtain the USP unit. The
unit of measurement A unit of measurement is a definite magnitude (mathematics), magnitude of a quantity, defined and adopted by convention or by law, that is used as a standard for measurement of the same kind of quantity. Any other quantity of that kind can ...
used in insulin therapy is not part of the
International System of Units The International System of Units, known by the international abbreviation SI in all languages and sometimes pleonastically as the SI system, is the modern form of the metric system and the world's most widely used system of measurement. E ...
(abbreviated SI) which is the modern form of the
metric system The metric system is a system of measurement that succeeded the Decimal, decimalised system based on the metre that had been introduced in French Revolution, France in the 1790s. The historical development of these systems culminated in the d ...
. Instead the
pharmacological Pharmacology is a branch of medicine, biology and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemica ...
international unit In pharmacology, the international unit (IU) is a unit of measurement for the effect, not mass of a substance; the variance is based on the biological activity or effect, for the purpose of easier comparison across similar ''forms'' of substance ...
(IU) is defined by the
WHO Expert Committee on Biological Standardization WHO Expert Committee on Biological Standardization is a functioning body of World Health Organization. The Expert Committee has been meeting annually since 1947. Reports The Committee reports are published as WHO Technical Report Series. All the re ...
.


Potential complications

The central problem for those requiring external insulin is picking the right dose of insulin and the right timing. Physiological regulation of blood glucose, as in the non-diabetic, would be best. Increased blood glucose levels after a meal is a stimulus for prompt release of insulin from the pancreas. The increased insulin level causes glucose absorption and storage in cells, reduces glycogen to glucose conversion, reducing blood glucose levels, and so reducing insulin release. The result is that the blood glucose level rises somewhat after eating, and within an hour or so, returns to the normal 'fasting' level. Even the best diabetic treatment with synthetic human insulin or even insulin analogs, however administered, falls far short of normal glucose control in the non-diabetic. Complicating matters is that the composition of the food eaten (see ''
glycemic index The glycemic (glycaemic) index (GI; ) is a number from 0 to 100 assigned to a food, with pure glucose arbitrarily given the value of 100, which represents the relative rise in the blood glucose level two hours after consuming that food. The GI of ...
'') affects intestinal absorption rates. Glucose from some foods is absorbed more (or less) rapidly than the same amount of glucose in other foods. In addition, fats and proteins cause delays in absorption of glucose from carbohydrates eaten at the same time. As well, exercise reduces the need for insulin even when all other factors remain the same, since working muscle has some ability to take up glucose without the help of insulin. Because of the complex and interacting factors, it is, in principle, impossible to know for certain how much insulin (and which type) is needed to 'cover' a particular meal to achieve a reasonable blood glucose level within an hour or two after eating. Non-diabetics' beta cells routinely and automatically manage this by continual glucose level monitoring and insulin release. All such decisions by a diabetic must be based on experience and training (i.e., at the direction of a physician, PA, or in some places a specialist diabetic educator) and, further, specifically based on the individual experience of the person. But it is not straightforward and should never be done by habit or routine. With some care however, it can be done reasonably well in clinical practice. For example, some people with diabetes require more insulin after drinking
skim milk Skimmed milk (British English), or skim milk (American English), is made when all the milkfat is removed from whole milk. It tends to contain around 0.1% fat. Background Historically, skimmed milk was used for fattening pigs, and was recommended ...
than they do after taking an equivalent amount of fat, protein, carbohydrate, and fluid in some other form. Their particular reaction to skimmed milk is different from other people with diabetes, but the same amount of whole milk is likely to cause a still different reaction even in that person. Whole milk contains considerable fat while skimmed milk has much less. It is a continual balancing act for all people with diabetes, especially for those taking insulin. People with insulin-dependent diabetes typically require some base level of insulin (basal insulin), as well as short-acting insulin to cover meals (bolus also known as mealtime or
prandial Prandial relates to a meal. Postprandial (from post prandium) means after eating a meal, while preprandial is before a meal. Usages of postprandial The term ''postprandial'' is used in many contexts. Gastronomic or social Refers to activities p ...
insulin). Maintaining the basal rate and the bolus rate is a continuous balancing act that people with insulin-dependent diabetes must manage each day. This is normally achieved through regular blood tests, although continuous blood sugar testing equipment (
Continuous Glucose Monitor A continuous glucose monitor (CGM) is a device used for monitoring blood glucose on a continual basis by insulin-requiring people with diabetes, e.g. people with type I, type II diabetes or other types of diabetes (e.g. gestational diabetes). A ...
s or CGMs) are now becoming available which could help to refine this balancing act once widespread usage becomes common.


Strategies

A long-acting insulin is used to approximate the basal secretion of insulin by the pancreas, which varies in the course of the day. NPH/isophane, lente, ultralente, glargine, and detemir may be used for this purpose. The advantage of NPH is its low cost, the fact that you can mix it with short-acting forms of insulin, thereby minimizing the number of injections that must be administered, and that the activity of NPH will peak 4–6 hours after administration, allowing a bedtime dose to balance the tendency of glucose to rise with the dawn, along with a smaller morning dose to balance the lower afternoon basal need and possibly an afternoon dose to cover evening need. A disadvantage of bedtime NPH is that if not taken late enough (near midnight) to place its peak shortly before dawn, it has the potential of causing hypoglycemia. One theoretical advantage of glargine and detemir is that they only need to be administered once a day, although in practice many people find that neither lasts a full 24 hours. They can be administered at any time during the day as well, provided that they are given at the same time every day. Another advantage of long-acting insulins is that the basal component of an insulin regimen (providing a minimum level of insulin throughout the day) can be decoupled from the prandial or bolus component (providing mealtime coverage via ultra-short-acting insulins), while regimens using NPH and regular insulin have the disadvantage that any dose adjustment affects both basal and prandial coverage. Glargine and detemir are significantly more expensive than NPH, lente and ultralente, and they cannot be mixed with other forms of insulin. A short-acting insulin is used to simulate the endogenous insulin surge produced in anticipation of eating. Regular insulin, lispro, aspart and glulisine can be used for this purpose. Regular insulin should be given with about a 30-minute lead-time prior to the meal to be maximally effective and to minimize the possibility of hypoglycemia. Lispro, aspart and glulisine are approved for dosage with the first bite of the meal, and may even be effective if given after completing the meal. The short-acting insulin is also used to correct hyperglycemia. The usual schedule for checking fingerstick blood glucose and administering insulin is before all meals and sometimes also at bedtime. More recent guidelines also call for a check 2 hours after a meal to ensure the meal has been 'covered' effectively.


Sliding scales

First described in 1934, what physicians typically refer to as sliding-scale insulin (SSI) is fast- or rapid-acting insulin only, given subcutaneously, typically at meal times and sometimes bedtime, but only when blood glucose is above a threshold (e.g. 10 mmol/L, 180 mg/dL). The so-called "sliding-scale" method is widely taught, although it has been heavily criticized. Sliding scale insulin (SSI) is not an effective way of managing long-term diabetes in individuals residing in nursing homes., which cites: * * * Sliding scale insulin leads to greater discomfort and increased nursing time. Sample regimen using insulin glargine and insulin lispro: * Insulin glargine: 20 units at bedtime


Carb counting and DAFNE

A more complicated method that allows greater freedom with meal times and snacks is " carb counting." This approach is taught to people who are diabetic in the UK and elsewhere as "Dose Adjustment For Normal Eating" o
DAFNE
In Europe, people who are not familiar with the DAFNE regime can take a
educational course
where the basic starting insulin dose guideline is "for every 10 g of carbohydrates you eat, take 1 unit of insulin". DAFNE courses also cover topics that naturally work alongside this regime, such as blood glucose monitoring, exercise and carbohydrate estimation to help the person work out their personal control requirements. People can also use their total daily dose (TDD) of insulin to estimate how many grams of carbohydrates will be "covered" by 1 unit of insulin, and using this result, estimate how many units of insulin should be administered depending on the carbohydrate content of their meal. For example, if the person determines that 1 unit of insulin will cover 15 grams of carbohydrates, then they must administer 5 units of insulin before consuming a meal that contains 75 grams of carbohydrates. Some alternative methods also consider the protein content of the meal (since excess dietary protein can be converted to glucose via
gluconeogenesis Gluconeogenesis (GNG) is a metabolic pathway that results in the generation of glucose from certain non-carbohydrate carbon substrates. It is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. In vertebrat ...
). With DAFNE, most dosages involve a fair degree of guesswork, especially with non-labeled foods, and will only work fairly consistently from one dosage to the next if the person is aware of their body's requirements. For example, a person finds they can take 1 unit of insulin to 10 g of carbohydrates in the morning and the evening, but find that their body requires more insulin for a meal in the middle of the day so they have to adjust to 1 unit per 8.5g of carbohydrates. Other less obvious factors that affect the body's use of insulin must also be taken into account. For example, some people may find that their bodies process insulin better on hot days so require less insulin. With this, the person again has to adjust their dose to the best of their understanding from their past experiences. The DAFNE regime requires the person to learn about their body's needs through experience, which takes time and patience, but it can then become effective.


Closed-loop predictive modeling

People with fluctuating insulin requirements may benefit from a closed-loop
predictive modeling Predictive modelling uses statistics to predict outcomes. Most often the event one wants to predict is in the future, but predictive modelling can be applied to any type of unknown event, regardless of when it occurred. For example, predictive mod ...
approach. As an extension on "carb counting", in this closed-loop predictive modeling approach, the four daily insulin dosages needed to reach the target blood sugar levels for the "normal" daily carbohydrate consumption and amount of physical activity, are continuously adjusted based on the pre-meal and pre-night blood sugar level readings. Each new blood sugar reading provides the feedback to fine-tune and track the body's insulin requirements. Within this strategy, the key specific factors, which have to be determined experimentally, are the blood sugar correction factor and the carbohydrate ratio. The blood sugar correction factor sets both the "proportional gain" and "integral gain" factors for the four
feedback loops Feedback occurs when outputs of a system are routed back as inputs as part of a chain of cause-and-effect that forms a circuit or loop. The system can then be said to ''feed back'' into itself. The notion of cause-and-effect has to be handled ...
. When taken too low, deviations from the target blood sugar level are not corrected for effectively, when taken too high, the blood sugar regulation will become unstable. Since in this approach, the carbohydrate ratio is only used to account for non-standard carbohydrate intakes, it is usually not required to work with meal specific ratios.


Dose calculation

Insulin dosage is given by the formula : \mathrm = \frac + \frac=\frac based on the person's blood glucose and carbohydrate intake and these constants: * ''TR'' = target rate * ''CF'' = corrective factor * ''KF'' = carbohydrate factor Blood glucose and target rate are expressed in mg/dL or mmol/L. Constants should be set by a physician or clinical pharmacist.


Abuse

The abuse of exogenous insulin carries with it an attendant risk of hypoglycemic coma and death when the amount used is in excess of that required to handle ingested carbohydrate. Acute risks include
brain damage Neurotrauma, brain damage or brain injury (BI) is the destruction or degeneration of brain cells. Brain injuries occur due to a wide range of internal and external factors. In general, brain damage refers to significant, undiscriminating t ...
,
paralysis Paralysis (also known as plegia) is a loss of motor function in one or more muscles. Paralysis can also be accompanied by a loss of feeling (sensory loss) in the affected area if there is sensory damage. In the United States, roughly 1 in 50 ...
, and
death Death is the irreversible cessation of all biological functions that sustain an organism. For organisms with a brain, death can also be defined as the irreversible cessation of functioning of the whole brain, including brainstem, and brain ...
. Symptoms may include dizziness, weakness, trembling,
palpitations Palpitations are perceived abnormalities of the heartbeat characterized by awareness of cardiac muscle contractions in the chest, which is further characterized by the hard, fast and/or irregular beatings of the heart. Symptoms include a rapi ...
, seizures, confusion, headache, drowsiness, coma,
diaphoresis Perspiration, also known as sweating, is the production of fluids secreted by the sweat glands in the skin of mammals. Two types of sweat glands can be found in humans: eccrine glands and apocrine glands. The eccrine sweat glands are distribut ...
and
nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
. All persons with overdoses should be referred for medical assessment and treatment, which may last for hours or days. Data from the US National Poison Data System (2013) indicates that 89.3% of insulin cases reported to poison centers are unintentional, as a result of therapeutic error. Another 10% of cases are intentional, and may reflect attempted suicide, abuse, criminal intent, secondary gain or other unknown reasons. Hypoglycemia that has been induced by exogenous insulin can be chemically detected by examining the ratio of insulin to
C-peptide The connecting peptide, or C-peptide, is a short 31-amino-acid polypeptide that connects insulin, insulin's A-chain to its B-chain in the proinsulin molecule. In the context of diabetes or hypoglycemia, a measurement of C-peptide blood serum lev ...
in peripheral circulation. It has been suggested that this type of approach could be used to detect exogenous insulin abuse by athletes. The possibility of using insulin in an attempt to improve athletic performance was suggested as early as the
1998 Winter Olympics The 1998 Winter Olympics, officially known as the and commonly known as Nagano 1998 ( ja, 長野1998), was a winter multi-sport event held from 7 to 22 February 1998, mainly in Nagano, Japan, with some events taking place in the ...
in
Nagano, Japan Nagano may refer to: Places * Nagano Prefecture, a prefecture in Japan ** Nagano (city), the capital city of the same prefecture *** Nagano 1998, the 1998 Winter Olympics *** Nagano Olympic Stadium, a baseball stadium in Nagano *** Nagano Univer ...
, as reported by Peter Sönksen in the July 2001 issue of ''
Journal of Endocrinology The ''Journal of Endocrinology'' is a monthly peer-reviewed scientific journal that publishes original research articles, reviews and commentaries. Its focus is on endocrine physiology and metabolism, including hormone secretion, hormone action, an ...
''. The question of whether non-diabetic athletes could legally use insulin was raised by a Russian medical officer. Whether insulin would actually improve athletic performance is unclear, but concerns about its use led the International Olympic Committee to ban use of the hormone by non-diabetic athletes in 1998. The book ''
Game of Shadows ''Game of Shadows: Barry Bonds, BALCO, and the Steroids Scandal that Rocked Professional Sports'' is a bestselling non-fiction book published on March 23, 2006, and written by Mark Fainaru-Wada and Lance Williams, reporters for the ''San Franci ...
'' (2001), by reporters Mark Fainaru-Wada and Lance Williams, included allegations that baseball player
Barry Bonds Barry Lamar Bonds (born July 24, 1964) is an American former professional baseball left fielder who played 22 seasons in Major League Baseball (MLB). Bonds was a member of the Pittsburgh Pirates from 1986 to 1992 and the San Francisco Giants f ...
used insulin (as well as other drugs) in the apparent belief that it would increase the effectiveness of the growth hormone he was alleged to be taking. Bonds eventually testified in front of a federal grand jury as part of a government investigation of
BALCO The Bay Area Laboratory Co-operative (BALCO) (1984–2003) was an American company led by founder and owner Victor Conte. In 2003, journalists Lance Williams and Mark Fainaru-Wada investigated the company's role in a drug sports scandal later re ...
. Bodybuilders in particular are claimed to be using exogenous insulin and other drugs in the belief that they will increase muscle mass. Bodybuilders have been described as injecting up to 10 IU of regular synthetic insulin before eating sugary meals. A 2008 report suggested that insulin is sometimes used in combination with
anabolic steroids Anabolic steroids, also known more properly as anabolic–androgenic steroids (AAS), are steroidal androgens that include natural androgens like testosterone as well as synthetic androgens that are structurally related and have similar effects t ...
and
growth hormone Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in h ...
(GH), and that "Athletes are exposing themselves to potential harm by self‐administering large doses of GH, IGF‐I and insulin". Insulin abuse has been mentioned as a possible factor in the deaths of bodybuilders Ghent Wakefield and
Rich Piana Richard Eugene Piana (September 26, 1970August 25, 2017) was an American bodybuilder, businessman, and YouTuber. He won the National Physique Committee (NPC) Mr. Teen California title in 1989, NPC Mr. California in 1998, and National Physique Com ...
. Insulin, human growth hormone (HGH) and insulin-like growth factor 1 (IGF-1) are self-administered by those looking to increase muscle mass beyond the scope offered by anabolic steroids alone. Their rationale is that since insulin and HGH act synergistically to promote growth, and since IGF-1 is a primary mediator of musculoskeletal growth, the 'stacking' of insulin, HGH and IGF-1 should offer a synergistic growth effect on skeletal muscle. This theory has been supported in recent years by top-level bodybuilders whose competition weight is in excess of of muscle, larger than that of competitors in the past, and with even lower levels of body fat.


Detection in biological fluids

Insulin is often measured in serum, plasma or blood in order to monitor therapy in people who are diabetic, confirm a diagnosis of poisoning in hospitalized persons or assist in a medicolegal investigation of suspicious death. Interpretation of the resulting insulin concentrations is complex, given the numerous types of insulin available, various routes of administration, the presence of anti-insulin antibodies in insulin-dependent diabetics and the ''ex vivo'' instability of the drug. Other potential confounding factors include the wide-ranging cross-reactivity of commercial insulin immunoassays for the biosynthetic insulin analogs, the use of high-dose intravenous insulin as an antidote to antihypertensive drug overdosage and postmortem redistribution of insulin within the body. The use of a chromatographic technique for insulin assay may be preferable to immunoassay in some circumstances, to avoid the issue of cross-reactivity affecting the quantitative result and also to assist identifying the specific type of insulin in the specimen.


Combination with other antidiabetic drugs

A combination therapy of insulin and other
antidiabetic drug Drugs used in diabetes treat diabetes mellitus by altering the glucose level in the blood. With the exceptions of insulin, most GLP receptor agonists ( liraglutide, exenatide, and others), and pramlintide, all are administered orally and are t ...
s appears to be most beneficial in people who are diabetic, who still have residual insulin secretory capacity. A combination of insulin therapy and
sulfonylurea Sulfonylureas (UK: sulphonylurea) are a class of organic compounds used in medicine and agriculture, for example as antidiabetic drugs widely used in the management of diabetes mellitus type 2. They act by increasing insulin release from the beta ...
is more effective than insulin alone in treating people with type 2 diabetes after secondary failure to oral drugs, leading to better glucose profiles and/or decreased insulin needs.


Society and culture


Economics

In the United States the unit price of insulin has increased steadily from 1991 to 2019. It rose threefold from 2002 to 2013. Costs can be as high as US$900 per month. Concerns were raised in 2016 of pharmaceutical companies working together to increase prices. In January 2019, lawmakers from the
United States House of Representatives The United States House of Representatives, often referred to as the House of Representatives, the U.S. House, or simply the House, is the Lower house, lower chamber of the United States Congress, with the United States Senate, Senate being ...
sent letters to insulin manufacturers
Eli Lilly and Co. Eli Lilly and Company is an American pharmaceutical company headquartered in Indianapolis, Indiana, with offices in 18 countries. Its products are sold in approximately 125 countries. The company was founded in 1876 by, and named after, Colonel ...
,
Sanofi Sanofi S.A. is a French multinational pharmaceutical and healthcare company headquartered in Paris, France. Originally, the corporation was established in 1973 and merged with Synthélabo in 1999 to form Sanofi-Synthélabo. In 2004, Sanofi-Syn ...
and
Novo Nordisk Novo Nordisk A/S is a Danish multinational pharmaceutical company headquartered in Bagsværd, Denmark, with production facilities in nine countries, and affiliates or offices in five countries. Novo Nordisk is controlled by majority shareholder ...
asking for explanations for their rapidly raising insulin prices. The annual cost of insulin for people with type 1 diabetes in the U.S. almost doubled from $2,900 to $5,700 over the period from 2012 to 2016. People in the U.S. pay two to six times more than the rest of the world, including Canada, for brand name prescription medicine, according to the International Federation of Health Plans. Canada, like many other industrialized countries, has price controls on the cost of pharmaceuticals. California, in July 2022, approved a budget that allocates $100 million for the state to create its own insulin at a close-to-cost price. Insulin, and all other medications, are supplied free of charge to people with diabetes by the
National Health Service The National Health Service (NHS) is the umbrella term for the publicly funded healthcare systems of the United Kingdom (UK). Since 1948, they have been funded out of general taxation. There are three systems which are referred to using the " ...
in the countries of the United Kingdom.


Regulatory status

In March 2020, the FDA changed the regulatory pathway for approval of new insulin products. Insulin is regulated as a biologic rather than as a drug. The changed status gives the FDA more flexibility for approval and labeling. In July 2021, the FDA approved insulin glargine-yfgn (Semglee), a biosimilar product that contains the long acting analog insulin glargine. Insulin glargine-yfgn is interchangeable and less expensive than the reference product,
insulin glargine Insulin glargine, sold under the brand name Lantus among others, is a long-acting modified form of medical insulin, used in the management of type I and type II diabetes. It is typically the recommended long acting insulin in the United King ...
(Lantus), which had been approved in 2000. The FDA requires that new insulin products are not inferior to existing insulin products with respect to reduction in hemoglobin A1c. See Misbin, RI (February 2022). Insulin – History from an FDA Insider. Politics and Prose Publishing, Washington DC. Text ISBN 978-I-62429-391-77


Research


Inhalation

In 2006 the U.S.
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
(FDA) approved the use of Exubera, the first inhalable insulin. It was withdrawn from the market by its maker as of third quarter 2007, due to lack of acceptance. Inhaled insulin claimed to have similar efficacy to injected insulin, both in terms of controlling glucose levels and blood half-life. Currently, inhaled insulin is short acting and is typically taken before meals; an injection of long-acting insulin at night is often still required. When people were switched from injected to inhaled insulin, no significant difference was observed in HbA1c levels over three months. Accurate dosing was a particular problem, although people showed no significant weight gain or pulmonary function decline over the length of the trial, when compared to the baseline. Following its commercial launch in 2005 in the United Kingdom, it was not (as of July 2006) recommended by
National Institute for Health and Clinical Excellence The National Institute for Health and Care Excellence (NICE) is an executive non-departmental public body of the Department of Health and Social Care in England that publishes guidelines in four areas: * the use of health technologies withi ...
for routine use, except in cases where there is "proven injection phobia diagnosed by a psychiatrist or psychologist". In January 2008, the world's largest insulin manufacturer,
Novo Nordisk Novo Nordisk A/S is a Danish multinational pharmaceutical company headquartered in Bagsværd, Denmark, with production facilities in nine countries, and affiliates or offices in five countries. Novo Nordisk is controlled by majority shareholder ...
, also announced that the company was discontinuing all further development of the company's own version of inhalable insulin, known as the AERx iDMS inhaled insulin system. Similarly,
Eli Lilly and Company Eli Lilly and Company is an American pharmaceutical company headquartered in Indianapolis, Indiana, with offices in 18 countries. Its products are sold in approximately 125 countries. The company was founded in 1876 by, and named after, Colonel ...
ended its efforts to develop its inhaled Air Insulin in March 2008. However, MannKind Corp. (majority owner,
Alfred E. Mann Alfred E. Mann (1925 – February 25, 2016), also known as Al Mann, was an American physicist, inventor, entrepreneur, and philanthropist. Early life and education Mann was born and raised to a Jewish family in Portland, Oregon. His father was ...
) remains optimistic about the concept.


Transdermal

There are several methods for transdermal delivery of insulin.
Pulsatile insulin Pulsatile intravenous insulin therapy, sometimes called metabolic activation therapy or cellular activation therapy, describes in a literal sense the intravenous injection of insulin in pulses versus continuous infusions. Injection of insulin in pu ...
uses microjets to pulse insulin into the person, mimicking the physiological secretions of insulin by the pancreas. Jet injection had different insulin delivery peaks and durations as compared to needle injection. Some diabetics may prefer jet injectors to hypodermic injection. Both electricity using
iontophoresis Iontophoresis is a process of transdermal drug delivery by use of a voltage gradient on the skin. Molecules are transported across the stratum corneum by electrophoresis and electroosmosis and the electric field can also increase the permeability ...
and ultrasound have been found to make the skin temporarily porous. The insulin administration aspect remains experimental, but the blood glucose test aspect of "wrist appliances" is commercially available. Researchers have produced a watch-like device that tests for blood glucose levels through the skin and administers corrective doses of insulin through pores in the skin. A similar device, but relying on skin-penetrating "microneedles", was in the animal testing stage in 2015.


Intranasal

Intranasal insulin is being investigated. A randomized controlled trial that will determine whether intranasal
insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
can delay or prevent the onset of type 1 diabetes in at-risk children and young adults is expected to yield results in 2016.


By mouth

The basic appeal of hypoglycemic agents by mouth is that most people would prefer a pill or an oral liquid to an injection. However, insulin is a
peptide hormone Peptide hormones or protein hormones are hormones whose molecules are peptide, or proteins, respectively. The latter have longer amino acid chain lengths than the former. These hormones have an effect on the endocrine system of animals, including h ...
, which is digested in the
stomach The stomach is a muscular, hollow organ in the gastrointestinal tract of humans and many other animals, including several invertebrates. The stomach has a dilated structure and functions as a vital organ in the digestive system. The stomach i ...
and gut and in order to be effective at controlling blood sugar, cannot be taken orally in its current form. The potential market for an oral form of insulin is assumed to be enormous, thus many laboratories have attempted to devise ways of moving enough intact insulin from the gut to the
portal vein The portal vein or hepatic portal vein (HPV) is a blood vessel that carries blood from the gastrointestinal tract, gallbladder, pancreas and spleen to the liver. This blood contains nutrients and toxins extracted from digested contents. Approxima ...
to have a measurable effect on blood sugar. A number of
derivatization Derivatization is a technique used in chemistry which converts a chemical compound into a product (the reaction's derivate) of similar chemical structure, called a derivative. Generally, a specific functional group of the compound participates ...
and
formulation Formulation is a term used in various senses in various applications, both the material and the abstract or formal. Its fundamental meaning is the putting together of components in appropriate relationships or structures, according to a formul ...
strategies are currently being pursued to in an attempt to develop an orally available insulin. Many of these approaches employ
nanoparticle A nanoparticle or ultrafine particle is usually defined as a particle of matter that is between 1 and 100 nanometres (nm) in diameter. The term is sometimes used for larger particles, up to 500 nm, or fibers and tubes that are less than 1 ...
delivery systems and several are being tested in
clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...
s.


Pancreatic transplantation

Another improvement would be a transplantation of the pancreas or beta cell to avoid periodic insulin administration. This would result in a self-regulating insulin source. Transplantation of an entire pancreas (as an individual
organ Organ may refer to: Biology * Organ (biology), a part of an organism Musical instruments * Organ (music), a family of keyboard musical instruments characterized by sustained tone ** Electronic organ, an electronic keyboard instrument ** Hammond ...
) is difficult and relatively uncommon. It is often performed in conjunction with
liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
or
kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...
transplant, although it can be done by itself. It is also possible to do a transplantation of only the pancreatic beta cells. However, islet transplants had been highly experimental for many years, but some researchers in
Alberta, Canada Alberta ( ) is one of the thirteen provinces and territories of Canada, provinces and territories of Canada. It is part of Western Canada and is one of the three Canadian Prairies, prairie provinces. Alberta is bordered by British Columbia to t ...
, have developed techniques with a high ''initial'' success rate (about 90% in one group). Nearly half of those who got an islet cell transplant were insulin-free one year after the operation; by the end of the second year that number drops to about one in seven. However, researchers at the University of Illinois at Chicago (UIC) have slightly modified the Edmonton Protocol procedure for islet cell transplantation and achieved insulin independence in diabetic people, with fewer but better-functioning pancreatic islet cells. Longer-term studies are needed to validate whether it improves the rate of insulin-independence. Beta cell transplant may become practical in the near future. Additionally, some researchers have explored the possibility of transplanting
genetically engineered Genetic engineering, also called genetic modification or genetic manipulation, is the modification and manipulation of an organism's genes using technology. It is a set of technologies used to change the genetic makeup of cells, including t ...
non-beta cells to secrete insulin. Clinically testable results are far from realization at this time. Several other non-transplant methods of automatic insulin delivery are being developed in research labs, but none is close to clinical approval.


References


External links

* * * {{DEFAULTSORT:Insulin Medication Insulin therapies Eli Lilly and Company brands Wikipedia medicine articles ready to translate World Health Organization essential medicines