Insulin is a protein hormone used as a drug to treat high blood glucose. These include type 1 diabetes mellitus, type 2 diabetes mellitus, gestational diabetes, and diabetic complications such as diabetic ketoacidosis and hyperosmolar hyperglycemic. It is also used in conjunction with glucose to treat high blood potassium levels. Usually given by injection under the skin, but some forms can also be used with injections to blood vessels or muscles.
A common side effect is low blood sugar. Other side effects may include pain or changes to the skin at the injection site, low blood potassium, and allergic reactions. Use during pregnancy is relatively safe for infants. Insulin can be made from pig or cow pancreas. Human versions can be made either by modifying the swine version or recombinant technology. It comes in three main types of short-acting (such as ordinary insulin), intermediate-acting (such as insulin NPH), and longer-acting (such as insulin glargine).
Insulin was first used as a drug in Canada by Charles Best and Frederick Banting in 1922. It is listed in the World Health Organization's Essential Drug List, the most effective and safe medication needed in the health system. The cost of grocery in developing countries is around US $ 2.39 to $ 10.61 per 1,000 iu (34.7 mg) of regular insulin and $ 2.23 to $ 10.35 per 1000 NPH insulin. In the UK 1,000 iu of regular insulin or NPH cost the NHS 7.48 pounds, while the amount of insulin glargine reaches 30.68 pounds.
Video Insulin (medication)
Medical use
Insulin is used to treat a number of diseases including diabetes and its acute complications such as diabetic ketoacidosis and hyperosmolar hyperglycemic. It is also used in conjunction with glucose to treat high blood potassium levels. Insulin was previously used in the treatment of psychiatry called shock insulin therapy.
Maps Insulin (medication)
Side effects
If too much insulin is being sent or the person who eats less than he or she is taking, there may be hypoglycemia. On the other hand, if too little insulin is given, there will be hyperglycemia. Both can be life-threatening.
Allergic
Allergy to Insulin products is rare with a prevalence of about 2%, most of which are not due to insulin itself but to preservatives added to insulin such as zinc, protamine, and meta-cresol. Most reactions are Type I hypersensitivity reactions and rarely cause anaphylaxis. Suspected allergies to insulin can be confirmed by a skin prick test, patch test and occasional skin biopsy. First-line therapy for insulin hypersensitivity reactions including symptomatic therapy with antihistamines. The affected persons then turn to preparations that do not contain any special agents that they react to or undergo desensitization.
Principles
Insulin is required for all animal life (excluding certain insects). The mechanism of action is almost identical in the nematode worms (eg, C. Elegans), fish, and mammals, and it is a protein that has been greatly preserved throughout the time of evolution. Insulin should be given to such deprived patients. Clinically, this condition is called type 1 diabetes mellitus.
Initial sources of insulin for clinical use in humans are pancreatic cows, horses, pigs or fish. Insulin from these sources is effective in humans because it is almost identical to human insulin (three different amino acids in bovine insulin, one difference in amino acids in porcine). Differences in the suitability of insulin derived from beef, pork, or fish derived for each patient have historically been caused by a lower preparatory purity resulting in an allergic reaction to the presence of non-insulin substances. Although purity has risen steadily since the 1920s finally achieving 99% purity in the mid-1970s thanks to the high-pressure liquid chromatography (HPLC) method, mild allergic reactions still occur occasionally, although similar types of allergic reactions are also known. occurs in response to synthetic "human" insulin varieties. Insulin production from animal pancreas extends for decades, but very few patients now rely on insulin from animal sources, mostly because some pharmaceutical companies sell it again.
Biosynthetic "human" insulin is now produced for widespread clinical use using genetic engineering techniques using recombinant DNA technology, which the manufacturer claims reduces the presence of many impurities. Eli Lilly marketed the first such insulin, Humulin, in 1982. Humulin was the first drug to be produced using modern genetic engineering techniques in which actual human DNA was inserted into a host cell ( E. coli in this case ). The host cells are then allowed to grow and reproduce normally, and since human DNA is inserted, they produce a synthetic version of human insulin. However, the clinical preparations made from insulin are distinct from endogenous human insulin in some important ways; an example is the absence of C-peptides which in recent years have proven to have a systemic effect on their own. Genentech developed the technique that Lilly used to produce Humulin, although the company never marketed the product itself commercially. Novo Nordisk has also developed genetically engineered insulin independently using the yeast process.
According to a survey by the International Diabetes Federation in 2002 on access and availability of insulin in its member states, about 70% of the insulin currently sold in the world is recombinant biosynthetic 'human' insulin. The majority of clinically used insulin is currently produced in this way, although clinical experience has provided conflicting evidence as to whether this insulin has a smaller likelihood of producing an allergic reaction. Adverse reactions have been reported; this includes the loss of warning signs that the patient may slip into a coma through hypoglycemia, seizures, memory hoses and loss of concentration. However, the position statement of the International Diabetes Federation is very clear in stating that "there is no extraordinary evidence to prefer one species of insulin than another" and "modern, highly refined animal insulin" remains a perfectly acceptable alternative. "
Since January 2006, all insulin distributed in the US and some other countries is synthetic or analogue "human" insulin. A special FDA import process is required to obtain the insulin of cow or pork derivatives used in the US, although there may be some stock of Lilly pig insulin made in 2005 or earlier, and pork insulin is also sold and marketed under trademark. Vetsulin (BC) in the US for animal use in the treatment of animal companion diabetes.
There are some problems with insulin as a clinical treatment for diabetes:
- Administration mode.
- Choosing the right dosage and time. The amount of carbohydrate a unit handling insulin varies between people and over days but the value between 7 and 20 grams per 1 IE is typical.
- Choosing the right insulin preparation (usually at 'onset velocity and action duration')).
- Adjust the dosage and time to adjust the time, amount, and type of food intake.
- Adjust the dosage and time to adjust the exercise.
- Adjust the dosage, type, and time to match other conditions, such as increased stress of the disease.
- Variability in absorption into the bloodstream through subcutaneous delivery
- The dose is non-physiological because only subcutaneous bolus doses given are not a combination of insulin and C-peptide are released gradually and directly into the portal vein.
- It's just a nuisance for patients to inject every time they eat carbohydrates or have high blood glucose readings.
- This is dangerous if something goes wrong (especially "too much" insulin).
Type
Insulin medical preparation is never just 'insulin in water'. Clinical insulin is a specially prepared mixture of insulin plus other substances including preservatives. This slows the absorption of insulin, adjusts the pH of the solution to reduce the reaction at the injection site, and so on.
Small variations of human insulin molecules called analog insulin, (technically "insulin receptor ligand") are so named because they are not technically insulin, but analogues that retain hormonal glucose management functions. They have absorption characteristics and activities that are currently not possible with subcutaneous injected insulin. They are absorbed rapidly in an attempt to mimic real beta cell insulin (such as with lispro insulin, aspart insulin, and insulin glulisine), or continue to be absorbed after injection rather than having a 'peak' followed by a decrease in faster or less insulin action (such as insulin detemir and insulin glargine), all while maintaining a lowering of insulin glucose in the human body. However, a number of meta-analyzes, including those conducted by Cochrane Collaboration in 2005, the German Institute for Quality and Cost-Effectiveness in the Healthcare Sector [IQWiG] were released in 2007, and the Canadian Agency for Medicine and Technology in Health (CADTH) was also released in 2007 has shown no firm advantage in the clinical use of insulin analog over a more conventional type of insulin.
Choosing the type of insulin and dose/time should be done by experienced medical professionals who work closely with diabetic patients.
Types of insulin commonly used are as follows.
Works quickly
Includes insulin analogue aspart , lispro , and glulisine . It starts working within 5 to 15 minutes and is active for 3 to 4 hours. Most insulin forms hexamets, which delay the entry of blood into active form; these analog insulin have no normal insulin activity. Newer varieties are now awaiting US regulatory approval designed to work quickly, but retain the same genetic structure as ordinary human insulin.
Short-acting
Includes regular insulin , which starts working in 30 minutes and is active about 5 to 8 hours. Intermediate-acting
Includes insulin NPH , which starts working within 1 to 3 hours and is active for 16 to 24 hours.
Long-acting
Includes the glargine analog and the detemir , each of which starts work in 1 to 2 hours and continues to active, without a peak or main dips, for about 24 hours, although this varies in many individuals.
Ultra-long acting
Currently it includes only the degludec analog, which starts working in 30 to 90 minutes and continues active for more than 24 hours.
Product combination insulin
Includes a combination of fast-acting insulin or short-acting with longer-acting insulin, usually insulin NPH . Combination products start working with shorter work insulin (5-15 minutes for fast action, and 30 minutes for short acting), and stay active for 16 to 24 hours. There are several variations with different proportions of mixed insulin (eg Novolog Mix 70/30 containing 70% aspart protamine [similar to NPH], and 30% aspart.)
Administrative method
Unlike many drugs, insulin can not be taken orally at this time. Like almost all other proteins inserted into the gastrointestinal tract, it is reduced to fragments (a component of a single amino acid), where all activity is lost. There are several studies on how to protect insulin from the digestive tract, so it can be administered in one pill. So far fully experimental.
Subcutaneous
Insulin is usually taken as a subcutaneous injection by a disposable syringe with a needle, insulin pump, or by using a repeated insulin pen with a needle. Patients who want to reduce skin puncture recurring insulin injections often use an injection port along with a syringe.
Schedule administration often tries to mimic the physiological secretion of insulin by the pancreas. Therefore, both long-acting insulin and short-acting insulin are usually used.
Insulin pump
The insulin pump is a reasonable solution for some people. The advantage for patients is better control over background or dose of 'basal' insulin, bolus doses calculated for unit fractions, and calculators in pumps that can help determine bolus drip dose. Limitations are cost, potential for hypoglycemic and hyperglycemic episodes, catheter problems, and no "closed loop" means controlling insulin delivery based on current blood glucose levels.
The insulin pump may be like an 'electric injector' attached to a temporarily planted catheter or cannula. Some who can not achieve adequate glucose control with conventional injection (or jet) can do so with the appropriate pump.
The inside catheter poses a risk of infection and ulceration, and some patients may also develop lipodystrophy due to infusion sets. This risk can often be minimized by keeping the infusion site clean. The insulin pump requires care and effort to be used properly.
Dosage and timing
Unit dose
An international insulin unit (1 IU) is defined as a "biological equivalent" of 34.7 Âμg pure crystalline insulin.
The first definition of the insulin unit is the amount needed to induce hypoglycemia in rabbits. This was set by James Collip at the University of Toronto in 1922. Of course, this depends on the size and diet of rabbits. The insulin unit is established by an insulin committee at the University of Toronto. This unit evolved eventually into the old USP insulin unit, where one unit (U) of insulin was set equal to the amount of insulin needed to reduce blood glucose concentration in fasting rabbits to 45 mg/dl (2.5 mmol/L). Once the chemical structure and mass of insulin are known, the insulin unit is defined by the pure crystalline insulin mass required to obtain the USP unit.
The unit of measurement used in insulin therapy is not part of the International System of Units (abbreviated SI) which is the modern form of the metric system. In contrast, the international pharmacology unit (IU) is defined by the WHO Expert Committee on Biological Standardization.
Potential complications
The main problem for those who need external insulin is choosing the right dose of insulin and the right time.
The physiological regulation of blood glucose, as in non-diabetics, is the best. Increased blood glucose levels after a meal is a stimulus to release insulin from the pancreas. Increased insulin levels lead to absorption of glucose and storage in cells, reducing glycogen to glucose conversion, reducing blood glucose levels, and reducing insulin release. The result is that blood glucose levels rise after meals, and within an hour or so, return to normal levels of 'fasting'. Even the best diabetes treatment with synthetic human insulin or even insulin analogues, but given, is far from normal glucose control in non-diabetics.
The tricky thing is that the composition of edible food (see glycemic index ) affects intestinal absorption rate. Glucose from some foods is absorbed more (or less) quickly than the same amount of glucose in other foods. In addition, fats and proteins cause a delay in the absorption of glucose from carbohydrates eaten at the same time. In addition, exercise reduces the need for insulin even when all other factors remain the same, because the working muscles have the ability to take glucose without the help of insulin.
Due to complex and interacting factors, in principle, it is impossible to know exactly how much insulin (and what kind) is required to 'close' certain foods to achieve a reasonable blood glucose level within an hour or two after eating. Non-diabetic beta cells routinely and automatically manage this by monitoring continuous glucose levels and insulin release. All such decisions by diabetes should be based on experience and training (ie, in the direction of the physician, PA, or in some places a specialist diabetes educator) and, furthermore, specifically based on individual patient experience. But not directly and should not be done with habits or routines. But with caution, it can be done fairly well in clinical practice. For example, some people with diabetes need more insulin after drinking skim milk than they do after taking the same amount of fat, protein, carbohydrates, and fluids in some other form. Their specific reactions to skimmed milk differ from others with diabetes, but the same amount of milk tends to cause different reactions even in that person. Whole milk contains lots of fat while skim milk has less. This is a sustainable balancing act for everyone with diabetes, especially for those who take insulin.
People with insulin-dependent diabetes usually require some basic levels of insulin (basal insulin), as well as short-acting insulin to cover food (bolus is also known as feeding time or prandial insulin). Maintaining basal levels and bolus levels is an ongoing balancing act that people with insulin-dependent diabetes should manage on a daily basis. This is usually achieved through regular blood tests, although continuous glucose monitors or CGMs are now available that can help to improve this balancing act after widespread use becomes common.
Strategy
Long-acting insulin is used to estimate the basal secretion of insulin by the pancreas, which varies in the course of the day. NPH/isophane, lente, ultralente, glargine, and detemir can be used for this purpose. The advantage of NPH is its low cost, the fact that you can mix it with short-term insulin forms, thus minimizing the amount of injections to be administered, and that NPH activity will peak 4-6 hours after administration, allowing sleep doses to balance the glucose tendency rising by dawn, along with smaller morning doses to balance the basal needs of the lower afternoons and possibly an afternoon dose to cover the needs of the night. The loss of NPH before bedtime is that if it is not taken too late (almost midnight) to place its peak just before dawn, it has the potential to cause hypoglycemia. One theoretical advantage of glargine and detemir is that they only need to be administered once a day, although in practice many patients find that no one lasts for 24 hours. They can be given anytime during the day, provided they are provided at the same time each day. Another advantage of long-acting insulin is that the basal component of the insulin regimen (providing a minimum level of insulin throughout the day) can be separated from prandial or bolus components (providing feeding time via ultra-short-acting insulin), 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 can not be mixed with other forms of insulin.
Short-acting insulin is used to simulate endogenous insulin spikes that are produced in anticipation of eating. Regular insulin, lispro, aspart and glulisine can be used for this purpose. Regular Insulin should be administered with about 30 minutes before meal time to be maximally effective and to minimize the possibility of hypoglycemia. Lispro, aspart and glulisine are approved for dose with the first bite of food, and may even be effective if given after completing the meal. Short-acting insulin is also used to improve hyperglycemia.
The usual schedule for checking fingerstick blood glucose and insulin delivery is before all foods and sometimes also at bedtime. The newer guidelines also require an inspection 2 hours after meals to ensure the food has been 'covered' effectively.
Slide scale
What doctors usually refer to as sliding-scale insulin (SSI) is fast-acting or fast-acting, administered subcutaneously, usually at meals and occasionally asleep, but only when blood glucose is above the threshold, usually 10 mmol/L (180 mg/dL). No basal insulin is given, usually resulting in an increase in blood glucose every morning, which is then pursued throughout the day, with repeated cycles the next day.
Insulin receptors generally determine the fixed amount of long-acting insulin to be given regularly, and a fixed amount of short-acting insulin before each meal ('shear scale' approach). However, the amount of short-acting insulin may vary depending on the preprandial patient's glucose fingerstick, to improve on pre-existing hyperglycemia. The so-called "shear scale" is still widely taught, albeit controversial. This was first described in 1934.
Sliding scale insulin (SSI) is not an effective way to treat long-term diabetes in individuals living in nursing homes. Shear insulin scales cause greater patient discomfort and improve nursing time.
Example of a regimen using insulin glargine and lispro insulin:
- Insulin glargine: 20 units at bedtime
Carbohydrate and DAFNE calculations
A more complicated method that allows greater freedom with mealtimes and snacks is "carbohydrate counting." This approach is taught to diabetic patients in the UK and elsewhere as "Dose Adjustment for Normal Eating" or DAFNE.
In Europe, patients who are not familiar with the DAFNE regime can take an educational course where the basic initial insulin dosage guidelines are "for every 10g of carbohydrates you eat, take 1 unit of insulin". The DAFNE course also covers topics that naturally work with this regime, such as blood glucose monitoring, exercise and carbohydrate estimation to help patients complete their personal control requirements.
Patients 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 use these results, estimating how many units of insulin should be administered depending on the carbohydrate content. their food. For example, if the patient determines that 1 unit of insulin will cover 15 grams of carbohydrates, then they should give 5 units of insulin before consuming foods containing 75 grams of carbohydrates.
Some alternative methods also consider the protein content of the food (since excess protein diet can be converted into glucose through gluconeogenesis).
With DAFNE, most doses involve a reasonable rate of estimate, especially with unlabeled foods, and will only work consistently enough from one dose to the next if patients know their body's needs. For example, a patient found they could take 1 unit to 10g of carbohydrates in the morning and evening, but found that their body needed more insulin to eat in the middle of the day so they had to adjust it to 1 unit per 8.5 g of carbohydrates.
Other less obvious factors that affect the use of insulin in the body should also be taken into account. For example, some patients may find that their bodies process insulin better on a hot day and thus require less insulin. With this, patients must adjust their doses with their best understanding of their past experiences.
The DAFNE regime requires patients to learn about their body needs through experience, which takes time and patience, but can then become effective.
Predictive closed-loop modeling
Patients with fluctuating insulin requirements may benefit from a closed-loop predictive modeling approach. As an extension to the "carbohydrate counting", in this closed predictive modeling approach, the four daily doses of insulin required to achieve the targeted blood sugar levels for "normal" daily carbohydrate consumption and physical activity amounts are continuously adjusted based on a pre- eat and pre-night. Any new blood sugar readings provide feedback to refine and track the body's insulin requirements. In this strategy, the key patient-specific factors, which must be determined experimentally, are factors of correction of blood sugar and carbohydrate ratio. The blood sugar correction factor establishes the factor of "proportional gain" and "integral gain" for four feedback rounds. When taken too low, the deviation from the target blood sugar level is not corrected effectively, when taken too high, the blood sugar regulation will become unstable. Because in this approach, the ratio of carbohydrates is only used to calculate non-standard carbohydrate intake, usually not necessary to work with a special ratio of food.
Appropriate modeling of the amount of insulin remaining to act in the patient's body is very important in this strategy, for example to ensure that any adjustments in the amount of basal insulin are taken into account when calculating the amount of bolus required for food. Because of the need to take into account each insulin activity profile, analyze past blood sugar trends, and factors in non-standard carbohydrate intake and exercise levels, this strategy requires a special smartphone application to handle all calculations, and to return meaningful dose recommendations. and expected blood sugar levels.
Dosing Calculation
based on patient's blood glucose and carbohydrate intake and these constants:
- TR = target rate
- CF = corrective factor
- KF = carbohydrate factor
Blood glucose and target levels are expressed in mg/dL or mmol/L. Constants should be established by the doctor or clinical pharmacist.
Abuse
On July 23, 2004, news reports claimed that a former leading international athlete athlete partner said his ex-partner had used insulin as a way of 'energizing' the body. There is no evidence to suggest it should act as a performance enhancer in non-diabetics. Poorly controlled diabetics are more susceptible than others to fatigue and fatigue, and properly administered insulin can relieve these symptoms.
Game of Shadows, by reporters Mark Fainaru-Wada and Lance Williams, including allegations that Barry Bonds uses insulin with a clear belief that it will increase the effectiveness of growth hormones he allegedly took. On top of this, non-prescribed insulin is a banned substance in the Olympics and other global competitions.
The use and abuse of exogenous insulin is claimed to be widespread among the bodybuilding community. Insulin, human growth hormone (HGH) and growth factors such as insulin 1 (IGF-1) are self-administered by those who want to increase muscle mass beyond the scope offered by anabolic steroids alone. Their reasoning is that because insulin and HGH act synergistically to promote growth, and because IGF-1 is a major mediator of musculoskeletal growth, insulin buildup, 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 weighs more than 50 lb (23 kg) of muscle, bigger than competitors in the past, and even with lower body fat levels. There are even some reactions to the 'weird' appearance of some of today's top-level professionals.
Bodybuilders claimed to inject up to 10 IU of synthetic insulin to act quickly after a meal containing carbohydrates and starch proteins, but little fat, in an effort to "force feed" muscle cells with the nutrients needed for growth, while preventing the growth of adipocytes (ie, cells -selsel fat). This can be done up to four times daily, after meals, for a total use of perhaps 40 IU of synthetic insulin per day. However, there are reports of a much heavier use, between bodybuilding and even "recreation".
Abuse of exogenous insulin carries a risk of hypoglycemic coma and death when the amount used is more than necessary to handle the digested carbohydrates. Acute risks include brain damage, paralysis, and death.
Detection in biological fluid
Insulin is often measured in serum, plasma or blood to monitor therapy in diabetic patients, confirming the diagnosis of poisoning in hospitalized people or assisting in the investigation of suspicious suspected medical deaths. The interpretation of the resulting insulin concentration is complex, given the many types of insulin available, the various delivery routes, the presence of anti-insulin antibodies in insulin-dependent diabetics and drug instability. Other potential confounding factors include extensive cross-reactivity of commercial insulin immunoassays for biosynthetic insulin analogues, the use of high-dose intravenous insulin as an antidote for overdose of antihypertensive drugs and postmortem insulin redistribution in the body. The use of chromatographic techniques for insulin examination may be better than immunoassay in some circumstances, to avoid cross-reactivity issues that affect quantitative outcomes and also to help identify specific types of insulin in the specimen.
Combination with other antidiabetic drugs
Combination therapy of insulin and other antidiabetic drugs seems most useful in diabetic patients who still have residual insulin secretion capacity. The combination of insulin and sulfonylurea therapy is more effective than insulin alone in treating patients with type 2 diabetes after secondary failure for oral drugs, leading to better glucose profiles and/or decreased insulin requirements.
History
- 1922 Frederick Banting, Charles Best, and James Collip used human beef extract extract in Toronto, Canada.
- 1922 Leonard Thompson became the first man to be treated with insulin.
- 1922 Elizabeth Hughes Gossett, daughter of US Secretary of State, became the first American to be treated in Toronto.
- 1923 Eli Lilly produces a purer amount of commercial insulin bovine than Banting et al. has been using
- 1923 Farbwerke Hoechst, one of the pioneers of Sanofi Aventis today, manufactures commercial quantities of bovin insulin in Germany
- 1923 Hagedorn founded Nordisk Insulin laboratory in Denmark - forerunner of Novo Nordisk today
- 1926 Nordisk receives a Danish charter to produce insulin as nonprofit
- 1936 Canadians D.M. Scott, A.M. Fisher formulates the zinc insulin mixture and licenses it to Novo
- 1936 Hagedorn found that adding protamin to insulin lengthens the duration of insulin action
- 1946 Nordisk formulates insulin Poropine isophane alias Protamine Hagedorn Neutral or insulin NPH
- 1946 Nordisk crystallizes a protamin and insulin mixture
- 1950 Nordisk markets insulin NPH
- 1953 Novo formulates Lente porcine and beef insulin by adding zinc for longer lasting insulin
- 1955 Frederick Sanger determines the amino acid sequence of insulin
- 1966 Synthesized by total synthesis by C.L. Tsou, Wang Yinglai, and co-workers
- 1969 Dorothy Crowfoot Hodgkin breaks insulin crystal structure with X-ray crystallography
- 1973 Purification of monocomponent (MC) insulin introduced
- 1973 US officially "standard" insulin sold for human use in the US to U-100 (100 units per milliliter). Prior to that, insulin was sold in a variety of strengths, including U-80 (80 units per milliliter) and U-40 formulations (40 units per milliliter), so efforts to "standardize" potentials aimed at reducing dose errors and easing doctors' insulin for the patient. Other countries also follow.
- 1978 Genentech produces biosynthetic 'human' insulin in bacteria Escherichia coli using recombinant DNA techniques, licensed for Eli Lilly
- 1981 Novo Nordisk chemically and enzymatically converts porcine into "human" insulin
- 1982 Genentech synthetic 'human' insulin (top) approved
- 1983 Eli Lilly and Company produces biosynthetic 'human' insulin with recombinant DNA technology, Humulin
- 1985 Axel Ullrich sequences cell membrane receptors.
- 1988 Novo Nordisk produces recombinant biosynthetic 'human' insulin
- 1996 Lilly Humalog "lispro" analogue insulin approved.
- 2000 Sanofi Aventis Lantus analog "glargine" insulin is approved for clinical use in the US and Europe.
- 2004 Sanofi Aventis Apulin of "insulin" analogue insulin "glulisine" is approved for clinical use in the US.
- 2006 Novo Nordisk Levemir "detemir" analogue insulin is approved for clinical use in the US.
Economy
Wholesale costs in developing countries are around US $ 2.39 to $ 10.61 per 1,000 per day of regular insulin and $ 2.23 to $ 10.35 per 1000 NPH of insulin. In the UK 1,000 iu of regular insulin or NPH cost the NHS Ã, £ 7.48, while the amount of insulin glargine cost Ã, Â £ 30.68.
In the United States, insulin prices have tripled from 2002 to 2013. Costs can reach US $ 900 per month. Concerns raised in 2016 pharmaceutical companies work together to raise prices.
Research
Inhale
In 2006, the US Food and Drug Administration approved the use of Exubera, the first insulin inhalable. It was withdrawn from the market by its maker in the third quarter of 2007, due to a lack of acceptance.
Inhaled insulin is claimed to have similar efficacy to injected insulin, both in terms of controlling glucose and blood-beating levels. Currently, the inhaled insulin is short acting and is usually taken before meals; a long-acting insulin injection at night is often still needed. When the patient was diverted from insulin injected into inhalation, no significant difference was observed at Hb A1c level for three months. Accurate doses are a special problem, although patients do not show significant weight gain or pulmonary function decline during the trial period, when compared to baseline.
After the commercial launch in 2005 in the UK, no (in July 2006) was recommended by the National Institute for Clinical Health and Excellence for routine use, except in cases where there was an "injection phobia proven to be diagnosed by a psychiatrist or psychologist".
In January 2008, the world's largest insulin manufacturer, Novo Nordisk, also announced that it halted any further development of an insulin inhalation version of a company known as the AERx iDMS inhalation insulin system. Similarly, Eli Lilly and the Company ended their efforts to develop Air Insulin inhaled in March 2008. However, MannKind Corp. (majority owner, Alfred E. Mann) remains optimistic about the concept.
Transdermal
There are several methods for transdermal insulin delivery. Pulsatile insulin uses microjets to drain insulin to the patient, mimicking the physiological secretion of insulin by the pancreas. Jet injection has a peak and the duration of insulin delivery is different compared to needle injection. Some diabetics find control possible with jet injectors, but not with hypodermic injection.
Both electricity using iontophoresis and ultrasound have been found to make the skin while porous. The administrative aspect of insulin remains experimental, but the aspect of blood glucose testing of "wrist equipment" is commercially available.
Researchers have produced devices such as clocks that test blood glucose levels through the skin and regulate insulin doses through the pores in the skin. Similar devices, but rely on "microneedles" that penetrate the skin, are in the testing phase of animals by 2015.
Intranasal
Intranasal insulin is being investigated. A randomized controlled trial that will determine whether intranasal insulin can delay or prevent type 1 diabetes in children at risk and young adults are expected to produce results by 2016.
By mouth
The basic appeal of hypoglycemic agents by mouth is that most people prefer pills or oral fluids for injections. However, insulin is a peptide hormone, digested in the stomach and intestines and to be effective in controlling blood sugar, can not be taken orally in its current form.
The potential market for oral insulin form is assumed to be enormous, so many laboratories have sought to find ways of transferring enough intact insulin from the intestine into the portal vein to have a measurable effect on blood sugar.
A number of derivatization and formulation strategies are currently being pursued in an effort to develop insulin available orally. Many of these approaches use nanoparticle delivery systems and some are being tested in clinical trials.
For example, Oralin is the pre-operative oral insulin under investigation. These drugs are given as oral sprays. It was evaluated compared with oral hypoglycemic agents, especially in patients with type 2 DM. Clinical data seemed promising, but further evaluation of its efficacy in type 1 DM was required.
Pancreatic transplant
Another improvement is the transplantation of pancreas or beta cells to avoid periodic insulin administration. This will produce a self-regulating insulin source. Transplantation of the entire pancreas (as an individual organ) is difficult and relatively rare. This is often done in conjunction with a liver or kidney transplant, although it can be done by itself. It is also possible to transplant only the pancreatic beta cells. However, islet transplants have been highly experimental over the years, but several researchers in Alberta, Canada, have developed techniques with a high initial success rate (about 90% in one group). Nearly half of those who received an insulin-free islet cell transplant one year after surgery; at 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 patients with fewer but better functioning pancreatic islet cells. Long-term studies are needed to validate whether it increases the level of insulin independence.
Beta cell transplantation can be practical in the near future. In addition, some researchers have explored the possibility of transplanting non-beta cells that are genetically engineered to secrete insulin. The results of clinical trials are far from the current realization. Several other non-transplant methods of automatic insulin delivery are being developed in research laboratories, but none approach clinical approval.
References
Source of the article : Wikipedia
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