What Are the Different Insulin Types?
Insulin is a protein hormone secreted by pancreatic islet beta cells in the pancreas stimulated by endogenous or exogenous substances such as glucose, lactose, ribose, arginine, glucagon and the like. Insulin is the only hormone in the body that lowers blood sugar and promotes glycogen, fat, and protein synthesis. Exogenous insulin is mainly used for the treatment of diabetes.
Insulin is a protein hormone secreted by pancreatic islet beta cells in the pancreas stimulated by endogenous or exogenous substances such as glucose, lactose, ribose, arginine, glucagon and the like. Insulin is the only hormone in the body that lowers blood sugar and promotes glycogen, fat, and protein synthesis. Exogenous insulin is mainly used for the treatment of diabetes.
- Chinese name
- insulin
- Foreign name
- Insulin
- Molecular weight
- 5807.69
- Molecular formula
- C257 H383 N65 O77 S6
- Character
- White or off-white crystalline powder
- Melting point
- 233 ° C (decomposed)
- Specific rotation
- -64 ° ± 8 ° (C = 2,0.003mol / L NaOH)
- PH
- Bisexual, isoelectric point pI5.35-5.45
- Chemical nature
- protein
Introduction to Insulin Compounds
Basic insulin information
Chinese name: insulin
English name: Insulin
Chinese alias: common insulin; pancreatic hormone; insulin; regular insulin; short-acting insulin
English alias: Insulin; RI; Insulyl; Crystalline Insulin; Regular Insulin
Molecular formula: C 256 H 381 N 65 O 76 S 6
Molecular weight: 5778
Source content: This strain is a peptide substance with hypoglycemic effect prepared from pig pancreas. Calculated on a dry basis, the potency per 1mg must not be less than 27 units. Each unit is equivalent to 0.0345mg of insulin.
System requirements: This product should be extracted from frozen pancreas of quarantine qualified pigs. The production process should meet the requirements of the current edition of the Good Manufacturing Practice for Drugs.
Insulin discovery
Insulin was first discovered by Canadians FG Banting and CH Best in 1921. 1 Islet beta cells under the microscope
Began to be used in the clinic in 922, so that the past incurable diabetic patients were saved. Until the early 1980s, the Institute of Nephrology Detection of the Chinese Academy of Sciences had almost all insulin used for clinical purposes extracted from pig and bovine pancreas. The insulin composition of different animals is different. The structure of pig and human insulin is most similar, with only one amino acid at the carboxyl terminus of the B chain being different. In the early 1980s, genetic engineering technology has been successfully used to produce human insulin in large quantities from microorganisms, and has been used clinically [1] .
In 1955, the British F. Sanger team determined the entire amino acid sequence of bovine insulin, opening the way for humans to understand the chemical structure of protein molecules. On September 17, 1965, Chinese scientists artificially synthesized crystalline bovine insulin with full biological activity. It was the first protein synthesized in the laboratory by artificial methods. Later, scientists in the United States and Federal Germany also completed similar jobs.
In the early 1970s, British and Chinese scientists successfully used X-ray diffraction to determine the three-dimensional structure of porcine insulin. These work laid the foundation for further research on the relationship between the molecular structure and function of insulin. People use chemical total synthesis and semi-synthetic methods to prepare analogs to study the effect of structural changes on biological functions; conduct comparative studies of different species of insulin; study abnormal insulin molecular diseases, that is, individual amino acids in insulin molecules are caused by mutations in insulin genes A molecular disease caused by change. These studies also have important practical significance for elucidating the etiology of certain diabetes.
First-generation insulin-animal insulin
In 1921, Frederick Banting and John Macleod collaborated to successfully extract the first insulin, the amino acid sequence of insulin molecules of mammals of different races (human, cattle, sheep, pigs, etc.) And the structure is slightly different, among which pig insulin is closest to human. Animal insulin is the earliest insulin injection preparation used in the treatment of diabetes. Generally, it is pig insulin. Pig insulin differs from human insulin by 1 to 4 amino acids, so it is prone to immune reactions, subcutaneous fat atrophy or hyperplasia at the injection site, and insulin allergic reactions. And because of its high immunogenicity, hyperglycemia and hypoglycemia easily occur, and insulin resistance is prone to occur.
Second-generation insulin-human insulin
In the 1980s, people expressed high-purity synthetic human insulin through genetic engineering (recombinant DNA) (transgenic) yeast (Saccharomyces cerevisiae. Pichia or Hansenula) or recombinant Chinese hamster ovary cells (CHO). The body's own insulin is the same.
Compared with animal insulin, human insulin has fewer allergic reactions or insulin resistance, so the phenomenon of subcutaneous fat atrophy also decreases; due to less human insulin antibodies, the injection volume is reduced by 30% on average compared to animal insulin; the stability of human insulin is higher than Animal insulin, human insulin can be stored at room temperature for about 4 weeks.
Physiological human insulin secretion pattern cannot be simulated in onset time, peak time, and duration of action. Need to inject 30 minutes before a meal, there is a higher risk of nighttime hypoglycemia.
Third-generation insulin-insulin analogs
In the late 1990s, in the in-depth study of the structure and composition of human insulin, it was found that the modification of the peptide chain: the use of genetic engineering technology to change the amino acid combination of certain parts of the insulin peptide chain; changing the isoelectric point; increasing hexamerization Body strength; replacing cobalt ions with cobalt ions; increasing the fatty acid chain in the molecule and increasing the binding to albumin may change its physicochemical and biological characteristics, so that insulin analogs that are more suitable for human physiological needs can be developed ( insulinsimilitude). Insulin analogs can be used immediately after a meal and are also called meal insulin or fast-acting insulin.
Insulin classification
Source: The control gene for insulin synthesis is on the short arm of the 11th pair of chromosomes. If the gene is normal, the structure of insulin produced is normal; if the gene is mutated, the structure of insulin produced is abnormal, which is a variant insulin. In the nucleus of cell, the DNA of the insulin gene region on the short arm of the 11th pair of chromosomes is transcribed into mRNA, and the mRNA moves from the nucleus to the endoplasmic reticulum of the cytoplasm and is translated into a preproinsulin composed of 105 amino acid residues. Proproinsulin removes its pro-peptide through proteolysis to generate a long peptide chain consisting of 86 amino acids-proinsulin (45343345). Proinsulin enters the Golgi apparatus with the microbubbles in the cytoplasm. After the action of proteolytic enzymes, the three arginine-linked chains 75, 55, and 6075 are cut off, and the broken chain generates inactive C peptides, and at the same time, insulin is produced and secreted. Beyond beta cells, enter the blood circulation. A small portion of proinsulin that has not been hydrolyzed by protease enters the blood circulation with insulin, and the biological activity of proinsulin is only 5% of insulin.
Inactivated.
The islet cells store approximately 200U of insulin and secrete approximately 40U per day. When fasting, the plasma insulin concentration is 5 to 15 U / mL. After meals, plasma insulin levels can increase 5 to 10 times.
1. Insulin for animals: It is extracted from the pancreas of pigs and cattle.
1. Ultra-short-term effect: 15 minutes after injection, peak concentration 1 ~ 2 hours (subcutaneous). (Eg insulin aspart, insulin lispro)
2, short-acting (quick-acting): 30 minutes after injection, peak concentration of 2 to 4 hours, lasting 5 to 8 hours (subcutaneous, intramuscular, intravenous injection). (Such as regular insulin, regular insulin)
3. Intermediate effect: It takes effect 2 to 4 hours after injection, peak concentration 6 to 12 hours, and lasts 24 to 28 hours (subcutaneous). (Such as low protamine zinc insulin)
4. Long-term effect: It takes effect 4-6 hours after injection, with two types of high 75527. (Protamine zinc insulin)
5. Super long-term effect: It takes effect 3-6 hours after injection, and the maintenance time is 6-24 hours (subcutaneous). (Insulin detemir, glargine)
6. Premix: effective after 0.5 hours after injection, and maintained for 24 hours (subcutaneous). (Biphasic insulin)
Insulin structure
Insulin structure
Animals of different races (humans, cattle, sheep, pigs, etc.) have roughly the same insulin function, with slightly different components. The figure shows the chemical structure of human insulin .
Insulin consists of two peptide chains, A and B. Human insulin (Insulin Human) A chain has 11 kinds of 21 amino acids, B chain has 15 kinds of 30 amino acids, and a total of 16 kinds of 51 amino acids. Among them, the sulfhydryl groups in the four cysteines of A7 (Cys) -B7 (Cys) and A20 (Cys) -B19 (Cys) form two disulfide bonds, connecting the two chains of A and B. In addition, there is also a disulfide bond between A6 (Cys) and A11 (Cys) in the A chain.
Insulin secretion
The speed of insulin biosynthesis is affected by the plasma glucose concentration. When the blood glucose concentration increases, the proinsulin content in cells increases, and insulin synthesis accelerates.
Insulin is synthesized in islet beta cells. Insulin has a molecular weight of 5700 and consists of two amino acid peptide chains. The A chain has 21 amino acids and the B chain has 30 amino acids. There are two disulfide bonds between the AB chains.
Insulin is secreted into the blood in the same molecule as C peptide. In patients treated with insulin clinically, the presence of insulin antibodies in the serum affects the measurement of blood insulin levels by radioimmunoassay. In this case, the endogenous insulin secretion status can be understood by measuring the plasma C peptide level.
Influencing factors
The secretion of insulin in the body is mainly affected by the following factors:
Stimulate insulin secretion
Plasma glucose concentration is the most important factor affecting insulin secretion. After oral or intravenous glucose injection, insulin release has a two-phase response. In the early fast phase, the insulin in the portal vein plasma reached its highest value within 2 minutes and then fell rapidly; in the delayed slow phase, the plasma insulin level gradually increased again after 10 minutes and continued for more than 1 hour. The early fast phase shows that glucose promotes the release of stored insulin, and the delayed slow phase shows insulin synthesis and proinsulin transition.
Consumption of foods with more protein After eating foods with more protein, the concentration of amino acids in the blood increases and insulin secretion also increases. Arginine, lysine, leucine, and phenylalanine all have strong effects on stimulating insulin secretion.
Increase in gastrointestinal hormones after meals Increase in gastrointestinal hormones after meals can promote insulin secretion, such as gastrin, secretin, gastrin, and intestinal vasoactive peptides can stimulate insulin secretion.
Autonomic nerve state promotes insulin secretion when the vagus nerve is excited; it inhibits insulin secretion when the sympathetic nerve is excited.
Insulin receptor
Biological effects of insulin at the cellular level are initiated by binding to specific receptors on target cell membranes. Insulin receptors are specific sites on the target cell membrane where insulin acts, and can only bind to insulin or proinsulin containing insulin molecules. They are highly specific and widely distributed. Receptor is a kind of glycoprotein. Each receptor is composed of two subunits, and , and two subunits each form a tetrameric receptor. The alpha subunit penetrates the cell membrane, one end is exposed on the cell membrane surface, and has an insulin binding site. The subunit extends from the cell membrane to the cytoplasm and is a functional unit of insulin-induced cell membrane and intracellular effects. After insulin binds to the subunit, the tyrosine kinase in the subunit is activated, which phosphorylates the receptor, produces a mediator, regulates the activity of the enzyme system in the cell, and controls substance metabolism. And two subunits each form a tetrameric receptor. The degree of binding of each cell to insulin depends on the number of receptors and affinity, both of which are regulated by plasma insulin concentrations. When the insulin concentration increases, the number of insulin receptors often decreases, which is called down regulation. Such as obese non-insulin-dependent diabetic patients because of the decline in the number of receptors on the fat cell membrane, clinically insulin-insensitive, said resistance. When obese non-insulin-dependent diabetic patients lose weight after diet control and physical exercise, the number of insulin receptors on the fat cell membrane increases, and the binding force with insulin is strengthened to improve blood glucose utilization. This is not only an important pathogenesis of obese non-insulin-dependent diabetes mellitus, but also a theoretical basis for weight loss during treatment.
Insulin metabolism
Insulin is a protein hormone secreted by islet cells stimulated by endogenous or exogenous substances such as glucose, lactose, ribose, arginine, glucagon and the like.
The first secreted is a long-chain polypeptide consisting of 84 amino acids, proinsulin. The specific proteases, proinsulin-converting enzymes (PC1 and PC2) and carboxypeptide E, convert the intermediate portion of proinsulin ( (Chain C), and the carboxy-terminal portion (chain A) and amino-terminal portion (chain B) of the proinsulin are bound together by disulfide bonds to form insulin.
Mature insulin is stored in secretory vesicles within islet cells and exists as a hexamer coordinated with zinc ions. Under external stimuli, insulin is released into the blood with secretory vesicles and exerts its physiological role.
Insulin secretion is divided into two parts, one part helps to maintain normal fasting blood glucose and is called basal insulin, and the other part is to reduce postprandial blood sugar and maintain normal postprandial blood glucose. . The early-phase secretion of mealtime insulin controls the magnitude and duration of postprandial blood glucose elevation, and its main role is to inhibit endogenous glucose production in the liver. Through this mechanism of action, blood glucose is controlled to a level close to the fasting state at any time; the peak postprandial blood glucose is below 7.0 mmol / L, and the blood glucose level is higher than 5.5 mmol / L for less than 30 minutes. Prior to the diagnosis of type 1 diabetes, the majority of patients with islet cells undergo autoimmune destruction, leading to reduced mealtime and basal insulin secretion. In patients with type 2 diabetes, the islet -cell function progresses slowly and often manifests as peripheral insulin resistance, but there is also a decrease in insulin phase secretion, so normal fasting blood glucose and elevated postprandial blood glucose can occur. In the end, the postprandial blood glucose level can reach four times that of a non-diabetic physiological state, and the blood glucose rises for several hours after a meal, so that it still rises significantly before the next meal. Novoline R is an insulin preparation to make up for insufficient insulin secretion during meals, and Novoline is an insulin analog preparation. Basal insulin is insulin that is continuously pulsed and secreted by islet cells for 24 hours. It is mainly used to maintain normal fasting blood glucose levels. Both the American Diabetes Association (ADA) and the European Diabetes Association (EASD) guidelines recommend that, after lifestyle intervention and oral diabetes treatment, if glycemic control is still not satisfactory, insulin therapy should be started as soon as possible, and basal insulin and oral hypoglycemic drugs are preferred . If this therapy still does not control blood sugar, according to the treatment circuit diagram of this guideline, it is recommended to add fast-acting insulin during meals on this basis. At present, the preparations used to make up for the deficiency of basal insulin are mainly basal insulin analogues detemir and the like.
Insulin is degraded by Insulin Degrading Enzyme (IDE). Amylin and beta amyloid peptides are also substrates of IDE.
Insulin fibrosis: After a lot of clinical medicine and scientific research, amyloid fibrosis of insulin is closely related to type 2 diabetes.
Biological effects of insulin
Pharmacological action
Treatment of diabetes and wasting diseases. Promote blood glucose into liver cells, muscle cells, fat cells and other tissue cells to synthesize glycogen to reduce blood sugar, and promote the synthesis of fat and protein.
Physiological effect
The main physiological role of insulin is to regulate metabolic processes. For glucose metabolism: promote the uptake and utilization of glucose by tissue cells, promote glycogen synthesis, inhibit gluconeogenesis, and reduce blood sugar; for fat metabolism: promote fatty acid synthesis and fat storage, reduce lipolysis; for proteins: promote amino acids into cells Promote all aspects of protein synthesis to increase protein synthesis. The overall effect is to promote anabolic. Insulin is the only hormone in the body that lowers blood sugar, and the only hormone that simultaneously promotes glycogen, fat, and protein synthesis. The mechanism of action belongs to the receptor tyrosine kinase mechanism.
Regulation of glucose metabolism
Insulin can promote the uptake and utilization of glucose by tissue cells in the whole body, and inhibit the breakdown of glycogen and glycogenogenesis. Therefore, insulin can reduce blood sugar. When too much insulin is secreted, blood sugar drops rapidly, and brain tissues are most affected, and convulsions, coma, and even insulin shock can occur. Conversely, insufficient insulin secretion or lack of insulin receptors often lead to elevated blood glucose; if the renal glucose threshold is exceeded, sugar is excreted from the urine, causing diabetes; meanwhile, changes in blood components (containing excess glucose) also cause high blood pressure, Coronary heart disease and retinal vascular disease. Insulin lowering blood sugar is the result of multiple effects:
(1) Promote target cell cell membrane carriers in muscle, adipose tissue, etc. to transport glucose from blood into cells.
(2) Covalent modification enhances phosphodiesterase activity, reduces cAMP levels, and increases cGMP concentration, thereby increasing glycogen synthase activity, reducing phosphorylase activity, accelerating glycogen synthesis, and inhibiting glycogen decomposition.
(3) Pyruvate dehydrogenase is activated by activating pyruvate dehydrogenase phosphatase, which accelerates the oxidation of pyruvate to acetyl-CoA and accelerates the aerobic oxidation of sugar.
(4) Inhibition of gluconeogenesis by inhibiting the synthesis of PEP carboxykinase and reducing raw materials of gluconeogenesis.
(5) Inhibit hormone-sensitive lipase in adipose tissue, slow down fat mobilization, and increase tissue utilization of glucose.
Regulate fat metabolism
Insulin can promote the synthesis and storage of fat, reduce the free fatty acids in the blood, and inhibit the decomposition and oxidation of fat. Insulin deficiency can cause fat metabolism disorders, reduced fat storage, increased breakdown, and increased blood lipids, which can cause arteriosclerosis over time, leading to serious diseases of the cardiovascular and cerebrovascular diseases; at the same time, insulin deficiency can lead to increased fat breakdown in the body and generate large amounts of ketones. Body, ketoacidosis occurs.
Regulation of protein metabolism
On the one hand, insulin promotes the uptake of amino acids and protein synthesis by cells, and on the other hand inhibits the breakdown of proteins, which is conducive to growth. The growth-promoting protein synthesis effect of pituitary growth hormone must be present in the presence of insulin. Therefore, insulin is also an indispensable hormone for growth.
other functions
Insulin can promote the potassium and magnesium ions through the cell membrane into the cell; it can promote the synthesis of DNA, RNA and ATP.
Insulin antihormone
Glucagon
Anti-insulin hormones in the body are mainly glucagon, epinephrine and norepinephrine, adrenocortical hormone, growth hormone and so on. They can all raise blood sugar.
(1) Glucagon (glucagon). Secreted by islet alpha cells, it fights insulin in regulating blood glucose concentration. The main function of glucagon is to quickly decompose glycogen in the liver, and promote the production and output of glucose in the liver.
Enters the blood circulation to raise blood sugar levels. Glucagon can also enhance the uptake of amino acids by liver cells, and can promote lipolysis in extrahepatic tissues, increase glycerol input to the liver, and provide a large amount of gluconeogenic ingredients to enhance gluconeogenesis. Glucagon and insulin coordinate the homeostasis of blood glucose levels.
When eating carbohydrates, a large amount of glucose is produced, which stimulates the secretion of insulin. At the same time, the secretion of glucagon is inhibited, and the insulin / glucagon ratio is significantly increased. At this time, the liver changes from a glucose-producing tissue to glucose conversion. An organ that stores glycogen for glycogen.
When starved, the levels of glucagon in the blood increase significantly while insulin levels decrease. The gluconeogenesis and glycogen breakdown are accelerated, and the liver continuously sends glucose to the blood. At the same time, due to lower insulin levels, muscle and adipose tissue's ability to use glucose is reduced, mainly using fatty acids, thereby saving glucose to ensure that the brain and other tissues have sufficient glucose supply.
(2) Epinephrine and norepinephrine. Epinephrine is secreted by the adrenal medulla, and norepinephrine is a secretion of the sympathetic nerve endings. When the stress or cold stimulates the sympathetic nerves in an excited state, the secretion of adrenaline and norepinephrine increases, which increases the liver glycogen breakdown output, prevents glucose from entering muscle and adipose tissue cells, and raises blood sugar.
(3) Growth hormone and growth hormone inhibitory hormone.
growth hormone. It is secreted by the anterior pituitary gland, which can promote human growth and regulate material metabolism in the body. Growth hormone mainly inhibits the use of glucose by muscle and adipose tissue, and at the same time promotes gluconeogenesis and glycogen breakdown in the liver, thereby increasing blood sugar. Growth hormone can promote fat breakdown and increase plasma free fatty acids. When starvation is reduced, insulin secretion is reduced, and growth hormone secretion is increased. As a result, blood glucose use and fat use are reduced, and plasma glucose and free fatty acid content are increased.
growth hormone inhibitory hormone. Secreted by islet D cells. Growth hormone release inhibiting hormone not only inhibits the secretion of pituitary growth hormone, but also inhibits insulin and glucagon secretion under physiological conditions. However, the growth hormone release-inhibiting hormone itself has no direct effect on liver glucose production or glucose utilization in circulation.
(4) Adrenal glucocorticoids. Adrenal glucocorticoids are secreted by the adrenal cortex (mainly cortisol, that is, hydrocortisone), which can promote the breakdown of extrahepatic tissue proteins, increase the number of amino acids entering the liver, and induce various key enzymes related to gluconeogenesis. Synthetic, thus promoting gluconeogenesis and raising blood sugar.
(5) Free nerve function may affect insulin secretion.
Promote insulin secretion when the vagus nerve is excited; inhibit insulin secretion when the sympathetic nerve is excited. From the above, the DNA of the gene region is transcribed into mRNA, generating a long peptide chain consisting of 86 amino acids-Proinsulin. Proinsulin enters the Golgi apparatus with the microbubbles in the cytoplasm. After the action of proteolytic enzymes, the three arginine-linked chains 31, 32, and 60 are cut off, and the above results are obtained!
Insulin insulin therapy
Indication
In patients with type 1 diabetes, due to impaired -cell function of their own islets, insulin secretion is absolutely inadequate. Insulin therapy is required at the time of onset, and life-long insulin replacement therapy is required to sustain life. About 5% of the total number of people with diabetes. On the basis of lifestyle and oral hypoglycemic drug combination therapy, patients with type 2 diabetes can start combination therapy with oral drugs and insulin if their blood sugar has not reached the control target. In general, when HbA1c is still greater than 7.0% after a combination of large doses of multiple oral drugs, insulin therapy can be considered. Wasting patients with new onset and difficult to distinguish from type 1 diabetes. In the course of diabetes (including newly diagnosed type 2 diabetics), when there is no apparent cause of weight loss, insulin therapy should be used as soon as possible. For patients with first-onset type 2 diabetes with high blood glucose, it is difficult to achieve satisfactory control of blood glucose with oral drugs, and rapid relief of hyperglycemia toxicity can partially reduce insulin resistance and reverse -cell function. Therefore, newly diagnosed type 2 diabetes is associated with Intensive insulin therapy can be used when there is significant hyperglycemia. There are also some special cases where insulin treatment is also required: perioperative period; when severe acute complications or stress states occur, temporary use of insulin is needed to pass the dangerous period, such as diabetic ketoacidosis, hypertonic hyperglycemia, Lactic acidosis, infection, etc .; severe chronic complications such as diabetic foot, severe diabetic nephropathy, etc .; combined with some serious diseases, such as coronary heart disease, cerebrovascular disease, blood disease, liver disease, etc .; women with gestational diabetes and diabetes with pregnancy During pregnancy, before and after childbirth, and during lactation, if the blood sugar cannot be controlled by diet alone, the insulin therapy should be used and oral hypoglycemic drugs should be disabled. People with secondary and specific diabetes.
preparation
According to the source and chemical structure, insulin can be divided into: animal insulin, human insulin, insulin
analog. Human insulin Ru Nuo Ling series, insulin analogs Ru Nuo Rui, Nuo Rui 30, Nuo Heping. According to the characteristics of action time, it can be divided into: fast-acting insulin analogs, short-acting insulins, intermediate-acting insulins, long-acting insulins (including long-acting insulin analogs) and pre-mixed insulins (pre-mixed insulin analogs). Common fast-acting insulin analogs such as Novo Rui, a long-acting insulin analog such as Nuo Heping. Clinical trials have shown that insulin analogues are superior to human insulin in mimicking physiological insulin secretion and reducing the risk of hypoglycemia.
Insulin is classified by length of effect:
1. Ultra-short-term effect: 15 minutes after injection, peak concentration 1 ~ 2 hours.
2, short-acting (quick-acting): 30 minutes after injection, peak concentration of 2 to 4 hours, lasting 5 to 8 hours.
4. Long-acting (protamine zinc insulin): It takes effect 4 to 6 hours after injection, and the peak concentration is 4 to 20 hours, which lasts 24 to 36 hours.
5. Pre-mixing: short-term and medium-effects are pre-mixed, which can be injected once, and the effect is fast (30 minutes), and the duration is up to 16-20 hours.
30% short-acting and 70% medium-effect premixes are common in the market, and short- and medium-effect premixes each account for 50%.
Use attention
After starting insulin treatment, diet control and exercise should be continued, and patient education should be strengthened. Patients should be encouraged and instructed to monitor their own blood glucose in order to adjust insulin dosage and prevent hypoglycemia. All patients who begin insulin therapy should be educated about hypoglycemia risk factors, symptoms, and self-help measures.
The insulin treatment plan should mimic the pattern of physiological insulin secretion, including basal and meal insulin supplements. The choice of the plan should be highly individualized, and the blood glucose compliance should be controlled as soon as possible to achieve a stable blood glucose compliance.
Learn to observe yourself often by pressing the injection site for induration and pain with your fingers. In severe cases, you should consult a professional medical staff, and avoid these parts when giving injections. Those who inject insulin should prepare their own blood glucose meter to ensure that they can self-test their blood glucose every day, understand the blood glucose fluctuations, and record the results each time so that the doctor can adjust the insulin dosage during the review.
Adverse effects of injection overdose
If you inject too much insulin during treatment, it will lead to hypoglycemia. When the poisoning is mild, it mainly affects the autonomic nervous system, manifested as hunger, dizziness, paleness, weakness, and sweating, but also tremor, discomfort in the heart area, face and limbs Numbness and headache. When the blood sugar is further reduced, it affects the central nervous system, dysphonia, diplopia, muscle tremor, ataxia, and subsequent coma and convulsions of varying degrees. This state is called insulin shock, which can be fatal if not rescued in time. .
Instructions for injection site
Insulin injection is a "technology" that people with diabetes should master. In addition to injection, the choice of site is also critical, because a suitable injection site not only reduces the risk of injection, but also helps insulin absorption.
The abdomen is the part that should be selected first because the subcutaneous fat in the abdomen is thicker, which can reduce the risk of injection into the muscle layer. It is the easiest to pick up the abdominal skin, and it is also the fastest place to absorb insulin. It should be injected 3 to 4 fingers away from the sides of the belly button. The thinner the subcutaneous layer is, the easier it is to penetrate into the muscle layer. This area is most suitable for injection of short-acting insulin or mixed and mixed insulin.
In addition, the outer thigh, the upper quarter of the upper arm, and the buttocks are also suitable sites for insulin injection.
Outer thigh: Thigh injection can only be performed from the front or the outer side, and there are more blood vessels and nerves distributed on the inner side. It is not suitable for injection. When injecting the thigh, be sure to pinch the skin or use a super-fine, ultra-short (5 mm) pen needle.
The outer quarter of the upper arm: This is the most unsuitable site for self-injection, because the subcutaneous tissue of the upper arm is thin and easy to inject into the muscle layer: you cannot pick up the skin by yourself during self-injection. When the upper arm must be injected, it is recommended to use an ultra-fine and ultra-short pen needle (5 mm) or to assist the injection by medical staff and family members.
Buttocks: Buttocks are suitable for injecting medium- and long-acting insulin (such as medium-acting insulin injected before bedtime), because the subcutaneous layer of the buttocks is thick and the absorption of insulin is slow. There is no risk of intramuscular injection from the skin.
Storage method
Insulin must be stored in a refrigerator below 10 ° C. It can remain active for 2 to 3 years in a refrigerator at a temperature of 2 ° C to 8 ° C, even if the insulin has been partially pumped. When using, the temperature can be less than 30 and less than 2 , but it must avoid sunlight to prevent failure.
Insulin in use, just keep it in the shade of the room. Bottled insulin in open bottles can be stored in the refrigerator freezer for about 3 months. Do not put the insulin refill in the refrigerator with the insulin pen, but keep it for 4 weeks.
Cloudy insulin may form clumps if shaken for several hours or not properly stored, and insulin should be discarded.
1. Insulin should avoid high temperature and direct sunlight.
2. Insulin should be stored in the refrigerator at 2-8 ° C. Unopened insulin should be used before the expiration date.
3. The shelf life of the opened insulin placed in the refrigerator is generally 1 month, indicating the opening time.
4. Remember not to put insulin in the freezing layer of the refrigerator. Frozen insulin cannot be used, but can only be placed in the refrigerator.
5. Remove insulin from the refrigerator before injection and leave it for 20 minutes at room temperature before injection.
6. The injection pen with insulin refill installed, please do not store it in the refrigerator, just place it in a cool place.
7. When travelling by air, carry insulin with you. Do not put it in checked luggage.
Insulin insulin response
Systemic reaction
Hypoglycemia: Most common. More common in type medium fragile or type medium and heavy, especially those who are wasting. Generally due to too much physical activity, occasionally or too little diet, weight loss, lost time or excessive dose. Symptoms include hunger, dizziness, weakness, sweating, palpitations, and even neurological symptoms, such as disorientation, irritability, incoherent speech, and erratic crying. Sometimes it can be more serious, even fainting, convulsions, symptoms like epilepsy, and coma. And died. During the course of treatment, patients should be taught to be familiar with this reaction and be vigilant at any time. Eat pastry confectionery or sugar water as soon as possible to relieve it. The heavier person should immediately inject more than 40% 50% glucose intravenously, followed by intravenous infusion of 10% glucose water until awake. Inject glucagon first, 1 mg each time subcutaneously or muscularly. If the hypoglycemic response lasts longer and is more severe, hydrocortisone can be used. Intravenous injection of 100 to 300 mg in 5% to 10% glucose water. When the hypoglycemia response recovers, the next dose must be carefully estimated and the condition analyzed to prevent recurrence. After repeated hypoglycemia, reactive hyperglycemia (Somogyi effect) can occur due to stimulation of islet cells and adrenals, which often leads to fragile type, which must be avoided as much as possible.
Allergic reactions: A few patients have allergic reactions, such as urticaria, angioedema, purpura, and very rarely have anaphylactic shock. This reaction is largely due to impurities in the formulation. The lighter can be treated with antihistamines, and the severer must be replaced with a high-purity preparation such as one-component human insulin. Because its amino acid sequence is the same as that of endogenous insulin and contains few impurities, it is extremely rare to cause allergies. Switch to oral medicine. When necessary, a small dose of insulin can also be used to desensitize subcutaneous injection.
(3) Insulin edema: Water loss and sodium loss often occur before diabetes is not controlled, and glucose is reduced in cells. Sodium retention and edema may occur 4 to 6 days after control, which may be related to insulin's promotion of renal tubular reabsorption of sodium, which is called insulin edema. .
Refractive errors: Sometimes patients feel blurred vision during insulin treatment. Due to the rapid drop in blood glucose during treatment, the osmotic pressure of the lens and the vitreous body is affected, the water in the lens escapes and the refractive index decreases, and hyperopia occurs. However, this is a temporary change, and usually disappears quickly as the blood glucose concentration returns to normal, without permanent changes. This kind of refractive mutation is more common in young patients with large blood sugar fluctuations.
Local reaction
Injection of local skin swelling, fever, and subcutaneous nodules occurred more often within a few weeks of the initial treatment of NPH or PZI. Due to the inclusion of protein and other impurities, it can disappear by itself after changing the attention site without affecting the efficacy.
Subcutaneous fat atrophy or hyperplasia, fat atrophy into depressed sebum loss, more common in young women and children's thighs, abdominal wall and other injection sites; subcutaneous tissue increased to form hard masses, more common in male hips and other injection sites, sometimes numb, tingling, can affect Absorption, the injection site must be replaced to ensure treatment.
Drug resistance
Very few patients have insulin resistance. The daily insulin requirement exceeds 200U for more than 48 hours. At the same time, those without secondary ketoacidosis and other endocrine diseases are called insulin resistance. This group does not include resistance caused by obesity, infection, liver disease, hemochromatosis, leukemia, rheumatoid arthritis, atrophic diabetes, etc. Immune response, due to the production of anti-insulin antibodies in the blood after insulin injection, generally belongs to the IgG class, especially bovine insulin is easy to produce. Therefore, insulin resistance here should not be confused with insulin resistance in pathophysiology.
Treatment plan:
Switching to single-component human insulin can significantly reduce antibody production and relieve drug resistance;
Try to switch to oral anti-diabetic drugs and their mutual combination;
In patients with significantly increased antibody concentration, try prednisone if necessary, 30mg 40mg / d, divided into 3 times. Most of them can also significantly reduce the insulin dose within 1 to 2 weeks, and gradually decrease after the effect, stop prednisone. During the course of treatment, the condition and blood glucose must be closely monitored to avoid repeated severe hypoglycemia when the resistance subsides.
Insulin treatment of nephropathy can only be said to be hypoglycemic. When patients use it, they must always check their blood glucose. Once hypoglycemia is found, insulin dosage should be adjusted in time.
Insulin medical examination
Insulin test name
insulin
Insulin classification
Hormone determination> Pancreatic endocrine function test
Principle of insulin measurement
RIA method: using non-equilibrium analysis method. First, the insulin anti-antibody and the unlabeled insulin (ie, the test sample or the standard) are fully reacted to form an insulin and insulin anti-antibody complex. The remaining unbound insulin anti-antibody reacts with I-insulin to form a complex of I-insulin and insulin anti-antibody. The free and bound fractions were separated with a secondary antibody, and the radioactivity of the precipitated fraction (B) was measured. According to the insulin standard curve, the insulin concentration in the serum sample can be found.
Insulin reagent
(1) I-insulin: add 10ml distilled water to each bottle when using.
(2) Insulin standard: 7 bottles of lyophilized powder, each bottle is fully dissolved by adding 1ml of distilled water, the concentration is 0, 5, 10, 20, 40, 80 and 160mIU / L.
(3) Anti-insulin anti-antibody: Dissolve in 10ml of distilled water, mix thoroughly and use.
Insulin method
Operate according to Table 1.
Thoroughly mix, let stand at 4 ° C for 20min, centrifuge at 2000g for 20min, discard the supernatant, and measure the radioactivity of the precipitate.
Normal insulin
5-20 U / ml.
Clinical significance of insulin test results
(1) Patients with type 1 diabetes are mostly below 5 U / ml, and plasma islet insulin levels in patients with type 2 diabetes may be normal, low, or higher than normal. Significant increase was hyperinsulinemia, suggesting insulin resistance. Plasma islet insulin concentration was measured at the same time as OGTT, and islet -cell function was understood to identify type 1 diabetes and type 2 diabetes. After fasting and glucose stimulation, insulin levels in patients with type 1 diabetes are low and show a low-level curve. In patients with type 2 diabetes, the peak of insulin secretion may be delayed or increased, and the first phase of insulin secretion may be reduced or absent. Compared to blood glucose levels, insulin secretion is low. The serum C-peptide can also be determined at the same time for identification.
(2) Decreased insulin in plasma islets can also be seen in secondary diabetes and islet B cell tumors, extrapancreatic tumors caused by pheochromocytoma, somatostatinoma, hyperaldosteronism, and primary hypoparathyroidism. , Hypoglycemia due to adrenal insufficiency and hypopituitarism.
(3) Most patients with syndrome X have obesity, hyperlipidemia, hypertension, and hyperinsulinemia.
Insulin note
Most of the insulin secreted from pancreatic cells is inactivated in the liver and kidneys, of which about 40% to 50% is inactivated through the portal vein into the liver. Therefore, liver and kidney function status, especially liver function, is an important factor affecting the insulin content in circulating blood. ; After using insulin, especially animal insulin, diabetic patients often produce insulin anti-antibodies in the body. Because insulin and insulin anti-antibodies can produce a high immune response, it can affect the determination of plasma islet insulin. In addition, the levels of proinsulin and preproinsulin in the blood and endocrine system diseases such as anterior pituitary, adrenal cortex, hyperthyroidism, thiazide diuretics, glucocorticoids and other drugs, as well as infection, fever, surgery and other stress states Is a common factor affecting insulin measurement.
Insulin- related diseases
Type 1 diabetes, diabetes, type 2 diabetes, pheochromocytoma, hypoparathyroidism, hypoglycemia, syndrome X, hyperlipidemia [2]
Insulin Pharmacopoeia Standard
Insulin source content
This strain is a peptide substance with hypoglycemic effect prepared from pig pancreas. Calculated on a dry basis, the potency per 1mg must not be less than 27 units.
Each unit is equivalent to 0.0345mg of insulin.
Insulin requirements
This product should be extracted from frozen pancreas of quarantine qualified pigs. The production process should meet the requirements of the current edition of the Good Manufacturing Practice for Drugs.
Insulin traits
This product is white or off-white crystalline powder.
This product is almost insoluble in water and ethanol; easily soluble in inorganic acid or sodium hydroxide solution.
Insulin identification
(1) In the chromatogram recorded under the content determination item, the retention time of the main peak of the test solution should be consistent with the retention time of the main peak of the reference solution.
(2) Take an appropriate amount of this product, use 0.1% trifluoroacetic acid solution to make a solution containing 10 mg per 1 ml, take 20 l, add 0.2 mol / L trimethylolaminomethane-hydrochloric acid buffer solution (pH 7.3) 20 l of% V8 enzyme solution and 140 l of water were mixed, and placed in a water bath at 37 ° C. for 2 hours, 3 l of phosphoric acid was added as a test solution; another appropriate amount of an insulin reference was prepared in the same manner as a reference solution. According to the chromatographic conditions under the content determination, 0.2mol / L sulfate buffer (pH 2.3)-acetonitrile (90:10) as the mobile phase A, acetonitrile-water (50:50) as the mobile phase B, according to the table below Perform a gradient elution. Take 25l each of the reference solution and the test solution, and inject them into the liquid chromatograph respectively to record the chromatogram. The peptide map of the test solution should be consistent with the peptide map of the reference solution.
| Time (minutes) | Mobile phase A (%) | Mobile phase B (%) |
| 0 | 90 | 10 |
| 60 | 55 | 45 |
| 70 | 55 | 45 |
Insulin test
Related protein
Take an appropriate amount of this product, and use 0.01mol / L hydrochloric acid solution to make a solution containing about 3.5mg per 1ml, as a test solution (provisional new, store below 10 ). According to the chromatographic conditions under the content determination, the 0.2 mol / L sulfate buffer (pH 2.3)-acetonitrile (82; 18) under the content determination is used as the mobile phase A, and the acetonitrile-water (50:50) is used as the mobile phase B Use the following table for gradient elution. The flow rate was adjusted so that the retention time of the insulin peak was about 25 minutes. 20l of the test solution was injected into the liquid chromatograph, and the chromatogram was recorded. According to the bee area normalization method, the A21 deaminated insulin should not be greater than 5.0%, and other related proteins should not be greater than 5.0%.
| Time (minutes) | Mobile phase A (%) | Mobile phase B (%) |
| 0 | 78 | twenty two |
| 36 | 78 | twenty two |
| 61 | 33 | 67 |
| 67 | 33 | 67 |
High molecular protein
Take an appropriate amount of this product and use 0.01mol / L hydrochloric acid solution to make a solution containing about 4mg per 1ml as the test solution. It was tested by molecular exclusion chromatography (Appendix VH of the second part of the Pharmacopoeia, 2010 edition). A hydrophilic modified silica gel was used as a filler (3-10 m); glacial acetic acid-acetonitrile-0.1% arginine solution (15:20:65) was used as a mobile phase; the flow rate was 0.5 ml per minute; and the detection wavelength was 276 nm. Take the insulin monomer-dimer reference substance (or take an appropriate amount of insulin and leave it at 60 ° C overnight), use 0.01mol / L hydrochloric acid solution to make a solution containing about 4mg per 1ml, and take 100l into the liquid chromatograph. Insulin The resolution of the monomer peak and the dimer peak should meet the requirements. Take 100l of the test solution, inject it into the liquid chromatograph, and record the chromatogram. Excluding other peak areas with retention times greater than the insulin peak, the peak area normalization method was used to calculate the peak area retention time less than the sum of all peak areas of the insulin peak.
Loss on drying
Take about 0.2g of this product, weigh it accurately, and dry it at 105 to constant weight, and the weight loss shall not exceed 10.0% (Appendix L of the second edition of the Pharmacopoeia of the 2010 edition).
Zinc
Take an appropriate amount of this product, accurately weigh, add 0.01mol / L hydrochloric acid solution to dissolve and quantitatively dilute to make a solution containing about 0.1mg per 1ml, as the test solution. In addition, accurately measure the appropriate amount of zinc single element standard solution (1000 g of zinc per 1 ml), and quantitatively dilute it with 0.01 mol / L hydrochloric acid solution to make 0.20 g, 0.40 g, 0.80 g, 1.00 g, and 1.20 g of zinc per 1 ml. Zinc standard solution. According to the atomic absorption spectrophotometry (the first method of Appendix IVD of the Pharmacopoeia of the 2010 edition), the absorbance was measured at a wavelength of 213.9 nm. Calculated on dry basis, the zinc content must not exceed 1.0%.
Bacterial endotoxin
Take this product, add 0.01mol / L hydrochloric acid solution to dissolve and dilute it to make a solution containing 5mg per 1ml, check according to law (Appendix E of the second edition of the Pharmacopoeia of 2010 Edition), and the amount of endotoxin in each 1mg of insulin should be less than 10EU.
Microbial Limit
Take 0.2g of this product and check it according to law (Appendix J of Part Two of the Pharmacopoeia of 2010 Edition). The number of bacteria per 1g must not exceed 300cfu.
Biological activity
Take an appropriate amount of this product and test it according to the insulin bioassay method (Appendix G of the second edition of the Pharmacopoeia 2010). The number of experimental animals in each group can be halved during the experiment. The experiment is designed randomly. V) Calculate the titer by random design method of medium-response parallel line measurement. The titer per 1 mg shall not be less than 15 units.
Determination of insulin content
It was determined by high performance liquid chromatography (Annex V D of Part Two of the Pharmacopoeia, 2010 Edition).
Chromatographic conditions and system suitability tests
Use octadecylsilane bonded silica as a filler (5 ~ 10m); use 0.2mol / L sulfate buffer solution (take 28.4g of anhydrous sodium sulfate, dissolve in water, add 2.7ml of phosphoric acid, and adjust the pH value with ethanolamine 2.3, add water to 1000ml)-acetonitrile (74:26) is the mobile phase; the column temperature is 40 ° C; the detection wavelength is 214nm. Take 20l of the system suitability test solution (take the islet cord reference product, use 0.01mol / L hydrochloric acid solution to make a solution containing about 40 units per 1ml, and leave at room temperature for at least 24 hours), inject the liquid chromatograph, and record the chromatogram The resolution between the insulin peak and the A21 deaminated insulin peak (the relative retention time with the insulin peak is about 1.2) should be no less than 1.8, and the tailing factor should be no more than 1.8.
Assay
Take an appropriate amount of this product, accurately weigh it, add 0.01mol / L hydrochloric acid solution to dissolve and quantitatively dilute it to make a solution containing about 40 units per 1ml (temporarily new, stored at 2 4 , use within 48 hours). Precisely measure 20l into the liquid chromatograph and record the chromatogram; take another appropriate amount of insulin reference and measure it in the same way. Calculate the sum of the area of the insulin peak and the area of the A21 deaminated insulin peak according to the external standard method to obtain [3] .
Insulin category
Hypoglycemic drugs.
Insulin storage
Shaded, sealed and stored below -15 ° C.
Insulin preparation
(1) Neutral insulin injection (2) Protamine zinc insulin injection
Insulin medication instructions
Pharmacological action of insulin
Promote blood glucose into liver cells, muscle cells, fat cells and other tissue cells to synthesize glycogen to reduce blood sugar, and promote the synthesis of fat and protein.
Insulin indication
Mainly used for diabetes, especially insulin-dependent diabetes:
1. Heavy, wasted, and malnourished;
2. Light and medium-sized patients who have failed treatment with diet and oral hypoglycemic drugs;
3. Combining severe metabolic disorders (such as ketoacidosis, hypertonic coma or lactic acidosis), severe infections, wasting diseases (such as tuberculosis, liver cirrhosis) and progressive retinal, renal, neurological and other diseases and acute myocardium Infarction, cerebrovascular accident;
4. Combined pregnancy, childbirth and major surgery. It can also be used to correct intracellular potassium deficiency.
Adverse insulin reaction
1. Most allergic reactions are caused by the use of bovine insulin, which can produce corresponding antibodies such as IgE and cause allergic reactions after entering the human body as alloproteins. The general reaction is mild and short-lived, occasionally causing anaphylactic shock. Can be replaced by porcine insulin, because it is closer to human insulin.
2. Hypoglycemia is caused by insulin overdose. Regular insulin can quickly reduce blood sugar, and symptoms such as hunger, sweating, rapid heartbeat, anxiety, tremor, etc. In severe cases, coma, convulsions and shock, and even brain damage and death may occur. Long-acting insulin has a slow blood glucose lowering effect, does not appear the above symptoms, and mainly manifests as headache, mental and emotional, and dyskinesia.
To prevent the serious consequences of hypoglycemia, patients should be taught to react well so that they can be detected and eaten early, or drink sugar water. In severe cases, 50% glucose should be injected immediately. Hypoglycemic coma and ketoacid toxic coma must be distinguished from non-ketogenic diabetic coma in diabetes.
3. Acute tolerance due to insulin resistance is often caused by stress states such as infection, trauma, surgery, and emotional stress. At this time, when the amount of anti-insulin in the blood increases or due to ketoacidosis, the presence of a large amount of free fatty acids and ketone bodies in the blood prevents the uptake and utilization of glucose. When acute tolerance occurs, insulin doses need to be increased by several thousand units for a short period of time. The causes of chronic tolerance are more complex (referring to those who require more than 200 U of insulin daily without complications). It may be that anti-insulin receptor antibody (AIRA) is produced in the body, and immunosuppressive agents can be used to control the symptoms, which can restore the patient's sensitivity to insulin. It may also be a change in the number of insulin receptors, such as in the case of hyperinsulinemia. , The number of insulin receptors on the target cell membrane is reduced; it may also be that the glucose transport system on the target cell membrane is abnormal. At this time, it is often effective to switch to other animal insulins or to use high-purity insulin and adjust the dosage appropriately. [2]
Insulin dosage usage
It is usually injected subcutaneously, 3 to 4 times a day. Use the most before breakfast. It is followed by lunch, before dinner, and the least amount before supper. Sometimes intramuscularly. Intravenous injections are used only in emergencies such as diabetic coma. Because the patient's insulin requirements are affected by factors such as dietary calories and ingredients, severity and stability, weight gain, physical activity intensity, number and affinity of insulin antibodies and receptors, the dosage used should be individualized. The dose can be determined according to the patient's urine sugar. Generally, one unit is injected for every 2 to 4 g of sugar in the 24-hour urine. People with medium diabetes need about 5 to 40 units per day and inject 30 minutes before each meal (to avoid hypoglycemia after administration). The dosage for heavier patients is above 40 units. For diabetic coma, the dosage is about 100 units, intravenously with glucose (50 ~ 100g). In addition, a small amount (5 to 10 units) can still be used for malnutrition, weight loss, vomiting in refractory pregnancy, and early cirrhosis (simultaneous injection of glucose).
Insulin considerations
1. Insulin excess can make blood sugar too low. Symptoms depend on the degree and speed of blood glucose reduction. Hunger, anxiety, increased pulse, dilated pupils, anxiety, dizziness, ataxia, tremor, coma, and even convulsions can occur. Edible sugar must be given in a timely manner. When hypoglycemia occurs, 50 ml of a 50% glucose solution is injected intravenously. If necessary, intravenously drip 5% glucose solution. Note that hypoglycemic coma must be distinguished from severe ketolipidemia. Sometimes rebound hyperglycemia occurs after hypoglycemia, the somogyi response. If urine glucose is negative before bedtime, and urine glucose is positive in the next morning, refer to the dosage of insulin. It should be considered that there may be hypoglycemia at night. At this time, you should try to reduce the insulin dose, and do not increase the insulin dose.
2. In order to prevent a sudden drop in blood sugar and a loss of consciousness when it is too late to call for help, each patient should keep a card with his illness and insulin usage, so that he can be rescued in time.
3. The injection site may have local reactions such as skin redness, subcutaneous nodules and subcutaneous fat atrophy. Therefore, the injection site needs to be changed frequently.
4. A few may occur urticaria, etc., occasionally anaphylactic shock (adrenaline can be used to rescue).
5. Very few patients can develop insulin resistance: that is, in the absence of ketoacidosis, the daily dosage of insulin is more than 200 units. The main reason may be infection, the use of corticosteroids, or the presence of insulin antibodies in the body, which can bind to insulin. At this time, you can change the preparation of different animal species or take oral hypoglycemic drugs.
6. Patients with hypoglycemia, cirrhosis, hemolytic jaundice, pancreatitis, nephritis, etc. should not be used.
7. Injections often contain preservatives, which are generally not suitable for intravenous injection. Intravenous injections should be used in ampoule insulin preparations.
Insulin drug interactions
1. Drugs that enhance its effect: oral anticoagulants, salicylates, sulfa drugs, methotrexate, etc. can compete with insulin for plasma proteins and increase free insulin in the blood; oral hypoglycemic drugs have synergy with insulin Effect; the use of anabolic hormones can reduce the amount of glucose sweetness and enhance the effect of insulin; ethanol, chloramphenicol and other reportedly can strengthen the effect of insulin.
2. Drugs that antagonize its effects: adrenocortical hormones, thyroid hormones, growth hormones, etc. can raise blood sugar, and when combined, they can counter the hypoglycemic effect of insulin, thiazide diuretics, oral contraceptives and niacin derivatives, which are also said to be It can reduce the hypoglycemic effect of insulin. Beta blockers can block the adrenaline-raising blood glucose response and interfere with the body's regulation of blood glucose function. When combined with insulin, pay attention to adjusting the dose, otherwise it may cause hypoglycemia [2] .
Insulin poisoning
Insulin is a polypeptide hormone extracted from the pancreas of domestic animals. According to its production source, insulin can be divided into four types: animal insulin, semi-synthetic human insulin, DNA recombinant biosynthetic human insulin, and insulin analogues. There are five types of effects: short-acting, short-acting, medium-effect, long-acting, and ultra-long-acting. In addition, there are ultra-short and medium-effect premixed insulins. It is mainly used to treat diabetes, especially insulin-dependent diabetes. It is also used in cases with severe metabolic disorders, pregnancy, childbirth and major surgery.
Insulin is a hormone secreted by the islet cells, which can accelerate the anaerobic hydrolysis and aerobic oxidation of glucose, promote glycogen synthesis, inhibit glycogen decomposition and gluconeogenesis, increase the use of glucose and reduce the production of glucose, thereby reducing blood sugar. Clinically, in the following cases, the injection dose is too large or the diet is unbalanced; after the application of low-purity insulin to high-purity insulin, the dose is not appropriately reduced; combined with severe liver and kidney disease, pituitary and thyroid hypofunction; combined use of anticoagulant and water Salicylate, sulfa, methotrexate and other drugs. After the human body has received multiple insulin injections for about one month, insulin antibodies can appear in its circulation, which can cause local or systemic allergic reactions. Repeated injections of insulin at the same site over a long period of time may cause atrophy or hypertrophy of local adipose tissue. Insulin can also cause increased sodium reabsorption and water and sodium retention, leading to edema. During the treatment of diabetes, when blood glucose drops rapidly, it affects the osmotic pressure of the lens and the vitreous body, causes the water in the lens to overflow and reduces the refractive index, leading to hyperopia.
Clinical manifestation
Hypoglycemic response
Symptoms of sympathetic nervous system excitement may occur, such as intense hunger, heavy sweating, trembling, palpitations, anxiety, weakness, pale faces, etc .; severe hypoglycemia symptoms, when the cerebral cortex is involved, manifested as inattention, dizziness , Drowsiness, dullness, visual impairment, unstable gait, may also have hallucinations such as hallucinations, agitation, and strange behaviors. When the subcortical center, midbrain, and medulla are involved, unconsciousness and dance-like movements may occur. Even tonicity, clonic spasm, positive cone tract signs, even coma, and decreased blood pressure; if the condition is severe and lasts for a long time, the brain cells are irreversibly damaged, showing certain characteristics of the cerebral cortex, leaving personality changes, dementia And other symptoms. The elderly, especially those with a long history of diabetes or a history of insulin injections, often lack the typical symptoms of hypoglycemia, and once hypoglycemia occurs, they appear unconscious. Hypoglycemia in neonates and infants is mainly convulsive.
2. Allergic reactions
Rarely, redness, swelling, burning sensation, itching may occur locally, and systemic reactions may include urticaria, nausea, vomiting, diarrhea, angioedema, asthma, and occasionally anaphylactic shock.
3. Edema
Mild edema may occur at the beginning of treatment, and a few may be generalized edema.
4. Skin
Redness at the injection site, subcutaneous nodules and subcutaneous fat atrophy or hypertrophy.
5. Visual impairment
Some patients have refractive errors that can cause blurred vision.
Laboratory inspection
Blood tests can prove poison. The blood glucose was lower than 2.8mmol / L during the onset of hypoglycemia.
diagnosis
The main points of diagnosis of insulin poisoning are:
1. A history of insulin injection.
2. Clinical manifestations
(1) Hypoglycemia: symptomatic hyperexcitation may occur, and severe hypoglycemia may occur. Blood glucose was below 2.8mmol / L at the onset.
(2) Allergic reactions: local reactions such as redness and swelling, and / or systemic reactions such as urticaria, angioedema, and asthma, with occasional anaphylactic shock.
(3) Edema: Mild edema and / or systemic edema.
(4) Subcutaneous nodules and subcutaneous fat atrophy or hypertrophy appear on the skin at the injection site.
(5) Some patients have blurred vision.
3. Drug analysis Check for poisons in blood.
treatment
The main points of treatment for insulin poisoning are:
1. Treatment of hypoglycemia
Light people eat sweets, syrup and other foods, you can ease. In severe cases, 60% to 100ml of 50% glucose injection must be injected intravenously, and then 5% to 10% glucose injection is continuously infused. Those whose blood sugar cannot reach the standard or who is unconscious can be injected subcutaneously with glucagon 0.5 1mg. Those with unconsciousness are mostly cerebral edema and can be injected intravenously with mannitol and glucocorticoids. For those who are injected with long-acting insulin, they must be closely observed for several days to prevent repeated hypoglycemia.
2. Treatment of allergic reactions
For local responders, most do not need to take special treatment, and they can subside naturally. If it persists, you can change the type of insulin preparation, use antihistamines or glucocorticoids, and desensitization therapy. Patients with severe allergic reactions must stop or temporarily discontinue insulin therapy.
3. Treatment of insulin edema
Patients with mild symptoms can resolve naturally, and those with severe or congestive heart failure should be treated symptomatically.
4. Local fat atrophy or hypertrophy
Because insulin is injected at the same site for a long time, it can recover slowly and naturally after stopping injection at the site of injection. To prevent this, the site of injection should be changed frequently. Refractive errors are mostly temporary changes and often recover naturally within a few weeks [4] .
Insulin specifications
Injection: 400 units (10ml), 800 units (10ml) per bottle. Needle (powder): 50u, 100u, 400u.
