What is the difference between insulin degludec, insulin detemir and insulin glargine?👌👌👌

Among the hypoglycemic drugs, insulin is the most effective one. When the pancreatic function of diabetic patients is severely deteriorated, oral hypoglycemic drugs are contraindicated or the treatment effect is not good, insulin will become a very important therapeutic drug. Among the long-acting insulins, insulin degludec, insulin detemir and insulin glargine are the most commonly used clinically. What is the difference between them?

What types of insulin are commonly used?

Commonly used insulin can generally be divided into recombinant human insulin and human insulin analogs.

• Recombinant human insulin: Protamine recombinant human insulin. It is an intermediate-acting insulin.
• Human insulin analogs: Short-acting human insulin analogs include insulin aspart, insulin lispro, and insulin glulisine. Long-acting human insulin analogs are insulin degludec, insulin detemir and insulin glargine. 

Recombinant human insulin, insulin degludec and insulin detemir formulations are generally valid for 30 months. Insulin glargine preparations are generally valid for 36 months. This is because the A chain of human insulin contains 21 amino acid residues and the B chain contains 30 amino acid residues. Insulin glargine replaces the acid-sensitive asparagine with glycine at position 21 of the A chain. Glycine has a neutral charge. It will be more stable in an acidic environment. Insulin should be sealed and refrigerated at 2 to 8°C before first use. It is sufficient to store insulin at room temperature and it can be stored for up to 8 weeks after first use.

What is the difference in the duration of their action?

In the body, the half-life of insulin is only about a few minutes. The subcutaneous absorption rate is the main factor affecting the duration of insulin action.

	A chain	B chain
Human insulin	Aspartic acid. (21st)	Lysine. (29th) Threonine. (30th)
Insulin degludec	Aspartic acid. (21st)	Lysine. (29th) Glutamate. (30th) 16 carbon fatty diacids.
Insulin detemir	Aspartic acid. (21st)	Lysine. (29th) 14 carbon fatty diacids. (30th)
Insulin glargine	Glycine. (21st)	Lysine. (29th) Threonine. (30th) Arginine. Arginine.

Insulin degludec: The threonine at the end of its B chain has been removed. Instead, a glutamate is attached to the lysine at 29th and a 16-carbon fatty diacid is linked to glutamate. When insulin degludec is injected subcutaneously, it forms stable polyhexamers and continuously releases insulin monomers over an extended period of time. Insulin degludec reversibly binds to albumin after entering the blood. Its protein binding rate is greater than 99%. This can further extend the time to reach the target tissue. The duration of action of insulin degludec is greater than 42 hours.

Insulin detemir: The threonine at the end of its B chain has been removed and a 14-carbon fatty diacid is attached to the lysine at 29th. Insulin detemir formed double hexamers after subcutaneous injection and sustained the release of insulin monomers over an extended period of time. Its duration of action is approximately 16 to 24 hours.

Insulin glargine: It is the addition of two arginines to the end of the B chain of insulin. It changes the isoelectric point of insulin from pH 5.4 to pH 6.7. They form fine precipitates when injected subcutaneously (pH about 7.4). These microprecipitates can sustain the release of insulin monomers for about 30 hours.

What is the difference in the frequency of their use?

The absorption of insulin degludec, insulin detemir, and insulin glargine is smooth and slow. Therefore, they can only be used as basal insulin drugs to lower fasting blood sugar.

	Insulin degludec	Insulin detemir	Insulin glargine
Recommended usage	Administer 1 time a day. It can be administered at any time throughout the day. However, it is best to maintain the same dosing time each day.	Administer 1 to 2 times a day. If administered twice daily, the second dose can be optionally given at dinner, before bedtime or 12 hours after the morning injection.	Administer 1 time a day. It can be administered at any time throughout the day. However, it must maintain the same dosing time each day.
Protein binding rate	>99%	>90%	Unknown
Duration of action	>42 hours	16 to 24 hours	30 hours

What is the difference in their indications?

Their indications will vary slightly.

	Type 1 diabetes	Type 2 diabetes	Gestational diabetes	Diabetes in children
Neutral protamine zinc insulin	✓	✓	✓	✓
Insulin degludec	✓	✓	-	≥6 years old
Insulin detemir	✓	✓	It can be considered for use.	≥6 years old
Insulin glargine	-	✓	-	-

What is the difference between their adverse reactions?

All insulin drugs can cause fatal hypoglycemia. However, insulin degludec has a longer duration of action (>42 hours) and tends to have no peaks, so it has a lower risk of overall hypoglycemia and nocturnal hypoglycemia.

Because insulin increases fat and protein synthesis, it can cause weight gain. However, some studies have pointed out that although insulin detemir has a similar hypoglycemic effect as insulin glargine, it is less likely to cause weight gain.

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What is heat apoplexy and its medical treatment?🌞🌞🌞

Summer is coming, and there have been hot weather in many places around the world recently. Some people even died of heat. In fact, hot weather has caused far more deaths around the world than many other natural disasters. With the recent hot weather, there have been news reports of people diagnosed with heat apoplexy and deaths. So what exactly is heat apoplexy? How should it be treated and what treatments are available?

What is heat apoplexy?

Heat apoplexy is a very severe form of heat stroke. It is caused by the body's thermoregulatory function being impaired by the high temperature and high humidity environment. The human body dissipates heat less than it produces heat. Its core temperature can quickly rise above 40oC. It will be accompanied by severe acute heat-induced diseases such as disturbance of consciousness, burning skin, disturbance of multiple organ functions (such as cardiovascular function, coagulation function, respiratory function, etc.) and even failure. The most dangerous type of heatstroke is heat apoplexy. Its fatality rate can be as high as 21 to 63%.

What are the types of heat apoplexy?

Classic heat apoplexy is more common in the following groups of people:

• Children, infants, elderly people over 70 years old and other people with poor thermoregulation function.
• Mental disorders, physical disabilities and other reasons make it impossible to leave the high temperature environment, replenish water or cool down in time.
• People with neurological diseases, anhidrosis, obesity, cardiovascular diseases and other diseases.
• Traffic police, sanitation workers and other people who need to work in a high temperature and high humidity environment for a long time.

Exertional heat apoplexy is more common in healthy young people who engage in high-intensity activities when the temperature and humidity are high.

How is heat apoplexy treated?

The treatment of heat apoplexy should take the following measures as early as possible:

1. Cool down.
2. Expand blood volume.
3. Blood purification.
4. Calm down.
5. Tracheal intubation.
6. Anticoagulation.
7. Anti-inflammatory.
8. Enteral nutrition.
9. Dehydration prevents edema.
10. Immunomodulatory.

In addition, patients are prohibited from surgery during the coagulation disorder.

The main treatment for heat apoplexy patients is rapid, effective and sustained cooling. Common cooling methods can use ice water bath, hypothermic blanket, ice water therapy and so on. Cold water immersion therapy is an efficient, non-invasive and rapid cooling method. It is often used in younger patients. However, it affects venous circulation and increases mortality in elderly patients, so elderly patients generally do not use this therapy.

Patients with heat apoplexy should not use large amounts of alcohol rubbing their body to cool down. Because when a patient has heat apoplexy, the blood vessels in their skin dilate. At this time, if a large amount of alcohol is used on the epidermis to cool down, the alcohol will be absorbed into the blood through the skin blood vessels and become toxic. Therefore, patients with heat apoplexy are prohibited from using large amounts of alcohol to cool down.

What are the medicines for heat apoplexy treatment?

Infusion: It is commonly used for intravenous infusion of Ringer's injection or 0.9% saline. However, the patient's urine output, cardiorespiratory function, and blood volume status should be assessed before fluid infusion, followed by rapid fluid resuscitation. Patients should avoid fluid overload conditions. In addition, patients should avoid large infusion of glucose injection in the early stage. It can cause a patient's blood sodium to drop rapidly over a short period of time. It can make nerve damage worse.

α-receptor agonists: Vasopressors such as epinephrine or norepinephrine may be infused in shock patients who are poorly resuscitated by infusion. However, α-receptor agonists also constrict the blood vessels of the skin and make external cooling measures less effective. Therefore, patients should try to avoid using them.

Sedatives: Cooling measures may cause shiver in the patient. The shivering process can exacerbate the condition by increasing the patient's endogenous heat production. Therefore, short-acting benzodiazepines such as lorazepam and midazolam may be recommended for intravenous administration during cooling measures to prevent or control shiver. The patient's core body cooling process can also be improved by benzodiazepines. Chlorpromazine may be considered if benzodiazepines are ineffective. However, the anticholinergic effects of chlorpromazine may induce or exacerbate the hypotensive complications of heat apoplexy.

Treatment of complications of heat apoplexy: Patients with heat apoplexy may develop respiratory dysfunction, hypotension, cerebral edema, cardiac insufficiency, electrolyte abnormalities and other related complications. Patients with these symptoms should be treated with corresponding drugs or other treatment methods.

Antipyretic and analgesic drugs are contraindicated: Drugs such as aspirin, acetaminophen, and ibuprofen have no effect on the hyperthermic state of patients with heat apoplexy. The cooling mechanism of antipyretic analgesics is by inhibiting the production of prostaglandins in the hypothalamus, so that the set point that regulates the central body temperature is down-regulated. However, the thermoset point in heat apoplexy patients did not change, so there was no efficacy. In addition, the common adverse reactions of antipyretic analgesics are the same as the common complications of heat stroke (such as disseminated intravascular coagulation, liver injury, acute kidney injury and gastrointestinal bleeding, etc.). These symptoms may be induced or exacerbated by use. 

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What are the precautions for osteoporosis treatment drugs?🦴🦴🦴

Osteoporosis is a systemic metabolic bone disease in which bone mass and
bone density decrease due to different reasons. Osteoporosis is common in postmenopausal women and older men. It is a very common bone disease. It is characterized by increased bone fragility and increased susceptibility to fractures. Osteoporosis can be divided into primary osteoporosis and secondary osteoporosis according to different etiologies.

What is primary osteoporosis?

Primary osteoporosis includes postmenopausal osteoporosis (type I), senile osteoporosis (type II) and idiopathic osteoporosis. Postmenopausal osteoporosis generally occurs within 5 to 10 years after menopause in women. Senile osteoporosis usually occurs after age 70. Idiopathic osteoporosis occurs mainly in adolescents.

What is secondary osteoporosis?

Secondary osteoporosis refers to osteoporosis caused by drugs (such as proton pump inhibitors, antiviral drugs, glucocorticoids, etc.) and/or diseases affecting bone metabolism and other causes.

What medicines are available for the treatment of osteoporosis?

Osteoporosis treatment drugs mainly include basic supplements for bone health, bone resorption inhibitors, bone formation promoters, active vitamin D and its analogs.

Basic supplements for bone health.

The basic supplements for osteoporosis prevention and treatment are calcium and vitamin D.

Calcium: 

• Commonly used are calcium citrate and calcium carbonate. Although calcium citrate has a lower calcium content, its better water solubility can reduce the occurrence of kidney stones. It is suitable for patients who are at risk of kidney stones or who are achlorhydric. Calcium carbonate has a higher calcium content. It is easily soluble in gastric acid and has a high absorption rate by the human body. 
• Epigastric discomfort and constipation are their common adverse effects. Calcium citrate has relatively few gastrointestinal adverse effects. Calcium should be avoided in patients with hypercalcemia and hypercalciuria. High-dose calcium may increase the risk of cardiovascular disease and kidney stones. Fluoroquinolones will complex with calcium ions in calcium. This hinders the absorption of the drug and can easily lead to the failure of anti-infective therapy.

Vitamin D:

• The combination of vitamin D and calcium reduces the risk of osteoporotic fractures. In addition, the efficacy of other anti-osteoporosis drugs can be enhanced by adequate vitamin D supplementation. Elderly osteoporosis patients who are obviously deficient in vitamin D should use vitamin D supplementation, and at the same time, they can use active vitamin D to treat osteoporosis under the guidance of doctors.
• Urinary and serum calcium concentrations should be monitored regularly when taking vitamin D to prevent hypercalcemia and hyperphosphatemia. In addition, taking active vitamin D to correct basal vitamin D deficiency is generally not recommended. Supplemental therapy with larger doses of vitamin D is not recommended for multiple doses within a year.

Bone resorption inhibitors.

Such drugs mainly include bisphosphonates, calcitonins and selective estrogen receptor modulators.

Bisphosphonates:

• Broad-spectrum anti-fracture drugs such as alendronate, risedronate, and zoledronic acid are the preferred drugs. Oral bisphosphonates such as alendronate and risedronate should be the first choice for people with low bone mineral density but no history of fractures and people with low or moderate fracture risk. Injectable forms such as zoledronic acid may be considered in elderly patients with multiple vertebral or hip fractures, as well as in people with high fracture risk, very low bone mineral density, contraindications, or oral intolerance. Lumbar spine and hip bone mineral density in people with osteoporosis can be improved with zoledronic acid. It reduces the risk of vertebral, nonvertebral and hip fractures.
• Their adverse reactions include renal toxicity, osteonecrosis of the jaw, atypical femoral fractures, transient flu-like symptoms, and gastrointestinal reactions. Bisphosphonates should be used with caution in patients with reflux esophagitis, active gastric and duodenal ulcers, and functional esophageal dysfunction. Bisphosphonates are not recommended for patients with severe oral disease or in need of dental surgery. They should also be contraindicated in patients with creatinine clearance <35ml/min. After 3 years of intravenous bisphosphonate use or 5 years of oral bisphosphonates, patients should be reassessed to determine whether continued use of the drug is required.

Calcitonin drugs:

• The biological activity of osteoclasts can be inhibited by calcitonin drugs. They reduce the number of osteoclasts and the loss of bone mass. They also relieve bone pain and increase bone mass. In particular, it can significantly relieve bone pain caused by osteoporosis and fractures.
• Their main adverse reactions are nausea, facial flushing, etc., and occasionally allergic phenomena occur. Because calcitonins have the potential to increase the risk of developing tumors, they should generally not be used continuously for more than 3 months.

Selective estrogen receptor modulators:

• A commonly used selective estrogen receptor modulator is raloxifene. It is indicated for the treatment of postmenopausal osteoporosis and for reducing the risk of vertebral fractures.
• Raloxifene may cause pulmonary embolism and deep vein thrombosis. Therefore, it is contraindicated in those with a history of venous thrombosis and those with thrombophilia (such as those who are sedentary or bedridden for a long time). In addition, the risk of thromboembolism in patients should be strictly assessed before administration.

Bone formation promoter.

Parathyroid hormone analog:

• Teriparatide is a parathyroid hormone analog. It stimulates osteoblast activity by intermittently administering small doses. It increases bone density and promotes bone formation. It also reduces the risk of non-vertebral and vertebral fractures.
• Dizziness, headache, nausea and limb pain are its common adverse effects. Because of the risk of osteosarcoma formation after two years of teriparatide use, it should not be given for more than two years. Patients should also be treated with anti-resorptive drugs sequentially after drug discontinuation to maintain or increase the patient's bone density. This continuously reduces the risk of fractures.

Active vitamin D and its analogs.

These drugs are suitable for patients with impaired renal function, reduction or deficiency of 1-alpha-hydroxylase, and the elderly.

Alpha-calcidol, calcitriol:

• Although α-calcidol does not need to be activated by renal metabolism, it needs to be activated by 25-hydroxylase in the liver to have biological activity. Calcitriol itself has biological activity. In addition, the effect of calcitriol to increase blood calcium will be stronger than that of α-calcidol. However, it has a shorter half-life than alpha-calcidol and loses its efficacy about 2 to 3 days after stopping the drug. After you stop taking alpha-calcidol, it takes about 1 week for it to stop working.
• Active vitamin D and its analogs have a significantly higher risk of hypercalciuria relative to vitamin D. The risk of hypercalcemia increases with higher doses, especially when combined with calcium supplements. Therefore, patients' urinary calcium and serum calcium should be monitored during treatment, especially when combined with calcium supplements. Active vitamin D and its analogs are used with caution in patients with kidney stones and are contraindicated in patients with hypercalcemia. It also increases the risk of hypercalcemia when combined with thiazide diuretics. It may cause hypermagnesemia when used with magnesium-containing drugs, especially in patients with chronic renal failure. It can induce cardiac arrhythmias when combined with digitalis.

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