What is the difference between acarbose, miglitol and voglibose?📏📏📏

Acarbose, miglitol and voglibose are commonly used clinical α-glucosidase inhibitors. Although they all belong to the same type of hypoglycemic drugs, there are some differences between them and the choice of drugs is also different.

What is the mechanism of action of α-glucosidase inhibitors?

α-glucosidase inhibitors reversibly inhibit α-glucosidase. They inhibit the degradation of disaccharides, oligosaccharides and polysaccharides to glucose and other monosaccharides. As a result, the absorption and decomposition of carbohydrates will be delayed, which will lower the patient's postprandial blood sugar.

It can be seen from the figure above that the structures of glucose and miglitol are very similar. Therefore, α-glucosidase inhibitors have good inhibitory effects on various α-glucosidases.

	Acarbose	Miglitol	Voglibose
Maltase	+	+	++
Isomaltase	+	+	+
Sucrase	+	+	++
Glucoamylase	+	+	-
α-amylase	+	+	-
Trehalase	-	+	-
Lactase	-	+	-

Since acarbose, miglitol and voglibose all have strong inhibitory effects on sucrase, sucrose or starch should not be used in hypoglycemic conditions in patients taking α-glucosidase inhibitors to correct blood sugar in patients. These foods are less effective at correcting blood sugar levels for this condition. Glucose or honey should be consumed to correct blood sugar in these patients.

What are the clinical applications of α-glucosidase inhibitors?

α-glucosidase inhibitors are indicated for patients with elevated postprandial blood glucose following a carbohydrate-based diet. Some researchers have evaluated clinical studies on patients with type 2 diabetes, and the results show that α-glucosidase inhibitors can reduce the HbA1c of patients by about 0.5% and reduce their weight. Studies have shown that acarbose can reduce the risk of developing diabetes by 25% in patients with impaired glucose tolerance within 3.3 years. Therefore, acarbose can be used to treat patients with type 2 diabetes and reduce postprandial blood glucose in patients with impaired glucose tolerance.

Drug Name	Common dosage forms
Acarbose	Oral regular-release dosage form.
	Chewable tablet.
Miglitol	Oral regular-release dosage form.
Voglibose	Oral regular-release dosage form.
Oral regular-release dosage forms include regular tablets, soft capsules, hard capsules and enteric-coated capsules.

Effects of α-glucosidase inhibitors on the liver.

Acarbose: 1 to 2% of orally administered acarbose is absorbed through the gut. In addition, digestive enzymes and intestinal bacteria will also break down some of the acarbose. These amounts add up to about 35% of the dose. High doses of acarbose may cause asymptomatic liver enzyme elevations. Therefore, monitoring of changes in liver enzymes in patients should be considered during the first 6 to 12 months of treatment. Acarbose is contraindicated in patients with severe liver disease.

Miglitol: Miglitol can be completely absorbed after oral administration of 25 mg. 100mg of miglitol is only about 50 to 70% absorbed. Miglitol is not metabolized in the body. Therefore, there is no mention of hepatotoxicity in its labelling. In addition, the incidence of rash when taking miglitol orally is about 4.3%. This rash is usually temporary.

Voglibose: After oral administration of voglibose, voglibose could not be detected in the patient's plasma and urine. However, less than 0.1% of patients will develop fulminant hepatitis, severe liver dysfunction with elevated ALT and AST, or jaundice after taking voglibose. Voglibose should be used with caution in patients with severe hepatic impairment.

What are the drug interactions of acarbose, miglitol and voglibose?

Common ground: The clinical efficacy of α-glucosidase inhibitors is suppressed by digestive enzyme preparations and intestinal adsorbents.

The difference:

1. Acarbose: The bioavailability of digoxin can be affected by acarbose. Therefore, the dose of digoxin needs to be adjusted when the two are used at the same time.
2. Miglitol: Studies have shown that when healthy people take digoxin and miglitol at the same time, the plasma concentration of miglitol will be reduced by 19 to 28%. However, in diabetic patients taking digoxin, the concentration of digoxin in their blood will not change due to the combination of miglitol. In addition, the bioavailability of ranitidine and propranolol was decreased by about 60% and 40%, respectively, by miglitol.
3. Voglibose: Its instruction manual does not mention the above interaction.

What is the dosage of acarbose, miglitol and voglibose?

Acarbose: The initial dose is 50mg three times a day, and then gradually increased to 100mg three times a day. For individual patients, the dose can be increased to 200 mg three times a day. Acarbose needs to be swallowed whole immediately before a meal or chewed with food at the beginning.

Miglitol: The general recommended initial dose is 25 mg three times a day. The recommended maintenance dose is 50 mg three times a day. Its maximum recommended dose is 100 mg three times daily. Miglitol needs to be taken at the beginning of each meal.

Voglibose: The dosage for adults is generally 0.2 mg three times a day. If the curative effect of the patient is not obvious, the dosage can be increased to 0.3mg each time. Voglibose needs to be taken orally before meals, and meals need to be taken immediately after taking the medicine.

α-glucosidase inhibitors slow the digestion and absorption of carbohydrates in the small intestine. Flatulence is caused by bacteria in the colon that interact with unabsorbed sugars. It may cause bloating, abdominal pain, and diarrhea. Therefore, α-glucosidase inhibitors need to be started with small doses. This can reduce the occurrence of gastrointestinal reactions.

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What is diabetic ketoacidosis❓❓❓

One of the most common acute complications of diabetes is diabetic
ketoacidosis. The fatality rate of diabetic ketoacidosis in elderly patients with diabetes is as high as 5 to 16%. Therefore, we should master the diagnosis and treatment of diabetic ketoacidosis.

What are ketone bodies?

Fats are broken down into glycerol and fatty acids. Fatty acids are oxidatively broken down in the liver to form acetone, β-hydroxybutyric acid and acetoacetic acid. These three intermediate products are collectively referred to as ketone bodies. Since both acetoacetic acid and beta-hydroxybutyric acid are acidic substances, they can cause acidosis when they accumulate in large amounts in the body. In the blood, acetone accounts for only about 2% of the total ketone bodies, acetoacetic acid accounts for 28% and β-hydroxybutyric acid accounts for 70%. The blood concentration of β-hydroxybutyrate can directly reflect the ketone bodies in the body. However, the urine ketone measurement method can only measure acetone and acetoacetic acid, but not β-hydroxybutyric acid. 

What are the main causes of diabetic ketoacidosis?

Infection is the most common cause of diabetic ketoacidosis. Inappropriate dose reduction or interruption of insulin therapy is also a common cause of it. Insulin promotes the synthesis of fatty acids and glycerol into fat. When a patient's insulin is acutely deficient, it accelerates the breakdown of fat and increases the concentration of free fatty acids. Increased free fatty acid concentrations are oxidatively broken down in the liver to generate large amounts of ketone bodies. It will cause ketoacidosis.

How can a patient be diagnosed with diabetic ketoacidosis?

A lack of insulin in diabetics can increase blood sugar and accelerate fat breakdown. Hyperglycemia can cause osmotic diuresis. It causes dehydration and electrolyte loss in patients. Accelerated lipolysis increases free fatty acids in the patient's body. The oxidation and decomposition of fatty acids into ketone bodies will also increase. It can cause acidosis in patients.

Laboratory tests:

Blood sugar > 13.9 mmol/L.

Blood ketone ≥ 3 mmol/L or urine ketone(++).

Blood pH < 7.3 and/or HCO₃- < 18 mmol/L.

Diabetic ketoacidosis can be diagnosed with the above test results. The normal blood ketone value is 0.03 to 0.5 mmol/L. Plasma pH is normal 7.35 to 7.45. Serum HCO₃^- normal value is 22 to 27mmol/L. The clinical manifestations of diabetic ketoacidosis are lethargy, headache, abdominal pain, nausea, vomiting and rapid breathing (the exhaled breath will smell like rotten apples with acetone). Severe cases can cause dehydration, varying degrees of disturbance of consciousness and even coma.

What is the treatment for diabetic ketoacidosis?

Rehydration therapy: It is the primary treatment for patients with diabetic ketoacidosis. 0.9% Sodium Chloride Injection is the recommended treatment of choice. In principle, the rehydration treatment should be fast first and then slow. 1.0 to 1.5 L of normal saline should be infused during the first hour, and pre-estimated fluid losses should be replenished within the first 24 hours.

Insulin therapy: Insulin doesn't just lower a patient's blood sugar. It also reduces fat breakdown and inhibits the production of ketone bodies. Insulin is recommended as a continuous intravenous infusion of 0.1 U/kg/h. Insulin will generally correct ketosis more slowly than hyperglycemia. Therefore, when the patient's blood glucose was lowered to 11.1 mmol/L, the insulin input needed to be reduced and the patient started to be given 5% dextrose. It can maintain the patient's blood sugar at 8.3 to 11.1 mmol/L until the diabetic ketoacidosis is relieved.

Potassium supplementation therapy: If the patient's serum potassium is less than 3.3mmol/L, potassium supplementation therapy should be given priority to the patient. Insulin therapy should be started when the patient's serum potassium rises to 3.3 mmol/L. Cell membrane Na+-K⁺-ATPase is activated by insulin. It increases the intracellular potassium concentration, thereby reducing the blood potassium concentration. If the patient has normal urine output but serum potassium is less than 5.2 mmol/L after starting rehydration therapy and insulin, the patient should receive intravenous potassium supplementation. In general, 1.5 to 3.0 g of potassium chloride is added to each liter of infusion solution to maintain the patient's serum potassium level between 4 and 5 mmol/L.

Correction of acidosis: lipolysis is inhibited by insulin. It reduces the production of ketone bodies so that the acidosis is corrected. If the patient's circulation is not depleted, they generally do not need additional alkaline supplements. Generally, the use of 5% sodium bicarbonate solution for alkaline supplementation is only considered in the case of patients whose pH is less than or equal to 6.9.

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New findings on metformin.👀👀👀

Every once in a while, new benefits of metformin are discovered. Earlier this
year, a large cohort study conducted by researchers from the University of Southern Denmark in Denmark and Stanford University in the United States also found new findings on metformin. The study noted that men took metformin in the three months before conception (during sperm development). His male offspring will be more prone to reproductive organ defects at birth. The incidence of severe defects of the genitals or urinary tract was 3.39 times that of the control group. They also found that a man taking metformin for a year before or after the 90 days window period for sperm production did not affect his male offspring. However, it is worth noting that the findings of this study are only preliminary and observational and require further confirmation. Men who are taking metformin do not need to stop taking metformin before trying to conceive. In fact, many reasons for miscarriage are due to problems with men's sperm. It takes about 90 days for sperm to develop, form and finally mature in the epididymis. Therefore, men should also prepare for pregnancy three months in advance to improve the quantity and quality of sperm.

Mechanism of action of metformin.

Metformin reduces postprandial blood glucose levels by delaying intestinal absorption of glucose, increasing GLP-1 levels, reducing peripheral insulin resistance, and increasing muscle tissue uptake and utilization of glucose. It also reduces fasting blood glucose levels by reducing hepatic insulin resistance and reducing hepatic glucose output. The reduction in postprandial blood glucose and fasting blood glucose results in a reduction in HbA1c.

Common adverse reactions of metformin.

Common adverse reactions to metformin are headache, nausea, vomiting, bloating, indigestion, abdominal discomfort, diarrhea and fatigue. Most patients experience adverse reactions within the first 10 weeks of treatment. These adverse reactions generally will be gradually tolerated or disappear with the extension of treatment time. 

Therapeutic dose of metformin.

The minimum recommended dose of metformin is 500 mg per day and the optimal effective dose is 2000 mg per day. The maximum dose for adults in ordinary tablets is 2550 mg per day and the maximum recommended dose in extended-release formulations is 2000 mg per day. Switching to metformin sustained-release preparations, starting with small doses and gradually increasing the dose are all effective ways to reduce the occurrence of adverse reactions. In addition, long-term use of metformin may affect the absorption of vitamin B12, resulting in a decrease in vitamin B12 levels in the patient's body.

Other effects of metformin.

Cardiovascular protection.

Insulin resistance in diabetic and non-diabetic patients is improved by metformin. This reduces basal and post-load insulin levels, which directly and indirectly protects the cardiovascular system.

Improve blood lipid levels.

Fat synthesis and metabolism are improved by metformin. Studies have shown that metformin can significantly reduce triglyceride, LDL-cholesterol and total cholesterol levels in patients with type 2 diabetes, but it did not significantly alter the effect of HDL-cholesterol.

Improve the effect of non-alcoholic fatty liver.

Generally, patients with nonalcoholic fatty liver disease can safely take metformin. Unless the patient has significant hepatic impairment (such as serum transaminases greater than three times the upper limit of normal), hepatic insufficiency, or decompensated cirrhosis.

Treatment of polycystic ovary syndrome.

Polycystic ovary syndrome is a heterogeneous disorder characterized by polycystic ovary morphology, ovarian dysfunction, and hyperandrogenism. Its pathogenesis is unclear. Patients usually have varying degrees of hyperinsulinemia. There is medical evidence that metformin reduces androgen levels, plasma insulin levels and increases estradiol levels. It can improve menstrual regularity, improve hirsutism and induce ovulation in polycystic ovary syndrome patients.

Antitumor effect.

Diabetes may be a risk factor for a variety of tumors, including breast, pancreatic, colorectal, and endometrial cancers. Several studies have shown that metformin inhibits tumor initiation and progression. It reduces the risk of breast, lung, rectal, prostate and other cancers.

Other potential effects of metformin.

Alter gut flora.

A study found that the gut microbiome of patients with type 2 diabetes was favorably changed by metformin.

Reduce the risk of Parkinson's disease in patients with type 2 diabetes.

Metformin promotes the growth of new neurons and repairs damage to the nervous system.

Reversal of left ventricular hypertrophy in non-diabetic patients.

Studies have shown that metformin can improve vascular endothelial cell function, delay myocardial cell apoptosis, inhibit ventricular remodeling, and reduce patient weight. These effects may reverse left ventricular hypertrophy in non-diabetic patients.

Prevent age-related macular degeneration.

A study found that people with type 2 diabetes who took metformin had a significantly lower incidence of age-related macular degeneration. This may be related to the antioxidant and anti-inflammatory functions of metformin.

Reversal of pulmonary fibrosis.

Studies have shown that the use of metformin can re-sensitize myofibroblasts to apoptosis. And in mouse models, metformin can speed up the ablation of already fibrotic tissue.

Promote hair growth.

Studies have found that metformin can stimulate telogen hair follicles to enter the growth phase and promote hair growth in mice.

Reduce the risk of blood clots caused by haze.

There are animal studies showing that inflammation caused by smog is prevented by metformin. It inhibits the formation of arterial blood clots, thereby reducing the risk of cardiovascular disease.

Reduce adverse effects of glucocorticoid therapy.

Some studies have shown that patients treated with glucocorticoids and metformin have the possibility of reversing the adverse effects of glucocorticoids.

Finally, metformin can cause fatal lactic acidosis. Therefore, metformin should be used under the guidance of a doctor or pharmacist. Although new effects of metformin are frequently discovered recently, few of them are certified by medical guidelines.

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What is the difference between alogliptin, linagliptin, saxagliptin, sitagliptin and vildagliptin?📊📊📊

Dipeptidyl peptidase-4 (DPP-4) inhibitor is a new type of oral hypoglycemic drug with the fastest growing clinical use recently. Alogliptin, linagliptin, saxagliptin, sitagliptin and vildagliptin all belong to this class of drugs, but what exactly is the difference between them?

What is the mechanism of action of DPP-4 inhibitors?

Intestinal cells are stimulated by food (especially carbohydrates) to secrete hormones (such as GIP and GLP-1) that increase insulin secretion. And 70 to 80% of the incretin activity is produced by GLP-1.

DPP-4 in the human body can easily degrade GLP-1. It results in a half-life of GLP-1 in plasma of less than two minutes. Concentrations of endogenous GLP-1 are elevated two to threefold by the efficacy of DPP-4 inhibitors in inhibiting DPP-4. The effects of promoting insulin secretion and inhibiting glucagon secretion of GLP-1 are glucose concentration-dependent. Therefore, DPP-4 inhibitors do not increase the risk of hypoglycemia and are therefore suitable for use in the elderly.

What is the difference in chemical structure between DPP-4 inhibitors?

Alogliptin

Linagliptin

Saxagliptin

Sitagliptin

Vildagliptin

What is the difference between the dosage of DPP-4 inhibitors?

1. Alogliptin: It is a DPP-4 competitive inhibitor. It binds non-covalently to the active site of DPP-4. Therefore, its half-life is relatively long, up to 21 hours. Alogliptin is taken once a day, 25 mg each time.
2. Linagliptin: It is a DPP-4 competitive inhibitor. It binds non-covalently to the active site of DPP-4. Therefore, its half-life is 12 hours. Linagliptin is taken once a day, 5 mg each time.
3. Saxagliptin: It binds covalently to the active site of DPP-4. Therefore, its dissociation and association will be slower. This makes its half-life only 2.5 hours, but its hypoglycemic effect lasts longer. Saxagliptin is taken once a day, 5 mg each time.
4. Sitagliptin: It is a DPP-4 competitive inhibitor. It binds non-covalently to the active site of DPP-4. Therefore, its half-life is about 12 hours. Sitagliptin is taken once a day, 100 mg each time.
5. Vildagliptin: It is also covalently bound to the active site of DPP-4. Its half-life is 3 hours. Vildagliptin is taken twice a day, 50 mg each time.

Food does not affect the absorption of the above DPP-4 inhibitors.

Precautions for use in patients with renal insufficiency.

1. Alogliptin: It is rarely metabolized in the body and its metabolites are also active. Its bioavailability can reach 100%. It rarely interacts with other medicines. About 76% of alogliptin is excreted through the kidneys. Therefore, its dosage should be adjusted when it is used in patients with renal insufficiency.
2. Linagliptin: It is rarely metabolized in the body. Its metabolites are inactive. Its bioavailability is about 30%. It rarely interacts with other medicines. Less than 5% of the administered dose of linagliptin is excreted by the kidneys. Therefore, it does not require dose adjustment when used in patients with renal insufficiency.
3. Saxagliptin: It is metabolized by CYP3A4/5. Its metabolites are active. Its bioavailability is about 67%. It rarely interacts with other medicines. Its usual dose is 5 mg once a day. However, when it is co-administered with potent CYP3A4/5 drugs such as itraconazole, clarithromycin and atazanavir, the dose of saxagliptin should not exceed 2.5 mg per day. About 75% of saxagliptin is excreted through the kidneys. Therefore, its dosage should be adjusted when it is used in patients with renal insufficiency.
4. Sitagliptin: It is rarely metabolized in the body. Its metabolites are inactive. Its bioavailability is about 87%. It rarely interacts with other medicines. About 79% of sitagliptin is excreted by the kidneys. Therefore, its dosage should be adjusted when it is used in patients with renal insufficiency.
5. Vildagliptin: It is not metabolized by CYP enzymes, but inactivated by hydrolysis. Its bioavailability is about 85%. It is less likely to interact with other drugs. About 85% of vildagliptin is excreted through the kidneys. Therefore, its dosage should be adjusted when it is used in patients with renal insufficiency.

What are the common adverse reactions of DPP-4 inhibitors?

It is possible that DPP-4 inhibitors increase GLP-1 levels. This can be associated with delayed gastric emptying and appetite suppression. Therefore, DPP-4 inhibitors can cause stomach upset. Their main adverse reactions are upper respiratory tract infection, nasopharyngitis and headache. Less common adverse reactions are hypersensitivity reactions and angioedema. 

In addition, alogliptin and saxagliptin have the potential to increase the risk of heart failure hospitalization events. Therefore, when a patient has risk factors for heart failure, the patient should be observed for symptoms and signs of heart failure during treatment.

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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 medications are available to treat peripheral neuropathy caused by diabetes?💊💊💊

Diabetes can lead to many complications. Common complications include retinopathy (the leading cause of blindness in adults), stroke (two to four times as common in people with diabetes as in non-diabetic patients), cardiovascular disease (about 80% of patients die from cardiovascular events), diabetes Nephropathy (one of the leading causes of end-stage renal disease), diabetic foot (which is characterized by high amputation rates and high mortality), diabetic neuropathy (the leading cause of non-traumatic amputations). The most common chronic complication is diabetic peripheral neuropathy. Its prevalence is over 50%. The following will introduce the common symptoms of peripheral neuropathy and what treatments are available.

Common symptoms of diabetic peripheral neuropathy.

Diabetic peripheral neuropathy can occur even in prediabetes. It recommends that patients be screened for diabetic peripheral neuropathy when they are diagnosed with type 2 diabetes. Then patients should also receive relevant screening at least once a year. Common clinical symptoms are as follows:

Distal symmetric polyneuropathy: This lesion begins distally (finger or toe) and progresses proximally (wrist or ankle). Its clinical manifestations are acupuncture, numbness, burning, and ant line feeling in bilateral extremities. Some patients have hypoesthesia, the limbs seem to be wearing gloves or socks, and they are not sensitive to stimuli such as heat, cold, and touch. There are also patients with spontaneous skin acupuncture, burning, and even knife-like pain symptoms.

Autonomic neuropathy:

• Cardiovascular autonomic neuropathy: orthostatic hypotension, resting tachycardia, syncope, etc.
• Gastrointestinal autonomic neuropathy: hiccups, dysphagia, gastroparesis, diarrhea, constipation, etc.
• Urogenital autonomic neuropathy: urinary incontinence, urinary retention, voiding disorders, urinary tract infections, etc.
• Other autonomic neuropathy: Decreased or no sweating. Hands and feet will become dry and cracked, making them prone to infection.

Pathogenesis of diabetic peripheral neuropathy.

Its pathogenesis has not yet been fully elucidated. It is mainly considered to be related to the accumulation of sorbitol, dyslipidemia, hyperglycemia, oxidative stress, and microcirculation disorders.

The accumulation of sorbitol:

Most of the glucose is generally metabolized by the glycolysis and pentose phosphate pathways. Less than 3% of glucose is metabolized via the sorbitol bypass pathway. 

When blood sugar rises uncontrollably, the level of glucose in nerve tissue and blood vessels also increases significantly. This condition causes more aldose reductase to be activated, resulting in a marked enhancement of the sorbitol pathway. Sorbitol accumulates in nerve tissue and blood vessels. The accumulation of sorbitol in nerve tissue can damage peripheral nerves.

What medications are commonly used to treat diabetic peripheral neuropathy?

Apart from improving glycemic control in patients, there is currently no effective treatment for the underlying nerve damage. Because some drugs are off-label use, doctors should use with caution.

Methylcobalamin: It is an active vitamin B12 preparation. It can enter nerve cells more easily than inactive vitamin B12 (cyanocobalamin). It promotes nerve myelination and axon regeneration. It is a drug that nourishes the nerves. Oral mecobalamin 3 times a day, 500 μg each time, for at least 3 months. If there is no effect after taking it for more than three months, there is no need to continue taking it.

α-lipoic acid: It is an antioxidant factor and acts as an anti-oxidative stress. It inhibits aldose reductase and reduces lipid oxidation in nerve tissue. Oral lipoic acid 3 times a day, 0.2g each time. Or take it orally once a day, 0.6g each time, half an hour before breakfast. The absorption of lipoic acid is affected by food, so it should not be taken with food.

Epalrestat: It is a drug that inhibits aldose reductase activity. It prevents sorbitol from building up in the nerves, improving nerve conduction velocity and symptoms caused by diabetic neuropathy. Epalrestat is taken orally three times a day, 50 mg each time, before meals. If epalrestat is not effective for more than 3 months, it is not necessary to continue taking it. In addition, the patient's urine may appear brownish-red after taking it, which is normal.

Pancreatic kininogenase enteric-coated tablet: Plasmin is activated by it and reduces blood viscosity. It also activates phospholipase A2, preventing thrombosis and platelet aggregation. It can improve the microcirculation of the body. Pancreatic kininogenase enteric-coated tablet is to be taken 120 to 240 units 3 times daily on an empty stomach. Since it is an enteric-coated tablet, it needs to be swallowed whole to prevent it from being destroyed in the stomach.

Pregabalin: It binds to calcium channels in the central nervous system. It reduces the release of calcium channels in the central nervous system, thereby inhibiting central sensitization and hyperalgesia. This can reduce pain. The initial dose of pregabalin is 150 mg daily in 2 to 3 divided doses, with subsequent dose adjustments to 300 to 600 mg daily. Its common side effects are drowsiness and dizziness. In addition, it can cause weight gain and the patient's dosage of antidiabetic drugs may need to be adjusted.

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