Keywords：专著资料, 全文在线浏览, 中西医结合, 第8部分
- Other drugs: Drugs like furazolidone, aminophylline, methimazole, metronidazole, and tolbutamide can all delay the excretion of sulfonylureas in the body, prolonging their effects and leading to hypoglycemic reactions. 6. Hormonal drugs that raise blood sugar—such as cortisone, hydrocortisone, prednisone, dexamethasone, epinephrine, norepinephrine, thyroxine, glucagon, and sympathomimetic drugs like ephedrine and phenylephrine—all increase gluconeogenesis and glycogen breakdown, thereby raising blood sugar levels. 7. Estrogen, nicotinic acid, and phentolamine can increase blood sugar by inhibiting insulin receptor sensitivity, counteracting the hypoglycemic effects of sulfonylureas. 8. Phenytoin, indomethacin, and diuretics such as hydrochlorothiazide, chlorothiazide, and furosemide all inhibit insulin secretion from pancreatic β-cells, causing patients' blood sugar levels to rise. II. Biguanide hypoglycemic agents These are suitable for obese type 2 diabetes patients, reducing both fasting and postprandial blood glucose levels. Their mechanism of action differs from that of sulfonylureas: they do not stimulate insulin secretion and do not cause hypoglycemia. The mechanisms are as follows: ① They inhibit intestinal absorption of glucose, thus lowering postprandial blood glucose, and also suppress the absorption of amino acids, fats, and cholesterol in the small intestine, primarily acting in the middle section of the small intestine. ② They enhance glucose uptake and utilization by peripheral tissues. Biguanides increase the permeability of muscle cell membranes to glucose, improve the affinity between insulin and its receptors, promote glucose uptake, utilization, and aerobic oxidation, and also stimulate anaerobic glycolysis, thereby increasing basal glucose utilization. ③ They inhibit hepatic gluconeogenesis, reducing hepatic glucose output. ④ Lipid-lowering effect: They inhibit intestinal cholesterol biosynthesis and storage, thus lowering total cholesterol (Tch), triglycerides (TG), low-density lipoprotein (LDL-C), and very-low-density lipoprotein (VLDL-C), while increasing high-density lipoprotein (HDL-C). (1) Indications for biguanide hypoglycemic agents ① Obese type 2 diabetes patients whose blood sugar control is unsatisfactory with diet and exercise alone can use biguanides to not only lower blood sugar but also reduce weight. ② For type 2 diabetes patients who do not respond well to sulfonylureas, combining biguanides often yields better results. ③ Suitable for diabetic patients with hyperlipidemia. ④ For type 1 diabetes, adding biguanides to insulin therapy can enhance efficacy and reduce insulin dosage. (2) Dosage and administration of biguanides ① Metformin (Glucophage, Medicon, Dihua Tangding, Glucobay): 250–1500 mg daily, divided into three doses after meals. It has a significant hypoglycemic effect and can also lower lipids, making it suitable for obese type 2 diabetic patients with atherosclerosis. After oral administration, 90% is excreted by the kidneys, so it is contraindicated for people with liver or kidney dysfunction, alcoholism, or cardiopulmonary insufficiency. ② Phenformin (Glucotrol, DBI): 25–50 mg each time, three times daily, taken during meals to reduce gastrointestinal side effects. Its main feature is lowering hyperglycemia caused by diabetes without affecting normal blood sugar levels; major side effects include loss of appetite, nausea, vomiting, bloating, and diarrhea, and large doses may lead to lactic acidosis. It is contraindicated for patients with liver or kidney dysfunction. (3) Contraindications for biguanides ① Mild early-stage type 2 diabetes patients whose condition can be controlled through diet and exercise; ② Type 1 diabetes patients or severe type 2 diabetes patients cannot rely solely on biguanides to control blood sugar; ③ Patients with ketoacidosis, hyperosmolar coma, lactic acidosis, severe infections, trauma, surgery, pregnancy, childbirth, heart failure, myocardial infarction, liver or kidney dysfunction, or cerebrovascular disease are contraindicated. ④ If severe gastrointestinal symptoms such as nausea, vomiting, bloating, or diarrhea occur after taking the medication, discontinue use. III. Alpha-glucosidase inhibitors These are third-generation oral hypoglycemic agents, primarily working by delaying glucose absorption in the small intestine and lowering postprandial blood glucose. For type 2 diabetes patients, when used in conjunction with dietary therapy, these drugs can reduce postprandial blood glucose by 20%–25% and fasting blood glucose by 10%. (1) Mechanism of action of alpha-glucosidase inhibitors (1) Carbohydrates in food (mainly starch and sucrose) are broken down into monosaccharides (glucose and fructose) under the action of salivary amylase, pancreatic α-amylase, and intestinal epithelial α-glucosidase, and then absorbed. Alpha-glucosidase inhibitors in the small intestinal epithelium can inhibit α-amylase, glucose amylase, and sucrase, slowing down the rate at which starch and sucrose are converted into glucose and fructose, thereby delaying the digestion and absorption of starch and sucrose in the intestine and reducing postprandial hyperglycemia. However, alpha-glucosidase inhibitors have no effect on the absorption of monosaccharides and will not cause hypoglycemia. (2) Improving lipid metabolism: They can reduce the synthesis of very-low-density lipoproteins, thereby lowering triglyceride levels. They can also improve fat metabolism, reducing blood cholesterol and free fatty acids, which helps delay the onset of atherosclerosis and vascular complications. (3) Regulating hormonal effects: Alpha-glucosidase inhibitors can regulate hormone levels along the gut–insulin axis, feedback-inhibiting the postprandial increases in intestinal inhibitory hormones, intestinal secretory hormones, C-peptide, and pancreatic stimulatory hormones. (2) Indications for alpha-glucosidase inhibitors ① Suitable for type 2 diabetes patients receiving drug treatment in addition to diet and exercise, with better postprandial blood glucose-lowering effects than biguanide hypoglycemic agents. ② For type 2 diabetes patients whose blood sugar control is unsatisfactory with sulfonylureas and biguanides, alpha-glucosidase inhibitors can be used in combination. ③ For type 1 diabetes patients, using alpha-glucosidase inhibitors in conjunction with insulin can reduce insulin dosage, control postprandial hyperglycemia, and avoid hypoglycemic reactions. This is because relying solely on insulin makes it difficult to suppress the early postprandial rise in blood sugar; if the insulin dosage is increased to achieve this suppression, late postprandial hypoglycemia is more likely to occur. Therefore, combining alpha-glucosidase inhibitors can both lower early postprandial hyperglycemia and, due to reduced insulin dosage, prevent late postprandial hypoglycemia. (3) Common formulations of alpha-glucosidase inhibitors In recent years, acarbose (Precose) has been clinically used, with an average daily dose of 100–300 mg, divided into three doses to be chewed before meals or with the first bite of food. Other alpha-glucosidase inhibitors developed in recent years include voglibose (Galvus), which has a hypoglycemic effect 190–270 times stronger than Precose, with a daily dose of 0.3–0.9 mg, divided into three doses to be taken before or during meals. There is also miglitol abroad, which is a similar drug. (4) Side effects and contraindications of alpha-glucosidase inhibitors Using alpha-glucosidase inhibitors alone will not cause hypoglycemia, but if used in combination with sulfonylureas and biguanides, the additive effects of the drugs may lead to hypoglycemia, and when correcting hypoglycemia, intravenous glucose should be administered rather than bread or sucrose. Common side effects of taking alpha-glucosidase inhibitors include bloating, increased flatulence, intestinal rumbling, diarrhea, nausea, vomiting, and constipation; reducing the dose or stopping the medication will usually eliminate these side effects. Patients with allergies to this class of drugs or those prone to hypoglycemia should avoid using them. It is also advisable to avoid taking them concurrently with antacids, cholestyramine, digestive enzyme preparations, or intestinal adsorbents, as these can reduce the hypoglycemic effect of the drugs. People with obvious gastrointestinal dysfunction and pregnant women should also avoid using this class of drugs. IV. Insulin microcapsules (INC) This is a new type of oral insulin formulation currently being researched domestically. The formulation uses cyanoacrylate n-butyl ester insulin microcapsules, which protect the drug from being degraded by gastric and pancreatic enzymes, allowing it to be absorbed in the intestine. The drug takes effect one hour after ingestion, reaches peak efficacy four hours later, and lowers blood sugar by 98%; the effect lasts for 24 hours. V. Other oral hypoglycemic agents For example, the glucagon analogs currently under development—1-α-trinitrophenyl histidine, 12-high arginine-GG, and Des-His(Hlu⁹)-GG amide—can competitively bind to glucagon receptors without activating them, thereby inhibiting glycogen breakdown and gluconeogenesis. Thiazolidinedione derivatives under development mainly work by enhancing tissue sensitivity to insulin; formulations include ciglitazone, which reduces insulin resistance, lowers blood sugar and insulin levels, and reduces triglycerides; troglitazone, taken at 200–800 mg daily, can lower both fasting and postprandial blood sugar levels; pioglitazone, whose main function is to increase glucose uptake, oxidation, and lipid synthesis in fat and muscle cells, thereby lowering blood sugar; and englitazone, which enhances fat cell glucose uptake, thus lowering blood sugar. Other agents such as guarana, seaweed products, and gluconeogenesis enzyme preparations also have some hypoglycemic effect. Organic chromium preparations—including high-chromium yeast, low-chromium yeast, and methylchromium—can lower blood sugar, reduce total cholesterol and triglycerides, and increase high-density lipoprotein for diabetic patients deficient in chromium. VI. Traditional Chinese medicine Single herbs such as gourd, guava, bitter melon, toon root, lychee seed, silkworm pupa, mulberry bark, ginseng, salvia miltiorrhiza, anemarrhena, aconite, polygonatum, corn silk, ophiopogon, rehmannia, cortex dictamni, yam, cistanche, etc., all have certain hypoglycemic effects. Section 6: Insulin therapy Since Canadian scientists Banting, Best, and Collip successfully extracted insulin from cow pancreas in 1921 and Burrough first used it clinically to treat diabetes the following year, insulin's role in treating diabetes remains irreplaceable to this day. (1) Diabetic patients who need insulin therapy (1) Type 1 diabetes patients, regardless of whether they have ketoacidosis or not, should receive insulin therapy immediately upon diagnosis. This is because type 1 diabetic patients exhibit obvious pathological changes in the pancreas—about 50%–70% have pancreatitis, with only about 10% of the normal number of β-cells remaining, resulting in weakened or lost insulin-secreting function and absolute insulin deficiency in the body. Therefore, lifelong insulin replacement therapy is necessary. (2) Type 2 diabetes patients who develop acute complications such as ketoacidosis, hyperosmolar coma, or lactic acidosis, or who experience infections, surgeries, traumas, pregnancies, acute myocardial infarctions, or treatments with adrenal cortical hormones, also require insulin therapy to control their condition. (3) Type 2 diabetes patients whose fasting blood glucose exceeds 11.1 mmol/L within three months of onset despite having already taken the maximum dose of sulfonylureas indicate that oral hypoglycemic drugs have become secondarily ineffective, necessitating the addition of insulin therapy. (4) Diabetic patients with chronic complications such as retinopathy, diabetic nephropathy, diabetic neuropathy, as well as concurrent cardiovascular and cerebrovascular diseases, skin infections, tuberculosis, etc., are also suitable for insulin therapy. (5) Secondary diabetes, such as acromegaly, Cushing's syndrome, pancreatitis, or diabetes caused by fibrocystic pancreatic disease, requires insulin therapy. (2) How to use insulin to treat diabetes
- Insulin therapy for type 1 diabetes: Inject short-acting insulin subcutaneously half an hour before each of the three daily meals. To better control blood sugar levels, some patients may add a medium-acting insulin injection before bedtime. Adjust the injection dosage based on the patient's four daily blood sugar monitoring results—measure blood sugar before each meal and before bed—to keep blood sugar within normal or near-normal ranges, thereby reducing the incidence of retinal, renal, neurological, and large-vessel complications. Currently, insulin pumps are available for clinical use—one is a continuous subcutaneous insulin infusion pump, and the other is an intraperitoneal implantable insulin infusion pump, which better mimics the physiological pathway of insulin absorption in the human body.
- Insulin therapy for type 2 diabetes (1) Combination therapy: When starting insulin therapy for type 2 diabetes patients, combination therapy should be prioritized—add a medium-acting insulin injection (NPH) before bedtime on top of the original full-dose oral hypoglycemic drugs, which can quickly bring most patients' fasting blood sugar down to the ideal control level without causing severe hypoglycemia. The injection dosage should be adjusted according to fasting blood sugar monitoring levels and varies from person to person. This therapy is suitable for obese type 2 diabetes patients. (2) Routine insulin therapy: According to clinical reports, for type 2 diabetes patients, injecting mixed insulin (medium-acting + short-acting) before breakfast and dinner, or using mixed insulin before breakfast and medium-acting insulin before bed, can both achieve strict blood sugar control throughout the day without needing multiple injections per day. As for the ratio of medium-acting insulin (NPH) to regular insulin (RI) in mixed insulin, it should vary from person to person. Generally, the ratio is 7:3, but it can also be adjusted to 8:2 or 6:4 depending on the condition. A disadvantage of insulin therapy is that it can lead to weight gain and hyperinsulinemia, so dietary therapy and exercise must be strengthened during treatment. (3) Short-term insulin therapy: Some type 2 diabetes patients can significantly improve the function of pancreatic β-cells and the effectiveness of oral hypoglycemic drugs after short-term intensive insulin therapy. For diabetic patients who have received insulin therapy due to infection, surgery, trauma, pregnancy, or psychological stress, once these factors are eliminated, they can resume oral hypoglycemic drug treatment.
- How to determine the initial insulin dosage? Since many factors can affect insulin action and everyone's sensitivity to exogenous insulin varies, the dosage must be individualized. Even for the same patient, the required insulin dosage needs to be adjusted at any time according to changes in diet, activity level, and mood to achieve satisfactory disease control. The following three methods can be used to determine the initial insulin dosage. (1) Calculation based on fasting blood glucose: Daily insulin dosage = (fasting blood glucose in grams - 0.1) × (2–3) × body weight (kg). For example, a patient whose diet and activity level are fixed has a fasting blood glucose of 280 mg/dL (15.6 mmol/L) and weighs 50 kg; according to the above formula, the daily insulin dosage would be 18–27 units. (2) Estimating dosage based on disease severity: Research shows that a normal person needs 40–50 units of insulin per day. Therefore, most patients can start with 18–24 units per day and adjust the dosage every 3–5 days based on urine sugar and blood sugar levels. Generally, for every "+" in urine sugar during fasting, add 4 units of insulin; to avoid hypoglycemia, administer only half the estimated amount. (3) Estimating dosage based on body weight: For type 1 diabetes patients, start treatment with 0.5–0.8 units per kilogram of body weight, generally not exceeding 1.0 unit per kilogram; for type 2 diabetes patients, estimate the initial dosage at 0.3–0.8 units per kilogram of body weight. (3) Side effects of insulin therapy
- Prone to hyperinsulinemia: Type 2 diabetes patients, especially obese ones, tend to develop hyperinsulinemia due to higher insulin dosages, and both animal experiments and clinical studies have proven that hyperinsulinemia can accelerate the occurrence and progression of atherosclerosis. For such patients, it is recommended to combine metformin or Precose with insulin therapy and strengthen dietary and exercise therapies to reduce insulin dosage.
- Weight gain: Type 2 diabetic patients, especially the elderly, are prone to abdominal obesity when treated with insulin, and abdominal obesity is a risk factor for cardiovascular complications. Therefore, when using insulin to treat diabetic patients, it is best to combine it with metformin or Precose and emphasize dietary and exercise therapies to reduce insulin dosage while maintaining good blood sugar control.
- Hypoglycemic reactions: Whether type 1 or type 2 diabetes patients, hypoglycemic reactions can occur during insulin therapy, exacerbating brain nerve damage and potentially leading to cerebral thrombosis, epilepsy, coma, or even death. Therefore, it is crucial to master the dosage when using insulin. Once early signs of hypoglycemia appear—such as hunger, dizziness, weakness, spontaneous sweating, palpitations, pale complexion, and rapid pulse—it is essential to immediately consume pastries, sweets, or sugary drinks, or receive intravenous injection of 50% glucose, 20–40 ml, and if necessary, inject 100–300 mg of hydrocortisone into 5%–10% glucose intravenously.
This chapter is prepared for online research and reading; for external materials, please align with original publications and the review process.