Insulin resistance

　　There are many causes of insulin resistance, including genetic factors or primary insulin resistance such as abnormal insulin structure, the presence of insulin antibodies in the body, mutations in insulin receptors or post-insulin receptor genes (such as mutations in the Glut4 gene, glucose kinase gene, and insulin receptor substrate gene, etc.). Most primary insulin resistance is caused by polygene mutations and often results from the synergistic effect of polygene mutations leading to insulin resistance. In addition to the aforementioned genetic factors, many environmental factors also participate in or cause insulin resistance, known as secondary insulin resistance. These include obesity (the main cause of insulin resistance, especially central obesity; this is mainly related to insufficient physical activity and excessive intake of dietary energy, with 80% of type 2 diabetes patients diagnosed with obesity), long-term hyperglycemia, hypertriglyceridemia, certain drugs such as corticosteroids, certain trace element deficiencies such as chromium and vanadium deficiencies, pregnancy, and an increase in insulin antagonist hormones in the body.

　　Tumor necrosis factor alpha (TNF-a) levels increase. Enhanced TNF-a activity can promote fat decomposition, leading to an increase in plasma FFA levels, inhibit the activity of tyrosine kinase in insulin receptors of muscle tissue, inhibit the phosphorylation of IRS-1 and the expression of Glut4, resulting in insulin resistance and hyperinsulinemia. In recent years, it has also been found that adipocytes can secrete resistin, which can reduce glucose uptake after insulin stimulation and recover tissue glucose uptake after neutralizing resistin. Other factors such as leptin resistance and the decrease or weakening of adiponectin levels or activity are also related to insulin resistance. An increase in triglyceride (TG) content in skeletal muscle cells is also considered one of the causes of insulin resistance, and excessive accumulation of TG in B cells can lead to a decrease in their function.

　　So-called insulin resistance refers to the phenomenon that an abnormally high dose of insulin is required to produce a normal response. In essence, it is a phenomenon that insulin promotes the decrease in the utilization of glucose by tissues, which is the fundamental cause of the occurrence and development of type 2 diabetes and runs throughout the lifetime of patients with type 2 diabetes.

　　Insulin resistance and metabolic syndrome refer to the phenomenon of multiple metabolic disorders such as hyperglycemia, hyperlipidemia, hypercoagulability, hyperuricemia, hypertension, and obesity clustering in the same body. The clinical manifestations include hyperglycemia, hyperinsulinemia, lipid disorder (elevated blood free fatty acids, cholesterol, triglycerides, and low-density lipoprotein cholesterol, decreased high-density lipoprotein cholesterol), overweight or obesity (body mass index over 25), hypertension, etc.

　　Enhancing exercise, controlling diet, and reducing weight: Emphasize a reasonable diet plan for overweight individuals, and engage in long-term, scientific, and regular exercise to reduce weight and maintain weight within the ideal range, which is the basis for reducing insulin resistance and treating metabolic syndrome. Additionally, exercise itself can enhance the body's sensitivity to insulin, especially in skeletal muscles, and help correct various metabolic disorders, which is beneficial for reducing blood glucose and blood pressure, and improving lipid metabolism.

　　1. Normal blood glucose clamp technique

　　2. Insulin suppression test

　　3. Mini-model method

　　4. Glucose tolerance test with simultaneous measurement of insulin release curve

　　5. Insulin tolerance test

　　6. Glucagon test

　　7. Continuous infusion of glucose model analysis

　　8. Fasting insulin

　　In summary, there are many methods to detect insulin resistance. An ideal method for detecting insulin resistance should meet the following criteria: ① accurate and precise results; ② safe and harmless to the human body; ③ simple operation, not time-consuming, and low cost; ④ not dependent on blood glucose concentration; ⑤ reflect insulin sensitivity within the physiological range of insulin action; ⑥ not confused by the glucose effect. At present, there is no ideal indicator that fully meets the above criteria.

　　There is no effective treatment for primary or hereditary insulin resistance, but for high-risk populations with a history of insulin resistance, such as first-degree relatives with a family history of diabetes, hypertension, hyperlipidemia, low birth weight infants, or a history of intrauterine malnutrition, it is especially important to avoid obesity in their postnatal life to prevent the occurrence of insulin resistance as much as possible. For those who have shown signs of insulin resistance, different methods should be adopted to alleviate factors that cause or worsen insulin resistance, and individualized treatment should be given to the different components of metabolic syndrome that individuals have.

　　One, strengthen exercise, control diet,

　　Emphasize a reasonable diet plan and weight loss for the obese. At the same time, carry out long-term, scientific, and regular exercise to reduce weight.

　　Two, ideal blood sugar control

　　Insulin resistance leads to hyperglycemia, and long-term hyperglycemia further exacerbates the insulin resistance state of tissues such as muscles, fats, and the liver through its 'glucose toxicity'. Therefore, in clinical practice, maintaining good blood sugar control through reasonable hypoglycemic treatment for hyperglycemia in patients with type 2 diabetes can help alleviate insulin resistance. In recent years, many clinical studies have reported that for patients with newly diagnosed significantly elevated blood sugar or secondary failure of oral antidiabetic drugs in type 2 diabetes, insulin intensification therapy can stabilize blood sugar control and significantly improve insulin resistance in the short term, thereby helping to control blood sugar in the future.

　　Three, reasonable selection of antidiabetic drugs

　　For patients with type 2 diabetes who are overweight or moderately obese (mainly with insulin resistance), antihypertensive drugs should be preferred (such as thiazolidinedione derivatives, also known as insulin sensitizers - rosiglitazone or pioglitazone; biguanide drugs or glucosidase inhibitors - Byetta), and for type 2 diabetes patients treated with sulfonylurea drugs or insulin, if blood sugar control is not ideal, the above antihyperglycemic drugs can be combined according to specific circumstances, which can have a synergistic effect on lowering blood sugar.

　　Four, the treatment of insulin resistance with thiazolidinedione derivatives (TZD)

　　There is now sufficient laboratory and clinical evidence to confirm that thiazolidinedione drugs are potent insulin sensitizers. Compared with placebo, TZDs such as rosiglitazone can reduce insulin resistance in type 2 diabetes by 33% (evaluated by the HOMA-IR index), increase muscle glucose uptake by 38% (evaluated by the hyperinsulinemic-euglycemic clamp test), and increase overall glucose uptake by 44%. In combination therapy, metformin and sulfonylurea drugs combined with rosiglitazone can reduce insulin resistance by 21% and 32% respectively, and their duration of action can last for at least 24 months or longer.

　　Five, individualized selection of antihypertensive drugs

　　Many patients with hypertension often have insulin resistance, and diuretics and beta-blockers may worsen insulin resistance, have adverse effects on glucose metabolism, and should be avoided for long-term high-dose use. Calcium channel blockers have no adverse effects on glucose metabolism; alpha-blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers can slightly improve insulin resistance while lowering blood pressure, and may reduce the risk of diabetes in patients with hypertension to some extent.

　　6. Correcting lipid metabolism disorders

　　Dyslipidemia such as hypertriglyceridemia and hyper游离 fatty acidemia are closely related to insulin resistance, and hypertriglyceridemia and hyper游离 fatty acidemia further exacerbate insulin resistance. The use of lipid-lowering drugs to improve lipid metabolism can reduce insulin resistance. Thiazolidinedione derivatives such as rosiglitazone improve insulin resistance in part due to their reduction of blood free fatty acids.

　　7. Supplement trace elements

　　Deficiencies in trace elements such as chromium and vanadium may be related to insulin resistance, and appropriately supplementing trivalent chromium ions and trace elements vanadium is beneficial to reducing insulin resistance.

　　1. Hypoglycemic drugs When the fasting blood glucose is greater than 6.7 millimoles per liter, the further increase in blood glucose inhibits insulin secretion, and glucose uptake also decreases at this time. Therefore, insulin and hypoglycemic drugs used to lower blood glucose have the effect of reducing insulin resistance. In recent years, the anti-insulin resistance effect of metformin has been favored. Metformin has the effect of lowering blood glucose and also lowering blood lipids. Alpha-glucosidase inhibitors can reduce postprandial blood glucose and also reduce plasma insulin levels, reducing insulin resistance. The new drug voglibose (trade name Bexin), with a treatment dose smaller than that of acarbose, also has a lower incidence of gastrointestinal reactions.

　　2. Insulin sensitizers Thiazolidinediones and vanadates as insulin sensitizers have been studied extensively recently. The thiazolidinedione troglitazone regulates glucose and lipid metabolism simultaneously through multiple complex pathways, improving insulin resistance.

　　3. Angiotensin-converting enzyme inhibitors of antihypertensive drugs This type of antihypertensive drug can reduce blood pressure, reduce insulin resistance, and reduce the occurrence of cardiovascular events in both diabetic and non-diabetic hypertension.

　　4. Cholesterol-lowering drugs According to the study of the correlation between hyperlipidemia and insulin resistance, recently, the UK Prospective Diabetes Study Group (UKPDS) is undertaking a study to evaluate the therapeutic significance of cholesterol-lowering drugs in the treatment of insulin resistance in diabetes.