Insulin resistance is due to decreased insulin sensitivity

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Insulin resistance is due to decreased insulin sensitivity

2016-07-23 16:07:25 516 ℃

Director of the PLA No.306 Hospital, Liu Yanjun

One: what is insulin resistance

Insulin resistance (English: insulin resistance) refers to the fat cells, muscle cells and liver cells of normal concentration insulin producing inadequate response to the phenomenon, i.e., these cells need higher insulin concentrations to respond to insulin.

In the fat cells, insulin resistance leads to the hydrolysis of stored triglycerides, and increase the content of free fatty acids in plasma. In muscle cells, insulin resistance reduces glucose uptake; in the liver cells, glucose reserves, both common cause increased blood sugar levels. High insulin and high glucose levels in the plasma induced by insulin resistance often lead to metabolic syndrome, gout, and type 2 diabetes.

Insulin resistance theory ends with a lack of insulin secretion to explain the history of diabetes. More realistically reproduce the complexity of the human body, to provide academic support for the behavior of medical technology. More scientific to guide the direction of the movement of patients with diabetes.

Two: the cause of the formation of insulin resistance

Lead to insulin resistance in the pathogenesis of many, including genetic factors or primary insulin resistance such as the structure of insulin abnormalities, in vivo in the presence of insulin antibody, insulin receptor and insulin receptor gene mutations, such as GLUT4 gene mutations and mutations of the glucokinase gene and insulin receptor substrate gene mutation), primary insulin resistance to most is caused by mutations in the gene, and often multiple mutations cooperate to induce insulin resistance.

In addition to the genetic factors, many environmental factors also participate in or lead to insulin resistance, known as secondary to insulin resistance, such as obesity is leading to insulin resistance is the main reason, especially central obesity; the main and long-term exercise deficiency and dietary energy intake too much about, diagnosis of type 2 diabetes mellitus patients with 80% of patients with obesity), long-term high blood sugar, high travel from fatty acids and some drugs such as lack of glucocorticoid, some trace elements such as chromium and vanadium deficiency, pregnancy and in vivo insulin antagonistic hormones increase.

Another reason is the increase in tumor necrosis factor A (TNF-a). TNF-a enhanced activity can promote fat decomposition induced by plasma FFA levels increased muscle insulin receptor tyrosine kinase activity inhibition, inhibition of phosphorylation of IRS-1 and GLUT4 expression, which leads to insulin resistance and hyperinsulinemia. In recent years is that fat cells can secrete resistin resistin reduced insulin stimulated glucose uptake and neutralization of resistin tissue uptake of glucose recovery. Others, such as leptin resistance and decreased adiponectin levels or decreased activity, are also associated with insulin resistance. In skeletal muscle cells, the increase in triglyceride (TG) content is also considered to be one of the causes of insulin resistance, B cells in the accumulation of excessive TG can cause its functional decline.

Three: the monitoring method of insulin resistance


Euglycemic insulin clamp technique (eict) is currently recognized testing insulin resistance, and is considered to be the gold standard of evaluation of other detection insulin resistance method. This method is of exogenous insulin sensitivity method for determination of tissue and fast continuous insulin infusion the plasma insulin concentrations increased rapidly and maintained at a certain level, change glucose infusion rate to stabilize blood sugar levels at baseline. In those levels by inhibiting hepatic glucose output and endogenous insulin secretion that blockade of endogenous glucose insulin feedback when glucose infusion rate equal to the rate of exogenous insulin mediated glucose metabolism by. The specific method is: 12h fasting blood samples were drawn for measurement of plasma glucose and insulin values and intravenous infusion of insulin. 5mU mg-kg-1, min, 10min, the blood insulin levels maintained at L 100mU/, this rate remains constant, then static drops 2% glucose (2 mg - kg-1 - min-1'), once every 5 min, blood glucose monitoring, and Harvard pump adjustment of glucose transport rate of infusion (glucose infusion rate, GIR), exogenous insulin clamp glucose to normal level (5. 2 + 0.1 mmol / L), lasting 60min. Serum insulin concentration in the 50mU/L above can inhibit 90% of endogenous hepatic glucose production and therefore clamp test when reaching high insulin homeostasis of exogenous glucose transport rate (GIR) is equal to the peripheral tissue glucose utilization value (m). At this time, the gir can be as the evaluation of human pancreatic islet hormone sensitivity index, this is the insulin sensitivity index, application of more ordinary.

TwoInsulin inhibition test

Insulin inhibits the insulin suppression test (IST) test by Shen in 1970, was the first to put forward, the method is to subjects intravenous propranolol 5mg, after 5min with constant infusion pump infusion composed of propranolol, epinephrine and glucose and insulin mixed solution, to suppress hepatic glucose output and endogenous insulin secretion. In this steady state, the plasma glucose concentration directly reflects the sensitivity of the tissue to the exogenous insulin. Harano in 1977 to ist was improved, the somatostatin instead of epinephrine and propranolol, on the grounds that propranolol and adrenaline can cause subjects increased heart rate slows down, blood pressure and blood redistribution and other side effects, and adrenaline can make fat decomposition, of glucagon and growth hormone secretion inhibition is not sufficient; somatostatin can fully inhibited glycogenolysis and inhibition of insulin, glucagon and growth hormone secretion, do not have a direct effect on the fat metabolism, does not cause cardiovascular responses. The use of somatostatin is more safe and reliable, IST is a simple and easy method, but the results are not accurate clamping method.

ThreeMicro model method

The minimal model technique (MMT) is using the computer simulation of the relationship between the body's blood sugar and insulin dynamic metabolism, and work out the said insulin resistance degree of insulin sensitivity index (ISI) and does not depend on the effectiveness of its action of insulin glucose metabolism (SG). But not oral glucose, but intravenous injection of a dose of glucose. Then frequently check blood glucose and insulin of about 30 samples, it is known as the frequently sampled intravenous glucose tolerance test. According to the kinetic relationship between glucose and insulin (blood concentration curve), ISI. If the beta cell function is too low, it is necessary to inject 1 times D860 or insulin before the injection of glucose. Otherwise the insulin curve is too low to calculate the error. Specific methods for the morning fasting test (after fasting l0h). First supine rest for 30 min, about the elbow and wrist, the retention of a venous channel, one side for to glucose, the other side is used as blood samples were collected. Injection of glucose in accordance with 0.3g/kg calculation, the beta cell function to reflect the poor in the glucose 20min after injection of 0 3G of toluene, the sodium salt of sodium, the complete no beta cell function to inject a dose of exogenous insulin 75mU/kg. Blood sampling time of the initial 3H a total of 30 blood samples, the data of each point of the computer to calculate the ISI and SG. Later, Steil and other small model technology to improve, the number of blood samples to be reduced to 12 times, and a good correlation with the standard method, Chen Jiawei (1996) reduced to 14. By comparative analysis and reduces the sample does not significantly affect the results and SG is refers to the body does not rely on their own insulin to glucose metabolism ability, when reduced SG that glucose metabolism ability obviously will reduce caused by the clinical significance of abnormal glucose tolerance, and even lead to the occurrence of type 2 diabetes.

Normal and non diabetic hypertension patients with insulin sensitive index (used to measure insulin sensitivity), and insulin on glucose acute response between 0~19min exist hyperbolic relationship. When the decreased insulin sensitivity, in order to maintain normal blood glucose concentrations, insulin secretion must have substantial growth. However, when the beta cells are no longer able to continue the high level of insulin secretion (ie, beta cell dysfunction), accompanied by compensatory insulin resistance in patients with insulin resistance will be converted into glucose tolerance. Therefore, in the minimal model technique, the first phase (0~19min) insulin secretion is not only the multi sample intravenous glucose tolerance combined with insulin secretion in experiment is an important part, and it may also is an early description of islet beta cell dysfunction in an index.

FourGlucose tolerance test and insulin release curve

The merits of this kind of method is compare and block the glucose insulin feedback and did not interfere with the physiological mechanism of glucose insulin feedback; and stimulate glucose insulin feedback method in glucose tolerance test ((OGTT) comparison (MMT), is more in line with the physiological experiments, usual physiological conditions, glucose is in gastrointestinal indirect and in the blood circulation directly in the pancreas induced insulin secretion, and intravenous glucose tolerance test, there is no glucose in the gastrointestinal tract caused by indirect effect of insulin secretion; and the basic state of the method, OGTT mathematical model contains more information.

FiveInsulin glucose tolerance test

The insulin tolerance test (ITT) was first proposed by Alford in 1977. Method: the catheter is inserted into a vein of the arm, the arm into the 40% - 50% in the incubator, the arterial blood, t 0 minutes, press 0. LU/kg fast static injection of short acting insulin, t 0, 3, 6, 9, 12, 15, 20, 30 minutes and there are 9 time points to take blood samples determined glucose concentration, ISI=0.693/T1/2 (T1 / 2 for 3~30min blood glucose curve slope) in the application and reliability of ITT question, because the test in insulin induced glucose decrease in glucagon and catecholamine secretion against accommodative response. Studies have found that this antagonism occurs after the insulin injection of insulin, 15~20min, hypoglycemia occurs more in the 20min. In 1994 Gelding proposed small dose short term of ITT improved, the amount of insulin by 0. LU/kg instead of 0. 05U/kg and test time from 30min shortened to 15 min, which can avoid insulin induced glucose decreased to counter regulatory response to assess insulin resistance deviation. Practice has proved that small doses of short time ITT more secure and reliable. In short, I'I'T is a simple and crude way to assess insulin resistance.

SixPancreatic glucagon test

Glucagon test (GT) is a traditional method for evaluating the function of pancreatic beta cells. 1995 Castillo design a GT assessment insulin resistance. Methods: according to the lmg/m2, fast static note glucagon), make blood sugar free increased 20 min, 20 min with a similar insulin pump device (Biostator) continuous glucose monitoring system, and according to the principle of negative feedback regulation of infusion of short acting insulin 30 min, so that blood glucose control in basic level, by comparing the blood glucose decreased and into the amount of insulin in the blood circulation that the ISI. This is a more accurate method, but need to the Biostator device, and the cost is high.

SevenContinuous glucose infusion model

Continuous glucose infusion model analysis (CIGMA) was designed to evaluate the computer model of insulin resistance based on the glucose and insulin metabolism kinetics data of Hosker in 1985. This technique is: glucose according to the amount of 5 mg / kg per minute continuous fixed transmission 60min after injection, respectively in 50, 55, 60 min after a total of three times take blood glucose and insulin concentrations were measured, three times the average concentration as the plasma glucose and insulin concentrations. According to the concentration, the insulin resistance value was detected from the CIGMA computer model diagram. Although this method is simple, it can only be a rough evaluation of insulin resistance.


Fasting insulin is a better indicator of insulin resistance in the population. Fasting insulin levels were higher in the group with normal or elevated blood glucose levels, indicating the presence of insulin resistance. But in patients with diabetes and fasting insulin clamp technique than normal low correlation coefficient. This is because is currently recognized as the "gold standard" clamp technique measured by whole-body glucose uptake is only reflected in the role of insulin in peripheral tissues, and insulin levels by the island of Langerhans resistance and insulin secretion decided to jointly. Beta cells in peripheral tissue insulin resistance reaction is the secretion of large amounts of insulin to maintain glucose in the normal range, when pancreatic insulin hyper secretion decline occurs sugar intolerance. Therefore, in type 2 diabetic patients with insulin secretion defects and insulin action defect coexist. Even if these patients are in a state of significant insulin resistance, their insulin levels are not high due to the dysfunction of insulin. Nevertheless, studies have consistently shown that very good correlation with in patients with type 2 diabetes fasting insulin levels and clamp technique. Classic insulin RIA is the general level of insulin, proinsulin and intermediary metabolism product and not true insulin level, so the result error is inevitable, conditions should be determined plasma true insulin levels to avoid error.

Anyway, many methods to detect insulin resistance, an ideal detection of insulin resistance method should meet the following criteria: the precise and accurate; security II, on the human body without damage; (3) has the advantages of simple operation, less time consuming, low cost; (4) does not depend on the concentration of glucose in the blood; in the role of insulin within the physiological range reflecting the insulin sensitivity; and not to be confuse the glucose effect. At present, there is no way to fully meet the above criteria of the ideal index.

Four: high blood sugar - mainly from insulin resistance

It is well known that human body can only fall blood sugar hormone is secreted by human pancreatic beta cell insulin, can not drop too much glucose only two reasons. The insulin secretion function of loss, the body can not produce their own insulin (type 1 diabetes, accounted for 5-10% of patients with type 2 diabetes mellitus (T2DM); second, defects in insulin action that insulin resistance (type 2 diabetes, which accounts for 90-95% of patients with type 2 diabetes mellitus (T2DM). Recently, a large number of clinical observation at home and abroad found that the majority of patients with type 2 diabetes, insulin secretion is even higher, but it does not fall too high blood sugar. What is the reason? This is mainly because of the presence of insulin resistance (or decreased insulin sensitivity). If the lack of insulin, with sufficient amounts of insulin problems should be solved, if the diabetic patients with a relatively adequate amounts of insulin. At the same time, the United some drugs, but sugar is still not up to standard ideal. The main reason is within the body of the insulin resistance. The latest version of "internal medicine" also pointed out that in the fat cells, insulin resistance leads to the hydrolysis of stored triglycerides, and increase the content of free fatty acids in plasma. In muscle cells, insulin resistance reduces glucose uptake; in the liver cells, glucose reserves, both common cause increased blood sugar levels. High insulin and high glucose levels in the plasma induced by insulin resistance often lead to metabolic syndrome, gout, and type 2 diabetes. Five: insulin resistance - along with the whole process of type 2 diabetes mellitus type 2 diabetes mellitus (T2DM), also known as non insulin dependent diabetes mellitus (NIDDM), accounting for 90-50% the incidence of diabetes. Its characteristic is that the human body itself can produce insulin, but the cell can not respond to insulin, so that the blood glucose lowering effect is low, that is, insulin resistance (or insulin sensitivity decreased). Insulin resistance precedes the occurrence of diabetes, and in its action, the increased insulin secretion in the early stage of the disease is increased to maintain normal glucose tolerance. When the insulin resistance was further aggravated, the insulin compensatory secretion decreased or the two appeared at the same time, the disease gradually decreased to the sugar tolerance and diabetes, blood sugar began to rise. High blood sugar, high travel increased plasma free fatty acids (FFA) and resistin, further inhibits insulin signal transduction pathway, increased insulin resistance and clinical performance for duration of diabetes progression and deterioration. WHO latest survey found that insulin resistance is one of the basic aspects of the significant characteristics and pathogenesis of type 2 diabetes, running through the whole process of the occurrence and development of disease. Six: how do patients know that they are insulin resistance? If the use of more reasonable insulin dosage, combined with the help of oral hypoglycemic drugs is still not enough, (especially the stomach is prone to insulin resistance). Second, is has a reasonable diet, exercise and insulin injections have no problem, blood sugar is still not satisfied, indicating that insulin in your body is not good, this time can be to the hospital to check endogenous islet function, if endogenous islet function can also, exogenous added it is not enough for so many, certainly is insulin resistance. At this time, it should be used more clearly to help and overcome the problem of insulin resistance. Seven: what are the consequences of insulin resistance? Consequences one: lead to difficult to reduce blood sugar, complications inevitable. Due to insulin resistance, resulting in liver, muscle and fat cells can't effectively transformed the blood glucose, blood glucose rising, erodes vessels, cell, cause multi system damage and lead to eye, kidney, nerve, heart, blood vessels and other tissues and organs of the chronic of disease, dysfunction and failure; serious illness or stress can occur when acute and severe metabolic disorders, such as acute complication of diabetic ketoacidosis (DKA), hyperosmolar coma. Consequences two: lead to increase the burden of pancreatic secretion, and ultimately the loss of the secretion function. Due to insulin resistance, the original insulin content in the blood has been unable to reduce the high blood sugar, in order to protect themselves, the brain center will require the pancreas to secrete more insulin for hypoglycemic. With the passage of time, the increase of insulin resistance, the gradual increase in blood glucose, the burden of pancreatic secretion will be more and more large. Pancreas long time no rest, overload work, eventually fatigue, degeneration, necrosis, completely lost the function of insulin secretion, and ultimately must rely on foreign aid insulin to maintain life. Eight: prevention and treatment of diabetes, improve insulin sensitivity is the key! Increase insulin sensitivity, so that the peripheral tissues (skeletal muscle, fat) on glucose utilization function can be enhanced, can effectively reduce blood glucose, control the occurrence, development and deterioration of diabetic complications. Improving insulin sensitivity is helpful to the recovery of pancreatic beta cells. To restore the function of pancreatic beta cells, we must first reduce the burden on the islets. Increase insulin sensitivity, reduce the high blood sugar, ease the pressure on the pancreatic secretion, so that the pancreatic beta cells to repair and restore. The key to prevention and treatment of type 2 diabetes mellitus is to improve the sensitivity of insulin. Insulin sensitivity, reversing insulin resistance has become a hot research topic at home and abroad, and it is a new treatment strategy for type 2 diabetes mellitus. The lack of metformin and rosiglitazone, which is commonly added to the drug, is a common agent. The preliminary effect can be, but the long-term effect is gradually decreasing, and it is easy to appear drug resistance. Recent GlaxoSmithKline of the UK best-selling global Avandia (rosiglitazone) safety door events, more remind people, in the choice of drugs sensitizer prevention of diabetes and, also must be aware of the dangers of long-term accumulation of irreversible. It is understood that Avandia has been in many countries were forced to stop. Resistant starch - a new hot spot in 1982, Dr. Englyst, UK, in the quantitative analysis of dietary fiber, found a new material, which is called resistant starch. Resistant starch is not digested in small intestine and can be fermented by E. coli, which has a lot of good nutritional and physiological functions. Resistant starch can resist the decomposition of enzymes, slow release of glucose in the body, has a lower insulin response, can control blood sugar balance, reduce the sense of hunger, especially suitable for the consumption of diabetic patients. For patients with type 2 diabetes, resistant starch has the effect of increasing the sense of fullness, delaying glucose absorption, improving insulin resistance, reducing blood sugar, controlling the complications, relieving the pressure of pancreatic secretion, regulating metabolism disorders and so on. In addition, resistant starch can reduce blood fat, constipation, detoxification, anti-cancer effect.