Causes and pathogenesis of metabolic syndrome
Last reviewed: 23.04.2024
All iLive content is medically reviewed or fact checked to ensure as much factual accuracy as possible.
We have strict sourcing guidelines and only link to reputable media sites, academic research institutions and, whenever possible, medically peer reviewed studies. Note that the numbers in parentheses ([1], [2], etc.) are clickable links to these studies.
If you feel that any of our content is inaccurate, out-of-date, or otherwise questionable, please select it and press Ctrl + Enter.
Causes of Metabolic Syndrome
The main cause of development of the metabolic syndrome is congenital or acquired insulin resistance, i.e. Insensitivity of peripheral tissues (liver, muscles, adipose tissue, etc.) to insulin. The genetic predisposition to insulin resistance is associated with the mutation of many genes. At the same time, a hypothesis is advanced according to which insulin resistance is not the cause of the development of the metabolic syndrome, but also its one component. This conclusion came from the study of the prevalence of metabolic syndrome components in different ethnic groups (blacks, white Americans and Americans of Mexican descent). The analysis of the data obtained suggested the presence of a different genetic factor in the etiology of the metabolic syndrome. Such a hypothetical factor was called factor Z. It interacts with insulin with sensitive tissues, Endothelium, the regulating system of arterial pressure, the exchange of lipids and lipoproteins and causes respectively the development of insulin resistance, atherosclerosis, arterial hypertension, dyslipidemia. Hyperinsulinemia in metabolic syndrome is considered as a compensatory state of the body against the background of insulin resistance.
External factors that contribute to the development of insulin resistance are abundant food intake, sedentary lifestyle, obesity and socio-cultural features of life. With obesity, the level of FFA in the blood plasma is elevated. FFAs inhibit the action of insulin in the muscle and liver tissues and suppress glucose-stimulated insulin secretion.
[Pathogenesis of metabolic syndrome
The main mechanism of development of the metabolic syndrome lies in the development of hypersensitivity of the hypothalamic-pituitary-adrenal system. The body's response to chronic stress (depression, anxiety, smoking, alcohol use) is manifested by acute activation of this axis. Increases the synthesis of cortisol, which affects the metabolism of glucose and lipids. Cortisol reduces the sensitivity of muscle and liver tissues to insulin and thus contributes to the formation of insulin resistance. In addition to increasing the secretion of cortisol and ACTH, women are increasing the synthesis of testosterone and androstenedione, which leads to the development of hyperandrogenism. This is facilitated by a decrease in their level of globulin, which binds sex hormones. In men, the level of testosterone is reduced due to the inhibitory effect of ACTH on gonadoliberin. Low testosterone levels in men and high in women also contribute to the development of insulin resistance. A high level of cortisol and insulin, a low level of growth hormone, and in men - testosterone contribute to excessive deposition of adipose tissue, mainly in the abdominal region. This is due to the high density of receptors for steroid hormones in adipocytes of visceral fat. Thus, an increase in the activity of the hypothalamic-pituitary-adrenal system can explain the development of insulin resistance and visceral obesity, which are the main signs of the metabolic syndrome.
In response to insulin resistance, hyperinsulinemia, which plays a key role in the development of the metabolic syndrome, is compensatory. The level of banal and postprandial (2 hours after eating or taking 75 g of glucose) of insulin in the metabolic syndrome is significantly increased, and this in turn increases the severity of insulin resistance. Insulin as a hormone, which has anabolic and aptylipolitic effects, promotes the proliferation and migration of smooth muscle cells of the vascular wall, as well as the development of obesity. These processes lead to the development of early atherosclerosis.
The risk of developing cardiovascular diseases in the metabolic syndrome rises by 2-5 times, and this is more associated with hyperinsulinemia. Insulin increases the rate of cholesterol synthesis and increases the number of receptors for LDL cholesterol on cell membranes, thereby increasing cholesterol uptake by cells. Along with this, the process of removing cholesterol from cells with HDL is inhibited. These changes in the cellular metabolism of cholesterol play a major role in the development of atherosclerotic plaque.
At the heart of the pathogenesis of arterial hypertension, as well as other components of the metabolic syndrome, are hyperinsulinemia and insulin resistance. Hyperinsulinemia leads to a chronic increase in the activity of the sympathetic nervous system and the retention of sodium in the renal tubules. These factors cause an increase in blood pressure. An important role is played by chronic stimulation of beta-adrenergic receptors, which causes lipolysis mainly in visceral adipose tissue and, thus, increases the level of FFA. In turn, SFA exacerbate insulin resistance and hyperinsulinemia.
In the metabolic syndrome, carbohydrate metabolism passes through three phases: from normoglycemia, with the already existing insulin resistance, through the phase of glucose tolerance impairment to the apparent type 2 diabetes mellitus. The pathogenesis of type 2 diabetes mellitus, in addition to insulin resistance, also presupposes the presence of a secretory insulin defect. There is confirmation that a high level of lipids in beta cells causes a violation of the secretion of insulin. Despite the fact that the daily amount of secreted insulin can be increased, the early phase of insulin secretion drops out and postprandial glycemia rises. Insulin resistance of hepatocytes is manifested by increased nighttime production of glucose by the liver, causing morning fasting hyperglycaemia.
The metabolic syndrome is characterized by the development of dyslipidemia - an increase in the serum level of triglycerides and a decrease in the level of HDL. The most common is an increase in atherogenic LDL. The basis of dyslipidemia is the processes of insulin resistance / hyperinsulinemia.
Hyperuricemia is considered one of the components of the metabolic syndrome, it is often combined with other components of the insulin resistance syndrome. The main cause of increased levels of uric acid in the blood plasma is chronic hyperinsulinemia - one of the most important pathophysiological disorders in the metabolic syndrome.
Disturbances to the hemostatic system in the metabolic syndrome are identical to those observed with diabetes mellitus, but after normalization of the state of carbohydrate metabolism they do not disappear. In the development of hypercoagulable state, in addition to diabetes mellitus, hyperinsulinemia, dyslipidemia, increased level of FFA, vitamin E deficiency, etc., play a role.