The metabolic syndrome “pathophysiology” dilemma is quite central in the latest scientific publications. It seems that it is still unknown, quite complex, and rather questionable and the research in the underlying process is still ongoing. As most of the patients with Syndrome X are older, obese, sedentary, and show a pronounced degree of insulin resistance, the most important factors in this order are: age, genetic, race, type of lifestyle, inactivity, level of stress, environmental toxins, use of pharmaceuticals, and a daily diet with constant elevated caloric intake. (Source, Wiki)
Some researchers consider metabolic syndrome the biggest controversy of 21st century. One of the missing links in the pathogenesis of syndrome X is obviously the long-unrecognized hepatic insulin resistance that appears to mediate the level of glucose intolerance, hyperglycemia, elevated triglycerides, and low good cholesterol (HDL)- abnormalities that contribute to the constellation of heart-disease risk factors called “metabolic syndrome.” The above liver insulin resistance does represent the newly discovered pathophysiologic link in the development of cardio-vascular disease (CVD) (Source, Diabetes and Wiki)
According to various literature data, there are varying degrees of insulin resistance and numerous factors that can consequently affect it. Some scientists believe that the insulin excess encourages depressed immunity, liver disease (fatty liver), gout, renal failure, polycystic ovary syndrome (PCOS), and Alzheimer’s disease, that are commonly associated with metabolic syndrome. Kahn et al. (2005) speculate that insulin resistance is related to dyslipidemia and glucose intolerance, while it is not related to obesity. Holt and Whitaker (2002) reiterate that insulin resiatance is the esential cause of the syndrome. The team believes that insulin resistance predisposed to obesity and glucose intolerance with consequent elevated blood sugar (hyperglycemia) that may finally lead to type 2 diabetes.
Multiple metabolic pathways are also proposed to link insulin resistance to the rest of metabolic risk factors. Modern medicine has ultimately recognized obesity as proinflammatory disorder associated with raised blood C-reactive protein (CRP) levels. It has been already proven that obesity causes insulin resistance, despite it is not related to elevated blood pressure.
A National Health and Nutrition Examination Survey (NHANES, 2005-2006) claims that impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) are the two main constituents of metabolic syndrome or prediabetes. Elevated insuline seems independently associated with prediabetes and may account for the association of being overweight and the clustering of all the above mentioned cardiometabolic risk factors with prediabetes.
Dyslipidemia and mainly lipid peroxidation play an important role in metabolic syndrome development. Oxidative stress has been implicated in the accelerated atherosclerosis and microvascular complications of diabetes mellitus, resulting in a widespread DNA cell damage. Oxidative damage stays central in metabolic syndrome etiopathogenesis. The appearance of malignant hypertension, dyslipidemia and type 2 diabetes mellitus, considered abnormalities of the metabolic syndrome cluster are described in the literature as secondary to, or exacerbated by obesity.
Syndrome X in older men and women is associated with excess accumulation of abdominal (belly fat) or intramuscular fat, even in completely normal-weight individuals. The authors teach that the influx of nonesterified fatty acids to the liver is tied into visceral fat accumulation as a contributing factor. (Source, Steady Health) Liver steatosis (or the fatty degeneration or the liver) has long been associated with long-term and excessive alcohol consumption. But there is another so called “non-alcoholic” liver steatosis, believed to be caused by a poor diet, loaded with simple sugars and constant use of complex carbohydrates. Also called a “non-alcoholic fatty liver disease” (NAFLD), or liver steatosis, the disorder affects about one third of the American adult population. While the numbers are progressively rising, people are unaware they have the above problem, as it rarely causes symptoms by itself, but when accelerates in its progression- it can lead to elevated level of increased mortality.
Central to atherosclerosis main cause and development combined with an earlier endothelial dysfunction is believed to be an oxidative damage of LDL cholesterol. Overproduction of very low-density lipoproteins (VLDL) is the hallmark of the dyslipidemia in metabolic syndrome development according to many trials. In a study done by Pittas at al. (2004), the connection between adipocytokines and insulin resistance is claimed as a major factor in the metabolic syndrome appearance.
Inflammation is another important culprit in the development of insulin resistance and metabolic syndrome. Main markers for diagnosing the degree of inflammation are C-reactive protein (CRP) test, plasma homocysteine test, and the red blood cells sedimentation rate test (ECR). (Source, Wiki and Answers). The pro-inflammatory component of metabolic syndrome has been increasingly recognized over the last decade as the missing link leading to the “deadly quartet” of metabolic abnormalities. (Source, Wiki)
The connection between glycated hemoglobin (HbA1C) and cardiovascular disease appearance is proved in a meta-analysis done by Selvin et al.(2004). Inflammation, in fact, participates in all stages of metabolic syndrome, not only during the process of initiation of metabolic cascade but also during the evolution of the metabolic syndrome effects. Metabolic syndrome is seen by many authors as final result of a vicious circle connection between obesity, insulin resistance, chronic inflammation and diabetes. (Source, Wiki)
The etiopathogenesis (the cause and development) of the metabolic syndrome has significant association with other chronic viral and bacterial infectious agents. A new study is turning to the bacterial etiology of metabolic syndrome appearance. According to Erol’s (2008) hypothesis, the appearance of visceral (belly fat) tissue is showing specific connection with the bacterium – Mycobacterium tuberculosis, suspected to be the main reason for the syndrome appearance. Chlamydia pneumonia, Helicobacter pylori, Cytomegalovirus (CMV) and Herpes simplex virus Type 1 (HSV-1) are blamed respectively for the bacterial and viral cause and development of the disease . It is yet to be studied and determined whether atherosclerosis is caused by direct specific activity of a pathogen or whether it is a result of proinflammatory (cytokines) activity or C reactive protein. (Source, Wiki)
While the underlying cause and development of metabolic syndrome is still a dilemma and subject of intense debate, both abnormal abdominal fat distribution and insulin resistance have been identified as potential and tightly interrelated causes leading to the metabolic consecutive damage.
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