In the quest to understand the causes and early symptoms of diabetes and other chronic diseases, metabolic inflammation is often mentioned. What is it, and what is its role in the early onset of these diseases? This article delves into the definition of the term, its presentation, and likely effects.
The occurrence of the metabolic syndrome has been on the rise in both developed and developing Countries. It can be described as a group of disorders including glucose intolerance, central obesity, hypertension, and lipid malfunctions present in various forms, depending upon the combination of the different components of the syndrome. Metabolic syndrome has been generally accepted to increase the risk for the development of Type 2 diabetes, cardiovascular disease, stroke, and cancer.
Inflammation is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants,and is a protective response involving immune cells, blood vessels, and molecular mediators. Immune signaling molecules called cytokines orchestrate inflammatory response when the harmful stimuli are detected. The inflammatory responses caused by both pathogens and wounding can cause damage to cells and tissue which in turn can induce further inflammatory responses.
The primary duty of inflammation is to isolate or rapidly destroy the underlying source of the disturbance, remove damaged tissue, and then restore tissue homeostasis. Excessive inflammation can have adverse effects, resulting in collateral damage and disease.
Metabolism can be described as the whole range of biochemical processes that occur within a living organism. Without a doubt, the relationship between inflammation and metabolism is complex. Several explanations have been proposed to explain the origin of the metabolic syndrome. Some consider an initial insulin resistant state progressing to the other components, while others view obesity as the main initiator of the syndrome.
More recently, the chronic low-grade inflammatory condition that often accompanies the metabolic syndrome has been implicated as a major factor both in the beginning of the metabolic syndrome and its associated pathophysiological consequences.
The inflammatory state that accompanies the metabolic syndrome does not completely fit into the classical definition of acute or chronic inflammation as it is not accompanied by infection; there is no massive tissue injury and the dimension of the inflammatory activation is also not large. It is therefore often called ‘low grade’ chronic inflammation or ‘meta-inflammation’, meaning metabolically-triggered inflammation or even ‘para-inflammation’ an intermediate state between basal and inflammatory states. Whatever the term used, the inflammatory process that characterizes the metabolic syndrome has its own unique features but its causes are far from being fully understood.
Despite it being an essential response to infection and tissue injury, inflammation has also been associated with several pathological processes. Excessive acute inflammation causes tissue damage and non-resolving inflammation leads to chronic tissue malfunction, suggesting a delicate balance between the rapid and effective response to distresses in tissue homeostasis and the collateral damage on tissue function.
As a cluster, obesity, raised fasting plasma glucose, high cholesterol and hypertension comprise the metabolic syndrome. We will have an in-depth discussion on some of these conditions in relation to metabolic inflammation:
Obesity is characterized by a low-grade chronic state of inflammation in which the level of pro-inflammatory cytokines such as TNF-α, IL-6 and CRP are increased. It is a state in which there is an over-accumulation of subcutaneous and/or abdominal fat (adipose tissue).
This adipose tissue is no longer considered inert and mainly devoted to storing energy; it is emerging as an active tissue in the regulation of physiological and pathological processes, including immunity and inflammation. Adipose tissue is also implicated in the development of chronic metabolic diseases such as type 2 diabetes mellitus or cardiovascular disease.
Obesity can therefore be caused by inflammatory and metabolic diseases. Diet or dietary patterns play critical roles in obesity and other pathophysiological conditions as well. It is therefore recommended for one to have a healthy diet and other nutrients that are generally considered to be beneficial.
4.2 Type 2 Diabetes Mellitus
Type 2 Diabetes is a disease of insulin resistance, where people produce too much insulin and their receptors don’t work. They become insulin resistant and the inflammation arises from excessive insulin.
It has been known for a while that there are higher levels of inflammation in the bodies of individuals with type 2 diabetes. The levels of certain inflammatory chemicals called cytokines are much higher in people with type 2 diabetes than in people who do not have diabetes.
The development of Type 2 diabetes is to a large extent driven by obesity and inactivity. Excess body fat, especially in the abdomen, leads to continuous (chronic), low levels of abnormal inflammation that alters insulin’s action and production. Chronic levels of free fatty acids and glucose as a result of insulin resistance induce further inflammation which results in increased cell death and impaired insulin secretion. This in turn prompts the progression from obesity and insulin resistance to full blown Type 2 Diabetes.
As type 2 diabetes starts to develop, the body becomes less sensitive to insulin and the resulting insulin resistance also leads to inflammation. A vicious cycle can result, with more inflammation causing more insulin resistance and vice versa. Blood sugar levels creep higher and higher, eventually resulting in hyperglycemia and other more serious effects of type 2 diabetes.
Heart disease is currently one of the major causes of disease and mortality facing humanity. Such a paradigm shift in disease pattern over the last century has been facilitated by the alarming global incidence of obesity and type 2 diabetes. Lately, there is an increasing focus on inflammation as one of the key factors in the pathophysiology of these disorders.
Early metabolic abnormalities that include weight gain, insulin resistance, and prehypertension and irregular blood lipid levels seem to have a complex relationship with diseases of the cardiovascular system.
Obesity increases the chances of diabetes, high blood pressure, pro-thrombotic state, and abnormal lipid presence. While inflammation and insulin resistance have direct antagonistic effects on the cardiac muscle, these metabolic irregularities as a whole lead to cardiovascular problems, warranting a multifaceted therapeutic and precautionary method of approach for the ‘Cardiovascular Metabolic Syndrome’ holistically.
4.4 Non-alcoholic Fatty Liver Disease
Non-alcoholic Fatty Liver Disease is the predominant cause of liver disease. Its prevalence reaches 30% of the population and up to 75–100% in people with obesity.Different degrees of severity characterize this disease. A great majority of patients do not display any symptoms, however, nearly 20% eventually progress to develop chronic hepatic inflammation which can lead to early hypertension, cirrhosis, cancer of the liver, and increased mortality.
NAFLD is linked to overweight or obesity, Insulin resistance (in which your cells don’t take up sugar in response to the hormone insulin), high blood sugar (hyperglycemia, indicating prediabetes or type 2 diabetes) and high levels of fats, particularly triglycerides, in the blood.
Although this is one of the most prevalent metabolic anomalies in humans, what triggers the inflammation has remained elusive.
The appearance of chronic diseases such as type 2 diabetes, atherosclerosis, non-alcoholic liver diseases, and gout seems to be fairly recent. Taking into account the generally late onset of these diseases in the life of an affected individual, the causes and effect of inflammation-induced metabolic disease needs to be looked at in-depth considering increased life expectancy and the Western lifestyle.
Understanding inflammation as a critical component of metabolic syndrome can shed some light on what metabolic inflammation is and how it very likely plays a significant role in the onset of these chronic diseases. In turn, care can be taken to prevent or even stop metabolic inflammation before it causes serious harm.
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