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Metabolic Inflammation: What is it?

Important Points:

  • Inflammation
  • cytokines
  • homeostasis
  • metabolic syndrome

Metabolic Inflammation: What is it?

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.

1. What is the metabolic syndrome?

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.

2. What is Inflammation?

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.

3. Inflammation and the metabolic syndrome

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.

4. Inflammation and its outcomes

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:

            4.1 Obesity

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.

               4.3 Atherosclerosis

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.

5. What then can be done?

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.

References

1.    NCBI ( 2007): Cardiovascular metabolic syndrome – an interplay of, obesity, inflammation, diabetes and coronary heart disease. Retrieved from.

 https://www.ncbi.nlm.nih.gov/pubmed/17391148

Current Research in Nutrition and Food Science (2015): Inflammation and Metabolic Syndrome- An Overview. Retrieved from http://www.foodandnutritionjournal.org/volume3number3/inflammation-and-metabolic-syndrome-an-overview/

3.    NCBI (2011): Inflammation and the Metabolic Syndrome. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3210244/

4.   NCBI (2013): Obesity, Inflammation and Diet. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3819692/

5.    WebMD: Diabetes and Inflammation. Retrieved from https://www.webmd.com/diabetes/type-2-diabetes-guide/inflammation-and-diabetes#1

6.    Wikipedia: Inflammation. Retrieved from https://en.wikipedia.org/wiki/Inflammation

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Unraveling the Metabolic Syndrome

Important Points:

  • Metabolic syndrome
  • Type 2 diabetes
  • Blood sugar
  • Insulin resistance

Unraveling the Metabolic Syndrome

Metabolic syndrome can be defined as a cluster of conditions that increase one’s risk for heart disease and type 2 diabetes. The cardinal signs involved include increased blood pressure, high blood sugar levels (insulin resistance), excess belly fat, high triglyceride levels, and low levels of good cholesterol (HDL). If you have at least three of them – you may already have the condition.

If you have any of the listed symptoms you should not panic as this is not a sure sign that you will develop heart disease or type 2 diabetes; however, it means that you should take caution because you are at a higher risk for developing either or both the diseases. Having more risk factors puts you at a greater risk as well.

Approximately 47 million Americans suffer from metabolic syndrome which translates to a staggering one in six people. There is a genetic link to this syndrome which mostly affects African-Americans, Hispanics, Asians, and Native Americans. The risks of developing metabolic syndrome increases as you age. Fortunately, aggressive lifestyle changes can delay or even prevent serious health problems for those at risk of developing the disease.

What are the Symptoms of Metabolic Syndrome?

Metabolic syndrome is a cluster of conditions that indicate an underlying disease process. Some conditions including elevated triglycerides, high blood sugar, and high blood pressure need to be lab tested which makes it harder to pick up on the symptoms of the syndrome. Generally, a large or increasing waist circumference together with one or two other lab-tested signs may be an indication of the syndrome.

What are the Causes of Metabolic Syndrome?

Metabolic syndrome is closely linked to a sedentary lifestyle defined as sitting or lying down for long hours without expending much energy. When this is combined with an unhealthy diet such as eating processed foods packed with empty calories, chances of developing metabolic syndrome are increased.

Metabolic syndrome is also linked to insulin resistance. When a person has insulin resistance their cells don’t respond normally to the hormone insulin which removes sugar from the blood and stores it in cells. This leads to an increase in blood sugar levels.

Abdominal obesity, having extra fat around the waist, is another risk factor for metabolic syndrome. Lastly, hormonal imbalance and conditions including polycystic ovarian syndrome may also contribute to the development of the metabolic syndrome.

Age and ethnicity are other risk factors as risk increases with age and metabolic syndrome is seen more in certain ethnicities such as Hispanics in the US.

What are the Complications of Metabolic Syndrome?

Having metabolic syndrome can predispose you to the risk of developing:

  • Type 2 diabetes. One of the signs of Metabolic Syndrome is insulin resistance which is a precursor to type 2 diabetes.
  • Heart Disease. High levels of bad cholesterol and high blood pressure due to metabolic syndrome can lead to atherosclerosis. Many times, this eventually leads to heart disease and increased risk for stroke.

How is Metabolic Syndrome Diagnosed?

There are a few signs that may point towards metabolic syndrome. They include:

  • Having a large waist circumference measuring at least 89 centimeters for women and 102 centimeters for men.
  • Having high triglyceride above 150 milligrams per deciliter (mg/dL).
  • Low “good” (HDL) cholesterol levels below 40 mg/dL in men or below 50 mg/dL in women.
  • Having increased blood pressure of 130/85 millimeters of mercury (mm Hg) or higher.
  • Having high blood sugar of 100 mg/dL (5.6 mmol/L) or higher.

How Can You Prevent Metabolic Syndrome

Metabolic syndrome is largely a diet and lifestyle enhanced condition. Making the following lifestyle changes can prevent conditions that cause it:

Regular exercise

Health experts recommend exercising for at least 30 minutes each day. This may include brisk walking, aerobics, or slow jogging. If you are at high risk for heart disease you will need to consult with your physician before you can engage in strenuous physical activity.

Lose Weight

If you have extra weight around the mid-section it may be wise to shed it off. You can achieve this through targeted weight lifting and controlling your calorie intake. Losing 7 to 10 percent of your body weight can reduce insulin resistance and blood pressure and also decrease your risk of diabetes. Avoid embarking on weight loss crush programs as you are bound to rebound and gain more weight than you had previously. Instead, work on a program that allows you to lose weight gradually and sustainably.

Adopt a healthy diet plan

A healthy heart diet should be comprised of:

  • Vegetables
  • Fruits
  • Unsaturated fats
  • Whole grains rich in fiber
  • White meat

You should avoid or limit your intake of the following:

  • Sugar-sweetened beverages
  • Processed foods
  • Red meat
  • Excess alcohol
  • Excess salt
  • Trans fats and saturated fats

Reducing or manage stress

Stress is a big contributor to unhealthy lifestyle patterns. If you are at high risk for developing metabolic syndrome regular distressing may be necessary for you. Exercises such as meditation and yoga can be good ways to help you relax. Listening to classical music, taking up a hobby or traveling for leisure can also be of help. Ultimately, you will need to commit to a healthy lifestyle which will not only lower your risk for metabolic syndrome but also reduce your risk for other chronic conditions such as cancer and osteoporosis.

References

1.   Medscape (2019): Metabolic Syndrome: A Growing Clinical Challenge: Epidemiology. Retrieved from https://www.medscape.org/viewarticle/484166_2

2.   Heart.org: What is Metabolic Syndrome? Retrieved from https://www.heart.org/en/health-topics/metabolic-syndrome

3.   WebMD: What is Metabolic Syndrome? Retrieved from https://www.webmd.com/heart/metabolic-syndrome/metabolic-syndrome-what-is-it#

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Metabolic inflammation as a cause of insulin resistance

Important Points:

Metabolic inflammation as a cause of insulin resistance

In previous articles, I have discussed the role of metabolic Inflammation in obesity and diabetes. Today, we will narrow down to the specifics of what insulin resistance is, its effects, and how metabolic inflammation increases the chances of one developing it.  

1. What is Insulin resistance?

Approximately 30% of Americans, and up to 50% in the 60 years and over bracket, have a silent blood sugar problem known as insulin resistance. It begins when cells in your muscles, body fat, and liver repel or ignore the signal sent out by the hormone insulin to take glucose from bloodstream into our cells for breakdown or storage. Glucose, commonly called blood sugar and is the body’s main source of fuel.

Insulin resistance increases the risk for prediabetes, Type 2 diabetes, and a host of other serious health problems, including heart attacks, strokes and cancer.

2. How does Insulin Resistance Develop?

Some factors that determine insulin resistance are aging and ethnicity, but the driving forces seems to be excess body weight, too much belly fat, a lack of exercise, smoking, and even sleep depravity.

As the insulin resistance develops, more insulin is produced by your body as it tries to fight back. After an accumulated period of time, several years even, the beta cells in your pancreas get worn out because of all the extra work and can no longer keep pace with the increased demand for insulin. Then – years after insulin resistance stealthily began – your blood sugar may spike and you may manifest prediabetes or type 2 diabetes. You are also at risk of developing non-alcoholic fatty liver disease (NAFLD), a condition that increases your risk for liver damage and heart disease.

3. What are the Signs and Symptoms of Insulin Resistance?

Insulin resistance does not always manifest to the naked eye but here are other possible signs that are visible:

  • A large waist. Experts say the best way to tell whether you’re at risk for insulin resistance involves a tape measure and moment of truth in front of the bathroom mirror. A waist that measures 35 inches or more for women, 40 or more for men (31.5 inches for women and 35.5 inches for men if you’re of Southeast Asian, Chinese or Japanese descent) increases the odds of insulin resistance and metabolic syndrome, which is also linked to insulin resistance.
  • Additional signs of metabolic syndrome. According to the National Institutes of Health, in addition to a large waist, if you have three or more of the following, you likely have metabolic syndrome, which creates insulin resistance.
  • High triglycerides. Levels of 150 or higher or taking medication to treat high levels of these blood fats.
  • Low HDLs. Low-density lipoprotein levels below 50 for women and 40 for men or taking medication to raise low high-density lipoprotein (HDL) levels.  
  • High blood pressure. Readings of 130/85 mmHg or higher or taking medication to control high blood pressure
  • High blood sugar. Levels of 100-125 mg/dl (the prediabetes range) or over 125 (diabetes).
  • High fasting blood sugar or you’re on medicine to treat high blood sugar. Mildly high blood sugar may be an early sign of diabetes.
  • Dark skin patches. If insulin resistance is severe, you may have visible skin changes including patches of darkened skin on the back of your neck or on your elbows, knees, knuckles or armpits. This discoloration is called acanthosis nigricans.

4. Chronic low-grade inflammation and the development of insulin resistance

As early as 1950’s, a connection between inflammation and insulin resistance seemed to present especially in the obese, but the mechanics of the link were unknown. Recently, this has become clearer. Research has shown an association between the body activating signal pathways for inflammation over and over and a decrease in insulin sensitivity which is a rise in insulin resistance. Elevated levels of many inflammation signaling molecules (cytokines) and the inflammatory marker C-reactive protein (CRP) were found in those with insulin resistance and its symptoms, especially those that were obese.

5. What Health Conditions are Related to Insulin Resistance?

An estimated 87 million American adults have prediabetes; 30-50% will go on to develop full-blown type 2 diabetes., and up to 80% of people with type 2 diabetes have NAFLD. But those aren’t the only threats posed by insulin resistance.

Thanks to years of high insulin levels followed by an onslaught of cell-damaging high blood sugar, people with insulin resistance, prediabetes, and type 2 diabetes are at high risk for cardiovascular disease. Insulin resistance doubles your risk for heart attack and stroke and triples the odds that your heart attack or ‘brain attack’ will be deadly, according to the International Diabetes Federation.

Meanwhile, insulin resistance and metabolic syndrome are also linked with higher risk for cancers of the bladder, breast, colon, cervix, pancreas, prostate and uterus. The connection: High insulin levels early in insulin resistance seem to fuel the growth of tumors and to suppress the body’s ability to protect itself by killing off malignant cells.

Research has also found a strong association between insulin resistance and memory function decline, increasing the risk for Alzheimer’s disease

Research has also found a strong association between insulin resistance and memory function decline, increasing the risk for Alzheimer’s disease.

6. Can understanding the causes of Insulin Resistance aid in future preventive approaches?

As obesity-associated chronic low-grade inflammation is responsible for the decrease of insulin sensitivity, so obesity is a major risk factor for insulin resistance and related diseases such as type 2 diabetes mellitus and metabolic syndromes. The state of low-grade inflammation is caused by over-nutrition which leads to lipid accumulation in adipocytes and interferes with insulin signaling and action. This interference only adds to the cascade of errors (pathogenesis) that leads to insulin resistance. It has been suggested that specific factors and signaling pathways are often correlated with each other; therefore, both the accumulation and the interference mentioned should be studied further to fully understand the connection between inflammation and insulin resistance.

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What is the relationship between metabolic Inflammation and type 2 diabetes?

Important Points:

  • Inflammation
  • Diabetes
  • Obesity
  • Metabolic syndrome
  • Beta cells

What is the relationship between metabolic Inflammation and type 2 diabetes?

A growing body of data shows that type 2 diabetes is at least in part rooted in inflammation. The higher a person’s body mass index, the more pro-inflammatory macrophages they have in their fat tissue and the higher their chances of developing Type 2 diabetes. In this article, we will highlight the emerging role of inflammation in the pathway that leads to diabetes. We will also analyze the implicated inflammatory pathways and biomarkers of inflammation in diabetes and metabolic diseases.

1. The Metabolic Syndrome and Metabolic Inflammation

Metabolic syndrome often precedes type 2 diabetes and cardiovascular disease and is characterized by high blood pressure, a large waist circumference, elevated fasting glucose and triglycerides, and low HDL cholesterol.

Metabolic inflammation (MI) is currently a hot research topic, wherein peculiarities in metabolic and inflammatory pathways are looked into for their possible contribution to atherosclerosis, Type 2 diabetes, and insulin resistance (IR). In MI, insulin signaling is hindered by obesity-related inflammation. Metabolically activated macrophages are key cells in the process believed to spike both pro- and anti-inflammatory pathways in reaction to excess fat.

Diabetes is a complex metabolic disorder affecting the glucose status of the human body. The main clinical diagnostic features are impaired glucose tolerance and hyperglycaemia which occur as the result of an absolute or relative insulin deficiency or resistance to its action. Chronic hyperglycaemia associated with diabetes can result in end organ dysfunction and failure and may involve the retina, kidneys, nerves, heart and blood vessels. There is a  clinical relationship between diabetes and atherosclerotic cardiovascular disease, with the risk for cardiovascular disease (CVD) being significantly elevated in patients with diabetes.

Typically, CVD occurs one to two decades earlier in people with diabetes, with more aggressive, severe and diffuse distribution.The first WHO global report on diabetes published in 2016 demonstrates that the number of adults living with diabetes has almost quadrupled since 1980 to 422 million adults and this is expected to rise to 552 million by 2030.Effective novel therapeutic approaches are needed for the treatment and/or prevention of diabetes and atherosclerotic disease.

Various proposals and hypotheses have been developed to describe the mechanisms involved in the propagation of diabetes, mainly focusing on Type 2. The increase in prevalence of the condition has been related to well-recognized risk factors, such as the adoption of a western lifestyle, lack of physical activity, and high sugar diet. 

Genetic predisposition, ethnicity, and aging are not modifiable risk factors for Type 2 diabetes, but other factors such as being overweight or obese, an unhealthy diet, insufficient physical activity, and smoking are modifiable through behavioral and environmental changes. However, increasing evidence has shown that inflammatory pathways are common in both the modifiable and non-modifiable factors.

 2. When was inflammation first thought to cause diabetes?

Observational studies provided the first evidence for the possible association between inflammation and diabetes. Over a century ago, the administration of high doses of salt led to decreased blood sugar in people with a suspected or definite diagnosis of diabetes.Later studies on the role of inflammation in diabetes revealed that this hypoglycaemic action was related to the inhibition of an enzyme which is one component in the insulin response pathway.

A landmark study to correlate inflammation with diabetes, conducted in animal models by Hotamisiligil et al. in 1993, revealed that tumor necrosis factor-alpha (TNF-alpha) played a role in obesity and particularly in insulin resistance and diabetes.Causal connections between inflammation and obesity or Type 2 diabetes were made because of these findings. 

Over the next decades, many studies provided more supporting evidence for the role of inflammation in the initiation and progression of diabetes.Accumulative evidence suggests that chronic inflammation in target cells of insulin action may contribute to obesity, insulin resistance, and related metabolic disorders including Type 2 diabetes. 

What is the relationship between Metabolic Disorders and Inflammation in Type 2 Diabetes?

In several studies, our understanding of insulin resistance and insulin secretion in the onset of Type 2 diabetes and its progression has been expanded.Subjects at risk of T2D display an initial state of insulin resistance compensated by hypersecretion of insulin in the beta cells. As it progresses, this shift in pancreatic function is eventually unable to cope with the required insulin secretion, and by the time diabetes is diagnosed, beta cells are no longer able to secrete enough insulin. 

Although the relative contribution of beta cell dysfunction and insulin resistance can vary in people with Type 2 diabetes, it is generally accepted that abnormal insulin sensitivity precedes the clinical diagnosis of diabetes by up to 15 years.Therefore, along with looking into the mechanism of insulin resistance, studies have investigated the pathways leading to beta cell failure.

3. Is there evidence of Inflammation in Other Organs in People with Type 2 Diabetes?

The evidence is inconclusive whether the inflammatory state in Type 2 diabetes can spread to other organs such as the liver, the neural system, and possibly skeletal muscle. More research is needed to determine this.

4. What are the Future Perspectives for the Treatment of Diabetes?

Below are some of the approaches currently being investigated.

  1. Gauging anti-inflammatory diets in streamlining an individual’s microbiome through innovative approaches for Type 2 diabetes
  2. Examining the effects of vitamin D supplementation on serum levels of inflammatory markers through clinical trials; results so far are inconsistent
  3. investigating whether antagonists of leukotriene production enzymes or receptor binding BLT1 have benefits for metabolic and cardiovascular health; results have not been reported yet

5. What is the future of understanding metabolic inflammation as a cause for diabetes?

Given the increasing prevalence of diabetes, it is crucial that research focuses on its prevention as well as its treatment. Heart disease, the metabolic syndrome and type 2 diabetes (T2D) all have a high level of circulatory cytokines as a result of inflammation. Inflammatory cytokines are produced by different cell types and secreted into the circulation, where they regulate different tissues through their local, central, and peripheral action.

An improved understanding of the mechanisms linking inflammation to diabetes and related complications has stimulated interest in targeting inflammatory pathways as part of the strategy to prevent or control diabetes and its complications.

Type 1 diabetes is considered to be more of an immunological response rather than a metabolic disorder and the preliminary results of trials using anti-inflammatory and immunomodulatory medication are promising. These treatments in combination with possible use of stem cells to regenerate pancreatic beta cells could potentially be the key to permanent treatment of Type 1 diabetes. Therefore, after a holistic review of the possible mechanisms that lead to Type 1 and Type 2 diabetes and the numerous already described inflammation pathways that are involved, it becomes more and more clear that future research should focus on simultaneous suppression of various inflammatory response pathways rather than focusing on one pathway at a time.