In our previous article, I introduced the term diabesity. In case you haven’t read it, you can check it here (link to what is diabesity). In a nutshell, diabesity is the description of diabetes type 2 when it occurs in the context of obesity. Diabesity is triggered by the onset of insulin resistance which means that insulin is not able to take out glucose from the bloodstream. Insulin resistance is often accompanied by excessive insulin as the beta cells of the pancreas keep producing more insulin to get rid of excess sugar. In this article, we will discuss what role inflammation plays and why it might be the most important mechanism fuelling the diabesity epidemic.
Why are anti-inflammatory drugs not the mainstay of diabetes type 2 treatment?
Before delving into the meat of the diabesity-inflammation pendulum, I decided to throw in a teaser. I will quote from an article published in JCI in 2006 titled “Inflammation and Insulin Resistance.”
“Clues to the involvement of inflammation in diabetes date back to more than a century ago when high doses of sodium salicylate (5.0–7.5 g/d) were first demonstrated to diminish glycosuria in diabetic patients having type 2 diabetes. In 1876 Ebstein concluded that sodium salicylate could make the symptoms of diabetes mellitus totally disappear.”
Why then are anti-inflammatory agents not the mainstay of diabetes type 2 treatment? This is indeed a controversial topic. However, it is believed that sodium salicylate was dropped because of the serious side effects it causes when given in high doses.
Now we can look at the pendulous relationship between diabesity and inflammation.
How does Inflammation Cause Diabesity?
There are several lines of evidence linking inflammation with obesity and diabetes. I will outline a few:
- Inflammatory markers are elevated prior to the diabesity.
Elevated levels of inflammatory cytokines could indicate future weight gain and obesity. A lab study also showed that an infusion of inflammatory cytokines into healthy mice causes insulin resistance.
This idea is also supported by the fact that people with other chronic inflammatory conditions are more likely to develop diabesity and type 2 diabetes.
- Inflammation causes insulin resistance
Inflammation of the fat tissue causes insulin resistance, which is the primary cause of diabesity. A small protein known as TNF-α which is released during inflammation has been shown to cause insulin resistance. Other inflammatory proteins such as MCP-1 and C-Reactive protein, have also been linked to insulin resistance.
- Inflammation in the brain causes leptin resistance
Inflammatory signaling in the hypothalamus has been linked to leptin resistance in both animals and humans. Leptin is produced in fat cells but exerts its effects primarily in the hypothalamus. It is the starvation hormone, but it is also referred to as the obesity hormone. Leptin resistance means that your body is no longer responsive to the hormone leptin. When this happens, your brain is fooled into believing that you are starving and hence you need to keep eating more and more food. Eventually, this leads to diabesity.
How Does Diabesity Cause Inflammation?
For a long time, it was believed that fat is an inert tissue with no biological activity. However, it is now known that fat is a metabolically active endocrine organ that produces hormones and inflammatory molecules. The feature of fat is the key to understanding its role in diabesity and inflammation.
- Diabesity induces inflammation as a protective mechanism.
Diabesity causes the buildup of fat around the waist. Fat storage is an anabolic process while inflammation is a catabolic process. The body may activate catabolism through inflammation so as to keep weight within acceptable limits. Experimentally induced inflammation in fat tissue has been shown to initiate weight loss and improve insulin resistance.
- Diabesity related stresses could cause inflammation
Obesity has been associated with chronic low-level inflammation. it is hypothesized that the stresses of diabesity are similar to the stresses caused by an infection. As a result, the body responds in a similar way by triggering inflammation.
Obesity has also been linked to the release of inflammatory compounds such as TNF-α. This means that the more fat tissue you have, the more inflammation you are likely to have.
The Chicken Versus The Egg
It is clear that there is a direct relationship between diabesity and inflammation. However, it is not very clear which factor precedes the other. Inflammation is both the cause and the result of diabesity. Inflammation plays a big role in causing diabesity. On the other hand, the occurrence of diabesity can further stimulate the production of inflammatory cytokines, forming a vicious cycle of inflammation and diabesity.
We can then confidently conclude that the best approach towards the treatment or prevention of diabesity has to begin with addressing the underlying inflammation. It should also involve treating inflammation once diabesity has occurred. The modern clinical approach is focused on regulating blood sugar without addressing inflammation. Unfortunately, such an approach is bound to produce inferior results.
References
1. ADA: Inflammation-Sensitive Plasma Proteins Are Associated With Future Weight Gain. Retrieved from https://diabetes.diabetesjournals.org/content/52/8/2097.full?ijkey=c30ecf67b38ac20bc59ecf06ac0a8cbb539532fc
2. NCBI (1993): Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/7678183?dopt=Abstract
3. NCBI (2012): Obesity is associated with hypothalamic injury in rodents and humans. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248304/
4. JCI (2005): Inflammation, stress, and diabetes. Retrieved from https://www.jci.org/articles/view/25102/version/1
Diabetes was the leading cause of death in the US in 2015. To date, it follows closely behind cardiovascular disease and cancer.
For many people, the diagnosis of type 2 diabetes can be devastating as this comes with lots of risks and uncertainties. Also, this implies having to grapple with increasing healthcare costs to manage the chronic condition. The cost of treating diabetes in the US is approximately $7,900 per person each year.
Just across in the UK, the National Health Service (NHS) is looking for ways to curb the diabetes type 2 epidemic which is causing a strain on the already overstretched NHS budget. Towards the end of last year, the NHS initiated a program that involves starting 5,000 patients on a liquid diet of just over 800 calories a day for 120 days in a bid to reverse the condition. This is part of the NHS Diabetes Prevention Programme (NHS DPP) intended for people who are at risk of type 2 diabetes The project comes after a highly successful trial of the same nature. This liquid diet is meant to restrict the calorie intake of the patients with the hope of helping them achieve a healthy weight and healthy lifestyle. In the end, these lifestyle changes should lead to diabetes reversal.
What is diabetes type 2?
Diabetes is a condition that causes an individual’s blood sugar levels to become too high. Type 2 diabetes happens when a person progressively becomes insensitive to the effects of insulin. The pancreas then secretes more insulin leading to too much insulin in the body. Eventually, the insulin levels may decline when the production sources are exhausted.
Diabetes type 2 is linked to obesity and cancer. Fortunately, it is preventable through diet and lifestyle changes.
In the US, there are about 100 million people living with diabetes or prediabetes. 9 out of 10 of diabetes cases have diabetes type 2. The study alluded to above suggested that a liquid diet could help in reversing diabetes in most patients.
What Is A Liquid Diet?
A liquid diet (like the one used in the study) is generally a very low-calorie diet. It usually involves eating around 800 calories a day or less. Just to put this in perspective: this is a third of what a man usually takes and half of what a woman should take.
The liquid diet consists of shakes and soups, according to the NHS. A person should use this diet for no more than 12 weeks and should do this only under strict medical supervision.
Side effects to expect include:
- Dry mouth
- Constipation
- Diarrhea
- Headaches
- Dizziness
- Cramps
- Hair thinning
This diet is not suitable for everyone.
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Successful trial
The milestone study is called DiRECT which is an acronym for Diabetes Remission Clinical Trial/ As much as the study is not complete, preliminary findings have caused lots of excitement. So much so that NHS England has committed to piloting a Type 2 diabetes remission programme in 2019 with about 5,000 study participants.
The first-year results showed that almost half (45.6%) of those who took part in the programme were in remission after a year. By the end of the second year, 70% were still in remission. Overall 30% of study participants were still in remission two years. This is encouraging for the diabetic community as it dispels that myth that this is an irreversible disease.
The second-year results showed a close correlation between diabetes type 2 remissions and weight loss. The majority of those who lost more than 10 kilos maintained remission after two years. Weight loss was also associated with improved quality of life, improved blood glucose (sugar) control, and a reduced need for diabetes medications.
The researchers admitted that this approach cannot work for everyone. It is important to understand the biology underlying remission before implementing any treatment.
What Is Diabetes Remission?
Diabetes remission means that a person with diagnosed diabetes can maintain normal blood glucose levels without using any medication. This doesn’t mean diabetes has gone for good, but that the person is living symptom-free and medication-free as well. A person in remission still needs regular check-up and follow up by a physician.
What Is The NHS Plan
The NHS long-term plan is to empower people living with type 2 diabetes to take charge of their own health needs. By limiting their calorie intake and reducing weight, most patients can achieve diabetes reversal.
Ultimately, this will result in lower healthcare costs for the NHS as well as individual patients. Speaking to news, NHS England chief executive Simon Stevens had this to say:
“However this isn’t a battle that the NHS can win on its own. The NHS pound will go further if the food industry also takes action to cut junk calories and added sugar and salt from processed food, TV suppers, and fast food takeaways.”
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References
- CDC: Death and Costs. Retrieved from https://www.cdc.gov/diabetes/data/statistics-report/deaths-cost.html
- iNews (2019): Type 2 diabetes patients to be prescribed very low-calorie liquid diet to reverse. Retrieved from https://inews.co.uk/news/type-2-diabetes-patients-prescription-very-low-calorie-liquid-diet-reverse-condition-198716
- BBC News (2018): Type 2 diabetes: NHS to offer 800-calorie diet treatment. Retrieved from https://www.bbc.com/news/health-46363869
- Diabetes UK: NHS England announces Type 2 remission pilot, and plans to double the size of the NHS England Diabetes Prevention Programme. Retrieved from https://www.diabetes.org.uk/about_us/news/nhs-type2-remission-pilot
The pancreas is an exocrine gland that produces two key hormones involved in the regulation of blood sugar: Insulin and Glucagon. Beta cells are distinctive cells within the pancreas that are responsible for the production of insulin. Why should you know about beta cells? Beta cells are linked to diabetes which is a disease of insulin resistance. Located within the islets of Langerhans (part of the pancreas), they’re one among a minimum of 5 differing types of islet cells that secrete hormones directly into the blood.
What is the role of beta cells?
The main role of beta cells is to provide and secrete insulin into the bloodstream when needed. When blood sugar levels begin to rise (e.g. when you are having a meal), beta cells quickly respond by secreting insulin into the bloodstream to take up the glucose being produced and store it in cells. Beta cells also increase the production of the hormone insulin in response to rising levels of glucose in the blood. This fast response to a spike in blood sugar typically takes about 10 minutes.
In people with diabetes, however, these cells are either attacked or destroyed by the system (type 1 diabetes), or become resistant to the effects of insulin (type 2 diabetes).
What Are Amylin and C-peptide
In addition to insulin, beta cells also produce two other products: Amylin and C-peptide, a byproduct of insulin production.
- Amylin slows the speed of glucose coming into the blood, making it a short-term regulator of blood sugar levels.
- C-peptide prevents vascular neuropathy as well as preventing the damage of arteries. You may have noticed that people suffering from severe diabetes will have problems with their nerves and sensation as well as arteries. This is due to the loss of this molecule when beta cells are destroyed.
C-peptide is secreted into the blood in equal quantities compared to insulin.
What Is The Role Of Beta Cells In Diabetes?
Type 1 Diabetes
In this type of diabetes, beta cells die from an immune attack; immune cells which normally fight harmful bacteria and viruses mistakenly destroys beta cells in the pancreas. How and why that happens isn’t clear, however, the results of a study published in early 2011 shows that these beta cells become stressed at the earliest stages of the illness.
In mice studies, cells respond to this stress by triggering a death pathway that leads to the loss of beta-cell function, and ultimately the loss of cell mass. In this case, stress on beta cells that results from an immune attack may be responsible for type 1 diabetes which mostly occurs in children. Type 1 diabetes has strong genetic links.
Type 2 Diabetes
In this type of diabetes, the body becomes immune to the effects of insulin, losing sensitivity to insulin over the course of time. Consequently, it tries to compensate by producing more insulin. Research has shown that chronically elevated blood sugar levels (chronic hyperglycemia) over a protracted amount of your time will result in beta cells burn out, which is also referred to as cell turnover. The exact cause of these is unclear; however, factors such as chronic low-grade inflammation could be contributing significantly.
Glucotoxicity which is the result of the accumulation of high levels of glucose is another factor as well. Other factors include the effects of lipoproteins, leptin, and cytokines which play a role in glucose regulation.
Insulin Resistance in Type 2 Diabetes
The beta cells of the pancreas work as extremely connected clusters called islets and their responses to rising blood sugar levels are coordinated by little groups of “leader cells.” Once blood sugar levels peak in blood, the leader cells are responsible for coordinating the other beta cells to initiate an appropriate response. It is possible that the leader cells are more metabolically active and more glucose-sensitive than the rest and they are the primary target for insulin resistance.
Insulin resistance in type 2 diabetes starts out with decreasing sensitivity to insulin which leads to an overproduction of insulin by the beta cells. Due to the increasing levels of insulin resistance, patients continue to suffer from elevated blood glucose levels with sweeping consequences. After a few years of sickness, internal insulin production dries up and patients need to start injecting insulin.
New Drug To Stimulate Growth of Beta Cells
Researchers from Mount Sinai Hospital have discovered a unique combination of medication that induces the growth of beta cells. The lead author of the study Andrew Stewart MD had this to say:
“We have discovered a drug combination that makes beta cells regenerate at rates that are suitable for treatment. The next big hurdle is figuring out how to deliver them directly to the pancreas.”
If beta cells can be stimulated to regenerate, then insulin resistance will no longer be an insurmountable obstacle for diabetics. If this new treatment is implemented it can provide the much-needed breakthrough in the treatment of diabetes.
- References
- Mayo Clinic: Type 2 diabetes. Retrieved from https://www.mayoclinic.org/diseases-conditions/type-2-diabetes/symptoms-causes/syc-20351193
- Mayo Clinic: Type 1 diabetes. Retrieved from https://www.mayoclinic.org/diseases-conditions/type-1-diabetes-in-children/symptoms-causes/syc-20355306
- NCBI (2008): Insulin signaling in the pancreatic beta-cell. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/18481923
- Science Daily (2018): Diabetes: New drug cocktail increases human beta cell proliferation at rapid rates. Retrieved from https://www.sciencedaily.com/releases/2018/12/181220111759.htm
Prediabetes is reversible, it doesn’t have to progress to diabetes.
If you have prediabetes, you should know you are definately not alone. In 2015, it was estimated that 84.1 million Americans age 18 and older suffered from this condition. That is a whopping 1 in 3 Americans!
Being prediabetic doesn’t mean you will certainly develop diabetes. It is however a warning of what could lie ahead. People with prediabetes have a higher risk for type 2 diabetes as opposed to someone with normal blood sugar levels.
Those chances increase if you don’t make any healthy changes to your diet or activity habits.
It is not all bleak though…. “It can be reversed and you can stop the progression to diabetes. You can take control of your health by making the right choices and actively monitoring your blood sugar to ensure you do not slip into a prediabetic state, or develop into a full diabetic.
What are indications that you might have diabetes or prediabetes?
Diabetes develops very gradually, it could take up to several years. It follows that when you’re in the prediabetes stage, you may not have any symptoms at all. You may, however, notice that: • you eat a standard American processed food diet
or • you’re hungrier than normal
• you’re losing weight, despite eating more
• you’re gaining weight, despite eating less
• you’re thirstier than normal
• you have to go to the bathroom more frequently
• you’re more tired than usual
All of these symptoms are typically associated with diabetes, so if you’re in the early stages of diabetes, you may notice them.
Most patients diagnosed with prediabetes have no idea they have it, it comes as a complete shock!!!!
Are you pre-diabetic? How can you tell? Can it be ignored?? Of all the chronic diseases currently known to mankind, diabetes is the most common. The onset of diabetes starts years before it becomes full-blown and starts affecting one’s health. How can you know if you are on the path to being a full-blown diabetic? What can you do to arrest and reverse this process?
Prediabetes is a “pre-diagnosis” of diabetes—a warning sign of sorts. It happens when your blood glucose level (blood sugar level) is higher than normal but not high enough to be considered diabetes.
Prediabetes is an indication that you could develop type 2 diabetes (T2D) if you don’t take some immediate and lasting lifestyle changes.
During the prediabetes phase, your pancreas still produces enough insulin in response to ingested carbohydrates. The insulin is less effective at removing the sugar from the bloodstream, though, so your blood sugar remains high. This condition is called insulin resistance. Your HgBA1C is greater than 5.6 but less than 6.5. Your fasting sugar is greater than 105.
You should be aggressively treated with lifestyle modification and possibly metformin if you have been diagnosed with prediabetes. A lot of tissue damage is occurring during this silent period.
Heart disease is currently one of the major causes of morbidity and correlates closely with the global incidence of obesity and type 2 diabetes.
Recently, there is an increasing focus on metainflammation as the primary pathophysiology.
Recent studies implicate early metabolic abnormalities (weight gain, insulin resistance, and prehypertension, and irregular blood lipid levels). A basic description would be that inflammation is secondary to insulin resistance, which in turn leads to obesity which increases the chances of diabetes, high blood pressure, prothrombotic state, and abnormal lipid presence.
For Type 2 Diabetes to occur, both insulin resistance and comparative inadequate insulin secretion must co-exist. For example, overweight individuals may have insulin resistance, but diabetes only develops in those who cannot increase insulin secretion sufficiently to compensate for their insulin resistance.
Unfortunately, this period of hyperinsulinemia prior to the collapse of insulin production permits is the cause of significant tissue damage.
The problem is that the disease of hyperinsulinemia is highly inflammatory and leads to almost all of the metabolic diseases of Western Society. Treating hyperinsulinemia with more insulin only accelerates the disease.
The correct treatment should be geared to reducing the insulin requirement, by reducing carbohydrate consumption.
Titanium dioxide (TiO2) nanoparticles are a commonly used whitening agent and have been considered an inert substance. It is classified as an Excipient (a pharmacologically inactive substance) by the FDA.
In the pharmaceutical industry, TiO2 is used in most sunscreens to block UVA and UVB rays, similar to zinc oxide. It is also commonly used as pigment for pharmaceutical products such as gelatin capsules, tablet coatings, and syrups. In the cosmetics industry, it is used in toothpaste, lipsticks, creams, ointments, and powders. TiO2 is found in more than 900 food products such as chewing gum and mayonnaise. The average adult consumes between 0.7 and 5.9 mg of TiO2 per kg of body weight (BW) per day throughout their life, and children are the most exposed consuming up to 32.4 mg TiO2/kg BW/day.
In a mouse study published in Frontiers in Nutrition, consumption of food containing TiO2 had a significant impact on the gut microbiota and promoted the growth of an undesirable biofilm. These changes were associated with colonic inflammation, demonstrated by decreased crypt length, infiltration of CD8+ T cells, increased macrophages as well as increased expression of inflammatory cytokines. These changes occurred after only a few weeks of daily TiO2 consumption.
Food-grade TiO2 is not inert, it impairs gut homeostasis which primes the host for disease development. Metainflammation from changes in gut permeability has been previously linked to:
• dementia
• auto-immune diseases
• cancer metastasis
• eczema
• asthma
• autism
Front. Nutr., 14 May 2019 | https://doi.org/10.3389/fnut.2019.00057
An explanation why motivation is reduced with metainflammation and a possible explanation why many patients with diabetes develop chronic pain pathologies with anhedonia, reflections on the addiction model of obesity.
The brain’s dopamine system, which drives motivation, is directly affected by chronic, low-grade inflammation. If your brain perceives that it is fighting off an infection or healing a wound, your brain recalibrates your motivation to do other things, so you don’t use up too much of your energy. This immune system mechanism regulates the use of energy resources during times of acute stress was likely adaptive in our ancestral environments, but the same mechanism to conserve energy for the immune system could become maladaptive when many people are less physically active and may have low-grade inflammation due to factors such as chronic stress, obesity, metabolic syndrome, or chronic pain.
Inflammatory cytokines have been shown to have a direct effect on mesolimbic dopamine (DA) that is associated with a reduced willingness to expend effort for reward. “the metabolic demands of chronic low-grade inflammation induce a reduction of striatal DA that in turn leads to a steeper effort-discounting curve because of reduced perceived ability (can’t) versus preference (won’t) for reward” ultimately contributing to motivational impairments
Michael T. Treadway, Jessica A. Cooper, Andrew H. Miller. Can’t or Won’t? Immunometabolic Constraints on Dopaminergic Drive. Trends in Cognitive Sciences, 2019; 23 (5): 435 DOI: 10.1016/j.tics.2019.03.003