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Metabolic Signals And Innate Immune Activation In Obesity

The interplay between immunity, inflammation, and metabolic changes is a growing field of research. Exciting new evidence is emerging with regard to their role in the regulation of metabolism and the activation of inflammatory pathways during the progression of metabolic disorders such as Type 2 Diabetes and Atherosclerosis.

  1. The innate immune system

The innate immune system is an evolutionarily conserved system that senses and defends against infection and irritation. Innate immune signaling is a complex cascade that quickly recognizes infectious threats through multiple germline-encoded cell surface or cytoplasmic receptors and transmits signals for the deployment of proper countermeasures through adaptors, kinases, and transcription factors, resulting in the production of cytokines.

As the first response of the innate immune system to pathogenic signals, inflammatory responses must be rapid and specific to establish a physical barrier against the spread of infection and must subsequently be terminated once the pathogens have been cleared. Long-lasting and low-grade chronic inflammation is a distinguishing feature of type 2 diabetes and cardiovascular diseases, which are currently major public health problems.

  1. How does the innate immune system work?

The ability of organisms to mount a response to infectious challenge without prior exposure is regulated by the coordinated interaction of components of the innate immune system. This preformed system is important to respond to exogenous stimuli such as bacterial, viral, and fungal infections. Beyond the initial response to a stressor, the innate immune system coordinates the resolution of inflammation, tissue repair, and the activation of the adaptive immune system to provide memory for future challenges.

While much of our understanding of innate immunity comes from models of infection, it is also clear that immune responses can be triggered by endogenous stimuli. Such mechanisms play a wide role in health and disease from the response to tissue injury, the direction of tissue remodeling, and the response to tumors.

  1. The Innate Immune Response to Obesity

The increased prevalence of obesity and overweight in adults continues to rise and contributes to morbidity and mortality that is estimated to cost $147 billion dollars a year in the U.S. (Finkelstein et al., 2009) and up to 0.6% of the gross domestic product of European countries (Muller-Riemenschneider et al., 2008). More ominous is the high rates of childhood obesity which is a strong predictor of adult obesity (Lee et al., 2009). This has also shifted the prevalence of adult diseases such as type 2 diabetes and pre-diabetes into childhood and has generated new treatment and prevention challenges (Lee, 2006; Lee et al., 2006). Relevant to this review, increases in inflammatory biomarkers such as C-reactive Protein (CRP) and neutrophilia are seen in obese children as young as 3 years of age (Skinner et al., 2010). This indicates that many of the origins of obesity-induced inflammation may actually be initiated during childhood. Therefore, many people will face a lifetime threat to health from obesity.

The long term duration of obesity-induced inflammation makes it challenging to describe this unique type of inflammatory activation based on classical models of innate immunity. Applying such models may be inaccurate and insufficient to encompass the events that are triggered by obesity in metabolic tissues such as fat. Furthermore, it is clear that the inflammation generated by obesity is not as high in amplitude as those seen in acute infectious settings (Hotamisligil, 2006). These unique challenges have led to the coining of the term “metal inflammation” to describe the chronic low-grade inflammatory events that occur in obesity and its associated diseases.

A frequently asked question is why would obesity trigger an immune response? For the most part, this question remains unanswered, but one answer to this may lie in the fact that many of the key regulators of metabolism also play critical roles in regulating inflammatory responses.

  1. Inflammation as a link between obesity and disease

The interest in obesity-induced inflammation relates to the understanding that inflammatory mechanisms are central to the pathogenesis of diseases such as heart disease that is modified by obesity.

It is impossible to cover the scope of all of these diseases so we will focus our attention on the inflammatory mechanisms of fatty liver disease and Type 2 Diabetes-related diseases with fundamental alterations in nutrient control derived from pro-inflammatory inputs. This will set the stage for future discussion of the innate immune components activated in obesity. I will highlight both clinical and pre-clinical studies in animal models of obesity that have built our understanding of the mechanisms that drive obesity-associated diseases.

4.1 Non-alcoholic Fatty Liver Disease (NAFLD)

The liver plays a critical role in the regulation of glucose and lipids levels in the blood. Obesity generates a number of physiologic changes in hepatocyte glucose production as well as lipid oxidation and storage. Unusual hepatic lipid accumulation is connected to many obesity-associated illnesses that include non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome. The metabolic changes that occur with hepatic lipid accumulation include hepatic insulin resistance which is related to inflammatory cytokine signals.

4.2 Type 2 Diabetes (T2D)

The regulation of glucose metabolism is securely coordinated between nutrient inputs regulated by the liver and gut, nutrient utilization and storage in muscle and fat, insulin secretion by the pancreas, and central signals from the hypothalamus that coordinate these responses. The dysregulation of almost all of these processes with obesity is now known to be associated with the activation of innate pro-inflammatory pathways. The net result of this is the generation of systemic insulin resistance and hyperglycemia.

  1. Why obesity affects the innate immune system

The blend of a sedentary lifestyle and surplus energy intake has led to an increased occurrence of obesity which constitutes a major risk factor for several comorbidities including type 2 diabetes and cardiovascular diseases. Intensive research during the last two decades has revealed that a characteristic feature of obesity linking it to insulin resistance is the presence of chronic low-grade inflammation being indicative of activation of the innate immune system.

Recent evidence suggests that activation of the innate immune system in the course of obesity is mediated by metabolic signals, such as free fatty acids (FFAs), being elevated in many obese subjects, through activation of pattern recognition receptors thereby leading to stimulation of critical inflammatory signaling cascades, like IκBα kinase/nuclear factor-κB (IKK/NF- κB), endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) and NOD-like receptor P3 (NLRP3) inflammasome pathway, that interfere with insulin signaling.

Exercise is one of the main prescribed interventions in obesity management improving insulin sensitivity and reducing obesity-induced chronic inflammation. A deeper understanding of the effects of exercise on inflammatory signaling pathways in obesity is useful to optimize preventive and therapeutic strategies to combat the increasing incidence of obesity and its comorbidities.

References:

  1. Journal of Biological Chemistry (2013): How Metabolism Generates Signals during Innate Immunity and Inflammation. Retrieved from http://www.jbc.org/content/288/32/22893.full.html
  2. Physiological Reviews (2018): Innate Immune Signaling and Its Role in Metabolic and Cardiovascular Diseases. Retrieved from https://www.physiology.org/doi/abs/10.1152/physrev.00065.2017
  3. NCBI (2012): Innate Immune Activation in Obesity. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3888776/
  4. NCBI (2015): Metabolic signals and innate immune activation in obesity and exercise. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/25825956

Soybean oil is the most widely produced and consumed edible oil in the U.S., consumption dramatically increased right before the beginnings of the 1970’s.

In the 1970s and 1980s, about 1:2,000 children had autism.

Today, the CDC estimates that 1:150 has an autism spectrum disorder or ASD.

A True Increase or Semantics?

More to come, tomorrow.

ENSURE PRE-SURGERY is specially designed to help reduce insulin resistance after surgery and improve patient outcomes. Designed to be consumed up to 2 hours before surgery. For oral use. Use under medical supervision. • #1 Doctor recommended brand.
• Has a recommended dose of carbohydrates (50 g per serving), as indicated by ERAS guidelines*, compared to regular sports drinks, which contain approximately 21 g per 12-fl-oz serving.
• Meets ERAS guidelines* for pre-surgery use of a clear carbohydrate beverage.1,2
• Meets American Society of Anesthesiologists (ASA®) guidelines† for use with preoperative fasting.3

The official Enhanced Recovery After Surgery (ERAS) Society’s recommendations for most common surgeries:
Evidence Level Moderate (for not recommending)
Recommendation grade strong

This is where marketing trumped medical care.

In actuality “Insulin resistance is a central metabolic change during surgical stress that is directly proportional to the magnitude of the operation.” This leads me to two opposing viewpoints, that need to be rectified:

Preoperatively administering glucose may, in fact, cause reactive hypoglycemia intra-operatively in the exact population you would want to avoid glycemic excursions.

Inadvertent intracranial hypotension with acute neuronal damage may result in penumbra extension of injury in the presence of hyperglycemia.

Perhaps, idealizing metabolic function should be the ideal preoperative therapy.

We are living in a diabetes pandemic.

But diabetes isn’t just about blood sugar, it’s systemic inflammation, incessant cravings-driven eating.

It’s obesity.

And it’s impacting our nation in ways most are completely unaware of.

From our children’s exposure to the U.S. dietary regulations in our public schools and the rise in ADD (Attention Deficit Disorder), to behavioral issues in the prison system where most inmates emerge severely diabetic.

We are generating a massive problem of staggering social disfunction most clearly evident in our nation’s urban areas. As a nation we are failing.

And our Forget To Eat™ Podcast guest, Dr. Gurpreet Padda is right in the middle of it. Based in St. Louis, MO, Dr. Padda and his Padda Institute is highly regarded as one of the best pain centers in St. Louis.

Watch: Rats, Food, Prisons… Reversing The Diabetes Pandemic

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Interview Transcription: Rats, Food, Prisons… Reversing The Diabetes Pandemic

 

B. McDermott: Welcome listeners. This is Barbara McDermott with SHIFT Formula and it’s my great privilege to share with you today our guest, Dr. Gurpreet Padda, an interventional pain physician.

Dr Padda, what makes you so interested in the metabolic field when your focus is on pain intervention?

Dr. G. Padda: I practice in the urban core, in St Louis city. What I found in the patients that I was practicing on, I could treat their pain directly, I could get to them and I could treat the one particular joint that was bad or the disc, but they would have a recurrence.

And they would keep recycling over and over and over again.

And so I tried to figure out why it is that they came to me in the first place, which was usually they had a traumatic event.

But why was it that their pain was maintained and then why was it that they would recycle? Why was it that they were coming back?

And so the initial thing is, you look at the patient and think, “Well, goodness, they’re really overweight”.

Because that’s what you see.

And then when you start measuring the metrics and you start looking at everything associated with them. You start spreading out from just the simple tests and you look at things like hemoglobin A1C, you look at insulin levels, you look at GGT for liver function, you look at homocysteine levels and transference, and you start getting a bigger picture of what’s going on.

You realize that the patients are severely metabolically inflamed.

 

The Metabolic Inflammation Un-Covery

Dr. G. Padda: I also have a background in addiction and that combination with my background in pain and this discovery, not discovery, but un-covery for me of metabolic inflammation basically brought me to a common nexus.

You know, here I am dealing with severely obese patients, patients with severe addictions and patients with severe chronic inflammation and pain.

They’re the same patients. It’s the same common nexus.

And so, that’s how I ended up in this field. I’m dealing with patients that are extremely sick, or they’ve become disabled because they can’t function.

The Cause of Metabolic Inflammation

And what’s causing that metabolic inflammation, it’s our food supply.

We have, an epidemic of obesity. We have an epidemic of addiction. We have an epidemic of chronic inflammatory conditions.

It’s all interrelated and pain is the common final pathway. It’s the scream that the body has, something is wrong. And that’s how they end up at me.

B. McDermott: The individuals in our SHIFT Community become much more powerfully aware of glucose-heavy foods.

It’s the carbohydrate category, and certainly the processed versions, that are our highest glucose heavy foods.

So, many in our community, just by down-shifting the amount of glucose, I call it going from glucose stacking to glucose tracking, they reduce glucose overburden and naturally their insulin levels follow.

And insulin levels start to drop as well. And the relief from pain comes very quickly when we understand the pathway. It’s really powerful.

Now, you mentioned obesity earlier. Is it an epidemic or is it pandemic?

Talk a little bit about that.

 

The Diabetes Pandemic

Dr.G. Padda: I use the word epidemic because that’s the one that everybody understands.

And I look at it this way. If I told you that there was a disease coming and it was going to affect 75% of the world’s population and 90% of the people that got this disease, we’re going to end up becoming pre-diabetic or diabetic and 30% of those, were going to end up with end-stage renal disease.

And just in the U. S. this disease was going to cost us $1.3 trillion a year.

You’d be worried, right?

Well, this disease is here. It is called pre-diabetes, diabetes and obesity.

This disease is right in front of us. One out of every five children has this.

So that’s why I call it an epidemic.

But it’s more than that. It’s a pandemic.

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The Animals That Are Eating Our Foods Are Getting The Same Diseases

Dr. G. Padda: You know that it’s usually an environmental cause and we call it a pandemic because the animals that eat the same food that we eat get the same diseases.

The monkeys get the same disease, the dogs get the same disease.

The cats get the same disease, the rats get the same disease.

Anything that eats the food that we eat gets this.

There was a beautiful study that was just done recently and it was done in New York City. And what they did was they looked at obese rats because we’ve never had obese rats until recently. But now we’ve got these lumbering giant rats that have severe diabetes who are cognitively impaired because they’ve gotten diabetes and insulin resistance in their brain.

So they are wandering around the cities in New York.

Normally rats are terrified of daylight and they scurry along the edges of things. Once you make a rat cognitively impaired, it just wanders in the middle of the street because it has lost its fear.

The rat is cognitively impaired.

This is very similar to what we have with Alzheimer’s and cognitive impairment as we have type three diabetes of the brain in humans.

So this is the pandemic that we face and that pandemic’s, central crux is our food supply.

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 I Love How SHIFT Addresses The Heart Of The Insulin Resistance Problem

You know, I love what you teach. Your concept of SHIFT.

And the reason why I love it is because it goes to the heart of the problem. The heart of the problem is insulin resistance.

And what happens when you shift your food supply, when you shift and change how you’re eating is that you have more hours that you’re not eating than you are eating.

And what that’s doing is it’s shifting the amount of stored glycogen that’s in your liver.

How We Become Insulin Resistant

Your liver has a glycogen carrying capacity of 500 grams. Your blood stream has a glucose carrying capacity of about five to 10, maybe 15 grams, but not more than that.

And if you’re eating 22 teaspoons of sugar a day, it only takes you one teaspoon to overwhelm your blood capacity.

The other 21 teaspoons go to your liver.

And if you never depleted the glycogen reserve in your liver in the first place, it overflows. You become insulin resistant.

You accumulate fat and you become pre-diabetic and then eventually diabetic.

So we need to have periods of time greater that we don’t eat. So we can deplete our glycogen reserves in our liver so that we can function.

And that’s one of the biggest problems that I find. We have a constant foraging of sugar and we never deplete the glycogen reserve that we have in our liver. And so we’re always at that full status. a

You have to deplete that glycogen reserve.

 

The Cravings Challenge

B. McDermott: And I guess the challenge we have for depleting our liver’s glycogen supply is the cravings.

Cravings are what many can’t rise above. You know, the chemistry driven desire to continue eating is virtually impossible to overcome. It’s so powerful. Talk about addiction, right?

Can you expand on why food and in particular glucose and fructose rich food addiction is a real and valid challenge for individuals?

How Food Addiction Happens

Dr. G.Padda: Yeah. So I think there are a couple of elements of addiction that we should discuss.

Our food supply is tainted.

And it’s tainted in such a way that our large food manufacturers are manipulating the amount of fructose.

High fructose corn syrup is supposed to be 55% fructose, 45% glucose. That’s what high fructose corn syrup is.

But the food industry is manipulating the food supply so that it’s 60% fructose instead of 55% fructose.

You’re probably wondering why they’re spending extra money to increase the amount of fructose. Because normally these companies want to save money.

So why are they doing this?

Fructose Activates More Dopamine

Because glucose does not activate as much dopamine release as does fructose.

LEARN MORE ABOUT THE WEIGHT LOSS SABOTEUR – DOPAMINE

Fructose kicks in the nucleus accumbens and dumps a bunch of dopamine.

So you end up with a tremendous surge of dopamine that makes you want to eat again and eat again and eat again.

So that’s issue one. Our food supply is tainted in such a way that the processed foods are hyper-addictive and that’s going to be a significant challenge.

How Loneliness And Lack Of Community Work Against Us

The second factor is that we have an epidemic of loneliness.

So researchers did an interesting rat study. We do rat studies all the time… and we just happen to be the rats in some cases.

But in this particular rat study they put the rats in a cage and offered them water, or cocaine plus water.

Well, each rat was alone. They found the water and drank that. It was okay.

But, when they found the cocaine-water they couldn’t stop drinking it.

They drank it to the point where they were unconscious.

They didn’t eat food. And eventually they died.

And so the natural conclusion from that was if you give an addictive substance to a rat, it’s going to consume that addictive substance to the point where it dies.

And so that was the initial conclusion.

Keep in mind, those rats could also be considered humans.

You give an addictive substance to a human, they’re going to eat it to the point where they die.

And on that basis, when we had people coming back from Vietnam, we knew that about 60% to 70% of them had been using heroin or some form of amphetamine or some form of opiate that was highly addicted.

We assumed that when these people came back from Vietnam, we would have zombies on the streets.

But that’s not what happened. Only 5% came back having an addiction.

What happened to the rest? Why weren’t they addicted?

Because in Vietnam they were addicted, but in the U.S. they weren’t addicted.

So they repeated the rat study. They gave the rats water or they gave the rats cocaine plus water.

But this time what they did was they put them in an enhanced environment. They were given the opportunity to play with other rats, to have sex with other rats, to have a maze and run around.

Low and behold, none of those rats died because they weren’t lonely.

They weren’t isolated.

They had other rats to play with.

The Power Of Community In Weight Loss Management

And so when I deal with weight loss management, my main thing is to generate a community for my people.

Whether that’s me interacting with their church groups and interacting in a way that allows them to communicate with each other and to co-share, we have to eliminate loneliness to treat addiction.

That’s how my addiction side becomes more and more relevant for me, it’s that we have to realize that a big part of addiction is loneliness. It’s not just the substance and it’s not just your genetics, it’s your interaction with society.

And we would think that we have all this cool tech that we have Facebook and we have Twitter, but that’s actually creating more loneliness because there’s not a true human interaction.

B. McDermott: Absolutely. You know that chemistry of ‘love’, right? How emotionally we experience the same neurotransmitters or feelings whether triggered by gossip, a chocolate chip cookie, or love.

There are emotional similarities between the three. Gossip meaning a good thing, being socially connected, in community, you know, it’s really powerful when you can whittle it all down.

What an excellent study to help us see it all so much more clearly.

You and I spoke a bit before this podcast about your work with the prison system. Do you want to segue into that?

 

How The 1980 Dietary Guidelines Change Paved The Way To Insulin Resistance, Obesity & Diabetes

Dr. G. Padda: Yeah. So I grew up, I actually grew up in India.

I moved to the U.S. when I was probably about eight or nine and I became integrated into the U.S. school system. So I was here in the early mid- seventies.

The dietary guidelines kicked in and were being discussed in 1977 and they were implemented in 1980.

The dietary guidelines from the U.S. specifically stipulated that we should eliminate saturated healthy fats and replace them with vegetable oil. And as we did that, they also recommended that artificial sweeteners were a good thing and that we should start using those.

And when we started to demonize fat, especially the good fat, and replaced those fats with vegetable oil, we also started to increase the amount of carbohydrates.

So it’s interesting, you know, here I was a little kid and I’m in India, we’re thin as a rail because we don’t have enough food and we use regular saturated fat.

And yet as I saw immigrants that were here in the U.S., and I was in the St. Louis City public school system, as we saw this transition. People started to get fatter.

And we really see the takeoff of obesity in 1977 to 1980 and there’s a direct vertical climb from there up and you can see it on every obesity epidemic chart that you can find.

The Obesity Connection To Jails & Schools

So we see this epidemic of obesity.

Why is this relevant to criminals? Why is this relevant to jails? Why is this relevant to schools? J

ails and schools are an amazing ‘rat cage’ because the dietary guidelines control the food that those kids get.

And a lot of times in the urban core, that may be the only meal of the day that the kid gets.

So the kids getting a specific meal formulated by U.S. dietary guidelines, that meal’s dietary guideline stipulates how much carbohydrate and how much vegetable oil they get.

What we found was that the rates of ADD (Attention Deficit Disorder), started to climb and by the mid-eighties we had a serious issue.

ADD rates were going up and in school, behavior issues for kids were going up and their exposure to criminality was going up and they were getting kicked out of school.

These kids were ending up in prison systems.

And the food is even more controlled in the prison system.

So now we have a prison system that’s feeding these kids turned criminals the very same diet that contributed to their incarceration in the first place.

And what happens is that these people end up becoming disenfranchised because when they get out, they can’t vote anymore and their specific community suffers because they lose the population that votes.

It suffers because they’ve lost the economic force that would have been productive. And we sideline these people and we disable them and then we have to pay for them.

So, as a society, what we’re doing is we’re creating our own mess.

We’re incarcerating people because of the food that we give them because it increases their likelihood of ADD and oppositional disorders.

And at the end of it, we end up basically criminalizing everything for them and they can never function.

So we end up caught. It ends up costing us as a society because of the food that we subsidize, that we pay for, to give to these people which becomes our large, large volume ‘rat study’.

So that’s how I got involved.

I’ve been working with groups like Exoneration Nation, which is people who have been released from prison and almost all of them come out with severe metabolic dysfunction.

Almost all of them are exposed to vegetable oil, high amounts of grain and high amounts of sugar.

And they’re all coming out of prison pre-diabetic or diabetic, or insulin resistant. And when you have that confluence, you increase the risk of solid tumors, you increase the risk of cancers, Alzheimer’s disease, and all of those other expenses, and it’s going to create a tragedy for us.

So I’ve been trying to work at the school system level and at the prison level to change those controlled environments to help people.

B. McDermott: Oh. On a very personal level, I can share this.

We have a dear friend who was incarcerated,  just for a few years. This man came out of prison so severely diabetic he could barely walk.

Since SHIFTing, he’s reversed that.

And as a past school teacher, I can’t tell you how many times I have seen children disciplined for a behavioral outburst after the parents and the faculty gave the children ridiculous amounts of sugar in the form of some kind of reward system.

We reward our children with the very kinds of foods that are going to promote their inability to control their behavior and cause emotional outbursts.

 

What’s Really Inside ‘Nutrition’ Bars?

Dr. G. Padda: Yeah. If you’ve ever been to a nutrition conference, which I’ve been to, the biggest sponsors of nutrition at these nutrition conferences are typically the big food companies.

These big food companies are basically selling quote ‘healthy bars’ and they’re basically Snickers bars.

And I don’t want to belittle Snickers. I’m not trying to, but, they’re basically candy bars.

They have some protein in them, but they’re basically processed high-glycemic index, processed sugar.

And even when it’s quote fiber, it still has a ton of other compounds in it. Some of the whitening agents cause tremendous leaky gut like titanium dioxide, which is basically what causes something to be white.

So, when we process these foods and we get farther and farther away from how they were really intended, that processing destroys our metabolism.

It destroys our gut bacteria. It changes the absorption of short chain fatty acids. And it changes the absorption of carbohydrate.

 

The Calorie Paradox & The Cereal Breakfast

So, it leads to what the calorie paradox is.

You know, a calorie of this is not equal to a calorie of that. It depends on what happens with that calorie and the information contained within it.

B. McDermott: Yeah, it’s so complicated. And yet when someone like you puts it out there in such simple terms it’s so much easier to understand.

But the application of food rules can be so tricky because my gosh, we’re inundated with so much misinformation. We’re bombarded with food marketing and messages, social cues, and so much more.

Dr. G. Padda: It’s like the message of cereal.

How ofter have we heard that breakfast is the most important meal of the day?

It’s not the best meal of the day for anyone except for the cereal company.

Because if you eat a cereal breakfast, two hours later, you’re going to be hungry. And then you’re gonna eat in two hours. And then you’ll eat in two hours after that, and then you’re going to eat in two hours after that, etc.

And if you spend your entire day eating every two hours, you never deplete your glycogen.

Watch: How Important Is Breakfast?

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How We Become Insulin Resistant

If you never deplete your glycogen, you became insulin resistant in 28 days. Later, you’re going to have a serious problem.

I’m surprised that we don’t have more diabetes.

I think that humans are very hard to kill. And I’m really surprised that not everybody’s diabetic because they should be based upon the way that we have feedings that are like goals to hit.

Thank God we have a complex adaptive system that allows the progeny to proceed.

But there are some serious issues with our food supply.

An Epidemic Of Impotence & Falling Birth Rates

We don’t have an epidemic of impotence just for nothing.

It’s another area that I find where people don’t realize that the vegetable oil antagonizes nitric oxide synthesis and nitrates. Nitric oxide synthesis is necessary to get erection. So that’s one of the reasons, it’s not the only reason, but it’s one of the reasons why our birth rates are falling.

It’s also the epigenetic effect of some of our sugars that we’re eating. We’re predisposing our kids to becoming diabetic. We’re doing that in the womb and we’re doing that a generation back.

So, what we’re dealing with is a massive thing. I would put this at a climate level. We’ve got a climate issue, but the dietary issue is a climate issue because it’s so pervasive.

B. McDermott: You hit the nail on the head for me, for the next generation.

Again, as a school teacher, as a parent, I see our children and our children’s children having to bear the burden of being raised in this environment. The least we can do is shed some light on it and make some changes in our own lives. Be an example, and get that ripple out effect going.

I’d love to see SHIFT getting into the school system. If our young people understood what it was all about. Place the power of knowledge in their hands. They’d say, “I can handle this.”

You know, any of us can SHIFT the way we eat if we just understand how it all works.

Dr. G. Padda: I agree with you.

It’s a fundamental misunderstanding, but it’s not amongst the lay public.

 

What 75% of Physicians Don’t Know About Cholesterol

I have to tell you about a study done by Credit Swiss, which is an insurance company.

There’s nobody smarter than an insurance company because they’re insuring when you die so that they don’t have to pay you. And they’re trying to figure it out because you’re paying them and they want to figure out how not to pay you.

So they’re trying to figure out if you’re going to die early or if you’re going to die late.

And they do all kinds of calculations and studies where they figured out how much do physicians know and what do physicians think?

And the vast majority of physicians continue to suppose that the saturated fat that you eat is the cholesterol in your bloodstream.

They have missed the point that the cholesterol in your bloodstream is not the saturated fat that you ate.

Just because you have cholesterol in your blood and it’s sitting as an atheroma on your coronary artery, that may not be the fat that you ate. That may be the secondary response from inflammation and that may be the recovery molecule.

That may be the marker of injury and it may not be the cause of injury.

What Causes High Cholesterol?

Glucose is a cause.

Glucose and vegetable oil and things that make leaky gut. Those are the causes and we need to take a step back.

We need to also recognize the incentive that a physician and others have that drives this.

 

Watch: Lower Cholesterol Naturally

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The Economics Of ‘Sick’

Because if I was playing a game and I was strategizing, I’d ask myself, “How do I make the most amount of money?” “Well, I’d want the sickest patients.”

“Okay, how do I get the sickest patients?” “

Well, I delay my treatment to the point where they’re sick and they’re dependent upon me.”

So what that means to me is if I’m treating pre-diabetic patients, I don’t want to treat them at a hemoglobin between 5.1 or 5.7, I’m going to wait until 6.5 when they’re on insulin.

And then they have to come in and I can possibly do an amputation or I can do X, Y, Z.

So institutions will wait until the hemoglobin A1C is sufficiently high enough to start some of the more expensive drugs and treatment.

So you know, I am a cynic.

I have a background in economics as well. And so I look at things as a game theory.

If I’m completely cynical, what would I do as a drug company, even though I was given insulin for a dollar and I was told to give it or provide it freely.

The answer is, I’m going to modify this free insulin a little bit so that I, as a drug company can charge for it. And that’s exactly what happened.

Get Your Free Insulin For Only $1,200 a Month

In 1923, Frederick Banting and John Macleod of Canada received the Nobel Prize for the discovery of insulin.

It was given by the Nobel laureates to the insulin companies who were to forever provide it for free.

But these companies changed insulin slightly so that they could charge $1,200 a month via a subscription program that you have to pay for for the rest of your life. That’s not cool, but that’s the model.

And so you know, you have to look at people’s drivers.

What Drives The Profits of Food Companies?

With big food companies, their driver is to sell as much food as they can at the lowest possible cost, at the highest frequency.

So they have to figure it out and they have to apply the technologies that they have.

When we got rid of smoking. When we finally said, “Hey, smoking is bad for you”, the big smoking companies moved over to the big food companies to figure out how to increase the likelihood of consumption.

And we’re going to see a similar thing with the marijuana industry. You’re going to see a large shift of the companies from alcohol and cigarettes and food infiltrating the marijuana industry to figure out how to make a previously non-addictive plant become hyper-addictive.

So we’re going to see a shift that will happen in the next five or 10 years.

You have to figure out what people’s motivations are.

B. McDermott: Well, Dr Padda, you made my day. You shared so many insightful and thought-provoking stories that really helped me visualize some powerful, but abstract concepts.

You know, I tend to be a bit naive.

That last story about the insulin, good grief. My daughter is insulin-dependent. The hardship is not only physical and emotional but financial, too.

One of my greatest victories is helping people get off insulin.

What a wonderful thing to not need to take insulin any longer. Powerful!

Thank you again, Dr. Padda, for taking the time to share your expertise.

I’d seen on your website something that spoke to me. You use the term ‘citizen scientist’.

You’re the kind of doctor who steps over the line and reaches down and lifts the rest of us up. You give us the awareness by simplifying the concepts that opens our eyes and makes us take a second look at things.

You know, when our loved ones are suffering, when people in our lives, or ourselves, are struggling we need to understand that the bigger powers really aren’t working for us.

I used to think my daughter was in good hands with all of her high paid experts. That she was truly supported by them. She wasn’t.

We must take matters into our own hands. We are ultimately responsible for ourselves. It takes rolling up our sleeves, digging in and taking a hard look at things.

Dr. G. Padda: And to be clear, my point is not to be a conspiracy person.

I don’t want to leave you guys there. But the motivations have to be perfectly clear for everyone to understand and to make the best decisions.

My hope is that people get the education that they need to take care of themselves.

B. McDermott: Absolutely. And we are not of the platform that medications are wrong or bad. Goodness, no.

A body needs insulin to stay alive.

But when we’re seduced or misled into believing it’s the answer.

Being told to just keep using it. That the only solution is to keep dosing more. That’s not good.

Dr. G. Padda: Thank you. It was wonderful.

You have a very wonderful voice and you know how to take really complex science and put it into a story complete with the research and anecdotal evidence.

That was great. Thank you so much.

You know, we’re of kin when it comes to time restricted nutrition.

I strongly urge people to, to restrict their feeding cycles. I believe in intermittent fasting strongly. And so, you know, I totally agree with what you guys are doing. That’s why I reached out to you to be a guest on the Forget To Eat™ Podcast.

B. McDermott: Thank you so much for that! Your validation is huge. We live it, continue to live it, continue to see our clients lives get so much better from it.

Okay. I’m gonna let you go. Enjoy the rest of your Saturday and we’ll be in touch. .

Thank you,

Dr. Padda!

Nearly 77% of the US population is now overweight. This dramatic change in the last 50 years is correlated with the availability of highly processed foods, and with a dramatic increase in chronic pain.

In a mouse model, high-calorie foods, which induces a dopamine release, disrupted normal feeding schedules, resulting in overconsumption.

Additionally, the “knockout” mouse model which had dopamine signaling disrupted, didn’t seek the dietary “rewarding pleasure,” maintained a normal eating schedule, and did not become obese.

Practical Conclusion:

Diet-induced obesity requires dopamine (DA)-Drd1 signaling

Avoid eating outside a normal eating window, typically less than eight hours out of 24, allowing glycogen depletion in the liver and preventing insulin resistance.

How is this relevant to chronic pain:

I practice in the field of interventional pain, addiction, and obesity/ metainflammation.
1. Patients with chronic pain have a signaling mechanism, whether induced by medications or their endogenous pain, that causes them to seek out dopaminergic stimulation, to relieve their pain.

2. Some of these dopaminergic stimulation can be substituted by dietary intake.

3. Excessive non-nutritive dietary intake leads to obesity and visceral adipose tissue accumulation, which is inflammatory.

4. Excessive inflammatory mediators aggravate pain, and the cycle repeats.

Could sugar self-substitution for opioids in our patient’s be leading to insulin resistance, obesity, T2DM?

In an experiment done on mini-pigs, they found that sugar can affect the brain’s reward system in a similar “manner similar to that of drugs of abuse”

Sugar’s impact on the brain’s reward system boils down to how it affects two types of receptors in the brain.

The first set is dopamine receptors — dopamine is a central player in the brain’s reward system, released during pleasurable activities.

The second set is opioid receptors, which are also found all over the brain but are particularly found in areas involved in eating-related rewards.

The sensitivity of both receptors was dampened when pigs were allowed unrestricted access to sugar water for one hour each day for twelve days. The pigs were also fed a normal diet, so sugar consumption was unrelated to their caloric needs.

After the first day, the sugar intake lowered the “availability” of opioid and dopamine receptors, essentially dampening the ability of these receptors to bind to their natural ligands. Both Opiate and Dopamine receptor binding was attenuated 14% in the anterior cingulate cortex and the nucleus accumbent, both are areas of the hedonic reward.

At the end of the 12 days, the scientists found that the pattern held — the availability of both types of receptors continued to decrease significantly.

Could sugar self-substitution for opioids in our patient’s be leading to insulin resistance, obesity, T2DM?

Winterdahl, M., Noer, O., Orlowski, D. et al. Sucrose intake lowers μ-opioid and dopamine D2/3 receptor availability in porcine brain. Sci Rep 9, 16918 (2019) DOI:10.1038/s41598-019-53430-9.

Padda Institute

Adipose tissue-derived proteins known to affect inflammation

TNF-α
IL-6
IL-1β
Leptin
Adiponectin
Resistin
Acylation-stimulating protein
SAA3
α1 acid glycoprotein
Pentraxin-3
IL-1 receptor antagonist
Macrophage migration inhibitory factor.

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 the bracket, have a silent blood sugar problem known as insulin resistance. Insulin resistance increases the risk for prediabetes, Type 2 diabetes and a host of other serious health problems, including heart attacks, strokes, and cancer.

What therefore is Insulin Resistance? It is when cells in your muscles, body fat and liver start repelling or ignoring the signal being sent out by the hormone, insulin—which is to take glucose from the bloodstream into our cells for breakdown or storage. Glucose, commonly called blood sugar, is the body’s main source of fuel.

  1. How does Insulin Resistance Develop?

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

With time, and 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 started – your blood sugar may spike and you may manifest prediabetes or type 2 diabetes. You are also at risk of developing the non-alcoholic fatty liver disease (NAFLD), a condition that increases your risk for liver damage and heart disease.

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

Insulin resistance does not always manifest to the naked eye but here are some signs to look out for:

  • 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)6 increases the odds of insulin resistance and metabolic syndrome, which is also linked to insulin resistance.
  • You have 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.
  • You develop dark skin patches. If insulin resistance is severe, you may have visible skin changes. These include patches of darkened skin on the back of your neck or on your elbows, knees, knuckles or armpits. This discoloration is called acanthosis nigricans.8
  1. Chronic low-grade inflammation and the development of insulin resistance

As early as the 1950’s, there was epidemiological evidence suggesting a correlation between inflammation and insulin-resistant states such as obesity, but the mechanistic links were unknown. In the last decade, however, it has become increasingly evident that obesity and the concomitant development of inflammation are major components of insulin resistance. Studies in human obesity and insulin resistance have revealed a clear association between the chronic activation of pro-inflammatory signaling pathways and decreased insulin sensitivity. For example, elevated levels of tumor necrosis factor-α (TNF), interleukin-6 (IL-6) and interleukin (IL-8) have all been reported in various diabetic and insulin-resistant states. In addition, the inflammatory marker C-reactive protein (CRP), a non-specific acute phase reactant, is commonly elevated in human insulin-resistant states. Also, experiments in naturally occurring rodent models of obesity, knockout and transgenic mice, as well as detailed studies of insulin signaling at the molecular level have begun to elucidate the mechanistic links between obesity-induced inflammation and insulin-resistant states.

  1. 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. In addition, 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.11, 12  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. 13

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

  1. Can understand 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, 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.

Obesity might increase the expression of some inflammatory cytokines and activate several signaling pathways, both of which are involved in the pathogenesis of insulin resistance by interfering with insulin signaling and action. It has been suggested that specific factors and signaling pathways are often correlated with each other; therefore, both of the fluctuations of cytokines and the status of relevant signaling pathways should be considered during studies analyzing inflammation-related insulin resistance.

References

  1. NCBI (2007): Inflammation and Insulin Resistance. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2246086/
  2. Scientific American(2009): Does Inflammation Trigger Insulin Resistance and Diabetes? Retrieved from https://www.scientificamerican.com/article/inflammatory-clues/
  1. NCBI (2006): Inflammation and Insulin Resistance. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1483173/
  2. org (2008): Skeletal muscle insulin resistance: role of inflammatory cytokines and reactive oxygen species. Retrieved from https://www.physiology.org/doi/full/10.1152/ajpregu.00561.2007
  3. Hindawi (2015): Mechanisms Linking Inflammation to Insulin Resistance. Retrieved from https://www.hindawi.com/journals/ije/2015/508409/
  1. Endocrineweb(2019): Insulin Resistance Causes and Symptoms. Retrieved from https://www.endocrineweb.com/conditions/type-2-diabetes/insulin-resistance-causes-symptoms

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 adipose tissue, and the higher their chances of developing T2D. In this article, we will highlight the emerging role of inflammation in the pathophysiology of 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. It is characterized by high blood pressure, a large waist circumference, elevated fasting glucose and triglycerides, and low HDL cholesterol.

Metabolic inflammation 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 impeded by inflammation caused by obesity. Metabolically activated macrophages are key cells in the process. They are believed to spike both pro- and anti-inflammatory pathways in reaction to lipid spillover from adipocytes.

Diabetes is a complex metabolic disorder affecting the glucose status of the human body. The main clinical diagnostic features are impaired glucose tolerance and hyperglycemia. These occur as the result of an absolute or relative insulin deficiency or resistance to its action. Chronic hyperglycemia associated with diabetes can result in end-organ dysfunction and failure which can 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 the 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. There is, therefore, a need for effective novel therapeutic approaches 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 T2D. The increase in the prevalence of the condition has been related to well-recognized risk factors, such as the adoption of a western lifestyle, sedentary lives, lack of physical activity and an energy-dense diet.

Genetic predisposition, ethnicity, and aging are not modifiable risk factors for T2D. 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 modifiable and non-modifiable factors.

  1. 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 sodium salicylate led to decreased glycosuria 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 the serine kinase IkappaB kinase-beta (IKKbeta), which correlates with the post-receptor action of insulin.

A landmark study to correlate inflammation with diabetes was conducted in animal models by Hotamisiligil et al., in 1993 and it revealed that the role of tumor necrosis factor-alpha (TNF-alpha) in obesity and particularly in insulin resistance and diabetes. Epidemiologic associations of inflammation with obesity and T2D were made when circulating concentrations of markers and mediators of inflammation and acute-phase reactants including fibrinogen, C-reactive protein, interleukin (IL)-6, plasminogen activator inhibitor-1, sialic acid, and white cells, have been shown to be elevated in these conditions.

Over the next decades, numerous studies on human and animal models provided further supporting evidence for the role of inflammation in the initiation and progression of diabetes. Accumulative evidence suggests that chronic activation of pro-inflammatory pathways in target cells of insulin action may contribute to obesity, insulin resistance and related metabolic disorders including T2D. The identification of potential pathways connecting inflammation to diabetes has produced growing interest in targeting inflammation to help prevent and control diabetes and related conditions, as well as improving risk stratification for diabetes by using inflammatory biomarkers as potential indexes.

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

In several pathophysiological studies carried out, our understanding of insulin resistance and secretion in the course of disease onset and 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. In the clinical course of the disease this pancreatic functional reserve 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 T2D, it is generally accepted that abnormal insulin sensitivity precedes the clinical diagnosis of diabetes by up to 15 years. Therefore, along with mechanistic studies investigating mechanisms forming the basis of insulin resistance, more recent research has also focused on the pathways leading to beta-cell failure.

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

There is inconclusive evidence that the inflammatory state in T2D can spread to other organs such as the liver, the neural system and possibly skeletal muscle. More research is needed to support this evidence.

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

Below are some of the approaches currently being investigated.

  1. Innovative approaches on T2D to gauge anti-inflammatory diets and moderate an individual’s microbiome are under study.
  2. Clinical trials examining the effects of vitamin D supplementation on serum levels of inflammatory markers have provided inconsistent results, with no evidence of effects in most trials, or effects on selected markers in others.
  3. There are also studies investigating whether antagonists of leukotriene production enzymes – 5-lipoxygenase (5-LO), 5-LO-activating protein and LTA4 hydrolase – or receptor binding BLT1 have cardiometabolic outcome benefits, however, these results have not yet been reported.
  4. The potential for targeting cholinergic pathways, immune modulation or other mediators of inflammation such as JNK and toll-like receptors (TLRs) are also being researched.
     
  1. What is the future of understanding metabolic inflammation as a cause of diabetes?

Given the increasing prevalence of diabetes, it is crucial that research focuses on its prevention as well as its treatment. Heart disease, metabolic syndrome and type 2 diabetes (T2D) all have in common the increased concentration 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.

T1D 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 the possible use of stem cells to regenerate pancreatic beta cells could potentially be the key to the permanent treatment of T1D. Therefore, after a holistic review of the possible mechanisms that lead to T1D and T2D 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.

References

  1. NCBI (2017): Nutritional modulation of metabolic inflammation. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/28710289
  1. EM-Consulte (2012): Inflammation and type 2 diabetes. Retrieved from https://www.em-consulte.com/en/article/735580
  1. ECR (2019): The Role Of Inflammation In Diabetes: Current Concepts And Future Perspectives. Retrieved from https://www.ecrjournal.com/articles/role-inflammation-diabetes-concepts-future

The modern diet contains a large number of simple sugars. From bread to donuts, to carbonated drinks to chocolate, cookies, and candy, everywhere you look, temptation abounds. The potential impact on the health of diets rich in free sugars, and particularly fructose, is of major concern. Does the sugar we take have an impact on insulin resistance and obesity? In this article, we look at this risk and the effects of insulin resistance.

  1. Sugar and Insulin resistance….

Sugar has a bittersweet reputation when it comes to health. It occurs naturally in all foods that contain carbohydrates, such as fruits and vegetables, grains, and dairy. Consuming whole foods that contain natural sugar is safe. Plant foods also have high amounts of fiber, essential minerals, and antioxidants, and dairy foods contain protein and calcium.

Where does the problem with sugar come about? Added sugar, which is usually extracted or synthesized ……

There is plenty of evidence to suggest that consuming too much sugar can have a negative effect on our metabolic health. Regular sugar consumption produces a constant release of the hormone insulin. Over a period of time, it can lead to serious problems, such as the synthesis of triglycerides, insulin resistance, fatty liver disease, type II diabetes, an increase in very-low-density lipoprotein (the bad kind of cholesterol), and the accumulation of fat on all tissues.

Added sugar intake may contribute to and certainly does exacerbate insulin resistance. For example, added sugar intake is associated with higher blood pressure, inflammation, weight gain, fatty liver disease, health issues that can lead to insulin resistance, and further exacerbation of these issues. Added sugars cater to particularly energy-hungry but metabolically inefficient cells, including senescent cells, cancerous cells, and even quickly proliferating pathogenic bacteria in the gut.

Several genetic and lifestyle factors can contribute to how likely you are to develop insulin resistance. But even if you have a genetic risk, you can help yourself with regular exercise, a balanced diet, avoidance of added dietary sugars, healthy sleep patterns, and stress reduction activities.

Risk factors for insulin resistance and prediabetes include:

  • Obesity
  • Aging
  • physical inactivity
  • high cholesterol
  • blood pressure
  • sleep disorders or circadian rhythm disruption

It is said that one in three Americans—including half of those age 60 and older— have insulin resistance.

  1. What exactly is Insulin Resistance?

Insulin resistance is when cells in your muscles, body fat, and liver start resisting or ignoring the signal that the hormone insulin is trying to send out—which is to grab glucose out of the bloodstream and put it into our cells. Glucose, also known as blood sugar, is the body’s main source of fuel. We get glucose from grains, fruit, vegetables, dairy products, and drinks that bring break down into carbohydrates.

  1. How does Insulin Resistance develop?

While genetics, aging, and ethnicity play roles in developing insulin sensitivity, the driving forces behind insulin resistance include excess body weight, too much belly fat, a lack of exercise, smoking, and even not getting enough sleep.

As insulin resistance develops, your body fights back by producing more insulin. Over months and years, the beta cells in your pancreas have been working so hard to make insulin get worn out and can no longer keep pace with the demand for more and more insulin. Then – years after insulin resistance silently began – your blood sugar may begin to rise, and you may develop prediabetes or type 2 diabetes. You may also develop non-alcoholic fatty liver disease (NAFLD), a growing problem associated with insulin resistance that boosts your risk for liver damage and heart disease.

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

Insulin resistance can be triggered by a combination of factors linked to weight, age, genetics, being sedentary, and smoking.

– Polycystic ovary syndrome (PCOS): Insulin resistance can worsen the symptoms of PCOS, which can include irregular menstrual cycles, infertility, and periods that cause pain.

– A large waist. Experts say the best way to tell whether you’re at risk for insulin resistance involves a tape measure and a moment of truth in front of the bathroom mirror. A waist that measures 35 inches or more for women and 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.

– You have 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.

– Acanthosis nigricans: This skin condition can develop in people with insulin resistance. It involves dark patches forming on the groin, armpits, and the back of the neck.

  1. What health conditions are related to Insulin Resistance?

The most common health condition related to Insulin Resistance is prediabetes and the resultant Type 2 Diabetes. Insulin resistance also doubles your risk for heart attack and stroke – and triples the odds that your heart attack or ‘brain attack’ will be deadly.
Insulin resistance and metabolic syndrome are also linked with a higher risk for cancers of the bladder, breast, colon, cervix, pancreas, prostate, and uterus. This is because the high insulin levels early in insulin resistance seem to fuel the growth of tumors and suppress the body’s ability to protect itself by killing off malignant cells.

Furthermore, research has found a strong association between insulin resistance and memory function decline, increasing the risk of Alzheimer’s disease.

  1. Can you prevent or reverse insulin resistance?

The good news is that, yes, insulin resistance can be prevented and also reversed in some cases. Here is what you can do:

  • Get recommended amounts of physical activity and structured exercise
  • Get adequate sleep
  • eat when the sun is up(we are more insulin resistant at night and after a night of poor sleep, due to disrupted circadian rhythms that help regulate our metabolic state)
  • Reducing stress and, therefore stress-related inflammation
  • Maintaining a healthy weight
  • Increasing your plant fiber intake.

All of the above can help improve your insulin sensitivity. It has been shown that combining both diet and exercise have the most impact on insulin sensitivity.

In a fascinating University of New Mexico School of Medicine, study published in the International Journal of Obesity, overweight people who lost 10% of their weight through diet plus exercise saw insulin sensitivity improve by an impressive 80%. Those who lost the same amount of weight through diet alone got a 38% increase. And those who simply got more exercise, but didn’t lose much weight, saw almost no shift in their level of insulin resistance.

Intermittent fasting is also another way in which you can reverse your insulin resistance. This is because it gives your body a break from insulin and glucose signaling pathways that promote cell proliferation and inflammation and may help increase insulin sensitivity.

  1. What, therefore, is the relationship between sugar and Insulin Resistance?

There is an association between diets high in sugars (predominantly sucrose) and the risk of disease, and experimental studies have shown that high intakes of fructose (over 100 g/d) can reduce insulin sensitivity. However, somewhat lower intakes may affect serum TG. The mechanisms for such associations or effects have not been convincingly demonstrated.

References:

  1. NCBI (2016): A review of recent evidence relating to sugars, insulin resistance, and diabetes. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5174139/
  1. Endocrineweb (2019): Insulin resistance causes and symptoms. Retrieved from https://www.endocrineweb.com/conditions/type-2-diabetes/insulin-resistance-causes-symptoms
  1. Medical News Today (2019): What to know about insulin resistance. Retrieved from https://www.medicalnewstoday.com/articles/305567.php
  1. The Sugar Movement (2016): Sugar vs Fat. Retrieved from https://thatsugarmovement.com/sugar-vs-fat/
  1. Harvard Health Publishing (2017): The sweet danger of sugar. Retrieved from https://www.health.harvard.edu/heart-health/the-sweet-danger-of-sugar
  1. NCBI (2014): Weight Loss, Exercise, or Both and Cardiometabolic Risk Factors in Obese Older Adults: Results of a Randomized Controlled Trial https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3835728/