The Paleo NP Podcast Episode #06: Metabolic Syndrome & Insulin Resistance



Something I'm loving this week
The science behind metabolic syndrome & insulin resistance
Testing for insulin resistance
Insulin resistance and other hormonal imbalances
Pre-diabetes and diabetes
Eating paleo for metabolic syndrome
Supplements to help manage insulin resistance and metabolic syndrome 

Theme music courtesy of

Podcast episodes also available on iTunes and Stitcher.

resources Mentioned in this episode:

The 30 Day Energy Reset book

Chris Kresser's interview with Dr. Cowan

Dr. Cowan's Garden website

Why you need 8 servings of vegetables per day


You’re listening to episode #6 of the Paleo NP Podcast

Something I'm loving this week

Hi friends! I’m excited to be back here with another episode of the Paleo NP podcast. Before I get into the meat of this week’s episode, I want to tell you about something I’m really loving this week. So a while back I heard a podcast (and honestly I can’t remember which one, but I can tell you that I was riding my bike down the bike path while I was listening to it) and it was an interview with a gentleman named Dr. Cowan who had a passion for vegetables. Anyway, if I can figure out what podcast it is I’ll link to it, but the point is that he makes vegetable powders and I’ve had a few of them for awhile but I have only recently discovered how great they are.

So there are tons of different options, I have the threefold blend which I think is chard, kale, beets, leeks, zucchini, and peppers. Anyway, the idea is that none of us get enough vegetables in our day. I try really hard and I probably get about 5 servings. But there was a study done that showed that you don’t really get a lot of the benefits of vegetables until you hit 8 servings per day.

So enter vegetable powders. Depending on the flavor profile you can literally stick them in everything. I’ve also got the beet powder which I put in my smoothies any time I make them. And the threefold blend is something that I sprinkle on meat or other veggies. It just gives it a little flavor and gives you a few extra servings of your daily veggies.

This is only even coming up because I made nachos for dinner a few nights ago and I was trying to figure out how to get some vegetables into them. I ended up just sprinkling two tablespoons of the veggie powder into the meat while it was cooking. It’s like instant veggie magic. Suddenly my veggie-free meal turned into a meal with tons of veggies.

Also, don’t let this be a substitute for eating actual vegetables, it’s just a great option for kids who might not love eating them or for anyone who is trying to fit more in. You’ve still got to eat your actual veggies though. I’ll put a link in the show notes so you can check out the website.

Metabolic syndrome and insulin resistance

So this week I wanted to talk about metabolic syndrome, what it is and why you should even care about it. Also how this relates to Paleo, because it definitely does. Also, biochemistry is not my forte, so I’m going to do my best to explain in clear terms what all of this stuff means. Fair warning, we are going to get kind of nerdy with science in this episode!

So what is metabolic syndrome? It’s a combination of several risk factors and in order to be diagnosed with metabolic syndrome you need to have three or more of the following: Elevated fasting blood sugar, elevated triglycerides, low HDL cholesterol (your good cholesterol), high blood pressure, and central obesity - which means that you carry your extra weight around your waist

The reason that I wanted to talk about this is because most people probably haven’t heard of it and probably at least 40% of the patients I saw in clinic had metabolic syndrome. Something called insulin resistance is also closely associated with metabolic syndrome and is thought to be the underlying mechanism of metabolic syndrome. Insulin resistance is when your cells are not very sensitive to insulin so it takes more insulin to get glucose out of your blood and into your cells (which is what insulin does). Insulin resistance can be caused by inflammation and insulin resistance leads to metabolic syndrome.

The underlying pathology of metabolic syndrome involves a complex cascade of events that occur within your cells. Insulin is a hormone whose action is needed for tissue development, growth, and maintaining glucose balance in the body. Insulin also has an effect on the breakdown of lipids (fats) by increasing the amount of fat that is made in your liver and adipose tissues.

Insulin resistance means that your tissues are less responsive to appropriate levels of insulin circulating in your blood. Insulin resistance in your muscle tissue causes decreased ability to get glucose out of your bloodstream as well as increased production of glucose. This happens because your muscle cells need glucose, but the cells can’t get it because they are resistant to the action of insulin so they send a signal that they need more glucose. One of the main features of metabolic syndrome is the impaired secretion of insulin by cells in your pancreas (called pancreatic beta cells) which leads to high blood sugar because of this defect in insulin secretion.

The timing of the insulin response also gets knocked out of whack because you have your muscle cells saying they need more glucose and then your pancreas can’t secrete the insulin your body needs to get the glucose into the cells, so it becomes an ugly cycle.

In the livers of healthy people, so people who do not have insulin resistance or metabolic syndrome, insulin inhibits the production and release of glucose by preventing gluconeogenesis and glycogenolysis. Gluconeogenesis is how you produce glucose from non-carbohydrate sources and glycogenolysis is the opposite so it’s the breakdown of glycogen to glucose. The main target of the action of insulin is skeletal muscle. Defects in the synthesis of glycogen is caused by defects in the glucose within the muscle. I guess I should mention that glycogen is the way that the body stores glucose for later use. It is stored in the liver. So there is a glucose transporter that carries glucose into cells. Something like exercise or insulin tells this transporter that it is time to move some glucose into the cells because the muscle cells need it.

Previous definitions of insulin resistance defined the condition in terms of the negative effects such as high blood sugar, or hyperglycemia, following a meal that was high in carbohydrates. Eventually the cells in the pancreas become unable to produce enough insulin to maintain normal blood glucose levels because they are being overworked by the constant influx of high carbohydrate meals. This is the defining characteristic of the transition from insulin resistance to type 2 diabetes. But it’s important to note that insulin resistance actually occurs at the cellular level (as we just talked about) despite the dysfunction of the pancreatic beta cells.

Studies have also shown that there are abnormalities in fatty acid metabolism present in insulin resistance as well. These abnormalities cause a build-up of fat in the muscle tissue, liver, and other organs. Lipotoxicity, a condition that develops when fat builds up in places other than adipose tissue, in the presence of elevated levels of free fatty acids in the blood is considered a hallmark sign of insulin resistance.

Chronic inflammation has also been linked to insulin resistance. The chemical messengers of inflammation, called cytokines, have been associated with many features of metabolic syndrome. These cytokines cause insulin resistance by causing some of the molecules that insulin acts on to undergo a chemical process called phosphorylation.

Have I lost you yet? I told you we were going to get nerdy with science. Bear with me, I’m going to bring this all together in a minute.

So because of what I just talked about with inflammation, insulin resistance, mostly in the skeletal muscle, shows up as a decrease in the creation of glycogen, as stimulated by insulin, because of decreased glucose transport. Once this happens, lipids start to accumulate in the cells of the liver and pancreas causing oxidative stress and changes in the metabolism of cells. Environmental toxins also play a role in insulin resistance and type 2 diabetes. BPA, found in many plastics, has been closely linked to insulin resistance and type 2 diabetes. In 2012 it was estimated that more than 90% of US residents had detectable levels of BPA in their urine. I would guess that this number has gone down a bit given all the awareness around BPA and the harm it causes. BPA appears to have an effect on the metabolism of glucose by several pathways including insulin resistance, the dysfunction of pancreatic beta cells (remember, those are the cells in your pancreas that produce insulin), inflammation, and oxidative stress.

Air and traffic pollution have also been linked to insulin resistance and increased risk of death, likely from type 2 diabetes. Something called Persistent organic pollutants, POPs, might also play a role in metabolic syndrome. POPs are compounds that do not dissolve well in water, but do dissolve well in lipids and they persist in the environment making them increase up the food chain (something eats something else that had a lot of these and then that animal ends up with a high concentration of POPs and so on).

Pesticides and solvents are the main sources of POPs. And because they are easily absorbed into fat they do not degrade easily and remain in the host for up to 10 years. In 2002, higher concentrations of POPs (mainly in the form of pesticides and herbicides) were associated with a higher rate of type 2 diabetes. And what I think is the most interesting piece of this is that obesity was NOT found to be a risk factor for type 2 diabetes in people who had no detectable levels of POPs in their system. One article even implied that virtually all of the risk of diabetes as it is related to obesity is attributable to POPs. That to me is so completely mind-blowing. And this actually highlights for me one of the major problems with our medical system, which I’m not going to get into too in depth right now, but as a healthcare provider I was taught essentially that obesity is one of the main risk factors for type 2 diabetes and that in order to prevent type 2 diabetes, you need to reduce body weight. But the study I just mentioned implied that the obesity that causes type 2 diabetes is actually caused by exposure to pesticides.

I would guess that a majority of medical practitioners don’t know that, but it’s almost like saying that for these people, developing type 2 diabetes isn’t really their fault. Now, I have no idea if in this case reducing body weight still reduces risk of type 2 diabetes (my guess is that it does), but it just kind of blows my mind that we look at treating things without ever really understanding what the root cause is.

So, before I move on I just want to recap the really high level stuff here. Essentially insulin resistance leads to metabolic syndrome, which eventually leads to type 2 diabetes. (I know you are asking why I couldn’t have just led with that and skipped all the gory details, but I think those are important too)

Testing for insulin resistance

One other thing that I want to mention before moving on - don’t worry, we are out of the nerdy science woods for now - is how this gets to be such a problem. If we know what the criteria for metabolic syndrome is, why is it such a problem? Why aren’t we treating it?

Well, the issue lies in the fact that by the time metabolic syndrome is diagnosed, it’s become a bigger issue - so, it’s already turned into pre-diabetes or diabetes. Many of the early signs often get labeled as something else. Common early signs of insulin resistance are low blood sugar, mood swings (triggered by big swings in blood sugar), fatigue, sugar and carb cravings, brain fog, weight gain, anxiety, and other mood issues. It’s also important to note that the presence of these symptoms do not always indicate insulin resistance.

The other issue is that most healthcare providers are not testing the right things. We are trained to test a person’s fasting blood glucose, so what their blood sugar is at least 8 hours after their last meal. And the guidelines that a majority of providers follow say that anything under 110 is really no big deal. Once you get into the 110 range, we start to pay closer attention to it and call you “pre-diabetic.” And once you hit 126 you officially get a diagnosis of diabetes and get put on medication. However, the scary part of this system is that your blood sugar is actually the last thing in the cascade to increase, so for a lot of people a fasting blood sugar test actually catches things too late.

Remember how we talked about all that sciencey stuff - well, your insulin is actually the first thing that gets whacky (remember that your muscle cells become resistant to insulin and tell your body that it needs to release more insulin so that you can get the sugar out of your blood and into your muscle cells). So abnormally high insulin is an earlier sign of diabetes and it may detect it decades sooner (yep, I said decades).

The gold standard for diagnosis of insulin resistance (and really it should become the standard for diabetes as well) is the 2 hour glucose tolerance test. This test can detect both high insulin levels and high blood sugar levels, but it isn’t a test that gets ordered very frequently. If you’ve ever had a baby, you’ve had a similar test (although it was probably a one hour or a three hour test) to determine if you have gestational diabetes.

A common trend is for people to have normal blood sugar, but high levels of insulin (because your cells are resistant to insulin it takes more insulin to maintain a normal blood sugar) and not yet have the diagnosis of prediabetes. It’s funny to me that insulin resistance contributes to most chronic disease in the united states, but almost 90% of people who have this condition have not been diagnosed...and it’s as simple as ordering one test. I get that the problem is time -no one wants to take 2 hours to find out if they have insulin resistance. But would you rather spend a couple of hours getting this test done, or spend the rest of your life with a chronic, and somewhat preventable, disease?

Insulin resistance and other hormonal imbalances

Remember that none of these things exist in a vacuum either, so it’s unlikely that you JUST have insulin resistance because insulin affects other hormones as well. There is some evidence that estrogen dominance is linked to decreased insulin sensitivity. And I’m not going to get too in the weeds here, but estrogen dominance doesn’t mean that you have high estrogen. Estrogen and progesterone are the two main female sex hormones and they need to exist in balance with each other. So if you have low estrogen, but lower progesterone then you can still have estrogen dominance.

There’s also cortisol, which is the stress hormone. So cortisol prepares your body for action during a fight or flight or stress response which causes energy to be moved out of storage and become readily available (so your body converts it’s glycogen stores into glucose). Under short term stress, insulin and cortisol have opposite effects (high levels of insulin cause your body to store energy in the form of glycogen and fat). In our modern society, non-physical stressors can increase cortisol. So relationship issues, problems with your children, and sleep deprivation, but none of these things result in vigorous physical activity to lower your blood sugar such as running away from a bear would. Because you aren’t burning off the excess glucose that was released by the cortisol your blood sugar can remained elevated for long periods of time which can trigger the release of insulin.

Since insulin is one of the drivers of obesity, it would make sense that chronic stress (and thus chronically elevated cortisol) leads to obesity. This can even be done artificially when a person is prescribed steroids for whatever reason. One of the major side effects of long-term steroid use is weight gain (among other things), because these medications are essentially artificial cortisol it would make sense that the effects are similar. And we’ve already discussed how elevated insulin levels lead to insulin resistance and metabolic syndrome. The other thing to consider in this situation of elevated cortisol is that progesterone is one of the main components needed to make cortisol. So when you have chronically high levels of cortisol, you are using up all of your progesterone, and when you have low progesterone, you end up with estrogen dominance. Estrogen dominance makes it much harder to lose weight, which only perpetuates this cycle.

There is also some evidence that estrogen deficiency (as may happen during menopause) can lead to the development of insulin resistance because estrogen plays an important role in glucose metabolism and insulin sensitivity in the cells.

Pre-Diabetes and diabetes

So I already mentioned that pre-diabetes is the diagnosis that you get before you are diagnosed with diabetes. If you are going based on blood sugar, it’s when your fasting blood sugar is between 110 and 125. In a standard medical practice, anything under 99 for a fasting glucose is considered normal. But in reality we would really like it to be under 90 for a fasting glucose number. Also remember that blood sugar is the last thing to increase in diabetes, which is why measuring insulin might be a better diagnostic tool. The other reason why blood sugar alone is not a great diagnostic tool is that your fasting blood sugar can actually increase if you are eating a lower carb diet. It’s kind of the same thing that we were talking about with hormones, but people who eat low carb might become slightly insulin resistant over time because the body downregulates how much insulin you need.

So, you aren’t eating as many carbs which means that you don’t need as much insulin, which means that you body slowly decrease the amount of insulin it produces because it just doesn’t need to make as much. So in this case it’s not a disease-state, but it’s still insulin resistance. This definitely doesn’t apply to everyone, but also remember from the Paleo 101 episode that sometimes people are unintentionally eating low carb on a Paleo diet. And this wouldn’t be an issue if you just started a paleo diet, but it could become one as time goes on, and is just something to be aware of when you are having labs done with your doctor or medical provider.

I also want to make sure that you understand that just because someone isn’t overweight, doesn’t meant that they can’t still have insulin resistance or metabolic syndrome (remember of the 5 criteria you only need 3). So just because someone is skinny or an athlete, doesn’t mean that this isn’t an issue for them. I’ve seen tall skinny marathon running dudes with fasting blood sugars in the 120s and insanely high cholesterol. Skinny doesn’t equal healthy even though type 2 diabetes tends to be a big issue for those who are overweight.

Eating Paleo for metabolic syndrome

Ok, so now the $100,000 question. What do we do about this? There’s a growing body of evidence to support the use of a Paleo diet in treating metabolic syndrome, insulin resistance, and diabetes. One study compared the Paleo diet with the diet recommended by the American Diabetes Association in people with type 2 diabetes. The study was short, only 14 days, and both groups showed improvements in weight and insulin sensitivity, only the paleo diet group had improvements in their fasting glucose and bad cholesterol levels.  A study done with people who already had metabolic syndrome showed that the paleo diet lowered blood pressure, cholesterol, and triglycerides after only 14 days. And had lowered them more than the diet recommended by the Dutch Health Council for those with metabolic syndrome. The shocking part for me with these studies was not that it improved the disease markers, but that it happened in as little as 14 days. I think that really speaks to the power of Paleo.

So other than eating a Paleo diet (you knew that was going to be the first thing I said, right?) what else can you do to get rid of insulin resistance and metabolic syndrome? I mean, the other big thing is lifestyle factors. Lack of exercise, diets high in refined carbohydrates and low in fiber are the main culprits when it comes to type 2 diabetes. In fact, at least 92% of all cases of type 2 diabetes are related to one of these factors. That means that 92% of type 2 diabetes cases are also preventable. And eating a Paleo diet takes care of over half of those factors. Just add a little bit of exercise to that and you can prevent almost every single case of type 2 diabetes in the US. That’s so great. And amazing! Exercise doesn’t have to be vigorous or long. At least 30 minutes five times per week has multiple benefits  including reducing overall inflammation in addition to helping maintain a normal blood sugar.

I have a friend who has type 2 diabetes that he controls mostly with his diet. And, I don’t recommend this approach, but if he eats something that’s higher in carbohydrates, he just rides his bike until his blood sugar gets to an appropriate level. Again, I don’t recommend this approach, but it really works for him. He knows how far or how long he needs to bike under certain circumstances and then he gets to have the occasional indulgence without worrying that his blood sugar is going to go crazy. He also rides his bike everywhere, so that’s helpful, but I think that just speaks to the importance of exercise. Because of the role of cortisol in all of this, stress management is also important.

There are also numerous supplements that have been shown to have a beneficial effect on glucose metabolism and insulin sensitivity. And as always, please consult your healthcare provider before starting any supplements! And these recommendations are meant to go along with the necessary dietary changes. Because you can’t supplement your way out of something without making changes elsewhere. Vitamin B6 deficiency is associated with a decrease in many of the enzymes that are needed to make glucose from non carb sources. Folic acid has been shown to protect against some of the damage that can occur to blood vessels in those with metabolic syndrome and might improve overall metabolic profiles. There is an inverse relationship between vitamin B12 and BMI - and in patients who have metabolic syndrome, folate and B12 decreases insulin resistance. People with metabolic syndrome have been shown to have low levels of vitamin C and vitamin C deficiency is associated with weight loss resistance. Vitamin D has been shown to reduce the likelihood of developing metabolic syndrome. In a study of young adults, there was an inverse relationship between blood glucose, insulin resistance, and vitamin D (so more vitamin D meant lower blood glucose and better insulin sensitivity). Magnesium plays a critical role in regulation of the action of insulin and the uptake of glucose by the cells. Higher Magnesium intake is associated with increased insulin sensitivity and a decreased risk of metabolic syndrome. And Americans are notoriously deficient in Magnesium in general, so even if you aren’t at risk for metabolic syndrome, you might consider some additional magnesium.

Some other supplements that could be helpful are Alpha lipoic acid, which is a powerful antioxidant , coenzyme Q10, which is important in conversion of carbohydrates to energy, and acetyl-L-carnitine, an amino acid that also plays an important role in energy metabolism.

Alright guys, if you are still listening, congrats! That’s all I’ve got for you this week. Thanks so much for listening. And as always, if you have questions, you can submit those on my website and if you are enjoying this show, I would love it if you would head over to iTunes and leave a review. See you next week!