Lipotoxicity: How Saturated Fat Raises Blood Sugar

NF-Nov24 Lipotoxicity How Saturated Fat Raises Blood Sugar copy.jpg

The reason those eating plant-based diets have less fat buildup in their muscle cells and less insulin resistance may be because saturated fats appear to impair blood sugar control the most.

The association between fat and insulin resistance is now widely accepted. Insulin resistance is due to so-called ectopic fat accumulation, the buildup of fat in places it's not supposed to be, like within our muscle cells. But not all fats affect the muscles the same. The type of fat, saturated vs. unsaturated, is critical. Saturated fats like palmitate, found mostly in meat, dairy and eggs, cause insulin resistance, but oleate, found mostly in nuts, olives and avocados may actually improve insulin sensitivity.

What makes saturated fat bad? Saturated fat causes more toxic breakdown products and mitochondrial dysfunction, and increases oxidative stress, free radicals and inflammation, establishing a vicious cycle of events in which saturated fat induces free radicals, causes dysfunction in the little power plants within our muscle cells (mitochondria), which then causes an increase in free radical production and an impairment of insulin signaling. I explain this in my video Lipotoxicity: How Saturated Fat Raises Blood Sugar.

Fat cells filled with saturated fat activate an inflammatory response to a far greater extent. This increased inflammation from saturated fat has been demonstrated to raise insulin resistance through free radical production. Saturated fat also has been shown to have a direct effect on skeletal muscle insulin resistance. Accumulation of saturated fat increases the amount of diacyl-glycerol in the muscles, which has been demonstrated to have a potent effect on muscle insulin resistance. You can take muscle biopsies from people and correlate the saturated fat buildup in their muscles with insulin resistance.

While monounsaturated fats are more likely to be detoxified or safely stored away, saturated fats create those toxic breakdown products like ceramide that causes lipotoxicity. Lipo- meaning fat, as in liposuction. This fat toxicity in our muscles is a well-known concept in the explanation of trigger for insulin resistance.

I've talked about the role saturated and trans fats contribute to the progression of other diseases, like autoimmune diseases, cancer and heart disease, but they can also cause insulin resistance, the underlying cause of prediabetes and type 2 diabetes. In the human diet, saturated fats are derived from animal sources while trans fats originate in meat and milk in addition to partially hydrogenated and refined vegetable oils.

That's why experimentally shifting people from animal fats to plant fats can improve insulin sensitivity. In a study done by Swedish researchers, insulin sensitivity was impaired on the diet with added butterfat, but not on the diet with added olive fat.

We know prolonged exposure of our muscles to high levels of fat leads to severe insulin resistance, with saturated fats demonstrated to be the worst, but they don't just lead to inhibition of insulin signaling, the activation of inflammatory pathways and the increase in free radicals, they also cause an alteration in gene expression. This can lead to a suppression of key mitochondrial enzymes like carnitine palmitoyltransferase, which finally solves the mystery of why those eating vegetarian have a 60 percent higher expression of that fat burning enzyme. They're eating less saturated fat.

So do those eating plant-based diets have less fat clogging their muscles and less insulin resistance too? There hasn't been any data available regarding the insulin sensitivity or inside muscle cell fat of those eating vegan or vegetarian... until now. Researchers at the Imperial College of London compared the insulin resistance and muscle fat of vegans versus omnivores. Those eating plant-based diets have the unfair advantage of being much slimmer, so they found omnivores who were as skinny as vegans to see if plant-based diets had a direct benefit, as opposed to indirectly pulling fat out of the muscles by helping people lose weight in general.

They found significantly less fat trapped in the muscle cells of vegans compared to omnivores at the same body weight, better insulin sensitivity, better blood sugar levels, better insulin levels and, excitingly, significantly improved beta-cell function (the cells in the pancreas that make the insulin). They conclude that eating plant-based is not only expected to be cardioprotective, helping prevent our #1 killer, heart disease, but that plant-based diets are beta-cell protective as well, helping also to prevent our seventh leading cause of death, diabetes.

This is the third of a three-part series, starting with What Causes Insulin Resistance? and The Spillover Effect Links Obesity to Diabetes.

Even if saturated fat weren't associated with heart disease, its effects on pancreatic function and insulin resistance in the muscles would be enough to warrant avoiding it. Despite popular press accounts, saturated fat intake remains the primary modifiable determinant of LDL cholesterol, the #1 risk factor for our #1 killer-heart disease. See The Saturated Fat Studies: Buttering Up the Public and The Saturated Fat Studies: Set Up to Fail.

How low should we shoot for in terms of saturated fat intake? As low as possible, according to the U.S. National Academies of Science Institute of Medicine: Trans Fat, Saturated Fat, and Cholesterol: Tolerable Upper Intake of Zero.

In health,

Michael Greger, M.D.

PS: If you haven't yet, you can subscribe to my free videos here and watch my live, year-in-review presentations:

Image Credit: Andrew Malone / Flickr

Original Link

Lipotoxicity: How Saturated Fat Raises Blood Sugar

NF-Nov24 Lipotoxicity How Saturated Fat Raises Blood Sugar copy.jpg

The reason those eating plant-based diets have less fat buildup in their muscle cells and less insulin resistance may be because saturated fats appear to impair blood sugar control the most.

The association between fat and insulin resistance is now widely accepted. Insulin resistance is due to so-called ectopic fat accumulation, the buildup of fat in places it's not supposed to be, like within our muscle cells. But not all fats affect the muscles the same. The type of fat, saturated vs. unsaturated, is critical. Saturated fats like palmitate, found mostly in meat, dairy and eggs, cause insulin resistance, but oleate, found mostly in nuts, olives and avocados may actually improve insulin sensitivity.

What makes saturated fat bad? Saturated fat causes more toxic breakdown products and mitochondrial dysfunction, and increases oxidative stress, free radicals and inflammation, establishing a vicious cycle of events in which saturated fat induces free radicals, causes dysfunction in the little power plants within our muscle cells (mitochondria), which then causes an increase in free radical production and an impairment of insulin signaling. I explain this in my video Lipotoxicity: How Saturated Fat Raises Blood Sugar.

Fat cells filled with saturated fat activate an inflammatory response to a far greater extent. This increased inflammation from saturated fat has been demonstrated to raise insulin resistance through free radical production. Saturated fat also has been shown to have a direct effect on skeletal muscle insulin resistance. Accumulation of saturated fat increases the amount of diacyl-glycerol in the muscles, which has been demonstrated to have a potent effect on muscle insulin resistance. You can take muscle biopsies from people and correlate the saturated fat buildup in their muscles with insulin resistance.

While monounsaturated fats are more likely to be detoxified or safely stored away, saturated fats create those toxic breakdown products like ceramide that causes lipotoxicity. Lipo- meaning fat, as in liposuction. This fat toxicity in our muscles is a well-known concept in the explanation of trigger for insulin resistance.

I've talked about the role saturated and trans fats contribute to the progression of other diseases, like autoimmune diseases, cancer and heart disease, but they can also cause insulin resistance, the underlying cause of prediabetes and type 2 diabetes. In the human diet, saturated fats are derived from animal sources while trans fats originate in meat and milk in addition to partially hydrogenated and refined vegetable oils.

That's why experimentally shifting people from animal fats to plant fats can improve insulin sensitivity. In a study done by Swedish researchers, insulin sensitivity was impaired on the diet with added butterfat, but not on the diet with added olive fat.

We know prolonged exposure of our muscles to high levels of fat leads to severe insulin resistance, with saturated fats demonstrated to be the worst, but they don't just lead to inhibition of insulin signaling, the activation of inflammatory pathways and the increase in free radicals, they also cause an alteration in gene expression. This can lead to a suppression of key mitochondrial enzymes like carnitine palmitoyltransferase, which finally solves the mystery of why those eating vegetarian have a 60 percent higher expression of that fat burning enzyme. They're eating less saturated fat.

So do those eating plant-based diets have less fat clogging their muscles and less insulin resistance too? There hasn't been any data available regarding the insulin sensitivity or inside muscle cell fat of those eating vegan or vegetarian... until now. Researchers at the Imperial College of London compared the insulin resistance and muscle fat of vegans versus omnivores. Those eating plant-based diets have the unfair advantage of being much slimmer, so they found omnivores who were as skinny as vegans to see if plant-based diets had a direct benefit, as opposed to indirectly pulling fat out of the muscles by helping people lose weight in general.

They found significantly less fat trapped in the muscle cells of vegans compared to omnivores at the same body weight, better insulin sensitivity, better blood sugar levels, better insulin levels and, excitingly, significantly improved beta-cell function (the cells in the pancreas that make the insulin). They conclude that eating plant-based is not only expected to be cardioprotective, helping prevent our #1 killer, heart disease, but that plant-based diets are beta-cell protective as well, helping also to prevent our seventh leading cause of death, diabetes.

This is the third of a three-part series, starting with What Causes Insulin Resistance? and The Spillover Effect Links Obesity to Diabetes.

Even if saturated fat weren't associated with heart disease, its effects on pancreatic function and insulin resistance in the muscles would be enough to warrant avoiding it. Despite popular press accounts, saturated fat intake remains the primary modifiable determinant of LDL cholesterol, the #1 risk factor for our #1 killer-heart disease. See The Saturated Fat Studies: Buttering Up the Public and The Saturated Fat Studies: Set Up to Fail.

How low should we shoot for in terms of saturated fat intake? As low as possible, according to the U.S. National Academies of Science Institute of Medicine: Trans Fat, Saturated Fat, and Cholesterol: Tolerable Upper Intake of Zero.

In health,

Michael Greger, M.D.

PS: If you haven't yet, you can subscribe to my free videos here and watch my live, year-in-review presentations:

Image Credit: Andrew Malone / Flickr

Original Link

Fat is the Cause of Type 2 Diabetes

NF-Nov17 What Causes Insulin Resistance copy.jpg

Studies dating back nearly a century noted a striking finding: If you take young, healthy people and split them up into two groups--half on a fat-rich diet and half on a carbohydrate-rich diet--we find that within just two days, glucose intolerance skyrockets in the fat group. The group that had been shoveling fat in ended up with twice the blood sugar. As the amount of fat in the diet goes up, so does one's blood sugar. Why would eating fat lead to higher blood sugar levels? It would take scientists nearly seven decades to unravel this mystery, but it would end up holding the key to our current understanding of the cause of type 2 diabetes.

The reason athletes carb-load before a race is to build up the fuel supply within their muscles. We break down the starch into glucose in our digestive tract, it circulates as blood glucose (blood sugar) and is taken up by our muscles to be stored and burnt for energy.

Blood sugar, though, is like a vampire. It needs an invitation to come into our cells. That invitation is insulin. Insulin is the key that unlocks the door that lets glucose in the blood enter muscle cells. When insulin attaches to the insulin receptor on the cell, it activates an enzyme, which activates another enzyme, which activates two more enzymes, which finally activates glucose transport (as diagrammed in my video What Causes Insulin Resistance?).

What if there was no insulin? Blood sugar would be stuck in the bloodstream banging on the door to our muscles, unable to get inside. With nowhere to go, sugar levels in the blood would rise and rise. That's what happens in type 1 diabetes: the cells in the pancreas that make insulin get destroyed, and without insulin, sugar in the blood can't get out of the blood into the muscles, and so blood sugar rises. But there's a second way we could end up with high blood sugar.

What if there's enough insulin, but the insulin doesn't work? The key is there, but something's gummed up the lock. This is insulin resistance. Our muscle cells become resistant to the effect of insulin. What's gumming up the locks on our muscle cells? What's preventing insulin from letting glucose in? Tiny droplets of fat inside our muscle cells, so-called intramyocellular lipid.

Fat in the bloodstream can build up inside the muscle cell, creating toxic fatty breakdown products and free radicals that block the insulin signaling process. No matter how much insulin we have in our blood, it's not able to sufficiently open the glucose gates and blood sugar levels build up in the blood. And this can happen within three hours. One hit of fat can start causing insulin resistance, inhibiting blood sugar uptake after just 160 minutes.

This mechanism by which fat induces insulin resistance wasn't known until fancy MRI techniques were developed to see what was happening inside people's muscles as fat was infused into their bloodstream. That's how we found that elevation of fat levels in the blood causes insulin resistance by inhibition of glucose transport into the muscles.

We can also do the opposite experiment. Lower the level of fat in people's blood and the insulin resistance comes right down. If we clear the fat out of the blood, we also clear the sugar out. That explains the finding that on the high fat, ketogenic diet, insulin doesn't work very well. Our bodies become insulin resistant. But as the amount of fat in our diet gets lower and lower, insulin works better and better--a clear demonstration that the sugar tolerance of even healthy individuals can be impaired by administering a low-carb, high-fat diet. We can decrease insulin resistance, however, by decreasing fat intake.

The effect is really dramatic--check out at least the end of my video What Causes Insulin Resistance? to see what happens as dietary fat intake drops.

The most concerning downside of low-carb diets, though, is heart health: Low Carb Diets and Coronary Blood Flow

This is the first of a 3-part series on the cause of type 2 diabetes, so as to better understand dietary interventions to prevent and treat the epidemic. In The Spillover Effect Links Obesity to Diabetes, I talk about how that fat can come either from our diet or excess fat stores, and then in Lipotoxicity: How Saturated Fat Raises Blood Sugar, I show how not all fats are equally to blame.

Here are some of my recent diabetes videos:

In health,

Michael Greger, M.D.

PS: If you haven't yet, you can subscribe to my free videos here and watch my live, year-in-review presentations:

Image Credit: [Gema Ibarra] © 123RF.com

Original Link

Fat is the Cause of Type 2 Diabetes

NF-Nov17 What Causes Insulin Resistance copy.jpg

Studies dating back nearly a century noted a striking finding: If you take young, healthy people and split them up into two groups--half on a fat-rich diet and half on a carbohydrate-rich diet--we find that within just two days, glucose intolerance skyrockets in the fat group. The group that had been shoveling fat in ended up with twice the blood sugar. As the amount of fat in the diet goes up, so does one's blood sugar. Why would eating fat lead to higher blood sugar levels? It would take scientists nearly seven decades to unravel this mystery, but it would end up holding the key to our current understanding of the cause of type 2 diabetes.

The reason athletes carb-load before a race is to build up the fuel supply within their muscles. We break down the starch into glucose in our digestive tract, it circulates as blood glucose (blood sugar) and is taken up by our muscles to be stored and burnt for energy.

Blood sugar, though, is like a vampire. It needs an invitation to come into our cells. That invitation is insulin. Insulin is the key that unlocks the door that lets glucose in the blood enter muscle cells. When insulin attaches to the insulin receptor on the cell, it activates an enzyme, which activates another enzyme, which activates two more enzymes, which finally activates glucose transport (as diagrammed in my video What Causes Insulin Resistance?).

What if there was no insulin? Blood sugar would be stuck in the bloodstream banging on the door to our muscles, unable to get inside. With nowhere to go, sugar levels in the blood would rise and rise. That's what happens in type 1 diabetes: the cells in the pancreas that make insulin get destroyed, and without insulin, sugar in the blood can't get out of the blood into the muscles, and so blood sugar rises. But there's a second way we could end up with high blood sugar.

What if there's enough insulin, but the insulin doesn't work? The key is there, but something's gummed up the lock. This is insulin resistance. Our muscle cells become resistant to the effect of insulin. What's gumming up the locks on our muscle cells? What's preventing insulin from letting glucose in? Tiny droplets of fat inside our muscle cells, so-called intramyocellular lipid.

Fat in the bloodstream can build up inside the muscle cell, creating toxic fatty breakdown products and free radicals that block the insulin signaling process. No matter how much insulin we have in our blood, it's not able to sufficiently open the glucose gates and blood sugar levels build up in the blood. And this can happen within three hours. One hit of fat can start causing insulin resistance, inhibiting blood sugar uptake after just 160 minutes.

This mechanism by which fat induces insulin resistance wasn't known until fancy MRI techniques were developed to see what was happening inside people's muscles as fat was infused into their bloodstream. That's how we found that elevation of fat levels in the blood causes insulin resistance by inhibition of glucose transport into the muscles.

We can also do the opposite experiment. Lower the level of fat in people's blood and the insulin resistance comes right down. If we clear the fat out of the blood, we also clear the sugar out. That explains the finding that on the high fat, ketogenic diet, insulin doesn't work very well. Our bodies become insulin resistant. But as the amount of fat in our diet gets lower and lower, insulin works better and better--a clear demonstration that the sugar tolerance of even healthy individuals can be impaired by administering a low-carb, high-fat diet. We can decrease insulin resistance, however, by decreasing fat intake.

The effect is really dramatic--check out at least the end of my video What Causes Insulin Resistance? to see what happens as dietary fat intake drops.

The most concerning downside of low-carb diets, though, is heart health: Low Carb Diets and Coronary Blood Flow

This is the first of a 3-part series on the cause of type 2 diabetes, so as to better understand dietary interventions to prevent and treat the epidemic. In The Spillover Effect Links Obesity to Diabetes, I talk about how that fat can come either from our diet or excess fat stores, and then in Lipotoxicity: How Saturated Fat Raises Blood Sugar, I show how not all fats are equally to blame.

Here are some of my recent diabetes videos:

In health,

Michael Greger, M.D.

PS: If you haven't yet, you can subscribe to my free videos here and watch my live, year-in-review presentations:

Image Credit: [Gema Ibarra] © 123RF.com

Original Link