Insuline Resistance, Fat, Carbs Diabetes and Holistic Medicine

Prediabetes and type 2 diabetes are caused by a drop in insulin sensitivity attributed in part to “intramyocellular lipid,” the buildup of fat inside muscle cells.

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 the other half on a carb-rich diet, within just two days, this is what happens. The glucose intolerance skyrockets in the fatty diet group. In response to the same sugar water challenge, the group that had been shoveling in fat ended up with twice the blood sugar.

As the amount of fat in the diet goes up, one’s blood sugar spikes. 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.

When athletes carb-load before a race, they’re trying to build up the fuel supply within their muscles. They break down the starch into glucose in their digestive tract. It circulates as blood glucose—blood sugar—and is taken up by our muscles, to be stored and burned for energy.

Blood sugar, though, is like a vampire. It needs an invitation to come into our cells. And, that invitation is insulin. Here’s a muscle cell. Here’s some blood sugar outside, waiting patiently to come in. Insulin is the key that unlocks the door to let sugar in our blood enter the muscle cell. When insulin attaches to the insulin receptor, it activates an enzyme, which activates another enzyme, which activates two more enzymes, which finally activate glucose transport, which acts as a gateway for glucose to enter the cell. So, insulin is the key that unlocks the door into our muscle cells.

What if there was no insulin, though? Well, blood sugar would be stuck out in the bloodstream, banging on the door to our muscles, and not able to get inside. And so, with nowhere to go, sugar levels 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 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 called insulin resistance. Our muscle cells become resistant to the effect of insulin. What’s gumming up the door locks on our muscle cells, preventing insulin from letting sugar in? Fat. What’s called intramyocellular lipid, or fat inside our muscle cells.

Fat in the bloodstream can build up inside the muscle cells, create toxic fatty breakdown products and free radicals that can block the signaling pathway process. So, no matter how much insulin we have out in our blood, it’s not able to open the glucose gates, and blood sugar levels build up in the blood.

This mechanism, by which fat (specifically saturated 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. And, that’s how scientists found that elevation of fat levels in the blood “causes insulin resistance by inhibition of glucose transport” into the muscles.

And, this can happen within just three hours. One hit of fat can start causing insulin resistance, inhibiting glucose uptake after just 160 minutes.

Same thing happens to adolescents. You infuse fat into their bloodstream. It builds up in their muscles, and decreases their insulin sensitivity—showing that increased fat in the blood can be an important contributor to insulin resistance.

Then, you can do the opposite experiment. Lower the level of fat in people’s blood, and the insulin resistance comes right down. Clear the fat out of the blood, and you can clear the sugar out of the blood. So, that explains this finding. On the high-fat diet, the ketogenic diet, insulin doesn’t work as well. Our bodies are insulin-resistant.

But, as the amount of fat in our diet gets lower and lower, insulin works better and better. This is a clear demonstration that the sugar tolerance of even healthy individuals can be “impaired by administering a low-carb, high-fat diet.” But, we can decrease insulin resistance—the cause of prediabetes, the cause of type 2 diabetes—by decreasing saturated fat intake.

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.

archinte.jamanetwork.com/article.aspx?articleid=535594

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.

www.ncbi.nlm.nih.gov/pubmed/10027589

Fat in the bloodstream can build up inside the muscle cells, 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.

www.ncbi.nlm.nih.gov/pubmed/10334314

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. www.ncbi.nlm.nih.gov/pmc/articles/PMC507380/

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.

www.ncbi.nlm.nih.gov/pubmed/0010480616

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

 Considerable scientific evidence shows that eating a medium-fat or high-fat diet causes large blood glucose swings after eating foods containing carbohydrates (1-17). (We categorize a medium-fat diet as one with greater than 30 grams of fat per day and a high-fat diet as one with greater than 60 grams of fat per day.On average, Americans eat over 70 grams of fat per day.)

People who adopt a truly low-fat diet (less than 30 grams of fat per day) are able to eat significantly more carbohydrate without blood glucose spikes, because the amount of fat in their muscles, liver, and blood is very low. By adopting a truly low-fat, plant-based whole foods diet, your insulin sensitivity will increase considerably since you will gain the ability to metabolize carbohydrates.

Unprocessed grains like quinoa, barley, spelt and buckwheat, and starches like root vegetables, bananas and grapes, are composed of branching chains of glucose molecules that are easily digestible by the body.  These foods should not be consumed infrequently and in moderation (1).

Vegetables grown above the found, legumes, lentils, and fruits with their skins intact, are much more difficult for the body to digest.  They tend to be very high in fibre.  These types of carbohydrates should be the primary source of carbohydrates in your diet (2).

Fibre – A Protective Carbohydrate

Fibre is a special type of carbohydrate because the body cannot break it down into its simple sugar molecules.  Fibre is also responsible for making you feel fuller, longer.  There are two main types of dietary fibre: insoluble and soluble fibre (3).

Insoluble fibre cannot dissolve in water.  It is also considered to be nature’s laxative because it helps move foods through your digestive tract by bulking up your stools and making them softer, and easier to pass.  In days past, it was often called “roughage”.

Soluble fibre can dissolve in water.  In the prescience of water it forms a gel, which slows down the digestive process by delaying the emptying of your stomach contents.  This phenomenon makes your feel fuller, longer, and this delay helps stabilize blood sugar levels.

Foods that are Excellent Sources of Fibre:

Raspberries, blueberries, black berries, strawberries, apples, pears, avocados, spinach, broccoli and carrots.  

Natural Fats

Fats usually take the longest to digest.  Their digestion process is initiated in the mouth where they are prepared for digestion in the small intestine.  Fats are virtually left untouched in the stomach until they reach the small intestine, where they are broken down and absorbed by the body (4).

Examples of Natural Fats:

Butter, coconut oil, olive oil, animal meat, poultry, fish, unprocessed cheeses, nuts, seeds, avocados, and avocado oil.

Vinegar

 

Vinegars (acetic acid) slow down the digestive process because they inactivate the production of certain digestive enzymes responsible for carbohydrate digestion.  This makes it a lot more difficult for the body to breakdown carbohydrates when eaten along with vinegar.  The vinegar forces the body to release the simple sugars from those carbohydrates slowly into the bloodstream preventing blood sugar spikes (5).  This is why people started putting vinegar on foods like French fries.

How to Make Carbohydrates More Difficult for the Body to Digest

www.sciencedirect.com/science/article/pii/S1756464613001874

You want to make your foods complicated to digest.  The more complicated they are to digest, the slower the release of sugar into your bloodstream.  If you are going to eat carbohydrates, make sure you consume them with fibre, fat, and vinegar when you can.  Combining these foods is the best strategy you have to stabilize your blood sugar levels.

Eating protein and vegetables before carbohydrates leads to lower post-meal glucose and insulin levels in obese patients with type 2 diabetes, Weill Cornell Medical College researchers found in a new study. This finding, published June 23 in the journal Diabetes Care, might impact the way clinicians advise diabetic patients and other high-risk individuals to eat, focusing not only on how much, but also on when carbohydrates are consumed.

care.diabetesjournals.org/content/38/7/e98.extract?sid=ea6d4bd4-98f6-4347-9238-15e2a4c019db

Very briefly: All agree healthy fat is better than bad fat. Healthy fat is better than refined carbohydrates. The disagreement is whether we should really eat a lot of healthy fat, like neurologist Dr. David Perlmutter, who pours olive oil on his morning eggs. Or should we severely limit healthy fat too like Drs. Dean Ornish and Joel Fuhrman who think the benefit doesn’t outweigh the calories consumed. Yes, pun.

For me, having diabetes, eating a diet plentiful with healthy fat and low in refined carbs is a no-brainer. Carbs raise blood sugar. Refined carbs spike blood sugar. Higher blood sugar requires more insulin. Insulin is a fat storage hormone. The more of it circulating in your blood stream, the more it’s causing calories to be stored — in the liver as fat.

Voila, you gain weight, mostly putting it around your belly, and you end up with fatty liver disease to boot. By the way, most people with Type 2 diabetes also have fatty liver disease and don’t know it.

As a society, we love our carbs, processed foods, and sugar. As a result, metabolic disorders are prominent and heart disease remains the number one killer in the US. This style of eating throws off our ability to have stable blood sugar levels which drives up inflammation, throws off hormones, and reduces our health and vitality. Taking steps to balance blood sugar is one of the first things I focus on when working with people to improve their health.

This strategy alone has a tremendous impact on overall health and certain foods are fantastic for this purpose. Incorporating the foods and herbs from this article into your daily nutrition plan is a great place to start.

Coconut

Coconut is an all-around superfood and one of the best things to make a staple in your diet. There’s coconut oil, butter, flakes, milk, and even flour. Each of these provide unique benefits and uses for helping to balance blood sugar.

First of all, coconut is an excellent source of healthy fats, particularly medium chain triglycerides (MCT). MCTs are types of fat that your body easily converts into a source of energy called ketones. When you burn ketones for energy instead of sugar, you naturally stabilize blood sugar and improve fat burning. These fats are found in most coconut products but are more prominent in coconut-based oil, butter, and milk.

You could also try supplementing your diet with MCT oil which is a more potent extraction from coconut oil.

Coconut also contains healthy fiber which is excellent for stabilizing blood sugar when combined with other sources of carbs (1, 2). Coconut flour, butter (or manna), and coconut flakes are all excellent for this. Coconut flour is also extremely low in carbs, making it an excellent alternative for baking (just try this coconut flour pizza crust).

Turmeric

Turmeric amazes me in its benefits. I especially love turmeric for blood sugar stability as I detailed in this article. In fact, I believe turmeric should be a staple for balancing blood sugar in a healthy diet.

The compounds in turmeric have been shown to improve insulin sensitivity which allows the body to deliver glucose to cells more effectively and prevent massive fluctuations in the blood (3).

Additionally, turmeric has been shown to act on the liver to regulate epigenetic (activation of genes) and enzymatic factors that all work together to stabilize blood sugar and triglyceride levels in people with diabetes.

Finally, turmeric is excellent for targeting and lowering inflammation throughout the body. Chronic inflammation can be a contributor to blood sugar imbalances as it can stimulate cortisol release and spike blood sugar. All around, turmeric is an excellent addition to stabilize blood sugar whether you use it in cooking or simply use it in supplemental form.

Cinnamon

Considered more precious than gold at some points in our history, cinnamon is currently an underrated superfood. Not only is it one of the most antioxidant-rich foods on the planet, but it tastes amazing and is excellent for stabilizing blood sugar. Cinnamon may also be helpful for fighting candida, which can be another consequence of a high sugar intake (4).

Similar to turmeric, cinnamon improves insulin sensitivity and allows glucose to be transported from the blood and into the cells much more efficiently. This effect reduces the need for as much insulin to be released and creates a more stable rise and fall in blood sugar that is not as detrimental to health as the rapid rise and fall found with high-sugar diets or those with diabetes.

There are generally two types of cinnamon that can be found in stores; cassia and Ceylon. Ceylon is considered to be more effective for stabilizing blood sugar. Additionally, Ceylon contains drastically lower amounts of a compound called coumarin, which is suspected to have undesirable effects on the liver when consumed in large amounts on a regular basis.

Raw Chocolate

I bet you never would have guessed that chocolate can help to stabilize your blood sugar. In, fact chocolate in its raw form is one of the most nutritious foods on the planet. It is packed with antioxidants, minerals like magnesium and chromium, and can even be a decent source of vitamin C.

Many people don’t know this but chromium is a powerful mineral that most of us simply do not get enough of. Chromium helps to improve the function of insulin to stabilize blood sugar and can also help reduce sugar cravings.

Raw chocolate is also a decent source of dietary zinc which can help to improve blood sugar stability as well.

The key here is to only buy raw chocolate or “cacao” as it would be written on the label. This is to ensure the highest nutrient density and therefore greatest potential for beneficial effects.

Organic Coffee

Coffee contains an impressive array of antioxidant compounds and nutrients that help to boost brain function, increase fat burning, and protect the body from a whole list of chronic diseases from heart disease to cancer. As long as you are consuming a high-quality organic coffee in moderate amounts, you can reap these benefits for yourself.

When it comes to blood sugar, coffee consumption has been shown as a negative risk factor for diabetes. Basically, drinking coffee is associated with a lower risk of diabetes.  Of course, it is very important not to drink it in the evening and I recommend keeping it to 1-3 cups a day max.

I am a strong advocate for a ketogenic diet in promoting balanced blood sugar levels. This is because when your body goes into a ketogenic state, it burns fat for energy instead of sugar and this naturally eliminates massive fluctuations in blood sugar.

A recent study performed on a small group of people showed that caffeine intake in the morning massively boosted ketone production to almost twice the amount (5). You can boost these benefits even further by drinking our turmeric fat burning coffee for breakfast which also contains sources of healthy fats to further promote ketone production.

Green Tea

If coffee isn’t your thing, this keto matcha green tea is also an excellent choice.

Similar to coffee, green tea is loaded with its own array of powerful antioxidants that help to fight inflammation, cancer, and all-cause mortality. The primary active component that is thought to be responsible for these benefits is the compound call Epigallocatechin gallate (EGCG for short).

Another benefit of green tea is that it improves fat burning and helps to stabilize blood sugar and protect you from diabetes and heart disease (6).

For the most concentrated benefits from green tea I would recommend matcha green tea, such as this one. Matcha is pulverized green tea leaves that can be consumed in their entirety for maximum extraction of nutrient.

For a powerful source of both coffee and green tea compounds (along with other powerful antioxidant compounds) I will often use Energy Charge as it is extremely effective, contains less caffeine than coffee, and offers the fat-burning benefits of green coffee bean.

Apple Cider Vinegar

Apple cider vinegar is a cheap way of balancing blood sugar that can be used in many ways. It contains acetic acid which helps to control fluctuations in blood sugar when combined with meals. Additionally, using apple cider vinegar may improve fat burning, improve digestion, and reduce carbohydrate cravings.

I will often recommend that people either consume a small amount of apple cider vinegar before meals or find ways to incorporate it into meals.

For example, I follow a cyclic ketogenic diet where I will consume higher carbohydrate meals once a week. Sometimes I will make a rice dish that incorporates coconut oil, grass-fed butter, turmeric, black pepper, and a slash of apple cider vinegar. This combination decreases the glycemic load of the meal drastically. 

Lemons and Limes

Similar to apple cider vinegar, lemons and limes provide a blood sugar stabilizing effect due to their naturally occurring citric acid. Citric acid behaves similarly to acetic acid by helping to lower the glycemic load of meals.

Many people simply prefer the citrus taste above the taste of vinegar in their meals and I will recommend using whichever you prefer.

Lemon juice can be squeezed fresh or bought bottled from an organic source. Simply sprinkle this on your foods or sip on lemon water throughout the day to acquire these benefits.

Avocados

Avocados are one of my favorite foods and I consume around 2-3 every day. They are loaded with minerals, fiber, and healthy fats that all help to stabilize blood sugar levels. Avocados are also a significant source of B vitamins which are important for energy production.

A lesser-known fact about avocados is that they contain a special type of sugar molecule called D-mannoheptulose. In fact, this type of sugar may actually have the ability to lower insulin levels.

For some of my favorite ways to use avocados on a daily basis, check out this article here.

Olives & Olive Oil

Many of the side effects associated with poor blood sugar imbalance are due to chronic inflammation. Sources of antioxidants will help to mitigate these side effects by protecting tissues from inflammation.

Olives and olive oil are an underestimated source of antioxidants that have been shown to protect the body from the damaging effects of diabetes such as neuropathy and heart disease.

Additionally, olive oil contains oleocanthal which is a powerful anti-inflammatory that acts on the COX enzyme system that has been associated with helping to reduce cancer risk, heart disease, and many other chronic diseases (7).

Blood sugar control is vital for overall health. Although, a ketogenic or low-carb diet is one of the most powerful strategies for improving blood sugar, these 12 foods have their own powerful benefits.

Begin incorporating these foods into your life and see the benefits they provide. If you are interested in beginning a ketogenic diet to take these benefits to the next level, check out this article here: How to Follow a Cyclic Ketogenic Diet.

Sources for this Article Include:

1. Trinidad TP, et al. Dietary fiber from coconut flour: A functional food. Innovative Food Science & Emerging Technologies. 2006 Dec; 7(4):309-317. DOI: 1016/j.ifset.2004.04.003

2. Trinidad TP, et al. Glycaemic index of different coconut (Cocos nucifera)-flour products in normal and diabetic subjects. British Journal of Nutrition; 2003 May;90:551-556. PMID: 13129460

3. Panzhinskiy, E., Hua, Y., Lapchak, P. A., Topchiy, E., Lehmann, T. E., Ren, J., & Nair, S. (2014). Novel curcumin derivative CNB-001 mitigates obesity-associated insulin resistance. The Journal of Pharmacology and Experimental Therapeutics349(2), 248–57. PMID: 24549372

4. ScienceDirect: A Comparison of Chemical, Antioxidant, and Microbial studies of cinnamon leaf and bark volatile oils, oleoresins and their constituents PMID:17408833

5. Vandenberghe, C., St-Pierre, V., Courchesne-Loyer, A., Hennebelle, M., Castellano, C.-A., & Cunnane, S. C. (2017). Caffeine intake increases plasma ketones: an acute metabolic study in humans. Canadian Journal of Physiology and Pharmacology, 95(4), 455–458. PMID: 28177691

6. Kim HM, Kim J. The Effects of Green Tea on Obesity and Type 2 Diabetes. Diabetes & Metabolism Journal. 2013 PMID: 23807919

7. Lucas, L., Russell, A., & Keast, R. (2011). Molecular Mechanisms of Inflammation. Anti-Inflammatory Benefits of Virgin Olive Oil and the Phenolic Compound Oleocanthal. Current Pharmaceutical Design, 17(8), 754–768. PMID: 21443487

8. Woo, H. W., Choi, B. Y., & Kim, M. K. (2016). Cross-sectional and longitudinal associations between egg consumption and metabolic syndrome in adults ≥ 40 years old: The yangpyeong cohort of the Korean genome and epidemiology study (KoGES-Yangpyeong). PLoS ONE, 11(1). PMID: 26808174

The hunger hormone ghrelin (the intermittent fasting crowd is likely going to dislike me for this one) is also a fat storing hormone. Ghrelin is released when we forgo food. Not only may it directly induce hunger AND cravings for sugary fatty and salty foods (research here & here & here), it has direct actions on the hypothalamus aiding fat storage (research here) and also increases the action of LPL and even results in more LPL being made so that when you do eat (research here)……you get fatter quicker. This is because ghrelin increases the mRNA expression of LPL.

Ghrelin should probably be called the yo-yo weight gain hormone, and those who practice eating less and exercising more are unwittingly raising their ghrelin and fat storing potential. The fact that ghrelin has some positive effects, like raising HGH, does not change these negative consequences. If and when fasters and low calorie dieters resume normal eating, fat gain comes and comes quickly. And this may largely be due to ghrelin (Ever meet anyone coming off strict diet restriction and getting fat quick? Is that ghrelin at work?)

And calories of course

Obviously calories matter and they matter a lot.  Fat is the least thermogenic, the least satiating and the most calorie dense of all the macronutrients. I know this will come as a surprise to many in the high fat low carb community especially as it pertains to their beliefs about fats satiating potential.  Fat combined with protein is very satiating.  Fat alone, not so much.  Once in ketosis, ketones are very satiating as well, but fat and ketones are not the same thing.  For more on this science read this blog.

TEXT UNDER CONSTRUTION

J Clin Invest. 1996 Jun 15; 97(12): 2859–2865.

doi:  10.1172/JCI118742

PMCID: PMC507380

Mechanism of free fatty acid-induced insulin resistance in humans.

M Roden, T B Price, G Perseghin, K F Petersen, D L Rothman, G W Cline, and G I Shulman

Author information ► Copyright and License information ►

This article has been cited by other articles in PMC.

Abstract

article-meta

To examine the mechanism by which lipids cause insulin resistance in humans, skeletal muscle glycogen and glucose-6-phosphate concentrations were measured every 15 min by simultaneous 13C and 31P nuclear magnetic resonance spectroscopy in nine healthy subjects in the presence of low (0.18 +/- 0.02 mM [mean +/- SEM]; control) or high (1.93 +/- 0.04 mM; lipid infusion) plasma free fatty acid levels under euglycemic (approximately 5.2 mM) hyperinsulinemic (approximately 400 pM) clamp conditions for 6 h. During the initial 3.5 h of the clamp the rate of whole-body glucose uptake was not affected by lipid infusion, but it then decreased continuously to be approximately 46% of control values after 6 h (P < 0.00001). Augmented lipid oxidation was accompanied by a approximately 40% reduction of oxidative glucose metabolism starting during the third hour of lipid infusion (P < 0.05). Rates of muscle glycogen synthesis were similar during the first 3 h of lipid and control infusion, but thereafter decreased to approximately 50% of control values (4.0 +/- 1.0 vs. 9.3 +/- 1.6 mumol/[kg.min], P < 0.05). Reduction of muscle glycogen synthesis by elevated plasma free fatty acids was preceded by a fall of muscle glucose-6-phosphate concentrations starting at approximately 1.5 h (195 +/- 25 vs. control: 237 +/- 26 mM; P < 0.01). Therefore in contrast to the originally postulated mechanism in which free fatty acids were thought to inhibit insulin-stimulated glucose uptake in muscle through initial inhibition of pyruvate dehydrogenase these results demonstrate that free fatty acids induce insulin resistance in humans by initial inhibition of glucose transport/phosphorylation which is then followed by an approximately 50% reduction in both the rate of muscle glycogen synthesis and glucose oxidation

M Roden, T B Price, G Perseghin, K F Petersen, D L Rothman, G W Cline, G I Shulman. Mechanism of free fatty acid-induced insulin resistance in humans. J Clin Invest. Jun 15, 1996; 97(12): 2859–2865.

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Metabolism. 2013 Mar;62(3):417-23. doi: 10.1016/j.metabol.2012.09.007. Epub 2012 Nov 1.

Effects of an overnight intravenous lipid infusion on intramyocellular lipid content and insulin sensitivity in African-American versus Caucasian adolescents.

Lee S1, Boesch C, Kuk JL, Arslanian S.

Author information

Abstract

OBJECTIVE:

To explain the predisposition for insulin resistance among African American (AA) adolescents, this study aimed to: 1) examine changes in intramyocellular lipid content (IMCL), and insulin sensitivity with intralipid (IL) infusion; and 2) determine whether the increase in IMCL is comparable between AA and Caucasian adolescents.

MATERIALS AND METHODS:

Thirteen AA and 15 Caucasian normal-weight adolescents (BMI <85th) underwent a 3-h hyperinsulinemic-euglycemic clamp, on two occasions in random order, after an overnight 12-h infusion of: 1) 20% IL and 2) normal saline (NS). IMCL was quantified by (1)H magnetic resonance spectroscopy in tibialis anterior muscle before and after IL infusion.

RESULTS:

During IL infusion, plasma TG, glycerol, FFA and fat oxidation increased significantly, with no race differences. Hepatic insulin sensitivity decreased with IL infusion with no difference between the groups. IL infusion was associated with a significant increase in IMCL, which was comparable between AA (Δ 105%; NS: 1.9±0.8 vs. IL: 3.9±1.6 mmol/kg wet weight) and Caucasian (Δ 86%; NS: 2.8±2.1 vs. IL: 5.2±2.4 mmol/kg wet weight), with similar reductions (P<0.01) in insulin sensitivity between the groups (Δ -44%: NS: 9.1±3.3 vs. IL: 5.1±1.8 mg/kg/min per μU/ml in AA) and (Δ -39%: NS: 12.9±6.0 vs. IL: 7.9±3.8 mg/kg/min per μU/ml in Caucasian) adolescents.

CONCLUSIONS:

In healthy adolescents, an acute elevation in plasma FFA with IL infusion is accompanied by significant increases in IMCL and reductions in insulin sensitivity with no race differential. Our findings suggest that AA normal-weight adolescents are not more susceptible than Caucasians to FFA-induced IMCL accumulation and insulin resistance.

Copyright © 2013 Elsevier Inc. All rights reserved.

S Lee, C Boesch, J L Kuk, S Arsianian. Effects of an overnight intravenous lipid infusion on intramyocellular lipid content and insulin sensitivity in African-American versus Caucasian adolescents. Metabolism. 2013 Mar;62(3):417-23.

Diabetes. 1999 Feb;48(2):358-64.

Rapid impairment of skeletal muscle glucose transport/phosphorylation by free fatty acids in humans.

Roden M1, Krssak M, Stingl H, Gruber S, Hofer A, Fürnsinn C, Moser E, Waldhäusl W.

Author information

Abstract

The initial effects of free fatty acids (FFAs) on glucose transport/phosphorylation were studied in seven healthy men in the presence of elevated (1.44 +/- 0.16 mmol/l), basal (0.35 +/- 0.06 mmol/l), and low (<0.01 mmol/l; control) plasma FFA concentrations (P < 0.05 between all groups) during euglycemic-hyperinsulinemic clamps. Concentrations of glucose-6-phosphate (G-6-P), inorganic phosphate (Pi), phosphocreatine, ADP, and pH in calf muscle were measured every 3.2 min for 180 min by using 31P nuclear magnetic resonance spectroscopy. Rates of whole-body glucose uptake increased similarly until 140 min but thereafter declined by approximately 20% in the presence of basal and high FFAs (42.8 +/- 3.6 and 41.6 +/- 3.3 vs.

CONTROL:

52.7 +/- 3.3 micromol x kg(-1) x min(-1), P < 0.05). The rise of intramuscular G-6-P concentrations was already blunted at 45 min of high FFA exposure (184 +/- 17 vs.

CONTROL:

238 +/- 17 micromol/l, P = 0.008). At 180 min, G-6-P was lower in the presence of both high and basal FFAs (197 +/- 21 and 213 +/- 18 vs.

CONTROL:

286 +/- 19 micromol/l, P < 0.05). Intramuscular pH decreased by -0.013 +/- 0.001 (P < 0.005) during control but increased by +0.008 +/- 0.002 (P < 0.05) during high FFA exposure, while Pi rose by approximately 0.39 mmol/l (P < 0.005) within 70 min and then slowly decreased in all studies. In conclusion, the lack of an initial peak and the early decline of muscle G-6-P concentrations suggest that even at physiological concentrations, FFAs primarily inhibit glucose transport/phosphorylation, preceding the reduction of whole-body glucose disposal by up to 120 min in humans.

M Roden, K Krssak, H Stingl, S Gruber, A Hofer, C Furnsinn, E Moser, W Waldhausl. Rapid impairment of skeletal muscle glucose transport/phosphorylation by free fatty acids in humans.

Diabetes reversal, not just treatment, should be a goal in the management of type 2 diabetes. Type 2 diabetes can be reversed with an extremely low calorie diet. Type 2 diabetes can also be reversed with an extremely healthy diet, but is that because it’s also low in calories? The study subjects lost as much weight on the green leafy vegetable-packed plant-based diet as the semi-starvation diet based on liquid meal replacements. So, does it matter what we’re eating as long as we’re eating few enough calories to lose 15 pounds a month?

Even if diabetes reversal is just about calorie restriction, instead of subsisting off largely sugar, powdered milk, corn syrup, and oil, on the plant-based diet at least one can eat food, in fact, pounds of food a day, as many low-cal veggies as we can stuff in our face. So, even if it only worked because it’s just another type of calorie restricted diet, it’s certainly a healthier version. But even participants who did not lose weight, or even gained weight eating enormous quantities of whole healthy plant foods, appeared to improve their diabetes. Thus, the beneficial effects of this kind of diet appear to extend beyond weight loss.

 The successful treatment of type 2 diabetes with a plant-based diet goes back to the 1930’s, providing incontestable evidence that a diet centered around vegetables, fruits, grains, and beans was more effective in controlling diabetes than any other dietary treatment. Randomized controlled trial: insulin needs were cut in half. A quarter ended up off insulin altogether, but again this was a low-calorie diet. Kempner reported similar results 20 years later with his rice and fruit diet, for the first time showing documented reversal of diabetic retinopathy in a quarter of his patients, something never even thought possible. An example was a 60-year-old diabetic woman already blind in one eye and could only see contours of large objects with the other. Five years later, on the diet, instead of it getting worse, it got better. She could make out faces, see signs, and read large newspaper print, in addition to being off insulin, with normal blood sugars and a 100 point drop in her cholesterol. Another patient went from just being able to read the big headlines to being able to read newsprint four months later. What was behind these remarkable reversals? Was it because the diet was extremely low-fat, no animal protein, no animal fat—or, was it because the diet was so restrictive and monotonous that the patients lost weight and improved their diabetes that way?

To tease that out, what we need is a study where they switch people to a healthy diet, but force them to eat so much that they don’t lose any weight. Then, we can see if a plant-based diet has benefits independent of all the weight loss. For that, we had to wait another 20 years, but here it is. Diets were designed to be weight-maintaining. Participants were weighed every day, and if they started losing weight, the researchers made them eat more food. In fact, so much food some of the participants had trouble eating it all, but they eventually adapted; so, there was no significant alterations in body weight despite restrictions of meat, dairy, and eggs, and enough whole plant foods—whole grains, beans, vegetables, and fruit—to provide 65 grams of fiber a day, four times what the Standard American Diet provides.

The control diet they used was the conventional diabetic diet, which actually had nearly twice the fiber content of the Standard American Diet; so, it was probably healthier than what they were used to eating. So, how did they do? With zero weight loss, did the dietary intervention still help? Here’s the before and after insulin requirements of the 20 people they put on the diet. This is the number of units of insulin they had to inject themselves with before and after going on the plant-based diet. Overall, insulin requirements were cut about 60%; half were able to get off insulin altogether, despite no change in weight. So, was this after five years, or seven months, like in the other studies I showed? No, 16 days.

So, we’re talking diabetics who’ve had diabetes as long as 20 years, injecting 20 units of insulin a day, and then, as few as 13 days later, they’re off insulin altogether, thanks to less than two weeks on a plant-based diet. Patient 15: 32 units of insulin on the control diet, and then, 18 days later, none. Lower blood sugars on 32 units less insulin. That’s the power of plants.

 

Below Fat and blood flow

 

 

 

 

 

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