A High-fat, Ketogenic Diet Causes Hepatic Insulin Resistance In Mice, Despite Increasing Energy Expenditure And Preventing Weight Gain
Go to: Low-carbohydrate, high-fat ketogenic diets (KD) have been suggested to be more effective in promoting weight loss than conventional caloric restriction, whereas their effect on hepatic glucose and lipid metabolism and the mechanisms by which they may promote weight loss remain controversial. The aim of this study was to explore the role of KD on liver and muscle insulin sensitivity, hepatic lipid metabolism, energy expenditure, and food intake. Using hyperinsulinemic-euglycemic clamps, we studied insulin action in mice fed a KD or regular chow (RC). Body composition was assessed by 1H magnetic resonance spectroscopy. Despite being 15% lighter (P < 0.001) than RC-fed mice because of a 17% increase in energy expenditure (P < 0.001), KD-fed mice manifested severe hepatic insulin resistance, as reflected by decreased suppression (0% vs. 100% in RC-fed mice, P < 0.01) of endogenous glucose production during the clamp. Hepatic insulin resistance could be attributed to a 350% increase in hepatic diacylglycerol content (P < 0.001), resulting in increased activation of PKCε (P < 0.05) and decreased insulin receptor substrate-2 tyrosine phosphorylation (P < 0.01). Food intake was 56% (P < 0.001) lower in KD-fed mice, despite similar caloric intake, and could partly be attributed to a more than threefold increase (P < 0.05) in plasma N-acylphosphatidylethanolamine concentrations. In conclusion, despite preventing weight gain in mice, KD induces hepatic insulin resistance secondary to increased hepatic diacylglycerol content. Given the key role of nonalcoholic fatty liver disease in the development of type 2 diabetes and the widespread use of KD for the treatment of obesity, these results may have potentially important clinical implications. Keywords: nonalcoholic fatty liv Continue reading >>
The Ketogenic Diet And Insulin Resistance
We recently touched on how you can use the ketogenic diet to control symptoms of diabetes such as elevated glucose and triglycerides. In this article, we examine research showing the impact that the ketogenic diet has on levels of the hormone insulin, a key regulator of blood sugar in the body. What is Insulin’s Role in the Body? Before we look at the research, we need to know our main players. Insulin is a protein-based hormone produced by beta-cells located in the pancreas. The pancreas, which is located under the stomach, also produces enzymes that aid with digestion. Insulin’s primary purpose is to regulate the metabolism of fats and carbohydrates. The digestive system breaks down carbohydrates, such as sugars and starches, into a molecule called glucose. This compound can be used by cells to produce energy through a process called cellular respiration. Insulin allows cells in the body absorb glucose, ultimately lowering levels of glucose in the blood stream. After a meal is consumed, blood glucose levels increase and the pancreas responds by releasing insulin into the blood. Insulin assists fat, liver, and muscle cells absorb glucose from the blood, resulting in lower levels of blood glucose. Insulin stimulates liver and muscle tissues to store excess glucose as a molecule called glycogen and also reduces glucose production by the liver. When blood sugar is low, the hormone glucagon (produced by alpha-cells in the pancreas) stimulate cells to break down glycogen into glucose that is subsequently released into the blood stream. In healthy people who do not have type II diabetes, these functions allow levels of blood glucose and insulin to stay in a normal range. What Is Insulin Resistance and Why Is It a Problem? Unfortunately, for many Americans and other peopl Continue reading >>
Is Your Fasting Blood Glucose Higher On Low Carb Or Keto? Five Things To Know
This past spring, after 18 months of great success on the keto diet, I tested my fasting blood sugar on my home glucose monitor for the first time in many months. The result shocked me. I had purchased the device, which also tests ketones, when I was diagnosed with pre-diabetes in the fall of 2015. As I embarked on low-carb keto eating, I tested my blood regularly. Soon my fasting blood sugar was once again in the healthy range. I was in optimal ketosis day after day. Not only that, I lost 10 lbs (5 kg) and felt fantastic — full of energy with no hunger or cravings. Before long I could predict the meter’s results based on what I was eating or doing. I put the meter away and got on with my happy, healthy keto life. When my doctor ordered some lab tests this spring, I brought the meter out again. While I had no health complaints, excellent blood pressure and stable weight, she wanted to see how my cholesterol, lipids, HbA1c, and fasting glucose were doing on my keto diet — and I was curious, too. To check the accuracy of my meter against the lab results, on the morning of the test I sat in my car outside the clinic at 7:30 am, and pricked my finger. I was expecting to see a lovely fasting blood glucose (FBG) of 4.7 or 4.8 mmol/l (85 mg/dl). It was 5.8! (103 mg/dl). What? I bailed on the tests and drove home — I didn’t want my doctor warning me I was pre-diabetic again when I had no explanation for that higher result. The next morning I tested again: 5.9! (104). Huh??? For the next two weeks I tested every morning. No matter what I did, my FBG would be in 5.7 to 6.0 (102 to 106 mg/dl), the pre-diabetic range again. One morning after a restless sleep it was even 6.2 mmol/l (113 mg/dl). But my ketones were still reading an optimal 1.5-2.5 mmol/l. I was still burnin Continue reading >>
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Ketogenic Diet Improves Insulin Sensitivity And Numerous Aging Markers
A physician conducted a decade-long experiment on the health effects of a ketogenic diet, using himself as the laboratory rat; he experienced improvement in insulin sensitivity, body fat, lipids, blood sugar, and other markers A ketogenic diet requires carbohydrate and protein restriction, with 50 to 80 percent of calories coming from fats; this forces your body to shift toward using ketones as its primary fuel source, instead of glucose Although your brain is more dependent on glucose than your heart, your liver can produce a ketone-like compound that your brain can efficiently use for energy Scientists extended the lifespan of mice by 20 percent by suppressing the activity of just one gene that helps control metabolism and energy balance; this is further evidence that longevity is tied to insulin signaling The best way to jumpstart your fat-burning/ketone-producing engine is by drastically reducing your consumption of sugar and grains, fasting intermittently, and maintaining a consistent exercise routine By Dr. Mercola We are just beginning to understand the biological intricacies of aging. A growing body of research is challenging the belief that aging is beyond your control, prompting scientists to begin thinking about ways we can slow our aging clocks to a slow crawl. Although this is a relatively new branch of science, there are some factors that appear to be key in controlling how quickly you age. One major factor seems to be insulin signaling and the metabolic "engines" you have running day to day, which are largely controlled by the foods you eat. In the first featured video, Dr. Peter Attia discusses how a ketogenic diet can optimize your metabolism. But before I discuss the specifics of this, I want to tell you about a remarkable mouse study, presented in the Continue reading >>
Fat Is Not The Cause Of Insulin Resistance
Fat Is NOT the Cause of Insulin Resistance Our Educational Content is Not Meant or Intended for Medical Advice or Treatment Fat is NOT the Cause of Insulin Resistance There isn't a relationship between eating saturated fats and diabetes. Insulin is a hormone that regulates blood sugars and lowers it. In the presence of insulin, you are not going to burn fat and it causes fat to be stored. Insulin resistance is different. As insulin connects to the cell, the cell does not absorb it anymore it blocks it. On the other side of the cell you have low insulin and the cell is starving of: Which then sends a signal back to produce more insulin. People with insulin resistance have 5 to 7 times more insulin than normal people. So many people have insulin resistance and dont even know it because it takes 10 years for it to develop it. It causes a stubborn belly fat and a fatty liver which cause insulin resistance. It's a huge ugly cycle. Guru's Give False Information About Diabetes There are gurus out there pushing this avoidance of saturated fats. Joslin Diabetes Center have 5 Myths on a section of their website that are bogus information.Some of the things they write as "Myths" are actualy true and what they report as "Facts" are way off. The following is from Joslin Diabete Center website under 'Diabetes and Nutrition': 5 Common Myths with People with Diabetes Debunked 1. People with diabetes have to eat different from their family, right? (Myth) "Fact: People with diabetes can eat the same foods their family eat. The Truth: Of course people with diabetes have to eat differently than their family. What if the family are eating sugar? 2. People with diabetes should never give in to food cravings. (Myth) Facts: If a craving does occur let yourself have a small taste of whatever y Continue reading >>
Are You Insulin Resistant?
Finding out you are insulin resistant doesn't mean much unless you understand what that implies, and how it effects your health. Insulin resistance is an condition in which the body is not responding properly to the hormone insulin. If faulty insulin signaling is not treated, it can develop into worsening conditions of metabolic syndrome, pre diabetes, and finally type 2 diabetes. What Causes the Insulin Resistant Condition? The insulin resistant condition is rooted in the metabolic effects of a high carb diet in combination with a lack of exercise. Weight gain is a symptom of insulin resistance, rather than a cause. Carbohydrates are foods which contain either some form of sugar or starch, or both. For instance, orange juice is full of fructose, a type of sugar, and white potatoes contain large amounts of starch. Both types of carbohydrate are broken down in the body into glucose, a simple sugar, which your cells can use for energy to do all the things that cells do. Since too much glucose in your body can be toxic, your pancreas releases a powerful hormone called insulin. Insulin works to control the amount of glucose in your bloodstream. It acts to quickly move glucose from your bloodstream and push it into your cells where it can be burned or stored. But there's a catch. To get the glucose into the cells, the cell's glucose "storage tanks" have to be empty. This is logical when you think about it. Imagine what would happen if you tried to fill up your car's gas tank if it were already full. And just like running a car burns up gasoline, when a person exercises, the glucose which is already in the glucose tanks get used. Now there is room for insulin to push the glucose made from the last meal into the muscle cell for fuel. If a person exercises frequently, lots of c Continue reading >>
Physiological Insulin Resistance
I’ve been meaning to do a deep dive into physiological insulin resistance for quite a while now, but the universe keeps conspiring to take my time. Because I haven’t had time to read, learn more and write about it, I thought I’d share the links I have accumulated thus far. Mostly because I’ve now been asked a variant of the following multiple times, or have seen the following posted on various forums for discussing nutrition, health, and low carbohydrate diets: “Why has my blood glucose gone up on a low carb diet?” Typically this is accompanied by a good deal of anxiety and fretting over glucometers. I should know, I watched my blood glucose increase by a few points as I’ve sustained my low carb diet. My understanding is that this is a known adaptation completely unrelated to the insulin resistance concomitant with diabetes. While I’m not the person you should ask about anything health related, I’ve wanted an answer to this question myself. The explanation I’ve read is that after going low carb, your muscle tissue becomes insulin resistant in order to preserve serum glucose availability for the brain. If your muscle tissue did not do this, reduced availability of glucose in the serum could (theoretically) put you in dire straights if your brain can’t meet minimal demand for glucose. (Mind you, even on a zero carb diet you can meet all your glucose requirements via gluconeogenesis. The point is, your body needs a way to tell your muscle mass to stop taking all the glucose it makes. This is that way.) Because of this physiological insulin resistance (which I should mention is a benign state that is not making your diabetic insulin resistance worse) you wouldn’t want to take an oral glucose tolerance test while you are low carbing. If you took a glu Continue reading >>
The Link Between Cancer, Insulin Resistance And A Ketogenic Diet | Real Meal Revolution
The link between Cancer, Insulin Resistance and a Ketogenic Diet Posted at 10:59h in All by Real Meal Revolution Research done by Dr Dominic DAgostino , Dr Thomas Seyfried and Dr Gary Fettke has revealed that cancer is predominantly a metabolic disease and not a genetic one as previously thought. Most cancer scientists have historically thought that cancer was a genetic disease, but only 5-10% of cancer is hereditary, says Dr DAgostino. A metabolic disease is one that disrupts normal metabolism, the process of converting food to energy on a cellular level. The mitochondria generate the energy that our cells need to do their job and are often referred to as the powerhouses of the cells. When carbs (made up of glucose) are ingested, they cause the blood glucose levels to rise. The hormone insulin, responsible for regulating energy usage in particular our relationship to carbs is secreted by the pancreas because a high blood glucose concentration is toxic for human tissues as it damages the structure of all proteins. According to Dr Fettke, we can only metabolise about one teaspoon (4 grams) of glucose at once and the rest is stored in the liver and muscles as glycogen, or if this cannot happen, it is stored as fat. The more carbs ingested, the more insulin is produced, the more our body becomes resistant. Insulin resistance occurs when the body does not respond to insulin correctly. This results in increased blood glucose levels, which cant be stored in the liver or muscles, so must be stored as fat. This is discussed in great detail, by Prof Noakes, in the Beginner Banting Online Program. Insulin is therefore the fat storing hormone, which leads to an expanding waistline. If a high carb diet is followed, and if unchecked, it can lead to obesity, metabolic syndrome (a co Continue reading >>
Dear Mark: Does Eating A Low Carb Diet Cause Insulin Resistance?
157 Comments Despite all the success you might have had with the Primal way of life, doubts can still nag at you. Maybe it’s something you read, or something someone said to you, or a disapproving glance or offhand comment from a person you otherwise respect, but it’s pretty common when you’re doing something, like giving up grains, avoiding processed food, or eating animal fat, that challenges deeply-and-widely held beliefs about health and wellness. It doesn’t really even matter that you’re losing weight or seem to be thriving; you may still have questions. That’s healthy and smart, and it’s totally natural. A question I’ve been getting of late is the effect of reducing carb intake on insulin sensitivity. It’s often bandied about that going low carb is good for folks with insulin resistance, but it’s also said that low carb can worsen insulin resistance. Are both true and, if so, how do they all jibe together? That’s what the reader was wondering with this week’s question: Hi Mark, I’ve been Primal for a few months now and love it. Lowering my carbs and upping my animal fat helped me lose weight and gain tons of energy (not too shabby for a middle-aged guy!). However, I’m a little worried. I’ve heard that low carb diets can increase insulin resistance. Even though I’ve done well and feel great, should I be worried about insulin resistance? Do I need to increase my carb intake? I always thought low carb Primal was supposed to improve insulin function. Vince Going Primal usually does improve insulin sensitivity, both directly and in a roundabout way. It improves directly because you lose weight, you reduce your intake of inflammatory foods, you lower systemic inflammation (by getting some sun, smart exercise, omega-3s, and reducing or dea Continue reading >>
Increased Insulin Resistance With A Low Carb Diet?
Diabetes Forum The Global Diabetes Community Find support, ask questions and share your experiences. Join the community Increased Insulin Resistance with a low carb diet? Bebo321 Family member Well-Known Member @azure @Brunneria @tim2000s , I would be interested to hear your thoughts on an observation of increased insulin resistance with a very low carb/keto diet. I was discussing this topic recently with somebody with T1D (we tried a food fast together over a number of days) They noticed that coming back out of the fast, their insulin requirements had increased fairly significantly in order to manage any carb they ate (the increased requirements only lasted a few days). Interestingly, their basal had remained exactly the same throughout the fast however and blood glucose levels had remained level. This would suggest that their 'insulin resistance' hadn't actually changed at all. What we considered had perhaps happened was that the body had become so effective at burning ketones and generating its own glucose requirements (gluconeogenesis), that once carbs were re-introduced, the body was fairly 'ambivalent' to it - after all, it had everything it needed to fuel itself perfectly well up until that point. Without cells calling out for a top up of glucose, more insulin would be required in order to be effective at taking the glucose out of the bloodstream. This was a temporary effect and therefore perhaps different to insulin resistance created through the build up of fat deposits. Anyway, I thought I would relay this to you (and anyone who might have their own experience to add). Perhaps it is misleading to think of the body's adaptation to a low carb diet as becoming 'insulin resistant' and it might be better instead to think of it becoming 'fat complient' It's referre Continue reading >>
Ketogenic Diet And Insulin Resistance
Ketogenic diets around the world have been known to be extremely effective in helping improve health and lose weight fast. The diet takes into account and addresses the underlying causes of your weight gain, which could include things such as hormonal imbalances. With the ketogenic diet, you are restricting your net carb intake to under 50 grams a day. With the number of restricted carbs, your body needs to reset its way of getting the fuel that it needs. See how a diet high in healthy fats can help improve insulin resistance by changing the bodies preferred fuel source from glucose to ketones. What is Insulin and Insulin Resistance Insulin is a fat storing hormone formed by the pancreas that enables your body to manage glucose and sugars from carbs within the food. It prevents blood sugar levels from hyperglycemia or reaching too high or hyperglycemia which is too low. Insulin resistance has many symptoms including sugar cravings, weight gain, high blood pressure, high cholesterol.(1) Insulin resistance is also linked to type 2 diabetes. Therefore, cutting out or reducing sugar in your meal planning will help prevent becoming diabetic. The worrying thing about insulin resistance is symptoms take a long time to appear. When symptoms surface such as weight gain, multiple other problems may creep up. Why You Gain Weight Insulin in your body helps to regulate your blood sugar levels. Blood sugar also referred to as glucose is the primary fuel in the body for energy and brain function. When blood sugar rises, the insulin your pancreas releases move the glucose into your bloodstream. If there is glucose in your system your body will burn it first for fuel. If your body is already filled with higher glucose levels, more cannot be broken down for fuel. So because of this, your Continue reading >>
Insulin And Keto: What You Need To Know
If you want to make keto really work for you, it helps to understand a little bit about how the diet does its magic and one of the big players here is the hormone insulin. Insulin does a whole lot of different things, but its best-known as the hormone that you make to metabolize carbs. Insulin gets a really bad rap in low-carb circles, to the point where it can get really oversimplified. Theres more to weight gain than insulin! For general health, insulin isnt necessarily bad , and its actually necessary for some health-related goals (for example, if you want to gain muscle, insulin is definitely your friend). But keto isnt just about general health. Keto is about a specific metabolic shift. If your goal is ketosis specifically, insulin is bad news heres what you need to know. The whole point of the ketogenic diet is that youre forcing your body to use ketone bodies for energy, instead of fat and carbohydrate. Thats what makes the diet work. Insulin suppresses ketone production . So if you want to get into ketosis and stay there, you want to minimize insulin as much as possible. Unless youre taking outside insulin, the easiest way to do this is by changing what you eat. Insulin is produced in response to different foods, so by changing your diet, you can minimize insulin production. Thats the point of a ketogenic diet. The ketogenic diet minimizes insulin production by restricting both carbs and protein the diet keeps carbs as low as possible and supplies just enough protein to meet your needs, but not more. To reduce insulin production, lower carbs Carbs raise insulin levels because you need insulin to metabolize carbs (use them for energy). The more carbs you eat, the more insulin you need. It works like this: when you eat something carb-heavy, the glucose (carbohydr Continue reading >>
Does Long Term Ketosis Cause Insulin Resistance?
“It’s a snake.” “It’s a wall.” “It’s a rope.” “It’s a fan.” “It’s a tree.” “It’s insulin resistance.” I’ve always been fascinated by those describing a “new finding” in medicine. I am reminded of the story of 5 men who, never having seen an elephant before, were blindfolded and asked to describe what he discovered. However, each man was introduced to a different part of the elephant. Each of them had a dramatically different description of the elephant and each made a conclusion that was very different from the others. What is fascinating, is that we usually make our “blindfolded comparisons” to those things we have seen or about which we have some descriptive understanding. Observing and describing human physiology is much like examining an elephant while blindfolded for the first time. This week’s “blind-folded finding” is what has been interpreted by some as “insulin resistance” made worse by a ketogenic diet. Really? This perked my curiosity, because I’ve personally been following a low-carbohydrate/ketogenic diet for 10 years and have thousands of patients doing the same. To this day, I’ve never seen insulin resistance “get worse.” In fact, it gets better. Clinically, it seems to take about 18-24 months to improve, but, it usually gets better. THE QUESTION – I’ve had three people from around the world contact me this week and ask why, after being on a ketogenic diet and “in ketosis,” they suddenly get a notably large blood glucose spike when they cheat. By notably large, I mean that their blood sugars rise to over 200 mg/dl within 2 hours of a carbohydrate containing meal. Now, they admit to rapid glucose recovery within an hour or two, and their hemoglobin A1c levels are subjectively normal (l Continue reading >>
Insulin Sensitivity: The Secret To Optimal Health
Insulin Sensitivity: The Secret to Optimal Health Insulin sensitivity is a vital mechanism in your body that determines how efficient your body utilizes the effects of insulin. People with low insulin sensitivity have a higher chance of developing metabolic diseases such as diabetes, obesity and heart disease. While some people may be born with healthier insulin sensitivity levels, there are several lifestyle changes you can make to improve it. The more insulin sensitive your body is, the more effective it is in utilizing carbohydrates for energy and the easier it becomes for your body to lose weight. Because of this, the weight loss industry has begun to magnify the importance of insulin sensitivity. Insulin is a crucial hormone secreted by your pancreas. Insulins job is to manage the nutrients you absorb from food. Insulin is known for its role in controlling blood sugar and carbohydrate consumption. When you eat carbs, it increases the level of blood sugar in your bloodstream. This is acknowledged by the cells in your pancreas which then releases insulin into the blood. Once the insulin is traveling in your bloodstream, it starts signaling the bodys cells that they should pick up sugar from the blood. The purpose of this cycle is to reduce the amount of sugar in your blood and place it where its supposed to, into cells for storage. This is crucial because abnormally high amounts of sugar in your blood can have harmful effects to your body and in some cases can lead to death if neglected. Insulin sensitivity is a system in the body that determines how effectively your body can utilize carbohydrates. Insulin sensitivity arbitrates how much insulin your body needs to produce to precipitate a certain amount of glucose (sugar). Its the mechanism in your body that determi Continue reading >>
A High-fat, Ketogenic Diet Causes Hepatic Insulin Resistance In Mice, Despite Increasing Energy Expenditure And Preventing Weight Gain
A high-fat, ketogenic diet causes hepatic insulin resistance in mice, despite increasing energy expenditure and preventing weight gain Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06536 Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06536 Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06536 Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06536 Address for reprint requests and other correspondence: G. I. Shulman, Depts. of Internal Medicine and Cellular and Molecular Physiology and Howard Hughes Medical Institute, Yale Univ. School of Medicine, New Haven, CT 06536 (e-mail: E-mail Address: [emailprotected] ). Low-carbohydrate, high-fat ketogenic diets (KD) have been suggested to be more effective in promoting weight loss than conventional caloric restriction, whereas their effect on hepatic glucose and lipid metabolism and the mechanisms by which they may promote weight loss remain controversial. The aim of this study was to explore the role of KD on liver and muscle insulin sensitivity, hepatic lipid metabolism, energy expenditure, and food intake. Using hyperinsulinemic-euglycemic clamps, we studied insulin action in mice fed a KD or regular chow (RC). Body composition was assessed by 1H magnetic resonance spectroscopy. Despite being 15% lighter (P < 0.001) than RC-fed mice because of a 17% increase in energy expenditure (P < 0.001), KD-fed mice manifested severe hepatic insulin resistance, as reflected by decreased suppression (0% vs. 100% in RC-fed mice, P < 0.01) of endogenous glucose production during the clamp. Hepatic insulin resistance could be attributed to a 350% increase in hepatic Continue reading >>