What Causes The Insulin Resistance Underlying Obesity?
Go to: NOT ALL FORMS OF OBESITY RESULT IN INSULIN RESISTANCE Obesity is the excessive growth of adipose tissue depots arising from the chronic consumption of calories in excess of the energetic needs of the individual. In humans, the expansion of adipose depots results from increased numbers of individual adipocytes (hyperplasia), and from the hypertrophy of adipocytes, in a depot-dependent fashion . Importantly, there is a large individual variation in the size and expandability of different adipose tissue depots in humans. This factor is critically important in understanding the relationship between obesity and insulin resistance, as expansion of some depots is associated with increased risk, whereas expansion of others is associated with decreased risk . Each standard deviation (SD) increase in subcutaneous adipose tissue mass decreases the odds of insulin resistance by 48%, whereas a SD increase in visceral adipose tissue mass increases the odds of insulin resistance by 80% [5▪]. These findings can explain the existence of ‘benign’ and ‘malign’ obesity wherein insulin resistance is not observed in all individuals with high BMIs. They may also explain the very high incidence of insulin resistance and diabetes in ethnic populations that display relatively low BMIs associated with high waist circumferences or waist-to-hip ratios, reflecting elevated visceral obesity . In this context, the mechanisms that control the expandability of subcutaneous adipose tissue, including its high capacity for adipocyte differentiation and lipid storage may be key factors in determining diabetes risk in obesity . The enhanced capacity for formation of adipocytes, inferred by the presence of hyperplasia in subcutaneous adipose tissue , correlates with decreased r Continue reading >>
Understanding Insulin Resistance
It's a precursor to diabetes, but it also can be reversed Though you may not be living with diabetes, your body could be battling against the hormone insulin. The condition, called insulin resistance, occurs when insulin can't effectively do its job. "People often don't realize that insulin resistance can develop into diabetes," said Dawn Sherr, a diabetes educator for the American Association of Diabetes Educators. "And if they're not aware they're insulin resistant, they don't know what steps they can take to prevent it." Insulin resistance is a fuzzy, often misunderstood concept. Here, we answer five common questions. Q: How does the body become resistant to insulin? A: When you eat, food is broken down into glucose to be used for energy. Insulin, a hormone produced in the pancreas, tempers the amount of sugar in the bloodstream by helping glucose get into the muscle, fat and/or liver cells. "We think of insulin as a 'key' that opens doors to the body's cells, so glucose can enter," said diabetes educator Gary Scheiner. With insulin resistance, it's like having locks that are frozen or rusty. The keys won't turn, and glucose can't get into the cell. The pancreas, alarmed by the increase in blood sugar, cranks out more insulin. Eventually, the overworked pancreas breaks down. Blood sugar levels rise even further, causing pre-diabetes and setting the stage for Type 2 diabetes. "Most people think of diabetes as high blood sugar caused by too little insulin," said Scheiner, the author of "Think Like a Pancreas. "But the insulin resistance is really the root cause of almost all cases of Type 2 diabetes. Q: What is pre-diabetes? A: The body's cells are insulin resistant; the levels of glucose in the blood are higher than normal, and the pancreas can't make enough insulin t Continue reading >>
What Causes Insulin Resistance? Part I
Insulin is an ancient hormone that influences many processes in the body. Its main role is to manage circulating concentrations of nutrients (principally glucose and fatty acids, the body's two main fuels), keeping them within a fairly narrow range*. It does this by encouraging the transport of nutrients into cells from the circulation, and discouraging the export of nutrients out of storage sites, in response to an increase in circulating nutrients (glucose or fatty acids). It therefore operates a negative feedback loop that constrains circulating nutrient concentrations. It also has many other functions that are tissue-specific. Insulin resistance is a state in which cells lose sensitivity to the effects of insulin, eventually leading to a diminished ability to control circulating nutrients (glucose and fatty acids). It is a major contributor to diabetes risk, and probably a contributor to the risk of cardiovascular disease, certain cancers and a number of other disorders. Why is it important to manage the concentration of circulating nutrients to keep them within a narrow range? The answer to that question is the crux of this post. Cellular Energy Excess There has been a tremendous amount of research into the molecular mechanisms of insulin resistance in the last few decades, and certain things have become clear about it. The first is that it appears to be a 'deliberate' process-- cells activate specific signaling pathways that down-regulate insulin responsiveness. The rationale for this becomes clear when one considers what insulin does: it drives energy into cells. Insulin resistance is how the cell says "stop sending me more energy-- I have too much already!" It is a deliberate response to mitigate the negative effects of cellular energy excess. Why would a cell w Continue reading >>
Insulin Resistance And Fat Loss
Question: Your books and work are amazing. Unless I misunderstood the point in UD2 Lyle speaks about weight loss and that insulin resistance can be beneficial. Could you explain more to me about your viewpoint on this as I dietician I always consider and read about it being unhelpful. I’m very interested in a new viewpoint. Answer: While I think I have addressed this on the site previously but since it’s somewhat counterintuitive and goes against what everyone believes (and is a little bit more complicated than what is written in my books or above), it’s worth going over again. As usual, I’ll need to provide some background. How Hormones Work A hormone is any substance in the body that causes something to happen elsewhere. Technically you can divide up neurotransmitters (which work locally) and hormones (which work elsewhere/all over the body) but this is unnecessary detail. So a hormone is released from some gland or another (i.e. thyroid from the thyroid gland, insulin from the pancreas), binds to a receptor somewhere and makes stuff happen (a technical term). The almost universal analogy for how hormones work is the lock and key analogy. The hormone is the key and its specific receptor is the lock. So the lock fits into the key and makes stuff happen (still a technical term). Every hormone has its own specific receptor (just as a key fits into one lock) but there can be something called cross-reactivity where one hormone kind of fits into a different hormone. Don’t worry about this. So insulin has an insulin receptor. When insulin binds to that receptor, stuff happens (see a trend here). And that insulin receptor is found all over the body, in the brain, in skeletal muscle, in the liver, and in fat cells. The last three are the key things to worry about her Continue reading >>
Practice Essentials Insulin resistance is a state in which a given concentration of insulin produces a less-than-expected biological effect. Insulin resistance has also been arbitrarily defined as the requirement of 200 or more units of insulin per day to attain glycemic control and to prevent ketosis. The syndromes of insulin resistance actually make up a broad clinical spectrum, which includes obesity, glucose intolerance, diabetes, and the metabolic syndrome, as well as an extreme insulin-resistant state. Many of these disorders are associated with various endocrine, metabolic, and genetic conditions. These syndromes may also be associated with immunological diseases and may exhibit distinct phenotypic characteristics. [1, 2, 3, 4, 5, 6, 7, 8] The metabolic syndrome —a state of insulin-resistance that is also known as either syndrome X or the dysmetabolic syndrome—has drawn the greatest attention because of its public health importance. In addition to hypertension, findings can include central obesity, peripheral arterial disease, type A syndrome, type B syndrome, ancanthosis nigricans, polycystic ovary syndrome, and other insulin-resistant states. In clinical practice, no single laboratory test is used to diagnose insulin resistance syndrome. Diagnosis is based on clinical findings corroborated with laboratory tests. Individual patients are screened based on the presence of comorbid conditions. Lab tests include the plasma glucose level, the fasting insulin level, and a lipid profile, among others. Treatment involves pharmacologic therapy to reduce insulin resistance, along with surgical management of underlying causes if appropriate. Comorbid conditions should be evaluated and addressed; this is generally feasible on an outpatient basis, though some patients wi Continue reading >>
Insulin resistance (IR) is a pathological condition in which cells fail to respond normally to the hormone insulin. The body produces insulin when glucose starts to be released into the bloodstream from the digestion of carbohydrates in the diet. Normally this insulin response triggers glucose being taken into body cells, to be used for energy, and inhibits the body from using fat for energy. The concentration of glucose in the blood decreases as a result, staying within the normal range even when a large amount of carbohydrates is consumed. When the body produces insulin under conditions of insulin resistance, the cells are resistant to the insulin and are unable to use it as effectively, leading to high blood sugar. Beta cells in the pancreas subsequently increase their production of insulin, further contributing to a high blood insulin level. This often remains undetected and can contribute to the development of type 2 diabetes or latent autoimmune diabetes of adults. Although this type of chronic insulin resistance is harmful, during acute illness it is actually a well-evolved protective mechanism. Recent investigations have revealed that insulin resistance helps to conserve the brain's glucose supply by preventing muscles from taking up excessive glucose. In theory, insulin resistance should even be strengthened under harsh metabolic conditions such as pregnancy, during which the expanding fetal brain demands more glucose. People who develop type 2 diabetes usually pass through earlier stages of insulin resistance and prediabetes, although those often go undiagnosed. Insulin resistance is a syndrome (a set of signs and symptoms) resulting from reduced insulin activity; it is also part of a larger constellation of symptoms called the metabolic syndrome. Insuli Continue reading >>
Causes Of Insulin Resistance
Several factors increase the risk of insulin resistance. While some of these risk factors are associated with lifestyle and can be modified, others are genetic or biochemical and therefore not modifiable. Insulin resistance is caused by a persistently high level of insulin over a prolonged period of time that eventually causes the body's sensitivity to insulin to decrease. Some of the risk factors for insulin resistance include: Lifestyle factors Obesity and a diet rich in fats and refined carbohydrates are factors thought to be associated with the development of insulin resistance. Abdominal fat, especially, is thought to play a role because it produces hormones that can trigger insulin resistance. Vitamin D A deficiency of Vitamin D in the diet may contribute to insulin resistance due to the role it plays in glucose tolerance through its effects on insulin secretion and insulin sensitivity. Diabetes Type 2 diabetics may have increased levels of insulin. In healthy people, the action of insulin is mediated on binding to insulin receptors present on various cellular targets such as fat cells, muscle cells and liver cells. In people with type 2 diabetes, high levels of blood sugar trigger high levels of insulin production and this leads to down regulation of the insulin receptors. This means there is a relative resistance to insulin despite the insulin levels being high. The initial cause of high blood sugar is brought about by high carbohydrate intake. Insulin resistance is thought to be connected to inflammation. In the case of prediabetes and type 2 diabetes, the immune system releases inflammatory mediators called cytokines which are thought to disturb the action of insulin. Damage caused by free radicals or oxidative stress has also been implicated in the developmen Continue reading >>
Insulin And Insulin Resistance
Go to: Abstract As obesity and diabetes reach epidemic proportions in the developed world, the role of insulin resistance and its consequences are gaining prominence. Understanding the role of insulin in wide-ranging physiological processes and the influences on its synthesis and secretion, alongside its actions from the molecular to the whole body level, has significant implications for much chronic disease seen in Westernised populations today. This review provides an overview of insulin, its history, structure, synthesis, secretion, actions and interactions followed by a discussion of insulin resistance and its associated clinical manifestations. Specific areas of focus include the actions of insulin and manifestations of insulin resistance in specific organs and tissues, physiological, environmental and pharmacological influences on insulin action and insulin resistance as well as clinical syndromes associated with insulin resistance. Clinical and functional measures of insulin resistance are also covered. Despite our incomplete understanding of the compl Continue reading >>
Does Fat Cause Insulin Resistance?
For decades now, we have been told that fatness (or “obesity”) is a major cause of diabetes. Health “experts” have warned about this, but they could never say how being overweight could cause insulin resistance (IR). Without IR, you can’t have Type 2 diabetes, so the whole “blame fat” theory has been suspect. Well, now they have a plausible explanation. Obesity may cause inflammation, causing IR, leading to diabetes. But is this theory true? Does adipose (fat) tissue really create inflammation? Or do both obesity and inflammation come from some other cause? Get ready for some science as I try to explore these questions. In a new report in the Journal of Leukocyte Biology, two Japanese scientists report that “obesity is associated with a state of chronic, low-grade inflammation.” They explain that as fat cells get larger, they seem to attract immune cells called macrophages. These cells produce inflammatory chemicals called cytokines that help cause insulin resistance. Chief among these chemicals are interleukin-6 and tumor necrosis factor-alpha. In animal models, insulin resistance doesn’t occur until after macrophages invade the fat cells. So the question remains, which comes first, the inflammation or the fatness? What draws the immune cells into adipose tissue? Remember that most overweight people never develop diabetes. And some overweight people have much more inflammation than others. (The same is true of thin people, of course.) Why do some develop this fat-related inflammation and some don’t? Some think that weight itself provokes inflammation. According to French scientists writing in the journal European Cytokine Network, weight loss is associated with reduced “macrophage infiltration” and reduced inflammation. Also, another chemical, Continue reading >>
Skeletal Muscle Insulin Resistance Is The Primary Defect In Type 2 Diabetes
Insulin resistance is a characteristic feature of type 2 diabetes and plays a major role in the pathogenesis of the disease (1,2). Although β-cell failure is the sine qua non for development of type 2 diabetes, skeletal muscle insulin resistance is considered to be the initiating or primary defect that is evident decades before β-cell failure and overt hyperglycemia develops (3,4). Insulin resistance is defined as a reduced response of target tissues (compared with subjects with normal glucose tolerance [NGT] without a family history of diabetes), such as the skeletal muscle, liver, and adipocytes, to insulin. Because skeletal muscle is the predominant site of insulin-mediated glucose uptake in the postprandial state, here we will focus on recent advances about the time of onset, as well as the mechanism, of the skeletal muscle insulin resistance. RESEARCH DESIGN AND METHODS The euglycemic insulin clamp technique (5) is considered to be the gold standard for measuring insulin action in vivo. With this technique, whole-body insulin action is quantified as the rate of exogenous glucose infusion (plus any residual hepatic glucose production) required to maintain the plasma glucose concentration at euglycemic levels in response to a fixed increment in the plasma insulin concentration. Because 80–90% of the infused glucose is taken up by skeletal muscle under conditions of euglycemic hyperinsulinemia, insulin sensitivity measured with the insulin clamp technique primarily reflects skeletal muscle (6). Another advantage of this technique is that it can be combined with indirect calorimetry to measure different substrate oxidation rates and with muscle biopsy to examine the biochemical/molecular etiology of the insulin resistance. Measurement of insulin sensitivity by the Continue reading >>
An Explanation Of Insulin Resistance
According to the medical literature, type 2 diabetes is a disease characterized by chronic hyperglycemia, i.e., abnormally high concentrations of blood sugar (serum glucose), in the presence of adequate amounts of insulin. This hyperglycemia is attributed to insulin resistance, a faulty condition in which serum insulin cannot act on insulin receptors in the walls of cells. This condition prevents the receptors from allowing glucose to pass from the blood into the cells. According to the biochemical literature, an insulin receptor is a protein molecule located in the wall of a cell. The structure of the molecule is such that a smaller molecule called a ligand may attach to it. There are two kinds of ligands: an agonist, which causes the receptor to function, and an antagonist, which does nothing but prevent the agonist from attaching to the receptor. Without an attached ligand, an insulin receptor cannot allow glucose molecules to pass from the blood into a cell. An insulin molecule is an agonist, and when one becomes a ligand, an insulin receptor can allow glucose molecules to pass into a cell. But the hormone cortisol is an insulin antagonist, and when a cortisol molecule becomes a ligand, it prevents an insulin molecule from becoming a ligand, which prevents glucose from passing from the blood into the cell involved. I believe that the action of cortisol as an insulin antagonist is a reasonable explanation of the condition that we call insulin resistance, in which case there is nothing wrong with the insulin receptors or the insulin. Insulin resistance, then, would be part of the natural functioning of an insulin receptor. There are reasons to believe that the brain is responsible for the production of excess cortisol for the purpose of preventing the loss of serum gl Continue reading >>
Obesity And Insulin Resistance
Insulin is a critical regulator of virtually all aspects of adipocyte biology, and adipocytes are one of the most highly insulin-responsive cell types. Insulin promotes adipocyte triglyceride stores by a number of mechanisms, including fostering the differentiation of preadipocytes to adipocytes and, in mature adipocytes, stimulating glucose transport and triglyceride synthesis (lipogenesis), as well as inhibiting lipolysis (Figure 1). Insulin also increases the uptake of fatty acids derived from circulating lipoproteins by stimulating lipoprotein lipase activity in adipose tissue. Insulin’s metabolic effects are mediated by a broad array of tissue-specific actions that involve rapid changes in protein phosphorylation and function, as well as changes in gene expression. The fundamental biologic importance of these actions of insulin is evidenced by the fact that the insulin signaling cascade which initiates these events is largely conserved in evolution from C. elegans to humans (2). Figure 1 Pleiotropic effects of insulin to promote adipose storage. Insulin stimulates differentiation of preadipocytes to adipocytes. In adipocytes, insulin promotes lipogenesis by stimulating the uptake of glucose and lipoprotein-derived fatty acids and by inducing ADD-1/SREBP-1c, which regulates genes promoting fatty acid synthesis and lipogenesis, not only in adipocytes but also in hepatocytes. Insulin may also regulate transcription through Forkhead transcription factors. Insulin diminishes triglyceride breakdown by inhibiting lipolysis. Many of these metabolic pathways are regulated by the PI3K signaling pathway. The initial molecular signal for insulin action involves activation of the insulin receptor tyrosine kinase, which results in phosphorylation of insulin receptor substrates Continue reading >>
What Causes Insulin Resistance? Lipid Overload
Over the past year I have interacted with hundreds of people with diabetes, and have come to learn one very important lesson that has changed my view of diabetes altogether. This realization came to me early on in my career as a nutrition and fitness coach for people with diabetes, and continues to hold true. While insulin resistance is a condition that is most commonly associated with type 2 diabetes, an increasing body of evidence is now shedding light on the fact that insulin resistance is a common thread that underlies many health conditions previously unassociated with blood sugar, including (but not limited to) heart disease, diabetes, atherosclerosis, the metabolic syndrome, obesity and cancer. What that means is simple: insulin resistance significantly increases your risk for the development of a collection of health conditions that can significantly reduce your quality of life and decrease your life expectancy. Watch this video for a synopsis of the causes of insulin resistance: What is insulin and why should you care? Insulin is a hormone which is released by the pancreas in response to rising blood glucose. When you consume carbohydrates, the glucose that enters the bloodstream knocks on the door of the beta cells in the pancreas as a signal to make insulin. Insulin serves as the key that unlocks the door to allow glucose to enter body tissues. Insulin tells your cells “Yoo hoo! Pick up this glucose. It’s all over the place.” Without insulin, cells in the liver, muscle, and fat have a difficult time vacuuming up glucose from the blood. These tissues are capable to vacuuming up only a small percentage (5-10%) of the glucose in circulation without the help of insulin. When insulin is present, the amount of glucose that can be transported into tissues sign Continue reading >>
What Is Insulin Resistance?
Insulin resistance is at the heart of type 2 diabetes, but can also impact others including those with type 1 diabetes. In simple terms, insulin resistance is when the body cannot use insulin effectively. When people goes from non-diabetic, to pre-diabetes, to type 2 diabetes, they are experiencing increasing levels of insulin resistance. People with type 1 diabetes can also experience insulin resistance and may find they need to increase their insulin dosages, while people with type 2 diabetes who are not on insulin would find they may need to add or increase their oral medication doses. *Speak with your doctor about adjusting your medications or insulin doses if you suspect insulin resistance is leading to higher blood sugar readings. Here are the three most common habits or changes in lifestyle than can lead to increase resistance to insulin: Weight-gain: Body fat blunts the body’s sensitivity to insulin. The higher amount of fat on your body, the more insulin your body needs in order to stabilize your blood sugar. If you’ve gone through a period in your life where you’ve gained weight, even five pounds, you may find that your insulin needs or medications need to be adjusted. Lack of exercise: When you exercise your body, you increase your metabolism both during the workout and overall as you’re more and more consistent. An increased metabolism means you’re burning more glucose for fuel simply when you’re at rest. When you stop exercising or don’t exercise at all, eventually this will lead to greater resistance to insulin because your body will have to work harder to burn through the glucose that exercise would have burned, by using it for fuel. Eating too many carbohydrates: Carbohydrates are the number one food your body requires insulin for in order Continue reading >>
What Causes Insulin Resistance?
Michael: You wrote: ” Part of the question in my mind are the relative benefits of higher HDL vs lower LDL; a topic I would love to see taken up on a NF video.” I have suggested that this be a topic of future videos. In the meantime, below is some information I’ve gathered about HDL which may be helpful to you. . **************** I am not an expert on the topic of HDL, but some of my favorite NutritionFacts forum members and some experts have had a thing or two to say on the matter. BOTTOM LINE: I synthesize the information below to mean we do not need to worry about HDL levels or HDL falling in the context of a whole plant food based diet, when LDL goes down or is already at a healthy level. . In other words, if you have high/unsafe cholesterol levels (total and LDL) overall, then also having high HDL can be protective (especially if you got that high HDL through exercise or some other healthy behavior rather than diet). But in the face of healthy LDL levels, the HDL level doesn’t seem to matter. I may be wrong about this, but see what you think. ************************************ . First, check out the following article from heart health expert Dean Ornish. He does a great job of explaining the role of HDL and when we need to worry about it’s levels vs when we do not. “A low HDL in the context of a healthy low-fat diet has a very different prognostic significance than a low HDL in someone eating a high-fat, high-cholesterol diet.” . Two of our more knowledgable forum particpants, Gatherer and Darryl, have put together for us some of the strongest evidence–a list of good studies. Gatherer wrote (from comment ) : . “”Don’t put too much stock in HDL levels. Here is a news release “Raising ‘good’ cholesterol doesn’t protect against heart di Continue reading >>