The Insulin Resistance Syndrome: Physiological Considerations
The insulin resistance syndrome, also referred to as the ‘metabolic syndrome’ or ‘syndrome X’, is associated with a primary cellular defect in insulin action (insulin resistance) and a compensatory increase in insulin secretion. The combination of insulin resistance and subsequent hyperinsulinaemia causes a number of metabolic and cardiovascular changes that result in a syndrome typically characterised by type 2 diabetes, obesity, dyslipidaemia, coronary artery disease and hypertension. Moreover, disturbances in sleep (sleep apnoea) and ovarian dysfunction are also characterised by insulin resistance. The pathophysiological basis for these disturbances reflects the impact of variable genetic and environmental influences. At a molecular level, insulin resistance involves defects of insulin signalling such as reduced insulin receptor tyrosine kinase activity and reduced post-receptor phosphorylation steps that impinge on metabolic and vascular effects of insulin. 1. Bajaj M, DeFronzo RA. Metabolic and molecular basis of insulin resistance. J Nucl Cardiol 2003;10:311–23. Google Scholar, Crossref, Medline 2. DeFronzo RA. Pathogenesis of type 2 diabetes mellitus: metabolic and molecular implications for identifying diabetes genes. Diabetes Rev 1997;5:117–19. Google Scholar 3. Grill V. A comparison of brain glucose metabolism in diabetes as measured by positron emission tomography or by arteriovenous techniques. Ann Med 1990;22:171–5. Google Scholar, Crossref, Medline 4. DeFronzo RA. Lilly Lecture. The triumvirate: beta cell, muscle, liver. A collusion responsible for NIDDM. Diabetes 1988;37:667–87. Google Scholar, Crossref, Medline 5. DeFronzo RA, Bonadonna RC, Ferrannini E. Pathogenesis of NIDDM. A balanced overview. Diabetes Care 1992;15:318–68. Google Sc 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 >>
Physiological Insulin Resistance = Low Carbohydrate Diet Induced Insulin Resistance
I’ll admit to breathing a sigh of relief back in October of 2007, when Peter at Hyperlipid posted about “Physiological insulin resistance.” Curiously, looking at the post again, I note that he didn’t capitalize the second two words—as though it’s not a proper name for a specific condition. Back in mid summer 2007 there was this thread on the Bernstein forum. Mark, posting as iwilsmar, asked about his gradual yet progressively rising fasting blood glucose (FBG) level over a 10 year period of paleolithic LC eating. Always eating less than 30g carbohydrate per day. Initially on LC his blood glucose was 83mg/dl but it has crept up, year by year, until now his FBG is up to 115mg/dl. Post prandial values are normal. He wanted to know if he was developing diabetes. […] What is happening? Well, the first thing is that LC eating rapidly induces insulin resistance. This is a completely and utterly normal physiological response to carbohydrate restriction. Carbohydrate restriction drops insulin levels. Low insulin levels activate hormone sensitive lipase. Fatty tissue breaks down and releases non esterified fatty acids. These are mostly taken up by muscle cells as fuel and automatically induce insulin resistance in those muscles. Whew! Now I had something to tell my dad and others who’d been faithfully doing LC and became horrified, then scared, at fasting blood glucose measurements (which is primarily how the health community screens people for diabetes). I really didn’t concern myself with it again—for all these last almost 7 years. OK, so long as post-prandial is fine (caveat: AFTER AN LC MEAL!), nothing to worry about; and combined with good HbA1c, and the fact that so far as we know, this condition will reverse in normal people after a few days of carbage, Continue reading >>
- The effect of a low-carbohydrate, ketogenic diet versus a low-glycemic index diet on glycemic control in type 2 diabetes mellitus
- The interpretation and effect of a low-carbohydrate diet in the management of type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials
- Pre-diabetes goes into remission on higher protein, lower carbohydrate diet (Zone diet balance)
Physiological Insulin Resistance
Back in mid summer 2007 there was this thread on the Bernstein forum. Mark, posting as iwilsmar, asked about his gradual yet progressively rising fasting blood glucose (FBG) level over a 10 year period of paleolithic LC eating. Always eating less than 30g carbohydrate per day. Initially on LC his blood glucose was 83mg/dl but it has crept up, year by year, until now his FBG is up to 115mg/dl. Post prandial values are normal. He wanted to know if he was developing diabetes. I've been thinking about this for some time as my own FBG is usually five point something mmol/l whole blood. Converting my whole blood values to Mark's USA plasma values, this works out at about 100-120mg/dl. Normal to prediabetic in modern parlance. However my HbA1c is only 4.4%, well toward the lower end of normality and healthy. That's always assuming that I don't have some horrible problem resulting in very rapid red blood cell turnover. I don't think so... I spend rather a lot of my life in mild ketosis, despite the 50g of carbs I eat per day. So I can run a moderate ketonuric urine sample with a random post-chocolate blood glucose value of 6.5mmol/l. What is happening? Well, the first thing is that LC eating rapidly induces insulin resistance. This is a completely and utterly normal physiological response to carbohydrate restriction. Carbohydrate restriction drops insulin levels. Low insulin levels activate hormone sensitive lipase. Fatty tissue breaks down and releases non esterified fatty acids. These are mostly taken up by muscle cells as fuel and automatically induce insulin resistance in those muscles. There are a couple of nice summaries by Brand Miller (from back in the days when she used her brain for thinking) here and here and Wolever has some grasp of the problem too. This is patentl Continue reading >>
Physiologic Insulin Resistance
I'm hoping you can give me a simple response to a mess I'veapparently created in my own body. I've queried Petro Dobromylskyj,because it was his blog entry of October 2007 ( )that began to explain to me what was happening to my metabolism. Icontacted Dawn Tasher ( www.peelingbacktheonionlayers.com )because she was a strongly recommended nutritionist, and shesuggested I get in touch with Paul Jaminet, whose work I'd seen onthe internet. I've also had no response from him. My own doctor(s)don't seem to have answers. Like Peter, I am a veterinarian so amused to creative problem solving, often making difficult diagnoseson patients who are incapable of giving any history whatsoever ontheir health condition. So here's my story. I have been a lacto-vegetarian for 45 years.Added in eggs about ten years ago. About 13 years ago, my husbandembarked on the classic Atkins diet - as a vegetarian - to try tolose weight. After two days of eating extremely low carbs, he saidhe didn't care if he never lost an ounce on the diet because hefelt ten years younger and was dedicating himself to living a lowcarb lifestyle forever. (He did end up losing 35 pounds and keepingit off). "Ten years younger" sounded great to me so I did myhomework and joined in. I never needed to lose weight - at 5'4", myweight has fluctuated between 108 and 114 pounds since high school.So - I've been eating VERY low carb (probably less than 40 gramsper day), with adequate calories, largely from fats, to maintain myweight for about thirteen years, feeling great, and enjoying what Ieat. BUT - my fasting blood sugars have been consistently high(103-107 range) for the past several years when I've had my annualmedical check-up. My A1c has always been OK, so my doc alwaysshrugged her shoulders and we both casually figured 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 >>
Physiological Insulin Resistance
I have been trying to find an answer to why my FBG levels have been increasing over the last couple of weeks. It is very frustrating and as a diabetic trying to reverse the disease it is scary (will this WOE work? Are the consequences of out of control diabetes, I am trying to escape, going to happen anyways?). I ran across a blog post that seems to describe what may be happening in my case. It is a possible phenomenon called Physiological Insulin Resistance. The High Blood Glucose Dilemma on Low Carb (LC) Diets If you are on a ketogenic or very low carb (VLC) diet (e.g. with 50-100gr carb/day and/or eating ketone producing MCT oils such as coconut oil), you m Low insulin levels activate hormone sensitive lipase. Fatty tissue breaks down and releases non-esterified fatty acids (NEFA). These are mostly taken up by muscle cells as fuel and automatically induce insulin resistance in those muscles. Palmitic acid is the primary NEFA released from human adipose tissue during fasting. Think of palmitic as a signal molecule to tell the muscles that inhibition of glucose uptake is needed and to tell the liver that increased gluconeogenesis is required because there is no food coming in. This in turns increases the blood sugar. One of the supporting blog post to the one posted above spoke of person experience.The author, like me, gets a consistent mild ketosis readings. Using Ketostix I am getting a consistent 15 dl reading and at high BG. You need to get calories from somewhere, should it be from carbohydrate or fat? I am going to continue reading/researching down this path to determine the implications. The author of the blogs conclusion was as long as his HbA1c is 4.4% he does not care about the high blood sugar readings. This is one voice so I want to learn more. Has anyone 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 >>
Insulin Resistance As A Physiological Defense Against Metabolic Stress: Implications For The Management Of Subsets Of Type 2 Diabetes.
Insulin resistance as a physiological defense against metabolic stress: implications for the management of subsets of type 2 diabetes. Department of Endocrinology at Canberra Hospital and the Australian National University Medical School, Canberra, Australia [email protected] Diabetes Research Unit, Boston University Medical Center, Boston, MA. Division of Metabolism, Endocrinology and Nutrition, VA Puget Sound Health Care System, and University of Washington, Seattle, WA. Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. CRCHUM and Montreal Diabetes Research Center and Departments of Nutrition and Biochemistry and Molecular Medicine, University of Montreal, Quebec, Canada. Diabetes. 2015 Mar;64(3):673-86. doi: 10.2337/db14-0694. Stratifying the management of type 2 diabetes (T2D) has to take into account marked variability in patient phenotype due to heterogeneity in its pathophysiology, different stages of the disease process, and multiple other patient factors including comorbidities. The focus here is on the very challenging subgroup of patients with T2D who are overweight or obese with insulin resistance (IR) and the most refractory hyperglycemia due to an inability to change lifestyle to reverse positive energy balance. For this subgroup of patients with T2D, we question the dogma that IR is primarily harmful to the body and should be counteracted at any cost. Instead we propose that IR, particularly in this high-risk subgroup, is a defense mechanism that protects critical tissues of the cardiovascular system from nutrient-induced injury. Overriding IR in an effort to lower plasma glucose levels, particularly with intensive insulin therapy, could therefor Continue reading >>
Insulin Resistance Is Good? – T2d 7
Everybody says that insulin resistance is bad. Very bad. It’s the root cause of type 2 diabetes (T2D), and metabolic syndrome, isn’t it? So, if it is so bad, why do we all develop it in the first place? What’s the root cause? My friend Dr. Gary Fettke from Tasmania wrote an illuminating book called ‘Inversion’ where he describes how you can learn a lot from looking at things from another perspective. Invert (turn upside down) your perspective, and see how your horizons are immensely broadened. So let’s look at why we develop insulin resistance. Why is it good? Root Cause Analysis What is the root cause of insulin resistance? Some people say inflammation or oxidative stress or free radicals causes insulin resistance. Those are total cop-out answers. Inflammation is the body’s non-specific response to injury. But what causes the injury in the first place? That’s the real problem. The inflammation is only the body’s response to whatever is causing the injury. Think about it this way. Suppose we are battlefield surgeons. After decades on the job, we decide that blood is bad. After all, every time we see blood, bad things are happening. When we don’t see blood, bad things are not happening. It must be the blood that is dangerous. So, deciding that blood is what is killing people, we invent a machine to suction all the blood of people. Genius! The problem, of course, is what’s causing the bleeding, rather than the blood itself. Look for the root cause. Bleeding’s only the response, not the cause. Bleeding is a marker for disease. So is inflammation. Something causes bleeding, the body’s non specific response. Something causes inflammation, the body’s non specific response. Gunshots cause bleeding, knife wounds cause bleeding, and shrapnel causes bl 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 >>
Physiological Insulin Resistance
Diabetes Forum The Global Diabetes Community Find support, ask questions and share your experiences. Join the community Hi, I have been doing a little reading on this subject but I`m still not sure if I have a handle on it or not and would like a little advice please. My understanding is as follows: A lot of t2`s have Pathological insulin resistance so that when we produce glucose our pancreas has to produce insulin but we don`t use it very well which means more insulin which causes weight gain and so on... A low carb diet produces less glucose which calls for less insulin which has to be a good thing presumably. However, carb restriction can also cause Physiological insulin resistance which, if I understand correctly, saves the smaller amount of glucose which is produced for the brain by making the muscles insulin resistant which leads to higher bg readings. Is my understanding anywhere close to correct and will these higher bg levels lead to a higher HBA1C ? Thank you for reading and please reply with your opinions. Chris. Hi, I have been doing a little reading on this subject but I`m still not sure if I have a handle on it or not and would like a little advice please. My understanding is as follows: A lot of t2`s have Pathological insulin resistance so that when we produce glucose our pancreas has to produce insulin but we don`t use it very well which means more insulin which causes weight gain and so on... A low carb diet produces less glucose which calls for less insulin which has to be a good thing presumably. However, carb restriction can also cause Physiological insulin resistance which, if I understand correctly, saves the smaller amount of glucose which is produced for the brain by making the muscles insulin resistant which leads to higher bg readings. Is my Continue reading >>
Ketogenic Diet And Physiological Insulin Resistance | Low Carb Diet And Dawn Phenomenon
Dawn Phenomenon Ketogenic Diet and Dawn Phenomenon ketogenic diet Physiological Insulin Resistance low carb diet Dawn Phenomenon Low Carb Diet Physiological Insulin Resistance Physiological Insulin Resistance Dawn Phenomenon and Physiological Insulin Resistance Have you been on a low-carb or ketogenic diet for some time no and perplexed why your morning blood glucose readings are on the high end? Did you know that it is quite common for long-term ketogenic dieters to have morning fasted blood glucose readings that average 100-125mg/dl? This is rather common, albeit normal and sometimes referred to as Dawn Phenomenon or Physiological Insulin Resistance. Dawn Phenomenon is a natural rise in blood sugar because o a surge of hormones secreted at night which trigger your liver to dump sugar into your blood to help prepare you for the day. Another term for this is Physiological Insulin Resistance. A good description of this phenomenon comes from Chris Kresser, M.S., L.Ac: Very low-carb diets will produce elevated fasting blood glucose levels. Why? Because low-carb diets induce insulin resistance. Restricting carbohydrates produces a natural drop in insulin levels, which in turn activates hormone sensitive lipase. Fat tissue is then broken down, and non-esterified fatty acids (a.k.a. free fatty acids or NEFA) are released into the bloodstream. These NEFA are taken up by the muscles, which use them as fuel. And since the muscles needs for fuel has been met, it decreases sensitivity to insulin. So, if you eat a low-carb diet and have borderline high Fasting Blood Glucose (i.e. 90-105), it may not be cause for concern. Your post-meal blood sugars and A1c levels are more important. One of the clearest explanations of physiological insulin resistance Ive seen comes fromPaul Jamine Continue reading >>
Ketoadaptation And Physiological Insulin Resistance
This is where the magic happens. Rat pups, fed a flaxseed oil-based ketogenic diet from weaning onward – note the drop-off in ketones after 2 weeks (Likhodii et al., 2002): Patient history: these rats have been “low carb” their whole lives. Side note: flaxseed oil is very ketogenic! (Likhodii et al., 2000): Flaxseed oil-based ketogenic diet produced higher ketones than 48h fasting; the same can’t be said for butter or lard. PUFAs in general are more ketogenic than saturated fats in humans, too (eg, Fuehrlein et al., 2004): Crisco keto (adult rats) (Rho et al., 1999): At this point, please just note the stunning consistency in the drop-off of ketones. Experiment 1 & 2 (above) are adult rats; they went through a period of high carb chow dieting, unlike experiment 3 and the rats in the first study, who were weaned onto ketogenic diets. Still same phenomenon: ~few weeks after initiation of ketogenic diet = breakpoint; ketones decline. Ketoadaptation: why do ketone levels decline? This happened in both rat studies above, Phinney 1983, and in many “n=1” practitioners. Possible explanation 1 (ketoadaptation): rat milk is kind of like a low carb diet; high in fat, but not low enough in other stuff to be ketogenic. -Hooded seal milk is practically heavy cream: imagine the amount of suction pups must need to apply. Poor mom, that’s gotta hurt; fortunately, lactation only lasts 4 days. -Rat milk is super-high protein. Therefore, weaning to the flaxseed oil-based keto diet is what really initiates ketoadaptation… which seems to take 2-3 weeks (judging by the decline in ketones [this is explained further below]). Possible explanation 2 (physiological insulin resistance): free fatty acids released faster then they’re burned, accumulate in skeletal muscle, induce mil Continue reading >>
Need Help With Insulin Resistance As A Result Of My Low Carb/vlc Diet. Anything Current?
I know there are other threads on this topic and I have read a lot of them. I just wonder if there is anything more current than this article from 2007 to help me understand this. Perhaps its still current and valid. Im unclear what to do exactly to reverse this, or do I even need to if its not "pathological". Summary: I am 5-8 pounds over-fat. 10-15 years of labs have all been good/very good for fasting Bg and insulin, until this recent one (the only one when I was low carb/vlc). My insulin was high at 9.00 on last fasting blood draw. Bg was 98 I have been eating high protein, high healthy fat, low carb or vlc. My current labs showed "pre-diabetes" 3 Foods to Remove from - The Fridge Forever Cut a bit of belly bloat each day, by avoiding these 3 foods nucific.com I got an at home glucometer. My Bg never goes too high but it doesn't recover either. Its stays around 100-111 after peaking at 123 or so. Oddly too is that every test is higher at 2 hours and even three than at one hour. Can somebody recommend one or two good resources for this issue. The frustration I'm having is that everything I read about insulin resistance says to "lower carb intake". That is what caused this issue it seems. Thank you. Edited to add: My A1C was not tested this time (arggg) although it was not optimal at all a year ago when it was tested and when my Fbg and insulin were way lower. A1C was 5.7 then. Thanks Continue reading >>