Oxidative Stress and Insulin Resistance
As we have discussed before, insulin resistance is a cardinal feature of type 2 diabetes, and is an important factor in many other illnesses. Last year saw the publication of a study from Albert Einstein College of Medicine in New York, showing that high levels of blood glucose induced an inflammatory response in fat cells, and reactive oxygen species was a key player in the process.
Now, a very interesting paper in the journal Nature indicates that fat storage cells exposed to chemicals (dexamethasone and tumor necrosis factor-α) raise the levels of reactive oxygen species and these raise insulin resistance. If the cells are then treated to suppress this production, insulin resistance falls. We have been interested in balancing the oxidant and antioxidant systems to reduce the risk of the complications of diabetes, but now it looks as if antioxidants may also help the underlying disease process itself.
In a future blog I’m going to explain why free radicals and oxidative stress are not all bad: they are key cancer killers!
And in one of the programs coming out later this year, I shall explain how to modulate oxidative stress to keep your systems in constant dynamic balance.
Technorati tags: Oxidative stress Inflammation Insulin resistance Free radicals
A New Way of Looking at – and Treating – Inflammation
Diseases of both large and small blood vessels are two of the biggest problem facing people with diabetes. Not only is it a huge clinical challenge, but also nature sometimes does our experiments for us. The high rates of coronary and peripheral vascular disease in diabetes can be seen as a kind of experiment of nature: a recognizable set of chemical abnormalities that might shed light on vascular diseases in general. It was those twin factors: a huge clinical problem, and an experiment of nature, that lead me to pick the topic of my research doctorate.
When I was working on my research doctorate in the mid 1980s, I came across a lot of old research that seemed to show links between inflammatory and autoimmune conditions like systemic lupus erythematosus and rheumatic fever, and the eventual development of coronary artery disease. There was also a lot of old and largely forgotten research about the link between some viral infections and the development of coronary artery disease and acute coronary artery occlusions, because some infections can make blood more “sticky.” Inflammation evolved as one of the body’s defence mechanisms.
So I made the proposal – revolutionary at the time – that diabetes, coronary artery disease and a range of other illnesses might be inflammatory rather than degenerative. I soon found inflammatory markers in people with diabetes, that helped predict when someone was running into trouble with their eyes, kidneys or heart. Even with stacks of data, I had to spend a lot of time defending that position, because it also implied that some illnesses thought to be irreversible might not be.
With the passage of time, it has tuned out that I was probably correct. Chronic inflammation, wherever it starts, mat have long-term effects on the body and on the mind. Chronic inflammation increases the risk of diseases of many blood vessels, as well as causing anemia, organic depression and cognitive impairment. Here is a partial list of common conditions in which inflammation is a prominent factor:
1. Rheumatoid arthritis
2. Systemic lupus erythematosus
3. Fibromyalgia
4. Chronic infections
5. Insulin resistance or metabolic syndrome
6. Arteriosclerosis
7. Diabetes mellitus
8. Hypertension
9. Asthma
10. Inflammatory bowel disease
11. Psoriasis
12. Migraine
13. Peripheral neuropathy
14. Alzheimer’s disease
15. Autism
16. Gingivitis
17. Cystitis
The reason for raising the issue is not to say “told you so!”
It is instead that we need to think about inflammation a little differently. There is a mountain of information about the physical aspects of inflammation. We can stop at the simple description of inflammation as a condition in which part of the body becomes reddened, swollen, hot, and usually painful, or we can look below the surface: we can examine inflammation not only as a physical problem, but also as a psychological, social, subtle and spiritual problem. Why bother? Because the deeper approach allows us to understand and to treat and transcend inflammation as never before.
I am going to write some more about specific ways to address inflammation and what it means in future articles. I would also like to direct you to the book Healing, Meaning and Purpose, in which I talk about specific approaches in more detail.
But I would like to start with this.
In Ayurvedic and homeopathic medicine, inflammation is a sign of an imbalance in the vital forces of the body, and the traditional Chinese system agrees: here inflammation is usually a manifestation of an excess of Yang Qi, or a deficiency of Yin Qi. Most of our lives are seriously out of balance: Yang Qi is like a rampaging lion that has been stimulated by:
Acidic foods;
Environmental toxins;
Unwanted sexual stimulation:
Noise;
Discordant music:
Constant demands from others:
Toxic relationships;
Years spent in front of television sets and limitless multi-tasking.
It should be no surprise to learn that all of these inflammatory conditions are increasing rapidly throughout the Western world. Not because we are getting better at identifying them, or we are living longer, but genuinely increasing.
It is wrong to put all the blame on poor diets or inadequate exercise. The problem is more subtle and is a reflection of distorted Information being fed to our bodies, minds, relationships, subtle systems and spiritual relationships.
The great news is that this simple conceptual shift gives us a whole load of new tools for handling these problems, and for using them as catalysts to growth.
In the next few weeks, I am going to drill down and give you some specific guidance that ties into the material in Healing, Meaning and Purpose and the next two that are on the launch pad.
Fasten your seat belt!
Technorati tags: Inflammation Aging Alzheimer’s disease Arteriosclerosis Neuropathy Autism Arthritis Systemic lupus erythrmatosus Fibromyalgia Inflammatory bowel disease Gingivitis
The Risks of “Pre-hypertension”
It often seems as if treatment guidelines change every year. The levels at which experts recommend treating cholesterol, glucose levels and blood pressure have all changed recently. Some cynics say that it’s all a device by drug companies to get more people on treatment, but that’s not really true. The guidelines change as we get more evidence that not treating something leads to bad consequences in the future. A good example would be the level at which experts recommend treating elevated blood glucose. The recommendation was changed when it was discovered that even small elevations of glucose could have a dramatic impact on the development of coronary artery disease.
We now have another change, this time with blood pressure. Everyone knows that high blood pressure can be dangerous. But researchers have recently defined something that we call pre-hypertension (a systolic blood pressure 120 to 139 mm Hg or diastolic blood pressure 80 to 89 mm Hg). What was not known for sure was what impact pre-hypertension would have on the incidence of cardiovascular disease.
A study published in the journal Hypertension has clarified the issue. The research involved 2629 people participating in the twelve-year-long Strong Heart Study. Pre-hypertension was more common in people with diabetes. And as expected, from the link between blood pressure and insulin resistance, impaired glucose tolerance or impaired fasting glucose in pre-hypertensive people greatly increased the risk of developing cardiovascular disease risk. We now need to do more research to see if interventions, such as drug treatment for blood pressure control for pre-hypertensive individuals are warranted. This is particularly important if people also have impaired fasting glucose, impaired glucose tolerance, or diabetes is warranted, because risk factors for coronary artery disease are cumulative: the more risk factors, the bigger the risk.
What this means is that your health care provider should help you keep your blood pressure lower than we thought, particularly if you have a personal or a family history of problems with blood glucose or of heart disease.
Technorati tags:Hypertension Insulin resistance Diabetes mellitus Coronary artery disease
Insulin Resistance, Insulin Resistance Syndrome and Race
I often hear clinicians say that they are not too clear about the differences between insulin resistance and insulin resistance syndrome. Let me define them, and then tell you why they are so important, and why everyone needs to be informed about them.
First, insulin is a hormone produced primarily in the cells of the Islets of Langerhans in the pancreas. It has over 500 functions in the human body, but its main actions are on the regulation of the metabolism of carbohydrates and fats. Insulin enables glucose – one of the major sources of energy – to move into many of the cells in the body. Insulin is also involved in the conversion of glucose to glycogen. These two actions lower the blood glucose level.
Insulin resistance is defined as an impaired biological response to insulin. It is a condition in which many of the cells of the body – mainly in the liver, fat and muscle – become resistant to the effects of insulin. The normal responses to a given amount of insulin are reduced. As a result, higher levels of insulin are needed in order for insulin to have its effects. There are many potential causes of insulin resistance: genetic; an increase in intra-abdominal fat; smoking cigarettes; being of low birth weight; and there are some prescription medicines that can cause insulin resistance. Insulin resistance is one of the underlying causes of type 2 (maturity onset) diabetes mellitus, as well as an array of other illnesses including polycystic ovarian syndrome. Most studies have suggested that around a third of people living in the United States and Western Europe have insulin resistance, and there are marked ethnic differences.
The insulin resistance syndrome has several other names: Metabolic syndrome; (Metabolic) Syndrome X; Dysmetabolic syndrome; Reaven’s syndrome; multiple metabolic syndrome. There are several sets of criteria for defining the insulin resistance syndrome. In the USA it is usually defined as the presence of 3 or more of the following:
1. Abdominal obesity (Waist circumference >40 inches in men; >35 inches in women
2. Glucose intolerance (fasting glucose ≥110 mg/dL)
3. Elevated blood pressure ≥130/85 mmHg
4. Triglycerides >150 mg/dL
5. Low HDL (Men: <40 mg/dL; women: <50 mg/dL)
There is a constant debate in the medical literature about whether insulin resistance syndrome is an illness, and what should be included in it. It is important, because it appears to predict the development of diabetes and coronary artery disease, and between 20 and 25% of the population of the Western world has it. So what normally happens is that a person develops insulin resistance, which eventually evolves into the insulin resistance syndrome, before diabetes and heart disease appears. There can be as long as twelve years between the development of insulin resistance, and the diagnosis of diabetes, and we have very good evidence that lifestyle changes can dramatically reduce the risk of moving from insulin resistance to the insulin resistance syndrome and diabetes.
It has become quite well-known that people of African and Asian Indian heritage are at increased risk of developing insulin resistance, and some of the sequelae of insulin resistance: insulin resistance syndrome, diabetes mellitus, hypertension and gout. These may in turn lead to increased rates of myocardial infarction and strokes. A study presented last Monday at ENDO 2006, the annual meeting of the Endocrine Society in Boston helps further clarify some of these ethnic differences. Researchers analyzed data from the Insulin Resistance Atherosclerosis Study (IRAS), designed to assess relationships between insulin resistance and cardiovascular disease in a large multi-ethnic population.
The investigators divided data from female IRAS participants into different groups based on body mass index (BMI), a measure of body fat based on height and weight. A BMI of less than 25 is usually considered "normal." The analysis revealed that 47 percent of black women of normal weight had insulin resistance, compared to less than 20 percent of the Hispanic or White women. Both insulin resistance and the likelihood of developing type 2 diabetes increase as obesity increases. It had long been suspected that there was an independent effect of race, but this study not only shows that race alone may influence insulin resistance, but that we may therefore need to change the definition of obesity in women of African heritage.
The news reports on this important finding failed to mention that previous research has found something very similar in Asians from India, China and Japan. Each of these ethnic groups may develop insulin resistance, insulin resistance syndrome and diabetes without being obese, though obesity dramatically increases their risks of running into trouble.
It is relatively simple and inexpensive to measure insulin resistance, and many metabolic experts, including your humble reporter, have, for more than a decade, been measuring it in high-risk individuals. Clearly we cannot do anything much about an ethnic or genetic risk, but we can alter the way in which the body responds to that risk. If a person is insulin resistant, diet, exercise, specific nutritional and herbal interventions and occasionally medications, may all reduce the risk of developing diabetes and heart disease.
Technorati tags:Insulin Insulin resistance Insulin resistance syndrome Metabolic syndrome Diabetes mellitus Obesity Hypertension Racial differences
Sleep, Weight, Insulin Resistance and Diabetes
I am often asked why there seem to be such close links between food and mood. Not just comfort eating, or the sudden shock of lots of carbs when we need an energy jolt, but why drugs that alter mood so often alter appetite?
You will probably not know this, gentle reader, but I only learned of it from reading scholarly papers. Apparently many people report that using marijuana makes them very hungry. On the other hand, cocaine and amphetamine affect not just the metabolism, but also appetite. The link has to do with the evolutionary development of feeding behaviors with the motivation to find food and to be satisfied by it.
Another link that has interested me for many years is the connection between metabolism and sleep. We have always presumed that this link has to do with hibernation: even humans have maintained some hibernation responses.
There is extremely good evidence that there is an inverse relationship between the number of hours that you sleep and an increase in your weight. There have been a great many studies on this, but one of the best was published by a group of researchers from the Mood and Anxiety Disorders Program, at the National Institute of Mental Health, the Psychiatric University Hospital, Zurich, Switzerland; University of Pittsburgh School of Medicine and the Department of Psychosocial Medicine, Zürich University Hospital, Switzerland in the Journal Sleep in 2004.
A report from the BBC concerning a study presented to the American Thoracic Society International Conference in San Diego provides yet more evidence of this link between sleep and weight. Researchers from Case Western Reserve University in Ohio, followed nearly 70,000 women for 16 years. They found that women who slept five or fewer hours a night were a third more likely to put on at least 33lbs (15kg) than sound sleepers during that time. It also found that compared with women who slept for seven hours a night. lighter sleepers were 15% more likely to become obese (have a Body Mass Index (BMI) of 30 or more. {BMI is calculated by dividing your weight in kilograms by the square of your height in meters}).
Previous studies, some of which I have reported before, have shown that after just a few days of sleep restriction, the hormones that control appetite cause people to become hungrier. However the women in the study appeared to eat less. I say “appeared to,” since the use of personal evaluations of food intake are notoriously inaccurate.
In dozens of countries arond the world, I am regarded as an authority in the fields of endocrinology, metabolism and nutrition. But when a group of us tried to estimate our daily intake and compare it with meticulous diaries, we discovered that we – a group of internationally renowned experts – were off by around 500 calories per day.
All kinds of explanations have been advanced, from people who didn’t sleep getting up and binge eating; to the effects of sleep-deprived people craving high carbohydrate, high fat food; to insomnia being a result of anxiety or depression that releases hormones that cause us to lay down fat in our tummies.
For all kinds of complex biochemical reasons, I have always felt that a lack of sleep would lead to an increase in insulin resistance, that may cause an increase in the deposition of fat in key regions of the body.
Some new research suggests that I may have been right on this one. A group based at Yale University School of Medicine, in New Haven, Connecticut has just published a report that should be of interest to all of us, and in particular you multi-tasking insomniacs out there.
The investigators studied a cohort of men from the Massachusetts Male Aging Study who did not have diabetes at baseline (1987–1989) and who were followed until 2004 to look for the development of diabetes mellitus. They came to the conclusion that BOTH very short and extra long sleep durations increase the risk of developing diabetes, independent of confounding factors.
The take home message?
If you do not get 7-8 hours sleep each night, you are vulnerable to a great many problems, and perhaps the biggest of all is the risk of weight gain, insulin resistance and diabetes mellitus.
I do not recommend using sleeping tablets unless absolutely necessary, and then for just a few days at a time. Instead follow all the sleep strategies that I have talked about in earlier blog entries.
During a recent visit to Danville, Virginia, I was delighted to learn that one of the non-pharmacological approaches that I have found helpful – putting a cold compress on the abdomen – was used by General Stonewall Jackson who used this very technique that I had to learn by going all the way to China.
The bottom line? Before your sleep gets disrupted by being overweight and you develop sleep apnea, try some simple sleep hygiene, and a few of these novel techniques.
Technorati tags: Insulin Insulin resistance Insulin resistance syndrome insomnia alternative medicine resilience
Calcium, Vitamin D, Diabetes and Schizophrenia
There are some odd puzzles in medicine. For more than 100 years it has been known that diabetes is more common in people suffering from schizophrenia, bipolar disorder and probably also depression. There has also been data indicating that some children with ADD and autism have metabolic disturbances that may underlie some of the cognitive difficulties. It has also been observed in Europe that dark skinned immigrants – whose skin coloring makes them less able to make Vitamin D – are more likely to develop diabetes. Some dark skinned immigrants are also far more likely to develop schizophrenia compared with their families that stayed in sunny tropical regions. Children – particularly boys – who are breastfed and/or have Vitamin D supplements in the first year of life are less likely to develop schizophrenia in later life. Vitamin D is not only involved in calcium absorption, but also in maintaining the integrity of cell membranes. So the link between diabetes and schizophrenia may have something to do with Vitamin D.
A new study just published in the journal Diabetes Care indicates that women with high intakes of vitamin D and calcium appear to have a lower risk of developing type 2 (maturity onset) diabetes. The study from Tufts-New England Medical Center looked at data on 83,779 women enrolled in the Nurses’ Health Study. The women had no history of diabetes, cardiovascular disease or cancer when they enrolled in the study. Vitamin D and calcium intake from foods and from supplements were evaluated every 2 to 4 years. Over the 20 years of follow-up a total of 4843 new cases of diabetes were discovered. The lowest risk of diabetes was observed among women with the highest combined intakes of calcium and vitamin D compared with those with the lowest.
These are important findings, because interventions to raise both vitamin D and calcium intake and quick, cheap and easy, and may significantly reduce the risk of developing type 2 diabetes.
So how much should we take? Although we should be able to make enough of our own Vitamin D by spending even ten minutes in the sun, not everyone can do that, the sun is not without its risks, and the mechanisms for making Vitamin D become less effective as we become older. Though a balanced diet should also help provide some vitamin D and enough calcium, the data indicates that we should take in at least 1200mg of calcium each day, and 400 International Units (10 micrograms) Vitamin D each day. It is possible, though uncommon for people to take too much Vitamin D, and that can have all manner of health consequences.
Technorati tags: vitamins, diabetes, schizophrenia, calcium, Vitamin D,
Lectins, Leptin and the China Study
I have just reviewed a most interesting book called The China Study at Amazon.
This book, touted as the most comprehensive study of nutrition ever conducted, is indeed a treasure trove of useful information. The first point that I particularly liked is that the author is not a reductionist. He understands that the idea of trying to reduce the value of foods to one food type or one nutrient is deeply flawed. Let me give you an example: there is some good evidence that tomato-derived lycopene has a great many health benefits, but that does not mean that the solution to all that ails us is a diet consisting solely of tomatoes. I was once asked to see a person who had a genuine problem with a series of food sensitivities: a well-meaning but poorly educated practitioner had put her on a diet of lettuce leaves, rice and spring water. Several months later I saw her because of profound weight loss and malnutrition. The problem was a lack of balance in the dietary approach, and failing to see the big picture.
T. Colin Campbell is definitely one who sees the big picture, both in terms of his own research, and the broader context. He rightly points out that trying to divorce nutrition from the whole diet and lifestyle is a fundamental mistake.
I noticed something rather interesting, which I have just seen picked up by another reviewer: there seems to be a strongly positive correlation between wheat consumption and the risk of sustaining a myocardial infarction.
The reason that I perked up on seeing this is that I have just been analyzing a paper from Lund in Sweden. The investigators’ fundamental premise is that the rise of agriculture and the consumption of cereals might be the underlying explanation for many of the diseases of affluence. The researchers did a study of pigs, and showed that by putting them on a cereal-free diet, the pigs’ insulin resistance, blood pressure and C-reactive protein all fell, which are excellent markers of cardiovascular health. They went even further and provided a biochemical explanation, pointing out that for all its many benefits, agriculture is exposing our bodies to novel lectins: plant proteins that bind to specific carbohydrate groups on cell membranes. (We met lectins in my previous posting on blood types). These lectins seem to have the worst type of biochemical properties that enable them to block the action of a key metabolic hormone called leptin. First discovered in 1994, leptin produces a satiety signal, telling your brain to stop eating. In some animals it may also cause insulin resistance. Leptin was very hot news a few years ago, because if an animal or a person is resistant to leptin, they become morbidly obese. So a number of pharmaceutical companies tried to develop obesity treatments based on leptin. Sadly, to date all of them have failed. It is not surprising that nutritional interventions based on modulating leptin have also been disappointing. At last count there were over 260 hormones and neurotransmitters involved in the maintenance of body-weight. So trying to manipulate just one of them is hardly likely to be crowned with success.
As I have said in other posts, there will always be someone, somewhere, who will respond to any kind of eating or life plan. The trick is in predicting who will respond to what, and in that we are still scratching our heads. So if you want an approach that has the highest overall chance of success at maintaining and improving your health, rather than just focusing on pounds, I’m going to repeat my advice from an earlier posting:
1. It is important for you to maintain your energy balance, between input and output
2. Calories do count
3. What you include in your diet is as important as what you exclude: we are designed to consume not just rice and lettuce, but an array of other nutrients.
4. Make only moderate dietary changes at any time: making big dietary changes can be a pretty violent attack on your body and your mind
5. Avoid the “trans-fatty acids”
6. Try to consume some omega-3 fatty acids every single day
7. Eat fewer simple carbohydrates
8. Use weight management and exercise strategies that enhance your overall health and well-being
9. Take more exercise: even small amounts can have a big effect.
And now I am going to add a tentative number 10:
10. If your weight and metabolic parameters are still not as they should be, discuss a gradual reduction of cereal intake with your health care provider, and how to ensure that you still get the amount of fiber that you need. Depending upon your own genetic make-up that may be the missing piece.
Technorati tags: The China Study, T. Colin Campbell, diet, lifestyle change, nutrition
The Fad-Free Diet: Glycemic Index, Glycemic Load and Dietary Fiber
This is the time of year when a lot of us are thinking about getting rid of those extra pounds that we put on over the holidays, and perhaps thinking ahead to swimsuit season. Thus, magazines are full of articles about diet and every day there are new advertisements for different weight loss products.
For several years now, many diet plans have revolved around the notion of the glycemic index of foods, which is an estimate of the average rise in blood glucose levels after eating a certain food, or of glycemic load, a ranking system of the carbohydrate content of foods based on their glycemic index. This has always seemed to be an attractive concept that is also easy to follow. Foods that have a high glycemic index cause blood glucose to rise rapidly. As a result insulin levels rise to try and compensate, and then an array of other hormones are released to try and re-establish biochemical balance.
Insulin is a complex hormone, with over 500 recognized actions in the body. Insulin resistance is a condition in which some of the cells of the body, primarily in the liver and in adipose or fat tissue and in muscle, become unable to respond to some of the actions of insulin. It is the opposite of insulin sensitivity. As a result, insulin levels begin to rise, until ultimately the pancreas can no longer keep up with the demand. Insulin resistance is known to be a key metabolic problem associated with many illnesses, including Type 2 diabetes, hypertension, high levels of triglycerides and sometimes cholesterol, polycystic ovarian syndrome and even some types of cancer. It is typically associated with an increase in abdominal obesity, though insulin resistance may also cause obesity.
There is an important article in this month’s issue of the journal, Diabetes Care that has examined the impact of the composition of the diet on insulin sensitivity, insulin secretion and fat in a study of 979 adults enrolled in the Insulin Resistance Atherosclerosis Study. The conclusions are interesting and important: glycemic index and glycemic load were not related to measures of insulin sensitivity or secretion, or to the amount of fat in the body. However, in line with other research studies, the intake of fiber in the diet was again found to have beneficial effects on insulin sensitivity, adiposity and the secretion of insulin by the pancreas.
The conclusions once again show us the importance of increasing fiber in our diets, and indicate that the diets based on glycemic index and glycemic load are probably on their last legs.
The study follows one using the Dietary Approaches to Stop Hypertension (DASH) diet published in the December issue of Diabetes Care. A well-conducted randomized showed that the diet, which is rich in fruits, vegetables, and low-fat dairy foods, lowered blood pressure and has beneficial effects on blood lipids.
The real trick is to follow some simple strategies for following through with your resolutions (see my post on January 4th), and to follow a balanced diet and exercise program. I only wish that there were some magic fix for dealing with weight problems, but sadly there does not seem to be. Despite an enormous amount of research, and thousands of diet plans, what we have learned is that some people will do fine on almost any kind of diet, but not everyone will benefit, and some diets can be risky if they are not well-balanced. In my book Healing, Meaning and Purpose, I outline some simple dietary principles that I have used with thousands of people with great success for over 25 years. In a nutshell:
1. Energy balance is important
2. Calories do count
3. What you include in your diet is as important as what you exclude
4. Make only moderate dietary changes at any time: making big dietary changes can be a pretty violent attack on your body and your mind
5. Avoid the “trans-fatty acids”
6. Try to consume some omega-3 fatty acids
7. Eat fewer simple carbohydrates: that advice still holds, despite the new study
8. Use weight management strategies that enhance your overall health and well-being
9. Take more exercise
I don’t think that it can get much simpler than that. Though when someone interviewed me recently, and asked for a one-liner, I said: “Avoiding eating anything white, unless it is a prescription medicine.” Overly simplistic, of course, but simple watch words that have helped an awful lot of people. Good luck!
Technorati tags: Diet, Glycemic index, Insulin resistance
