Richard G. Petty, MD

More Genes Involved in Obesity

I am impressed by the progress being made by some of my former colleagues who are busily unraveling the complex genetics of obesity.

In a paper in the journal Science a group of British scientists including Chris Ponting of the Medical Research Council Functional Genetics Unit in Oxford and Stephen O'Rahilly’s group at the  University of Cambridge, has made a second breakthrough in twelve months in understanding how a gene triggers weight gain in some individuals. In May we looked at the first piece of work on the gene called “FTO.”

At that time we learned that variations in the FTO gene influence people's risk of becoming obese. This particular gene was of great interest because the genetic variant in FTO that predisposes to obesity is very common in the population.

About half the British population carries a copy of the variant and they are on average 3-4 pounds heaver than those who do not have it. The 16 per cent of the population who carry two copies of the variant and are on average 6-7 pounds heavier. We also learned that carriers of the variant have an increased risk of diabetes. However the function of FTO was completely unknown.

The new paper shows that the FTO gene codes for an enzyme - 2-Oxoglutarate-Dependent Nucleic Acid Demethylase - that can act directly on DNA. This strongly suggests that FTO might have a role in controlling how and when genes are turned on and off.

The investigators also found that FTO is highly expressed in the hypothalamic region of the brain, which has important roles in the control of hunger and satiety. In certain areas of the hypothalamus, the levels of FTO are influenced by feeding and fasting.

This is a remarkable finding. That a gene involved in obesity and diabetes has a direct effect on DNA in specific regions of the brain is very exciting. It suggests that the gene is involved in influencing how well the brain senses hunger and fullness. Small molecules derived from metabolism can modulate the activity of FTO, so we can see a direct link form food to metabolism to DNA in the brain.

The findings raise all kinds of treatment possibilities and also confirm something that I have been teaching for three decades: weight control does not start with a diet. It starts between the ears. Until you have been shown how to re-program your brain, thoughts and emotions, your chance of successfully controlling your weight is, ahem, slim.

Nutrition and Female Fertility

Whoever said that “you are what you eat” was not wrong. The composition of our diets can affect everything from our moods to our risk of getting some types of cancer.

Now it looks as if nutrition may also be an essential part of helping at least one type of infertility.

There are literally hundreds of causes of infertility, but one of the more common ones in women is a problem with ovulation. A rapidly growing cause of ovulatory problems is the polycystic ovarian syndrome, which is itself associated with insulin resistance.

New research from Harvard School of Public Health is published today in the prestigious journal Obstetrics & Gynecology which suggests that women who followed a combination of five or more lifestyle factors, including changing specific aspects of their diets, had more than 80 percent less relative risk of infertility due to ovulatory disorders when compared with women on more unhealthy diets.

The investigators followed a group of 17,544 married women who were participating in the Nurses' Health Study II, which is based at the Brigham and Women's Hospital in Boston. The researchers created a scoring system on dietary and lifestyle factors that previous studies have found to predict ovulatory disorder infertility. Among those factors were:

• The ratio of mono-unsaturated to trans fats in diet
• Consumption of animal or vegetable protein consumption
• Carbohydrates consumption, which included both dietary fiber the glycemic index of foods
• Dairy consumption: both low- and high-fat
• Iron consumption
• Multivitamin use
• Body mass index
• Level of physical activity

The researchers then assigned a "fertility diet" score of one to five points. The higher the score, the lower the risk of infertility associated with ovulatory disorders.

The women with the highest fertility diet scores ate:

• Less trans fat
• Less sugar from simple carbohydrates
• More vegetable than animal protein
• More fiber and iron
• More multivitamins
• More high-fat dairy products and less low-fat dairy products

The more fertile women also had a lower BMI and exercised for longer periods of time each day.

This relationship between a higher "fertility diet" score and lesser risk for infertility was similar for different subgroups of women. It seemed to hold in many different age groups, and whether or not a woman had been pregnant in the past.

The effect size is impressive: women following five or more low-risk dietary and lifestyle habits have a six fold reduction in ovulatory infertility risk compared with women following none of them.

There are two surprises here. It has been believed that heavier – though not obese – women tended to be more fertile. That is not what this study found. Second,  the higher fertility rates of women who consume high-fat dairy products and less low-fat dairy products may seem counter-intuitive. But well-nourished women would be expected to have a higher chance of being fertile.

The take home message is this: if a woman is having problems with ovulation, sensible dietary choices and a moderate amount of physical activity may make a large difference in her chance of becoming fertile.

This all makes sense. From an evolutionary perspective it could be dangerous to bear a child while ingesting foods, chemical or toxins that could harm a baby, or could compromise the health of a pregnant mother.

"Nutrition can be compared with a chain in which all essential items are separate links. We know what happens if one link of a chain is weak or is missing. The whole chain falls apart.”
--Patrick Wright (American Director of the Institute for Research on Food-related Disease)

“Health requires healthy food.”
--Roger Williams (Indian-born American Chemist who did pioneering work on the Vitamin B Complex, 1893-1988)

The Evolving Obesity Pandemic

Here is something that is not too much of a shock. At least it isn’t until you look at the numbers.

People are getting heavier throughout the world, with the possible exception of south and east Asia. These are the conclusions of a one-day global “snapshot:” a single day in 2006 when doctors and nurses in 63 countries across five continents - not even including the United States – found that between half and two-thirds of men and women in were overweight or obese.

The study is being published in the journal Circulation and included 168,159 people. The initial results were published http://eurheartjsupp.oxfordjournals.org/cgi/content/abstract/8/suppl_B/B26 last year in the European Heart Journal, but this new report puts more “flesh” on the original report.

The International Day for the Evaluation of Obesity (IDEA) study looked at two measures of fatness - waist circumference and body mass index or BMI.

A BMI (weight in kg divided by square of height in meters) of 18.5 to 25 is considered healthy. A BMI over 25 is considered overweight and greater than 30 is obese. I shall have something to say about BMI in a moment.

In Eastern Asia 7% were obese, compared with:

• 36% of people in Canada
• 38% of women in Middle Eastern countries
• 40% in South Africa

Canada and South Africa led in the percentage of overweight people, with an average BMI of 29 among both men and women in Canada and 29 among South African women.

In Northern Europe men had an average BMI of 27 and women 26. In other words they were just into the overweight “category.” In southern Europe, the average BMI was 28. In Australia BMI for men was 28 and 27.5 for women. In Latin America the average BMI was just under 28.

Waist circumference was also high - 56% of men and 71% of women carried too much weight around their middle.

The overall frequency of heart disease was 16% in men and 13% in women. In Eastern European men, many of whom still smoke, the rates of heart disease, 27%, and women, 24%. By comparison in Canada the rate of heart disease in women was 8%, and in men 16%.

The rates of diabetes varied across regions. Overall, 13% of men and 11% of women were diagnosed with diabetes.

This means that the rest of the world is catching up with the United States, long considered the country with the worst weight problem.

An estimated two-thirds of Americans are overweight and a third of these are obese. In the US, the lifetime risk of developing diabetes, is also high - 33% for men and 38% for women.

In studies like these, a BMI over 25 is considered to be overweight and greater than 30 is obese. I have commented before about the limitations of using BMI, but it remains a way of getting an overall picture of what is happening in the body.

The findings are deeply worrying.

It is well known that increasing weight, particularly the amount of fat carried inside the abdomen – not the “lovers’ handles!” - increase the risk of coronary artery disease, Type II diabetes and other diseases including some cancers. That point about the “intra-abdominal” fat I all important. For years we have been told that even small increases in weight can do us harm, but that is not completely accurate. It is where the fat is deposited, not only how much we have. It is only when people become extremely obese all over that the risks of many diseases begin to climb.

The moral of the story?

Watch you the size of your abdomen, and stay tuned as I give you more advice about the Whole Person ways to control you weight.

Dopamine, Drugs and Diabetes

We recently talked about the increasing evidence that insulin has many extremely important roles in the brain.

New research by investigators at the Center for Molecular Neuroscience and the Institute of Imaging Science at Vanderbilt University Medical Center researchers, working with colleagues in Texas, has found that insulin levels affect the brain's dopamine systems. These systems are involved in motivation, reward, salience, movement and emotional processing. Disturbances in dopamine pathways have been implicated in substance abuse, as well as schizophrenia, bipolar disorder and attention deficit hyperactivity disorder (ADHD). Drugs that interfere with the dopamine pathways may produce Parkinsonism as well as elevations of the hormone prolactin.

The psychostimulant drugs amphetamine and cocaine, as well as related medications for ADHD, block the reuptake of the neurotransmitter dopamine by dopamine transporters (DATs) thereby increasing the level of dopamine signaling. Some of these compounds also cause a massive surge of dopamine through DATs, resulting in high levels of synaptic dopamine that alter attention, increases motor activity and plays an important role in the addictive properties of psychostimulants.

The reason for examining a possible relationship between dopamine and insulin goes back to the 1970s, when it was reported that amphetamine had no effect on diabetic animals and in the 1980s it was shown that diabetic rats did not show the usual stereotyped behaviors when given amphetamine. There were also odd reports about disturbances in the enzyme dopamine-beta-hydroxylase in experimental diabetes and changes in dopamine D1 receptors in the brains of rats with induced diabetes.

These observations lead to this new research into a possible link between insulin signaling and amphetamine action.

They used a standard a rat model of type 1 diabetes in which insulin levels are massively depleted, and then assessed the function of the dopaminergic pathway in the striatum, an area of the brain rich in dopamine.

In the absence of insulin, amphetamine-induced dopamine signaling was disrupted: dopamine release in the striatum was severely impaired and expression of DAT on the surface of the nerve terminal was significantly reduced.

The lack of the DAT protein on the plasma membrane prevents the amphetamine-induced increase in extracellular dopamine, and in turn, amphetamine fails to activate the dopamine pathways that stimulate reward, attention and movement.

The researchers then gave insulin into the brains of the diabetic animals and found that the system returns to normal, indicating that the lack of insulin in the striatum directly affected amphetamine action.

They also developed a probe for brain DAT activity using functional magnetic resonance imaging (fMRI). In normal, healthy rats with plenty of insulin, amphetamine increased neural activity in the striatum. But in diabetic animals, activity in the striatum was suppressed.

So there is a powerful interplay between dopamine neurotransmitter systems and insulin signaling mechanisms. The results are some of the first to link insulin levels and dopamine function in the brain and hold several implications for human health and disease.

We need to have another look at the effect of diabetes on the brain. We have known that people with diabetes are at increased risk of cognitive impairment and depression, and we had assumed that it was because of hypoglycemia and vascular disease. Those assumptions may have been wrong.

The findings may also be important for diseases with altered dopamine signaling, such as schizophrenia and ADHD. Insulin may have something to do with the underlying brain disturbances in ADHD. Then control of insulin levels and neuronal responses to the hormone may help determine the efficacy of psychostimulants in people with ADHD.

Every now and then you see people on psychostimulant medications who need huge doses. Perhaps their problem lies with insulin rather than dopamine.

Alzheimer’s Disease: Diabetes of the Third Kind?

Insulin may have some extremely important roles in the mind as well as the body.

Though best known for its role in promoting glucose uptake into cells, insulin has at least five hundred known functions in the human body. For many years nobody was sure whether insulin was important to the brain: neurons in the brain are unusual in that they do not need insulin to enter them. But then we discovered that insulin acts on other important metabolic processes in neurons. In the brain it also does duty as a chemical messenger and as a growth factor, and brain insulin signaling is crucial for the creation of memory. Over the years a number of theorists have suggested that some neurological and psychiatric illnesses could be a result of disturbances in insulin-related processes in the brain.

It is now beginning to look as if they may have been correct.

Some recent evidence has suggested that Alzheimer’s disease and diabetes mellitus share a number of common pathways and Alzheimer’s disease is associated with peripheral insulin resistance.

New research has been published by investigators from Northwestern University in the FASEB Journal - the journal of the Federation of American Societies for Experimental Biology –  that may finally nail down the reason why insulin signaling may stop working in Alzheimer’s disease.

The research team used mature cultures of neurons from the hippocampus of the brain to study synapses – the connection between neurons - that have been implicated in learning and memory mechanisms. They wanted to examine the effect of a toxic protein, known to attack memory-forming synapses, that is called  “ADDL” for "amyloid ß-derived diffusible ligand." ADDLS are small, soluble aggregated proteins that accumulate in the earliest stages of Alzheimer’s disease. The researchers had previously found that ADDLs bind very specifically at synapses, which in turn initiates deterioration of their function, shape and composition. They now went on and studied the synapses and their insulin receptors before and after ADDLs were introduced. Regions of the nerve with normal numbers of insulin receptors have no ADDL binding, but when the ADDLs are added they remove insulin receptors from nerve cells, effectively making them insulin resistant.

And an insulin resistant neuron cannot participate in the formation of memories.

This finding implies that there is a fundamental connection between diabetes and Alzheimer's disease, and this may in turn help us to see whether existing diabetes treatments might protect neurons from ADDLs and improve insulin signaling in people with Alzheimer's disease.

The first type of diabetes is Type 1, a.k.a. insulin-dependent or juvenile onset. The second is Type 2, a.k.a. non-insulin-dependent diabetes. So is Alzheimer's Type 3?

It has also been known for some time that physical exercise is one of the factors that may help reduce the chance of developing Alzheimer’s disease, and we may now have a mechanism by which it can help.

This is an extraordinarily interesting and important discovery that should lead to a whole new research angle, perhaps with medicines that are already available.

Diabetes, Inflammation and the Heart

One of the most worrying signs in people with type 1 diabetes is damage to the nerves supplying the heart. This is called cardiovascular autonomic neuropathy, and one of its first signs is a reduction in the normal heart rate variability (HRV).

It has been known for many years that people with both type 1 and type 2 diabetes have low grade inflammation, and inflammation can have profound effects on the activity of the autonomic nervous system.

A study from Sabadell in Spain has tried to sort out these links in a study of 120 people with longstanding type 1 diabetes.

They measured a great many things including tumor necrosis factor, alpha-receptors 1 and 2, IL-6, and C-reactive protein; insulin resistance and HRV in response to deep breathing and the Valsalva maneuver" forcibly exhaling against with mouth and nose closed.

They did indeed find a link between low-grade inflammation and early alterations in the nerve supply to the heart.

This is important information: when we proposed that inflammation might be an important player in diabetes back in the 1980s, it was greeted with disbelief. Twenty years on it looks as if we might have a whole new line of treatment on the horizon, which will include nutrition and exercise as well as supplements and medications.

Insulin Resistance and Cognition

I have talked a lot about insulin resistance and the problems that it can cause. It is one of the biggest threats facing the human population, with at least a third of Americans now being insulin resistant. It looks as there may be another complication of insulin resistance that we need to add to the list.

Researchers from Canada presented some interesting data (NR385) at the 2007 Annual Meeting of the American Psychiatric Association in San Diego last month.

There has been a great deal of concern that some newer antipsychotics may cause insulin resistance and perhaps diabetes, and the FDA has required all the newer antipsychotics to carry a warning about this potential problem. We also know that although these medicines can be very effective in treating some symptoms, they do not usually help cognition very much.

The researchers recruited 37 people with chronic schizophrenia and did neurocognitive tests on them while also measuring their insulin resistance.

They found a significant correlation between insulin resistance and neurocognitive functioning. It looks as if insulin signaling is important for processing information in the brain and insulin resistance interferes with the process.

Though this study look at a highly specialized group: people with chronic schizophrenia – there is some recent evidence to suggest that insulin resistance may be a factor in Alzheimer’s disease, and that people may develop cognitive impairments if they go on to develop insulin resistance syndrome or impaired fasting glucose.

Yet another good reason for using diet, exercise and sleep to try and present insulin resistance and maintain healthy glucose levels.

Regular readers will recall that there are five pillars of healthy aging and the prevention of cognitive decline:

1. Blood pressure
2. Physical activity
3. Mental activity
4. Supplements and moderate alcohol
5. Social engagement and level mood

We should now add avoidance of insulin resistance to the list. Taken together, the evidence suggests that we can dramatically reduce our risk of cognitive decline as we get older.

Insulin, Intestinal Metabolism and Arteriosclerosis

Here is some research that provides further evidence of the links between systems of the body.

Diets high in sugar and fats can cause chronic elevations of insulin. High levels of insulin are a key feature of insulin resistance, a metabolic problem that affects at least a third of people living in the Western world and is also growing extremely rapidly in much of the developing world. Insulin resistance may be caused by a diet or genetics, or most commonly a combination of the two. It is known that insulin resistance can lead to the development of diabetes and arterial disease. The question has been how?

Almost forty years ago it was first suggested that insulin itself might be the problem. Not only is insulin involved in metabolism, it is also a potent growth factor for some of the smooth muscle cells found in the wall of major blood vessels. There has also been a suspicion that some of the metabolic effects of insulin increase the risk of arteriosclerosis by actions in the liver and intestines.

In research published in the journal Atherosclerosis, nutritional scientists at the University of Alberta have found a connection between high insulin levels and dysfunction of intestinal lipid metabolism. The finding provides critical support for the notion that impaired intestinal metabolic function plays a critical role in the development of cardiovascular disease.

Using a type of obese rat, the researchers found that excessive insulin slows the removal of chylomicrons from the blood stream following a fatty meal. Chylomicrons transport dietary fat from the intestine to the rest of the body.

Excessive amounts of insulin appear to alter the dynamics of the walls of blood vessels, allowing chylomicrons and cholesterol to build up in them. Over time this build up may creates blockages in the flow of blood.

It is good to see research that is re-examining the role of chylomicrons in vascular disease. Interest in them began to wane about twenty years ago, and since then most of the research and most of the screening recommendations have been based on cholesterol. Most doctors have been taught that cardiovascular disease is connected to increased levels of low-density lipoprotein (LDL) cholesterol, which is derived from the liver. However, fifty per cent of cardiovascular disease events occur in the presence of normal LDL-cholesterol levels. That is one of the reasons why many experts in metabolism have been saying for years that we must not forget the contribution of triglyceride and chylomicrons. This research confirms that we were right.

Although there are no accepted guidelines on this, people at risk of developing cardiovascular disease should not only have their LDL-cholesterol and HDL-cholesterol levels checked, but should also have the level of chylomicrons measured.

Technically it is not a difficult thing to do, although not all laboratories are able to do it. If chylomicron levels are high, it is an extra incentive to reduce fat consumption, and there are new medicine being tested that may help reduce chylomicron levels.

This research provides yet more evidence about the importance of the intestine in general health and disease. I constantly have people telling me that certain diets, colonic irrigation or probiotics may improve intestinal health and therefore general health and well-being. They may be correct. But what we really need is research to discover if there are viable ways of improving intestinal health that can prevent disease onset and progression.

Half the Population Has Genes to Make Them Fat

I have talked a bit about my skepticism concerning the genetic contribution to obesity, insulin resistance and diabetes.

I was fascinated to see a huge fifteen year study that has just been published in the journal Science. I felt a touch of pride: back when the earth was new, I helped train more than one of the authors.

The study involved over 42,000 people and found an association with body mass index at every age [from seven to 70] in populations throughout the UK and Europe.

Unlike previous work, it shows a very common genetic link with mild obesity rather than a rare genetic link with extreme obesity.

There were 42 scientists in the group and they found that if people carry one copy of a variant in a gene called FTO, as does half of the general population, it will lead to a gain in weight of 2.6lb or put just over half an inch on their waists and raise their risk of being obese by one third. People with two copies of this variant in the FTO gene, which is the case in one in six of the population, then they will gain almost 7lb more than those who lack the variation and are at a 70 per cent higher risk of obesity.

The researchers then tested a further 37,000 people from Bristol, Dundee and Exeter as well as a number of other regions in Britain, Italy and Finland. In every case the same variant in the FTO gene - which is mostly present in the brain and pancreas, among other key tissues - was associated with type 2 diabetes and obesity.

They also showed that in children, this particular FTO variant was associated with increased body weight.

We hope that in the future, once we have found additional obesity genes, it may be possible to offer advice based on a person's genetic make-up. We all know that folk are eating more and doing less exercise, but some people gain more weight than others. Similarly two people on the same diet and exercise plan lose different amounts of weight. There are undoubtedly some unrecognized factors in weight gain, but genes remain in the mix.

Never be disheartened if your first attempt at diet and exercise is not crowned with success: they are only two of a dozen factors that play into weight control.

Do not fall into the fatalistic trap of thinking that biology is destiny.

We are talking about a factor that may modulate the way in which we control out weight.

As promised, I shall soon be publishing a book detailing specific methods for dealing with whichever ones are important in your life.

Your future lies in your hands: not in a string of chemicals.

 

The Causes and Consequences of Insulin Resistance

I have spent so much time talking about insulin resistance becuase it is one of the greatest medical threats facing the world.

It is estimated that approximately 33% of the adult population of the United States is insulin resistant, and if left untreated many will develop diabetes, hypertension and an array of other problems. It is an epidemic that is expected to swamp most health care systems around the world, yet sadly it may in most cases be preventable.

There is an enormous literature on insulin resistance. As of this afternoon there are almost 33,000 scientific papers on the subject.

I created this graphic to try and summarize the key points about insulin resistance: the main factors that may cause it, as well as the most important medical consequences.

(Click on the graphic to expand it.)

The Main Causes of Insulin Resistance are:

• Aging
• Intra-abdominal obesity
• Inactivity
• Glucose intolerance
• Genetics
• Fetal malnutrition
• Cigarette smoking
• Some medications

The Main Consequences of Insulin Resistance are:

• Type 2 diabetes mellitus
• Hypertension
• Arteriosclerosis
• Polycystic ovarian syndrome
• Non alcoholic fatty liver disease
• Disturbances in the function of the vascular endothelium
• Elevations of triglycerides and cholesterol
• Disturbances of clotting
• Disturnaces in kidney function
• DIsturbances in one type of heart rhythm
• Elevated uric acide levels
• Some malignancies

This is probably not a complete list, but it gives you a very good idea of the reasons for looking for insulin resistance. Many - but not all - experts now recommend measuring insulin resistance in people at high risk of developing any of these medical problems.

We have good evidence that lifestyle changes can prevent the development of many of these dire consequences, so it is certainly something worth discussing with your health care provider.

Insulin Resistance in the Brain and What It Means for Dieters

Most people have been taught that increasing weight is the cause of insulin resistance, which in turn may cause an array of different health problems. That is only half true: insulin resistance may contribute to the development of obesity, and once we start gaining abdominal fat then that may indeed contribute to insulin resistance. So a vicious circle is established in which insulin resistance helps cause obesity, which in turn causes more insulin resistance.

Another thing that we have been taught for half a century that the brain is an insulin-insensitive tissue. What that means is that the uptake and use of glucose by the brain is not affected by circulating levels of glucose and insulin. That has always seemed a bit strange, because insulin is very important in cognition. Some experts believe that disturbances of insulin and closely related hormone – insulin like growth factor 1 (IGF-1) are involved in the pathogenesis of Alzheimer’s disease. 

When someone is insulin resistant, they have high circulating levels of insulin, and an obvious question is whether these high insulin levels may interfere with the normal functions of the brain. This is not a new idea. It has been known for many years that high levels of triglycerides, that may be a marker for insulin resistance, may be associated with cognitive impairment in people with type 2 diabetes.

Now colleagues in London have found that people who have peripheral insulin resistance also have brain insulin resistance especially in two brain regions  - the ventral striatum and prefrontal cortex – that are involved in appetite and reward.

It looks as if one of the reasons why people with insulin resistance become obese is that the normal link between the control of food intake and energy balance is broken.

This is yet more evidence that a simple diet will not work in the long term. If the problem is metabolic and involves damage to the mechanisms that control eating, the only way to help is to use a combined approach that deals not only with the composition of the diet, but the precise time when people should eat, and the psychological and social barriers that are left over from millions of years of evolution. I outline a comprehensive and highly successful weight management technique in Healing, Meaning and Purpose. Over the last few months I have had an enormous number of requests to expand that material into another book, and in between writing this blog, I am hard at work on completing a full account of exactly what we do to help people manage their weight.

Race and Diabetes

It’s another one of those, “Everyone knows that…” facts. For forty years we have all been taught that some ethnic groups are at higher risk of developing insulin resistance and type 2 diabetes mellitus. So now “everyone knows that” African Americans, Native Americans and people from the Indian sub-continent are all genetically predisposed to these medical maladies.

Now it looks as if "everyone" might have been wrong.

James Neel first proposed the theory of the "thrifty genotype" in 1962. He suggested that cycles of feast and famine early in human history created a gene that helps the body use scarce nutrients - a gene that leads to obesity and diabetes in sedentary modern populations with ready and continuous access to food.

Several months ago I pointed out some of the problems with the thrifty genotype theory, and why many of us have become more convinced about the concept of the “thrifty phenotype.” I have many friends, colleagues and former trainees who have dedicated themselves to hunting for diabetes genes. As early as the mid-1980s I was worried that they were going to vanish down a rabbit hole.

It seemed illogical that a gene or genes could “explain” an illness that was, until recently, very rare. It would have to be a gene that was somehow switched on and off by diet or some other environmental factors. It is certainly possible but seemed implausible, given that there are dozens of genes designed to control food intake and metabolism. But my friends the gene jockeys had the louder voice, and it was good for them to see what they could find. Now, twenty years later, more than 250 genes have been studied as possible causes of type 2 diabetes, but together these genes explain less than 1 percent of diabetes prevalence worldwide.

There is an interesting piece of research published in the journal Perspectives in Biology and Medicine by a team of researchers from the United States and Australia, that supports what I was saying. The study was co-authored by UC Irvine anthropologist Michael Montoya, an anthropologist at the University of California at Irvine, together with an epidemiologist and population geneticist. Together they analyzed existing genetic studies published across a variety of disciplines. The team found no evidence to support the thrifty genotype theory.

They also found that in most existing studies of the suspected genes that contribute to diabetes in ethnic minorities, researchers had failed to control for the potential impact of social and environmental factors. If those factors are taken into account, other factors - such as poverty, housing segregation or poor diet - were stronger indicators of diabetes than genes.

As Montoya said,

"Our study challenges the presumption that Native American, Mexican American, African American, Australian Aborigine, or other indigenous groups are genetically prone to diabetes because the evidence demonstrates that higher rates of diabetes across population groups can be explained by non-genetic factors alone. Our study shows that by focusing on genes, researchers miss the more significant and alterable environmental causes of diabetes."

One of Montoya’s co-authors, Stephanie Malia Fullerton, a population geneticist and bioethicist at the University of Washington added,

"When it comes to diabetes, we're finding that genes are no more important for ethnic minorities than for anyone else."

This new critique of genetic and ethnic studies will need to be replicated, and it is a little bit of a surprise that such important work was published in Perspectives rather than one of the journals dedicated to epidemiology.

I have no inside knowledge about why the study was published where it was. But it often happens that it can be very difficult to get new research published if it contradicts the mainstream. There have been examples of experts squashing data that contradicts their own, but it is uncommon. Most of the time the difficulty in getting revolutionary new data published is not because of some conspiracy, but because any kind of evidence, particularly if it is radically different, attracts the most concentrated scrutiny by independent reviewers.

If this new data analysis is confirmed, it is going to mean a radical re-think about the ways in which we screen, manage and advise people from different ethnic groups.

It also confirms something that I've said a hundred times: Biology is Not Destiny.

Fats, Inflammation and Depression

We have talked before about the associations between inflammation and psychiatric illnesses.

There is yet more evidence in the shape of a study just published in the journal Psychosomatic Medicine. by Janice K. Kiecolt-Glaser and her colleagues from Ohio State University College of Medicine in Columbus.

The study involved 43 older adults with a mean age of 66.67 years, and the results suggests that the imbalance of omega-6 and omega-3 fatty acids in the typical American diet could be associated with the sharp increase in heart disease and depression seen over the past century. The more omega-6 fatty acids people had in their blood compared with omega-3 fatty acid levels, the higher their levels of the inflammatory mediators tumor necrosis factor-alpha and interleukin-6, and the greater the chance that they would suffer from depression. These are the same inflammatory mediators associated with insulin resistance, type 2 diabetes and coronary artery disease, all of which are more common in depression. And depression is more common in diabetes, arthritis and coronary artery disease than expected.

Our hunter-gatherer ancestors consumed two or three times as much omega-6 as omega-3, but today the average Western diet contains 15- to 17-times more omega-6 than omega-3. There were 6 individuals in the study who had been diagnosed with major depression, and they had nearly 18 times as much omega-6 as omega-3 in their blood, compared with about 13 times as much for subjects who didn't meet the criteria for major depression.

Depressed patients also had higher levels of tumor necrosis factor alpha, interleukin-6, and other inflammatory compounds. And as levels of depressive symptoms rose, so did the omega 6 and omega 3 ratio. So it seems as if the effects of diet and depression enhance each other. People who had few depressive symptoms and/or were on a well-balanced diet had low levels of inflammation in their blood. But when they became more depressed and their diets became worse – which is very common when people are depressed – then the inflammatory mediators in the blood surged.

Omega-3 fatty acids are found in foods such as fish, flax seed oil and walnuts, while omega-6 fatty acids are found in refined vegetable oils used to make everything from margarine to baked goods and snack foods. The amount of omega-6 fatty acids in the Western diet increased sharply once refined vegetable oils became part of the average diet in the early 20th century.

Depression alone is known to increase inflammation, the researchers note in their report, while a number of studies have found omega-3 supplements prevent depression.

So this more evidence for the value of eating fatty fish like salmon, mackerel or sardines two or three times a week, but be sure to avoid fish that may contain a lot of mercury. If you add more fruits and vegetables to your diet, you will also reduce your levels of omega-6 fatty acids.

I have just finished analyzing all the new literature on using fish oils for the prevention and treatment of psychological and psychiatric problems, and I am going to post my findings in the next couple of days.

Pesticides, Weight Gain and Insulin Resistance

On this blog and in Healing, Meaning and Purpose, I have talked about some of the less well recognized contributors to obesity, including:

1. Stress
2. Salt
3. Viruses
4. Pesticides
5. Intestinal bacteria

There is some new evidence from Korea published in the journal Diabetes Care, supporting the possible contribution of pesticides to insulin resistance.

People with high levels of persistent organic pollutants (POPs) in their blood were more likely to develop insulin resistance, which may lead to type 2 diabetes. Insulin resistance may also lead to obesity, hypertension and an array of other diseases. It is well recognized that increasing amounts of intra-abdominal fat may increase insulin resistance. It is less well known that this obesity is part of a viscous circle, with insulin resistance being associated with elevated insulin levels that may cause fat to be laid down throughout the body. Once the fat is laid down in the abdomen, it can break down, releasing fatty acids and triglycerides that in turn affect the breakdown of insulin by the liver and the release of insulin by the pancreas.

Previous research by the same group found a link between POPs and type 2 diabetes. This study confirms that background exposure to some POPs, chemicals such as organochlorine pesticides and polychlorinated biphenyls (PCBs), is also associated with insulin resistance among people who do not yet have diabetes.

The researchers also found that the association between organochlorine pesticides and insulin resistance became stronger as people got fatter. However, among people who had very low concentrations of pesticides in their blood, the researchers found little association between waist size and insulin resistance.

Some studies have suggested an association between background exposure to POPs and a variety of adverse health effects in humans and wildlife. POPs can be particularly problematic because they persist for long periods of time in the environment, accumulate up the food chain, and can travel great distances through the air and water. Therefore, even people and animals that live nowhere near a place where POPs are being applied often show high levels of these chemicals in their bloodstream.

An international treaty banning a dozen of the world's most dangerous POPs has helped reduce exposures, but many harmful chemicals remain in use and even those that have been banned may linger in our environment for years to come. For example, chlordane was banned two decades ago in the United States but continues to be present at high levels in our food supply.

The researchers concluded that some POPs "may be involved in the pathogenesis of insulin resistance." They advise urgent prospective studies among those who have background exposure to POPs, which mostly comes from eating fatty animal foods. Since obesity may increase the toxicity of POPs, controlling weight could also help to reduce the impacts of these molecules.

In separate research involving mice, Frederick vom Saal from the University of Missouri in Columbia, Missouri has studied the effects of a different class of endocrine-disrupting chemicals, including bisphenol-A (BPA). Not long ago, BPA made news in San Francisco, where there was a lot of controversy over an ordinance that seeks to ban its use in children's products. vom Saal's most recent work was presented at the 2007 Annual Meeting of the American Association for the Advancement of Science (AAAS). He found that endocrine-disrupting chemicals cause mice to be born at very low birth weights and then very rapidly gain abnormally large amounts of weight: they could more than double their body weight in just seven days. Vom Saal followed the mice as they got older and found that these mice were obese throughout their lives. He said studies of low-birth-weight children have shown a similar overcompensation after birth resulting in lifelong obesity.

(Regular readers might remember the concept of the thrifty phenotype, and see how this research ties in with that concept). More research must be done to determine which chemicals cause this metabolic effect. According to vom Saal, there are approximately 55,000 manmade chemicals in the world, and 1,000 of those might fall into the category of endocrine disrupting. These chemicals are found in common products, from plastic bottles and containers to pesticides and electronics.

These chemicals are so pervasive that it is difficult to avoid them, and there is scant evidence that "detoxification" helps clear them. That being said, and depsite the lack of evidence, we recommend certified organic produce and regular mild detoxification programs, together with nutritional support and  tapping therapies.

Medication-induced Weight Gain

It is not really a surprise that medicines that are designed to have effects on emotion might also have other effects. After all, emotion originally evolved as an outgrowth of the sympathetic nervous system, which, as every student of biology knows, is involved in the "Four F's:"

• Fear
• Fight
• Flight
• Sexual activity

So if powerful medicines influence emotion, they will likely also influence one or more of these.

Cocaine and amphetamine lead to a loss of appetite for food, though I am told that marijuana makes people hungry. I do not, of course, know that from personal experience.

Many antipsychotics, mood stabilizers and antidepressants cause weight gain by an array of different mechanisms.

New research published by colleagues from Johns Hopkins has done a lot to clarify the role of histamine in the appetite problems that often occur with antipsychotics.

You may be interested in reading more here.

The conclusion? Histamine has a major role to play in antipsychotic-induced appetite increase.

But it is not the only factor in the weight gain, insulin resistance and diabetes problems that seem to bedevil some of these medicines.

Before the book comes out, I shall write some more about the ways in which the Atlanta Approach successfully - and uniquely - deals with all of those problems.

Aging and Exercise

It is a common observation that it becomes more difficult to do a lot of exercise as we get older, and the biceps no longer bulge quite as much after an hour in the gym. We have to exercise harder to get the same results.

Metabolism slows down as well, and for years it has been assumed that those events are linked: we slow our metabolism and find exercise harder because we gradually lose muscle mass.

But new research shows that it isn’t quite so simple, and the results should encourage any of us over forty to stay in the gym.

A new study published in the journal Cell Metabolism will likely help our understanding of that difficulty, as well as unlocking another of the secrets of type 2 diabetes.

As we become older, we hide more fat in our muscles and livers, and this fat has been linked to the age-related rise in insulin resistance that may go on to cause type 2 diabetes and hypertension.

A research team from the Howard Hughes Medical Institute based at Yale University School of Medicine compared the skeletal muscle of rats aged three-month-old and two-year-olds.

They found that an enzyme called AMP-activated protein kinase (AMPK) slowed down its activity in the older animals. AMPK's role in skeletal muscle is to stimulate the body to burn off fat and to provide fuel for the cells. It does this by producing mitochondria – the power packs of the cell. So AMPK activity in our skeletal muscle does at least three things: it stimulates glucose uptake, increases fat oxidation and promotes the production of new mitochondria.

It has been known for some time that the skeletal muscles of marathon runners have a much greater mitochondrial content and a greater capacity to burn fat. This is probably linked to high levels of AMPK activity.

The animals were exposed to a chemicals that produce that produce acute or chronic stimulation of AMPK. They were also exercised and some were fed more food, each of which should stimulate the production of new mitochondria.

The researchers found that the older rats had lower AMPK activity than the younger animals. In addition, the muscle of young rats who did more exercise had double the normal AMPK activity while in older rats this effect was severely blunted.

The message is this: as we age it is not muscle mass but enzyme activity that falls first. We have to work harder when trying to maintain the same benefits from exercise as we did when we were young.

We know that loss of skeletal muscle mass and function as we age is a major problem that has a significant effect on quality of life of older people. If this study is confirmed in humans it would have enormous implications. In the older rats, the AMPK activity was almost gone, implying that no amount of exercise would bring those muscles back. But it would be good to know if we can work out some other methods for bringing those enzymes back to life.

Although the paper doesn’t mention it, there is also some evidence that AMPK activity may be important in controlling feeding behavior in the hypothalamus at the base of the brain and the “stress hormone” norepinephrine plays a critical role in the way in which exercise stimulates AMPK. As we get older we usually find that our tempers are less fiery and part of the reason for that is that we produce less norepinephrine.

Start exercising early in life, and never get out of the habit. For if you do, you might lose that AMPK activity forever.

“Wholesome physical exercise reconstitutes energy, stemming the aging process, making the body light and firm, while safeguarding against fatigue and inducing cheerfulness.”
--Sushruta Samhita (Indian Surgeon who wrote the book the Sushruta Samhita, c. 6th Century B.C.E.)

“Exercise is the chief source of improvement in our faculties.”
--Hugh Blair (Scottish Presbyterian Minister and Writer, 1718-1800)

“It is exercise alone that supports the spirits, and keeps the mind in vigor.”
Marcus Tullius Cicero (Roman Political Figure and Orator, c.106-43 B.C.E.)

Juices, Cardiovascular Disease and Cancer

There was an important study that came out a few months ago in the International Journal of Food Science and Nutrition.

Investigators from Dundee in Scotland decided to look at the health benefits of fresh fruit juice. While it is widely accepted that fruit and vegetables lower the risk of some cancers and of most cardiovascular diseases, the role of pure fruit and vegetable juices has never been clear. In fact many textbooks have said that 100 percent juices play a less significant role in reducing risk for both cancer and cardiovascular disease than whole fruits and vegetables since they contain less fiber, and it had been assumed that it was the fiber that was the key to their value.

The researchers analyzed a variety of studies that looked at risk reduction attributed to the effects of both fiber and antioxidants. They found that the positive impact offered by fruits and vegetables is derived not from just the fiber but also from antioxidants which are present in both juice and the whole fruit and vegetables. Juices are comparable in their ability to reduce cancer and cardiovascular risk compared to their whole fruit/vegetable counterparts.

This research  goes a long way in demonstrating that fruit and vegetable juices may play an important role in reducing the risk of various diseases.

A study published in the American Journal of Medicine in September found that consuming a variety of 100 percent fruit and vegetable juices was associated with a reduced risk for Alzheimer's disease. Japanese American individuals who drank three or more servings of fruit and vegetable juices per week had a 76 percent lower risk of developing Alzheimer's disease than those who drank juice less than once per week. That finding seemed robust, even taking into account other potential variables. So I think that we may be able to add juices to our strategies for reducing the risk of developing Alzheimer's disease as we get older.

There is another point of importance. Some of the fad diets claim that fruit juices should be avoided at all costs, since they can cause the release of insulin, and insulin is bad. Those proclamations have usually come from people with a limited background in biochemistry or metabolism. The research shows that they were not correct. The key is balance, and as part of a comprehensive nutritional approach, juicing can be very helpful.

And a final point: careful use of juices has long been one of the "secret" components of our system of weight management.

“Drinking freshly made juices and eating enough whole foods to provide adequate fiber is a sensible approach to a healthful diet.”
--Jay Kordich (American Health Expert, Author and Lecturer, 1921-)

“If people would only stop putting into their bodies the things that are creating their physical problems, and eat a predominantly raw vegetarian diet, along with raw vegetable juices, almost all physical problems would soon disappear from the face of the earth!”
--Reverend George M. Malkmus
 (American Minister and Originator of the Hallelujah Diet, 1934-)

Chromium

When talking about chromium we’re not talking about that stuff that gets applied to metals to make them shiny.

For more than 20 years I've been interested and intrigued by its role in metabolism. This month's issue of Harvard Men's Health Watch highlights some of the research indicating possible links between chromium deficiency and diabetes, high cholesterol, heart disease and weight management.

The journal is only available for subscribers, but let me summarize some of the data for you.

Chromium exists in many forms and not all are either absorbed or biologically active. Antacids, phytates found in grains and tannins found in tea may all lower the absorption of chromium.

A point that always comes up when we discuss supplements is that some people will feel that recommended daily allowances are too low and that using larger - sometimes vast - amounts will achieve additional biological effects. There is some evidence that very large amounts of chromium may damage cells in tissue culture but very little evidence for chromium toxicity in humans. People probably vary greatly in their tolerance to chromium.

1. Diabetes: Chromium has attracted most interest because of its action on the binding of insulin to at least one of the insulin receptors. Insulin is more effective if chromium is present. Chromium also has a positive influence on one of the glucose transporters in cultured fat cells. The effects of chromium on glucose and insulin seems to vary in different species. So it is difficult to extrapolate from an animal study to humans. In people with both the major types of diabetes, the consensus seems to be that chromium supplements containing 200-1,000 mcg chromium as chromium picolinate a day have been found to improve blood glucose control. Chromium picolinate is the most efficacious form of chromium supplementation. There is a small pilot study that found that in women with polycystic ovarian syndrome, a low dosage of chromium picolinate improved glucose tolerance, but did not help with the hormonal or ovulatory disturbances. This has just been confirmed in a study using a higher dosage (1,000 mcg/day). Based on a detailed review of the literature, the United States Food and Drug Administration (FDA) has determined that chromium - at least chromium picolinate - does not reduce the risk that you might develop insulin resistance or diabetes and the American Diabetes Association agrees that the benefit of chromium supplements has not been conclusively demonstrated.
2. Cholesterol: Chromium deficient rats develop high cholesterol levels. But the evidence that chromium supplementation helps cholesterol levels in humans is thin. Chromium may also help people with diabetes to lower their cholesterol levels. The published evidence indicates that any beneficial effects of chromium on cholesterol is much smaller than the effects of diet and exercise.
3. Coronary artery disease: There is a study suggesting a correlation between chromium levels and the risk of having a heart attack, with lower levels being associated with higher heart attack risk. That does not, of course, necessarily mean that taking chromium supplements will reduce the risk of a heart attack.
4. Weight management: Despite all the advertisements, chromium supplements have not been shown to be effective in producing sustained weight loss.

There remains a possibility that some other form of chromium may be more effective on some of these parameters. There has recently been some interest in a product called Diachrome, that contains chromium and biotin. There have been several very interesting presentations about it at international meetings, but we need to see if the results pass peer review and replication.

A diet containing plenty of whole grains, nuts, broccoli, and green beans, should provide you with enough chromium. Chances are that taking a supplement will not cause harm and may perhaps help if you are at high risk of diabetes. But the evidence is still controversial.

I know of several other studies that are underway, and I shall report them to you as they appear.

But for now, when it comes to buying supplements, this is another one of those times that I say, "Caveat emptor!"

Leg Length and Cognitive Reserve

I recently mentioned the "Barker Hypothesis" which says that fetal malnutrition is associated with many physical problems later in life.

Well the difficulties may not only be physical.

I would like to tell you about an important concept that we call "Cognitive reserve." This can be thought of as our cognitive resilience. This first came to light almost twenty years ago when a post-mortem study of 137 elderly people was published in the Annals of Neurology, and confirmed something that we had suspected for years: there was a large discrepancy between the degree of Alzheimer’s disease neuropathology and the clinical manifestations of the disease. Some people had extensive pathology but they  clinically had no or very little manifestations of the disease. The investigators also showed that these people had higher brain weights and greater number of neurons compared with age-matched controls. This lead to the idea that they had a greater "reserve." This is why building your brain throughout life is thought to reduce the ce of cognitive impaitrment later on.

Studies have shown that childhood cognition, educational attainment and adult occupation all independently contribute to cognitive reserve, and more recently it has been confirmed that education and the complexity of a person's occupation may both slow the rate of decline in people who already have Alzheimer's disease.

Although height is in part genetically determined, shorter leg length has been found to be associated with an adverse environment in early childhood. In a recent study of older Afro-Caribbean people living in London, shorter leg length was significantly associated with cognitive impairment, leading to the suggestion that shorter leg length may be a marker of early life stressors that then result in reduced cognitive reserve.

It is also worth recalling our discussion about the association between growth hormone and intelligence in children and between intelligence and head size.

And nutrition is one of the determinants of growth hormone synthesis and release.

Naturally this does not mean that less tall people will all get Alzheimer's disease. But these observations have a number of practical consequences. They re-emphasize the importance of good nutrition during pregnancy: something that is simply not available to over a third of the world's population. They also help us to identify some of the people who would most benefit from strategies to increase their cognitive reserve and to avoid some of the things that can strip it away from them.

Hormonal Disturbances and Bulimia

Bulimia, more accurately called bulimia nervosa, is an eating disorder that was first described by  Professor Gerald Russell in 1977 whilst he worked at the Royal Free Hospital,in London in 1977.

There are five criteria that have to be met for someone to be diagnosed with bulimia nervosa:

1. Recurrent episodes of binge eating. An episode of binge eating is characterized by both of the following:
• Eating, in a discrete period of time (e.g., within any two-hour period), an amount of food that is definitely larger than most people would eat during a similar period of time and under similar circumstances.
• A sense of lack of control over eating during the episode (e.g., a feeling that one cannot stop eating or control what or how much one is eating).
2. Recurrent inappropriate compensatory behavior in order to prevent weight gain, such as self-induced vomiting; misuse of laxatives, diuretics or other medications; fasting; or excessive exercise.
3. The binge eating and inappropriate compensatory behaviors both occur, on average, at least twice a week for three months.
4. Self-evaluation is unduly influenced by body shape and weight.
5. The disturbance does not occur exclusively during episodes of anorexia nervosa.

It has long been known that there can be a number of hormonal disturbances in people with both anorexia nervosa and bulimia, but it has never been clear whether they are a result of malnutrition, vomiting and/or the use of laxatives and diuretics. When we were both at the Maudsley Hospital in London, Gerald and I once spent several hours talking through the possibilities of doing some collaborative work on the hormonal problems in people with eating disorders. The list of disturbances was so long that we decided that we had other priorities.

So I am fascinated to see some new research from the Karolinska Hospital in Stockholm.

Amongst the most prominent problems in people with bulimia are menstrual irregularities and increased rates of polycystic ovarian syndrome (PCOS). A Dr Sabine Naessén studied 77 women with bulimia and 59 healthy volunteers.

As expected the women with bulimia had higher rates of menstrual disturbances, hirsutism and PCOS. And in line with previous research, levels of testosterone correlated with amounts of hirsutism.

The women with bulimia also had lower bone density, particularly if their menstrual cycles had stopped or if they had ever had anorexia nervosa.

She also found an association between two common polymorphisms in the estrogen receptor (ER) β gene and bulimia. She has speculated that this genetic variation might predispose women to the development of bulimia.

Her results suggest that some women with the condition may have too much of the male hormone testosterone. Half of the people treated for this imbalance reported less hunger, and fewer cravings for fatty and sugary foods.

This is important work. It is highly unlikely that eating disorders could ever be reduced to biochemical disturbances in the brain. There are so many environmental factors, for instance sexual abuse or other types of trauma, and even social pressure, that have been implicated in the etiology of the illness.

But the key point is this: why do some people develop an eating disorder after trauma while other do not? And why do some people develop eating disorders, even when they have never been traumatized in their lives?

The answer as always lies in the ways in which genes and the environment interact. If confirmed, this research may point the way toward some new ways of helping some people with this group of illnesses.

Psychiatry Below the Neck

There is more and more evidence that schizophrenia and bipolar disorder and perhaps also major depressive disorder, are illnesses affecting the whole body and not just the brain and mind.

It has been known for over a century that some physical problems, including type 2 diabetes mellitus, obesity, cardiovascular diseases and some forms of cancer appear to be more common in people with major mental illnesses. All of this was known long before the current concerns about obesity, diabetes and some antipsychotic medicines. It is also clear that the physical problems cannot just be explained away by social deprivation and poor lifestyle choices.

The new understanding of mental illness as a systemic problem, opens up some extraordinary opportunities for treatment and perhaps even for prevention. In some new research due to be published next month, investigators have identified some abnormal proteins in the liver and on red blood cells that are similar to some abnormal proteins already identified in the brain.

These proteins are primarily involved in energy metabolism in cells and in protection against oxidative stress. The implication from this is that schizophrenia and many of the associated health problems may be a consequence of impaired energy metabolism together with damage by free radicals.

You will see why this is so exciting: it looks as if we have an entirely new way of approaching, treating and perhaps preventing the most serious of mental illnesses.

Another Nail in the Coffin of BMI

In August I outlined some of our reasons for believing that the most common measure of overweight and obesity – the body mass index (BMI) – can be very misleading and should probably be abandoned, or at least consigned to the back burner.

A team at the Hammersmith Hospital in London led by Professor Jimmy Bell has been using a novel type of MRI scan to locate the distribution of fat in the body. The problem is that 40% of the population has "bad" fat around some of their internal organs including the heart, liver or pancreas, even though many appear thin. So even though they may look slim, they may still be at risk of conditions like insulin resistance, diabetes and hypertension because of this hidden fat.

As we have said before, from a health perspective, it is the distribution of fat that is all important, rather than just the amount of it. This study confirms what metabolic physicians have been saying for years: BMI gives you the wrong idea about how much fat you have.

Once you know about the distribution of your fat, we can design precise lifestyle changes to work on it. As an example, the strategies that we use for overall weight management are not the same as the strategies that we use for reducing intra-abdominal fat. There are very good physiological reasons why diet does little to reduce the fat around organs. It is there to provide fuel during exercise, so specific exercises are the way to rid yourself of this internal fat.

At the moment there are very few centers that can do this kind of scanning, but with the growing evidence of its importance, that is likely to change. In the meantime, be aware that aerobic exercise and strength training, particularly if it involves the large muscles of the back trunk and lower limbs is the quickest way to rid yourself of these dangerous fat deposits.

Fat in itself is essential for normal health, but fat in the wrong places can be a killer. And BMI tells you nothing about the fat lurking in the hidden parts of your anatomy.

Carpal Tunnel Syndrome and Diabetes

Carpal tunnel syndrome is a relatively common neurological problem in which the median nerve is compressed in the wrist.

The classical symptoms are:

• Tingling, numbness or burning in the fingers or hand, especially thumb, index, middle or ring fingers, but not your little finger. It is most typically present on waking, but can occur after using the hands. Some people "shake out" their hands to relieve their symptoms.
• Pain radiating or extending from the wrist up the arm to the shoulder or down into you’re the palm or fingers, especially after forceful or repetitive use.
• A sense of weakness in the hands and sometimes a tendency to drop things
• Numbness, especially in the tips of the thumb, index, middle and ring fingers.
• Eventually the small muscles that control the thumb, index and middle fingers can weaken and atrophy.

In many people there is not obvious cause, although it is more common in women approaching menopause, and these days it can be one of the problems associated with using a computer mouse of keyboard for long periods. Every student of health care learns that there is a great long list of causes including:

• Pregnancy
• Rheumatoid arthritis
• Trauma
• Hypothyroidism
• Diabetes
• Amyloidosis
• Acromegaly
• Myeloma
• Tumors

Although I was taught about carpal tunnel syndrome not just as a cause but also as a predictor of diabetes more than 30 years ago, it has been forgotten by some non-specialists.

There is some new research from King’s College in London that has suggested that carpal tunnel syndrome may be a harbinger of diabetes.

As many as 20% of people with diabetes have a compression neuropathy such as carpal tunnel syndrome, and in people with limited joint mobility – a complication of diabetes - the incidence may be as high as 75%. The new research indicates that carpal tunnel syndrome may precede the diagnosis of diabetes by up to 10 years. The work was based on an analysis of 2,655 people who were diagnosed with type 2 diabetes in 2003-2004. The researchers excluded people with other known risk factors for carpal tunnel syndrome. The relative risk for subsequently developing diabetes was 1.63.

This research shows once again that diabetes can sometimes make its presence felt years before it has been formally diagnosed. A study published in 2003 found that 56% of people with peripheral neuropathy of unknown cause actually had abnormal glucose tolerance tests.

Earlier this year, researchers form the Netherlands did a retrospective review of 516 people with carpal tunnel syndrome, and found only two people with diabetes. They therefore recommended that routine screening for diabetes was not worthwhile in otherwise typical carpal tunnel syndrome.

I disagree with them.

I think that it would be wise to screen people with carpal tunnel syndrome for any disturbances of glucose metabolism, including insulin resistance, and if they are at a particularly high risk of developing diabetes, it would be worth going ahead and doing a glucose tolerance test. We don’t often do them these days, but this would be one of those times.

Hostility and Insulin Resistance

Insulin resistance – a reduction in the body’s ability to respond to insulin – is something that should interest and concern all of us. Not only are a third of Americans insulin resistant, with much higher rates in people of African and Indian heritage, but also insulin resistance is the major predictor of the development of type 2 diabetes and of coronary artery disease.

We already knew that stress and certain personality factors, including hostility can be associated with insulin resistance. Now new research  from The Cleveland Clinic in Ohio has clarified the association.

The study involved 643 men with an average age of 63.1 years, and the findings are published in the current issue of Psychosomatic Medicine.

The researchers measured the subjects' urine levels of norepinephrine. Norepinephrine is one of the objective indicators of stress. The researchers used standard rating scale – the Minnesota Multiphasic Personality Inventory and the Cook-Medley Hostility scale - to measure hostility. Insulin resistance was measured using some highly validated methods: the homeostatic model assessment index; 2-hour post-challenge glucose and insulin levels. The study had to be large because some many things can influence insulin resistance: nine other common variables had to be factored in to the analysis.

The study found that there was a statistical interaction between hostility and stress level in predicting insulin resistance. More hostile people do not always have worse insulin resistance, but they do when they are under stress, particularly if it is high level and sustained stress.

The team also found that not all components of hostility are related to insulin resistance. For instance, cynicism is a personality trait that is strongly related to insulin resistance.

We do not know if stress management techniques can reduce the risk of developing insulin resistance in these high-risk people, but it is likely that they will.

Yoga, tai chi ch’uan, meditation, psychotherapy may all be helpful. The best results of all have been to combine one or other of these with homeopathy, flower essences and spiritual counseling. We have little empirical research for these combined approaches, but a great deal of clinical experience that they may be beneficial.

If you notice that you or someone around you has a hostile, cynical way of handling stress, let them know that they are at high risk of developing a physical illness, but that there is a great deal that they can do for themselves before they fall off the cliff.

Chloroquine, Insulin and Inflammation

Your humble reporter was fascinated to read about some new research using the anti-malarial agent chloroquine as a potential treatment for the insulin resistance syndrome.

I have a personal reason for being interested. Hypoglycemia (low blood glucose) is an occasional feature of treatment with chloroquine and in 1980 a study first indicated that chloroquine might slow the break down of insulin by the liver. In the early 1980s there were a flurry of papers indicating that chloroquine did some subtle things to insulin and insulin receptors in many tissues. So we came up with the idea of measuring its effects in humans. There was a memorable occasion on which I was doing an outpatient clinic with an intravenous line in my arm. (English doctors are well known for doing experiments on themselves: I had a professor in medical school who said that you should never do to a patient what you haven’t had done to yourself. I shall leave it to you, gentle reader, to wonder if I've tried everything....).

So there I am doing my clinic when, around 11AM I begin to feel really strange: my glucose level was almost unrecordable and my insulin level was off the chart. Nothing that couldn’t be solved with a large dollop of sugar, but it made me very sympathetic to people who get hypoglycemic from their regular treatments.

Sometimes Nature does our experiments for us: we did a lot of work on diabetes because it is associated with high rates of vascular disease. So understanding the mechanisms by which diabetes does that may help illuminate some of the cellular disturbances underlying arteriosclerosis in general. We are also interested in the few illnesses in which a single disturbed gene may lead to a definable set of signs and symptoms. There is a rare illness known as ataxia telangiectasia in which sufferers have a high risk of developing some cancers particularly lymphomas and leukemia. People with the illness are very sensitive to ionizing radiation, have a specific type of immune deficiency, degeneration of parts of the brain related to muscle function and coordination and they age prematurely. More than ten years ago it was discovered that a single gene - ataxia-telangiectasia mutated (ATM) gene – was responsible for the illness. The gene is responsible for producing a protein that recognizes damage to DNA. It now seems that ATM may also be linked to metabolic and cardiovascular diseases. It does this by inhibiting a protein called JNK, a stress kinase involved in inflammation with related effects in insulin resistance and atherosclerosis. So to everyone’s surprise a gene that can cause a rare disease can also cause insulin resistance.

In the November issue of Cell Metabolism, researchers at Washington University School of Medicine in St. Louis and St. Jude Children's Research Hospital in Memphis, Tennessee report that a small dose of chloroquine eased many symptoms of metabolic syndrome in mice, reducing blood pressure, decreasing hardening and narrowing of the arteries and improving blood sugar tolerance. The results suggest we may only need very low and perhaps infrequent doses of chloroquine to achieve similar effects in humans. Both insulin and chloroquine activate the ATM gene.

This adds to the data that some of the metabolic dysfunctions triggered by obesity may be linked to the inflammatory responses that go wrong in autoimmune disorders like arthritis and systemic lupus erythematosus.

And an older treatment for rheumatoid and lupus just happens to be chloroquine.

Chloroquine itself has some side effects, but this is important information that will help us design more effective and carefully targeted holistic treatments for both metabolic disturbances and inflammatory conditions. All in all, very good news indeed.

Aerobic Exercise, Diet and Abdominal Fat

Most of us are probably aware of the difference between fat inside the abdomen – “intra-abdominal,” also called visceral fat – and fat on the hips or the outside of the abdomen. The fat inside the abdomen is associated with insulin resistance, diabetes and at least a dozen other medical problems. This fat is also covered in cortisol receptors and breaks down and reforms extremely rapidly. By contrast the fat on the outside of the body has relatively few metabolic consequences until the amount of it becomes extreme.

Excess fat in general is not a good idea, but it is the intra-abdominal fat that is the best target for treatment.

New research has shown that the addition of aerobic exercise to a standard dietary weight loss program can preferentially reduce abdominal fat in overweight people.

The investigators did a twenty week prospective study in which looked at 45 obese women with an average age of 58 years. During the study the participants bought their own breakfast in consultation with a dietitian, but had their lunch and dinner prepared by the kitchen staff of the hospital. They were either told to continue with their normal routine of daily activities, or to do low-intensity or high-intensity aerobic exercise. The investigators not only did all the standard measurement on their volunteers, they also did fat biopsies and measured the size of the fat cells.

They all lost weight, but in the people who did the high-intensity aerobic exercise, they also had a reduction in the size of the fat cells in subcutaneous tissue taken from the abdomen.

This is interesting, but it’s necessary to sound a note of caution about the experiment: the investigators were measuring subcutaneous fat cells rather than the all important intra-abdominal fat cells. The trouble with measuring those is simply getting at them. It is not easy trying to get fat out of the abdomen without some invasive procedures.

Renal Cell Carcinoma and Bread

Renal cell carcinoma (RCC) is the most common type of kidney cancer, and accounts for 2 percent of all adult cancers. It has been known for some time that diet plays a role in RCC risk, but attempts to identify which foods have harmful or beneficial effects have been inconclusive.

The smart money has been on foods that elevate insulin levels, because RCC is one of the cancers associated with obesity, and some RCC cell lines grow when exposed to insulin or insulin-like growth factors.

A new study by researchers form the Institute of Pharmacological Research "Mario Negri" in Milan, conducted a large case-control study of 2301 Italians. They found a significant association between high bread consumption and renal cell carcinoma. Eating a lot of pasta and rice may also raise the risk, while eating many vegetables may lower the risk. The study published online October 20, 2006 in the International Journal of Cancer, the official journal of the International Union Against Cancer (UICC), and is available via Wiley InterScience.

The researchers enrolled 767 adults diagnosed with RCC and 1534 controls who did not have the disease between 1992 and 2004. Two controls were matched to each case by gender, age range, and location. The researchers collected sociodemographic information, height, weight, lifestyle habits and personal and family medical history from each participant. They also administered a 78-item food frequency questionnaire which asked about the average weekly consumption for each item over the previous two years. They then performed statistical analyses to discover odds ratios (OR) with a 95 percent confidence interval.

They found a significant direct association was observed for bread consumption and a higher RCC risk. A modest non-significant risk increase was also observed for pasta and rice. On the other hand an increasing intake of poultry, processed meat, and all vegetables, both raw and cooked, all reduced the risk of RCC.

These findings confirm our guess about insulin and/or insulin-like growth factors. This association between elevated cereal intake (bread, pasta and rice) is most likely due to the high glycemic index  of these foods, leading to an over-production of insulin and insulin-like growth factors.

The inverse relationship between vegetable consumption is consistent with previous studies and may be related to their content of vitamins, micronutrients or elements such as carotenoids, flavonoids and phytosterols.

This is not a perfect study: it is limited by the fact that the interviewers who gathered each participant's information and administered the food questionnaire were not blind to who was who. But its big strengths include the sample size and the reproducibility and validity of diet information.

This study is important and speaks to the point that we have made before: a balanced diet is key, and your body does not want to be exposed to constant variations in glucose or insulin.

It also confirms all the advice that we have been offering you about what and when to eat. Click on the links to review what I have said before!

À Votre Santé!

I am a wine buff. Several years ago I did a one year training with the Wine and Spirit Education Trust which turned me from a dilettante to someone who knew how to understand the subtlety of wines from one end of a vineyard or another. Oh yes, and how to get very good wine for not many $$.

I also learned a whole range of other new skills. Ever since then I've been interested in the health consequences of drinking wine. Of course, too much of a good thing isn't. But there has been so much evidence that certain types of wine, when used in moderation, can do wonderful things for your health.

This week has seen the publications of a paper in the journal Nature, that has been described by Steve Bloom from the Imperial College Faculty of Medicine like this: "It could be the breakthrough of the year, with massive possibilities for treating human beings."

Steve is not given to hyerbole, so what has got him so passionate?

The answer is that a chemical found in dark grapes and in red wine called resveratrol, that could make guilt-free gluttony a reality.

Why is this?

Previous research has revealed the substance has anti-ageing effects in some organisms, extending the lifespan of yeast by 60%, worms and flies by 30%, and fish by about 60%.

It has also been suggested the reported health benefits of red wine may also be due to resveratrol.

When given to mice, it countered some effects of a high-calorie diet, with 60% of the calories coming from fat, improving their health and increasing their life-span. The mice showed decreased glucose levels, healthier hearts and liver tissue, and better motor function compared with the mice on the same diet but without the supplement.The chemical could not reverse all consequences of overeating - the mice did not lose any weight.

The researchers also discovered that the chemical was extending the mice's life-span. The scientists estimated resveratrol reduced the risk of death in the mice by about 31%. After six months, resveratrol essentially prevented most of the negative effects of the high calorie diet in mice.

The exact mechanism of the chemical is not yet known, but the researchers believe it may be activating a gene called SIRT1, which is linked to a family of proteins thought to be involved with longevity.

This is not yet an invitation to enjoy limitless quatities of grapes or wine: a glass of red wine has only 0.3% of the relative resveratrol dose given to the gluttonous mice.

BTW, you may be interested to know that Nature is now providing an excellent podcast based on papers in this week's edition.

Alexithymia

There is an important psychological symptom that can cause a great deal of distress, particularly in relationships. It is called alexithymia.

The Harvard psychiatrist Peter Sifneos originally coined the term in 1972 to describe people who had extreme difficulty in emotional cognition. The word “alexithymia” literally means “no words for mood.” People with this problem lacked the ability to understanding, processing or describing their feelings verbally. As a result, most people who have the problem are largely unaware of their own feelings or what they signify. As a result they only rarely talk about their emotions or their emotional preferences, and they are largely unable to use their feelings or imagination to focus and fuel their drives and motivations.

People with alexithymia seem unable to fantasize and many report multiple somatic symptoms. However, alexithymia is also associated with a number of other complaints, such as hypertension, irritable bowel syndrome, substance use disorders, and some anxiety disorders. Their speech is often concrete, mundane and closely tied to external events. So they will describe physical symptoms rather than emotions, and don’t understand that their bodily sensations are signals of emotional distress.

Alexithymia lies on spectrum: regular readers will remember some of our discussions about categorical and dimensional diagnoses. For some people it is little more than an inability to get in touch with their emotions. But at the other end of the spectrum are a number of illnesses in which alexithymia may occur, including schizoid personality disorder, posttraumatic stress disorder, anorexia nervosa or Asperger's syndrome. It is also much more common in victims of trauma.

Much has been written about alexithymia: a literature search earlier today generated over 8,500 publications.

It is still not clear what causes alexithymia. But this much is clear: in some people, there is a strong inborn predisposition to developing it, while in others it can develop in response to life events such as being raised in a low socioeconomic group with little social stimulation, trauma or chronic stress. For this reason we often talk about primary and secondary alexithymia.

Some neuropsychological studies have indicated that alexithymia may be due to a disturbance to the right hemisphere of the brain, which usually plays a predominant role in processing emotions. Other studies show evidence that there may be a deficit in the transmission of information between the hemispheres of the brain, with emotional information from the right hemisphere not being properly transferred to the language regions in the left hemisphere. Other studies have suggested that alexithymia may be related to a dysfunction of the anterior cingulate cortex a region of the brain involved in the control of attention, empathy, emotion and the anticipation of rewards.

Alexithymia can have some serious consequences. Apart from making relationships very difficult, it is more common in people who have near-fatal asthma attacks or have poor diabetic control. People with a history of alcohol abuse who have alexithymia are more likely to relapse. Alexithymia may predispose people to developing the insulin resistance syndrome.

As you can see, alexithymia can be dangerous: we have to have words for our feelings, or the feelings will express themselves though our bodies. It can predispose us to just about every stress-related illness, and even some illnesses that we don’t normally think of as stress-related. Since alexithymia is all about an ability to express emotions, it can be thought of as a social or informational disease. If we cannot inform others about our wants and needs, and if our minds cannot send us signals to say that something is going wrong, there could be a catastrophe lying in wait for us.

People with extreme forms of alexithymia can be very difficult to help using conventional medicine.

However, many people have minor degrees of alexithymia, and these can be helped by therapies designed to help them express emotions:

1. First is to become aware of the problem: I’ve had good success with asking people to keep an emotions “log book:” if they are having odd symptoms, how good are they about having appropriate emotions? I ask them to keep a note of their emotions in response to normal interactions with other people, or while watching television or a movie. If the person feels nothing while watching something really emotional, that can help him or her see that there is a problem. Simply learning to be more expressive can help mild cases: there are an array of forms of psychotherapy that can help.
2. In mild cases, we have had some good results with flower essences. There’s not a shred of scientific proof that they help, but clinically they often do. The same goes for two other helpful approaches:
3. Homeopathy: there are over a dozen remedies that may help
4. Tapping therapies

Medicine and the Transformation of Illness

Something important has been happening in the medical field over the last century. And like most important concepts, once I mention it, everyone says, “Oh, that’s obvious.” Yet I have seen little discussion of it except in an occasional book or speculative paper.

The concept is this: modern medicine has been transforming the nature of illness in far-reaching ways. There are many illnesses that once were fatal, and which have now been transformed into chronic problems. Yet most conventional health care providers are still wedded to the short-term resolution of symptoms.

Let me give you three examples:

1. The first is diabetes mellitus. There are two main types, and at least ten subtypes. Type 1 diabetes is what used to be known as juvenile onset diabetes or insulin-dependent diabetes. It usually comes on in childhood or adolescence, is associated with severe damage to the beta cells in the pancreas that produce insulin. People with this problem usually become very sick very quickly and need insulin to keep them alive. Until 1922, when the first patient was treated with insulin derived from cows, the illness was usually fatal. Insulin transformed it into a chronic illness. People were kept alive, but now we saw the emergence of diabetic eye disease (cataracts and retinopathy), disease of the blood vessels supplying the limbs, heart and kidneys, kidney failure, infections and many other chronic problems. In 1935 Sir Harold Himsworth, the father of a friend of mine, identified a second type of diabetes. He published a classic paper on his discovery of insulin resistance in 1936. This is what is now known as Type 2 diabetes, and used to be called maturity onset diabetes. This is a more chronic illness, but carries many of the same complications. The point about these two types of diabetes is not just that they have disturbances of glucose and lipid metabolism. That on its own matters little. It is the long-term consequences of the elevated glucose and lipids that causes all the problems.
2. The second is hypertension. Again, this often used to be a fatal illness. Until the invention of the sphygmomanometer most people did not know that they had high blood pressure, and most often would die of strokes. Hypertension is now also a chronic illness. The problem is not the blood pressure itself, but the long-term consequences of an elevated blood pressure. That is why most physicians are now trying to prevent the damage to the heart, eyes and kidneys, instead of just focusing on the blood pressure numbers themselves.
3. The third is Lyme disease. This is a bacterial illness that is acquired by being bitten by a tick. It is said to be the fastest growing infectious disease in the United States, primarily because we are spending more time venturing into the wilderness, and the deer population – a major carrier of the tick – is increasing in most Eastern states. Lyme disease can make people very ill. We identify acute and chronic types. The acute can usually be treated if identified quickly and if the correct treatment is given. But sometimes identification can be very difficult, and inadequate or even inappropriate treatment may lead to the chronic form. We have even seen people who have been treated exactly as the experts say, but have still developed the chronic form of Lyme disease. The biggest problem with Lyme disease is that it is a great masquerader: it can look like so many other illnesses, from multiple sclerosis and rheumatoid arthritis to chronic fatigue syndrome and syphilis.

We could pick out other examples. I have mentioned some of the problems of thinking that attention deficit disorder is just a problem with getting good grades in school. When in reality the problem is that inadequately treated ADD is associated with a range of long-term problems that occur outside of school hours.

For many years now some practitioners have been warning about the long-term consequences of symptomatic treatment alone. One of the most eloquent critics of this way of treating people is the Greek homeopath and teacher George Vithoulkas. I like and respect George, but he takes a militant view, saying that conventional treatment simply suppresses illnesses, rather than treating them. His solution is to use homeopathy for everything. He is a genius and also a natural healer, so he can probably get away with that. Most of us cannot.

So the fundamental tenets of Integrated Medicine include medical treatment to deal with the acute problem, but a combination of approaches to prevent the problem from becoming chronic. Or if it has become chronic, then how to change its course over time.

As I’ve said before: Combinations are Key. Not randomly giving an antibiotic as well as a homepoathic remedy, but precisely tailoring the combination to the individual.

Glycemic Index Revisited

If you are anything like me, you probably find loads of adverts in your mailbox for magical ways to lose weight, either by using some form of the Atkins diet, manipulating cortisol (it doesn’t work), or by paying attention to the glycemic index of the food that you eat.

Last January I summarized some of the recent research that showed that 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, the intake of fiber in the diet was found to have beneficial effects on insulin sensitivity, adiposity and the secretion of insulin by the pancreas. I went on to give some uncontroversial advice on how to eat.

Nobody thought that the glycemic index issue was dead: insulin and the other hormones involved in fat and carbohydrate metabolism are powerful and have multiple roles in the body.

A study published in the Archives of Internal Medicine in July, helps further refine our understanding about glycemic index. High carbohydrate foods with a low glycemic index are the best way to reduce your risk of cardiovascular disease. The problem is that you want to avoid sudden surges in glucose after you eat a meal. What normally happens is that those surges are accompanied by sudden rises in triglycerides and insulin. The three together can cause all kinds of mischief to the insides of your blood vessels. High protein and low glycemic index diets will help with weight, but it’s only the combinations of high carbohydrates with low glycemic index that reduces the risk of vascular disease.

My redoubtable Web Mistress, Carol Kirshner, has found a most useful resource at the University of Sydney, that you can use to help guide your food choices.

This is such a useful resource that we are going to attach it to our blogs and websites.

However, it’s essential that we don’t get seduced by the idea that high carbohydrate/low glycemic index eating is the solution to all of our ills.

We still need to follow the basic principles of a balanced diet:

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 violent attack on your body and your mind
5. Avoid the “trans-fatty acids”
6. Try to consume some Mercury-free 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.
10. Make it a goal to gradually reduction your overall intake of cereals

Thrifty Genes, Thrifty Bodies and the Barker Hypothesis

“They have sown the wind, and they shall reap the whirlwind.”
--The Bible (Hosea, 8:7)

In 1962, a geneticist named James Neel first proposed a “thrifty gene” theory to explain why 60% of adult Pima Indians living in the United States have diabetes, and 95% are overweight. Neel’s theory was that populations like the Pimas, that have for millennia relied on farming, hunting and fishing for food, would experience alternating periods of feast and famine. Neel hypothesized that in order to adapt to these extreme changes in caloric needs, people developed a “thrifty gene” that allowed them to store fat during times of plenty so that they would not starve during times of famine.

A similar theory was advanced to explain the high rates of diabetes in people from the Indian subcontinent, once they are exposed to plentiful supplies of food. These was traced by the great Diaspora from central Asia at the end of the last age, when the ancestors of modern Indians and Pakistanis made the great trek through modern Afghanistan into the Indus valley. A journey that had been impossible at the height of the Ice Age and which was still difficult. The idea was that people who could quickly lay down a lot of intra-abdominal fat would have a huge survival advantage.

This is an attractive hypothesis, but here have always been some problems with it:

1. The gene or genes would have to be able to work with the environment: the Pimas of Mexico and people living in rural India do not have the high rates of diabetes and obesity
2. Despite looking for over 40 years, no such gene has yet been found
3. If the thrifty gene is so advantageous, why doesn’t everyone have it?
4. Until recently, famines were rare and usually occurred every 100-150 years. As John Speakman has pointed out that would mean that most human populations have experienced at most 100 famine events in the course of their evolutionary history
5. Famines do increase mortality but only in about 10% of the population
6. In famines most people die of disease rather than starvation, and the worst affected are the young. Having a “thrifty gene” would not help them survive starvation OR disease
7. Simple genetic models would suggest that famines would not provide enough selective advantage and there has not been enough time for a “thrifty gene” to have penetrated the population

There could yet be some complex genetic model involving “reserve” genes that appear when needed, or some epigenetic inheritance, but we have no evidence for that either.

A second concept is gaining a lot of traction. It is what is known as the “Thrifty phenotype,” and is part of a larger theory called the “Barker Hypothesis.” I’m going to stick my neck out, and predict that David Barker may receive the Nobel Prize in medicine for his discoveries. They are that important.

Essentially the Barker Hypothesis suggests that in addition to genetic, epigenetic and environmental factors in disease, there is another, and that is the intrauterine environment. The idea is that if a mother is malnourished, she can modify the development of her unborn child. From an evolutionary perspective, her body is preparing the unborn child to survive in an environment where food is in chronic short supply, resulting in the “Thrifty phenotype:” smaller body size, lower metabolic rate and a propensity to be less active.

The problem is this. If you are born with the thrifty phenotype and actually grow up in an affluent environment, you are more likely to develop obesity, diabetes and vascular disease later in life. If true – and virtually all the evidence suggest that it is – then it has serious implications for countries that are transitioning from sparse to better nutrition, and may have contributed to some of our current health problems. Many of us were born to mothers who had poor nutrition, either because of the Great Depression, the Second World War, poverty, or just plain poor information about good nutrition during pregnancy. And now we are reaping the whirlwind.

The hypothesis has become sophisticated. If you are born small or premature, then your liver and kidneys may not have completed their final growth spurt, which might predispose you to metabolic problems and hypertension.

The story of how this all came to light would be worthy of Sherlock Holmes himself. English counties used to have people who were responsible for providing midwifery services. In the county of Buckinghamshire a single midwife collected data for almost thirty years. Information about the mother, the length and weight of the baby and the weight of the placenta. Information that would be impossible to collect these days. Some civil libertarian somewhere would probably dream up some way of hiding this enormously important information.

David Barker discovered these extraordinarily good records, and then set about finding the adults that these babies had become. And what he found has changed medicine: babies who had small placentas – a good measure of being small or premature – were more likely to develop obesity, diabetes or hypertension as adults. Then he and others turned their attention to other early physical characteristics and found correlations with health later in life. The highest risk of coronary heart disease was seen amongst people who were born small and became heavier during childhood.

The practical implications?

Find out your own birth weight and anything else that you can about your early development.

If you were a very large baby (bigger than nine and a half pounds), it implies that your mother may perhaps have had a metabolic problem. If you were small (less than five and a half pounds), then you should get the regular health checks that we recommend for anyone in a “high risk” group.

BMI R.I.P.

For experts in metabolism, we have long worried about the over-emphasis on the use of body mass index (BMI) as the arbiter of a "healthy" weight. It is one of those measurements that is in some senses too easy, and the results are deceiving. I regularly see people claim that a certain BMI will "predict" the risk that someone will develop cardiovascular disease or diabetes. The truth is very diferent.

There are two ways to calculate your BMI:
1. Metric system - Kilograms and Metres
[Your weight] divided by [Your height squared]

2. Imperial System - Pounds and Inches
[You weight] divided by [Your height squared] times 703.5

A person is said to be healthy if his or her BMI is between 18.5 and 24.9.

The trouble with this is that the calculation lumps together fat and muscle: a muscular six foot tall football player weighing 300 pounds and with 3% body fat, would have an "unhealthy" BMI of 26.3. That is clearly absurd, and one of the reasons that most experts use BMI only as one part of an evaluation of health.

Our scepticism has been confirmed by an important study from the Mayo Clinic in Rochester, Minnesota, and published in this week's issue of the medical journal The Lancet.

The researchers looked at 40 studies involving 250,152 patients. Their analysis revealed that people with a BMI of 30-35 were at lower risk of cardiovascular disease than those whose BMI was below 20.

BMI does not correlate well with fat. A better way to distinguish between fat and muscle is to take a cross-sectional view of the abdomen, and to focus on the waist-hip ratio.

A separate study by researchers at the London School of Hygiene and Tropical Medicine of 14,833 people over the age of 75 was published in the American Journal of Clinical Nutrition. They also came to the conclusion that BMI is a poor indicator of health in both men and women in this age group. These researchers also agreed that waste-hip ratio was a better indicator of mortality risk.

This is all music to my ears. For almost three decades we have been teaching about the importance of  different stores of fat and the limitations of the BMI calculation. It has been known since the 1940s that gaining weight on the hips, or developing "lover's handles" are only very weak predictors of diabetes and vascular disease: it is the intra-abdominal fat that is the problem.

There are particular problems with using BMI in the elderly and in some ethnic groups, especially people from the Indian sub-continent and Japan.

The bottom line?

BMI is misleading, and in some age groups and races, grossly misleading.

Much better to use weight and waist-hip ratio.

And BMI only if there is a space on the medical forms where they still need to have it filled in.

 

Insulin Resistance, Polycystic Ovarian Syndrome and Sleep Apnea

Polycystic ovarian syndrome (PCOS) is a common endocrine disorder that affects between 5-10% of women in the Western World. It is a leading cause of infertility, and although the underlying cause is still speculative, it is very heavily associated with insulin resistance.

There was an International Consensus Workshop sponsored by the European Society of Human Reproduction and Embryology and the American Society of Reproductive Medicine came up with this set of criteria. PCOS is present if a woman has at least two out of three of:

1. Oligoovulation and/or anovulation (ovulating only occasionally or not  at all)
   
2. Excess androgen (male sex hormone) activity
3. Polycystic ovaries (which needs a gynecological ultrasonography) and other causes of PCOS are excluded

There is still a great deal of debate about the precise way to define the syndrome. We are currently preparing a scholarly article on the subject and our literature review has included over three thousand papers.

The combination of an excess of the male (androgenic) hormones and insulin resistance can cause an array of symptoms apart form the menstrual disturbances and infertility, including:
Central obesity
Acne
Hirsutism, while at the same time experiencing alopecia
Skin flaps and dark patches of skin, usually on the neck or in the armpit
Sleep apnea

It is the last of these that I would like to highlight today.

A new study by Dr. Esra Tasali and her colleagues from the University of Chicago has found that in women with PCOS, sleep apnea is, as expected, associated with high fasting insulin levels. Sleep apnea might worsen the metabolic consequences of insulin resistance.

Regular readers may recall that I highlighted the association between insomnia, insulin resistance, weight and diabetes a couple of months ago. Here we have yet more confirmation of this link.

Not getting enough sleep – for any reason - can play havoc with your metabolism. It seems that in women with PCOS, it’s really easy for a vicious circle to become established:
Insulin resistance -> weight gain -> sleep apnea -> insomnia -> more insulin resistance -> more weight gain and so on.

It is important for everyone to know about this association, because chances are that you know someone with PCOS and/or sleep apnea.

Measuring Insulin Resistance

After doing so much research, lecturing and writing about insulin resistance, I have constant requests for more information on how to measure it in clinical practice. This is not an academic exercise: it is estimated that a person on the road to developing type 2 diabetes may have been insulin resistant for as long as twelve years before the disease is diagnosed.

In high-risk populations, there is a lot of value in regularly checking plasma glucose, but the problem is that once glucose begins to rise, it implies that the pancreas can no longer keep up with the demand for insulin and that we may be passing the point of no return.

These are the most common questions that I get::

1. Should you be having your insulin level measured?
2. Should you have your insulin resistance measured?
3. What’s normal?

First, measuring insulin levels themselves is not of much value: they bounce around a good deal in the course of a day, and many things can alter your circulating insulin levels.

Second, accurate measurement of insulin resistance is an expensive and cumbersome procedure involving intravenous sampling of blood and in some cases also giving intravenous insulin.

Third, there is no such thing as “normal.” Results derived from any kind of test are a “reference range.” This means that they show how a result related to a large group of apparently healthy people. This is an important concept. I often have students say, “What’s normal?” There is no such thing. Blood tests help and guide us but can only be understood in the context of the whole person.

We never treat a laboratory value: we treat people. You may be interested to have a look at an earlier article about this important issue.

But all is not lost: we do have a blood test that can be used to guide us. We don’t have evidence to suggest that we should be using it to screen the whole population for insulin resistance. Instead it is a test to help guide us in high-risk populations. The test is called the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR).

The original paper was published by a group of experts form the university of Oxford in 1985. The drawback of the HOMA-IR is that it is a mathematical model, and it’s only as good as the accuracy of an individual laboratory’s insulin assay.

Since then, the HOMA-IR has been used in epidemiological studies such as the famous Framingham study and there has been a lot of work on trying to correlate the HOMA-IR with other measures of insulin resistance. There are now over one thousand papers that reference it, and we have had a great deal of experience in using it in our studies of insulin resistance in people with mental illness.

Apart from research, we only use the HOMA-IR as a guide in high-risk individuals. A simultaneous fasting glucose and insulin are taken.

Insulin resistance (HOMA IR) =
Fasting insulin (µU/ml) X Fasting glucose (mmol/l) divided by 22.5.

Most studies now suggest that the cut-off for insulin resistance should be 1.7; although some have been slightly more forgiving, and suggested that up to 2.5 may be acceptable. But remember that the HOMA-IR is only giving us an estimate to help with the overall evaluation of a high-risk individual, and we do not treat a laboratory value.

If the value is above 2.5 many experts would suggest intervention if there are also features of the insulin resistance syndrome. The key interventions are diet and exercise, both of which have been proven to reduce insulin resistance. A very interesting approach adopted in two European studies has been to treat high risk people with a medication called metformin, and were able to show that within a year several cardiovascular risk factors improved.

Gall Bladder Disease and Insulin Resistance

When I was a young student, everyone learned that gallstones were more common in people who were “Fat, female, fair and forty.” As you can see we lived in different times and nobody would say anything quite like that today. Not least because it’s now only partially correct. Gallstones are occurring at ever-earlier ages, because they are a recognized complication of obesity. And we all know that we are in the midst of a pandemic of overweight and obesity.

We have also been remarking on the number of people with bipolar disorder who have a history of gallstones.

For many years now, the explanation for the link has been to do with an increasing levels of cholesterol, which are a major precipitant of gallstones. There’s also evidence that high carbohydrate diets increase the risk of gallstones. Weight loss reduced the risk of developing them, though suddenly losing a lot of weight with an unbalanced diet may increase the risk of gallstones.

Now a paper from colleagues at three medical schools has just been published this month, and it helps clarify the connection. The conclusion of the scientists is important: insulin resistance itself seems to cause problems with the normal emptying of the gallbladder, and that would predispose people to the development of gallstones.

Insulin resistance is a feature of increasing weight. Several studies that have found increased rates of insulin resistance in people with bipolar disorder implying an increased risk of gallstones. Though gallbladder disease didn’t show up in a recent study from some friends in Toronto, I could not find any systematic studies of gallstones and bipolar disorder. And it is a study that needs to be done.

So there’s a tip for a researcher who can’t think of a project!

There's More to Weight Than Meets the Eye

There's an interesting article about the associations between obesity and mental illness.

We've all become so used to people telling us about the physical consequences of carrying extra weight, so it is interesting to learn that obesity may also be associated with higher rates of mental illness. We have here a typical chicken and egg problem.

Do people become depressed because they are overweight, or does depression and its treatments cause obesity? The answer is probably "Yes." It is both.

Depression may cause insulin resistance and hypercortisolemia, which may result in weight gain. But insulin resistance alters the kinetics of some of the amino acids that are the building blocks of key neurotransmitters in the brain.

And this study re-emphasizes the importance of treating the physical, psychological, social, subtle and spiritual aspects of a problem simultaneously. If we address only one of these dimensions, people will continue to suffer needlessly.

When our clinicians see overweight people with depression or bipolar disorder, they start by treating the mood disorder, but then immediately get to work on the weight problem. And all of it is part of the five vector, or five dimensional approach to treatment: physical, psychological, social, subtle and spiritual.

If we fail to respect and work with every aspect of a person, each problem will return to make us respond appropriately.

After all, illnesses are like any other problem: sent to educate us. Not just you, but also the person to whom you went for help.

Insulin Resistance, Diabetes and the Timing of Meals

At a meeting of the American Diabetes Association in June 2006, Professor Markus Stoffel from the Eidgenossische Technishe Hochschule in Zurich and Rockefeller University in New York, received the Outstanding Scientific Achievement Award for his extremely interesting and important research on the molecular mechanisms involved in the developmental insulin resistance.

This may sound as interesting as watching paint dry, but in actual fact the research is supremely practical, and may lead to a complete re-working of some commonly used dietary strategies.

Many physicians have not yet been taught that the liver is the key organ involved in the genesis of insulin resistance and of type 2 diabetes mellitus. Up to 90% of the glucose circulating in your blood has come from your liver. As the liver becomes less sensitive to the actions of insulin, it starts producing more glucose, particularly after meals. This in turn causes blood glucose to rise and with it insulin levels. One of the other consequences of insulin resistance is that the liver stops storing triglycerides, which then start circulating, while at the same time storing other types of fat, leading to what we call, not surprisingly, fatty liver. Or in the dog Latin that doctors use to confuse the general public, hepatic steatosis.

When we are fasting, the liver switches on banks of genes that produce the enzymes responsible for oxidizing fatty acids to produce fuel.

The main objective of a balanced diet is to maintain balance: we want to avoid sudden swings in glucose, fatty acids or insulin: it is these sudden changes that can cause inflammatory changes in blood vessels and in the liver and may lead to some of the circulatory problems that are such distressing complications of diabetes. We want to try and keep our insulin levels smooth and low. The best way not to do that is to have frequent high calorie snacks and to eat late at night. The best way is to follow the plans that I’ve talked about before. Eat little and often, keep the balance of nutrients just right, and be aware of the exact times at which you eat. Nothing except a little protein in the 2-3 hours before you retire for the night, and go very easy on alcohol, which can wreck your metabolism.

“The secret of life is balance, and the absence of balance is life's destruction.”
--Hazrat Inayat Khan (Founder of the Sufi Order of the West, 1882-1927)

Technorati tags: Insulin resistance Diabetes mellitus Fasting Weight management

Migraine and Bipolar Disorder

Back when the world was new, I cut my teeth in migraine research, and migraine and other headaches were the topic of my first book. So I’ve always kept an eye out for new developments.

There’s an interesting case report from India, about a nineteen year old who developed mild mania as part of the aura or warning of his attacks. This sort of case is interesting for what it might be able to teach us about each illness. It is also good for us to know that bipolar disorder is highly co-morbid: it is associated with many other illnesses apart from migraine:
1.    Anxiety disorders
2.    Substance abuse disorders
3.    Attention deficit disorders
4.    Personality disorders
5.    Impulse control disorders
6.    Eating disorders
7.    Insulin resistance
8.    Obesity
9.    Diabetes mellitus
10.  Cardiovascular diseases
11.  Pain disorders

This is why diligent clinicians are always on the lookout for bipolar disorder: if it is missed and remains untreated, it can cause havoc: suicide attempts, damaged relationships, substance abuse and general misery.

Migraine is one of the vascular headaches that is occasionally associated with an array of other vascular problems, like Raynaud’s phenomenon, ischemic heart disease and stroke. But the aura is something else altogether. For many years it was thought that the migrainous aura was a result of a reduction in blood flow to regions of the cerebral cortex. Almost 25 years ago that was shown to be inaccurate. It is due to a release of witches’ brew of excitatory and inhibitory amino acids in the cortex. It is highly likely that the release of excitatory amino acids is the explanation for the manic symptoms.

Migrainous mania is evidently rare, but apart from visual disturbances, I’ve seen all sorts of strange auras: sudden food cravings; intense sweating; extreme irritability and many other things besides.

The treatment of migraine still revolves around avoidance or modulation of triggers, pain relief and prophylaxis. The big change in recent years has been the increasing amount of experience and small amount of evidence indicating the value of non-pharmacological approaches like spinal manipulation, temporomandibular joint adjustment, acupuncture, the tapping therapies and homeopathy.

To an integrated practitioner, the key is to understand the problem as more than just headache: we can guide a person to see the problem in its broader context, as a challenge designed to find a path toward inner wellness. We also see it as a process that has meaning and purpose and is a Divinely inspired invitation to grow spiritually and as an individual.

That may sound a lot for a headache, but it is the best possible way to triumph over the problem!

“The cure of the part should not be attempted without treatment of the whole.”
--Plato (Athenian Philosopher, 428-348 B.C.E.)

Technorati tags: Migraine Bipolar disorder Insulin resistance Attention deficit disorder AnxietyIntegrated medicine

How Many Angels Can Dance on the Head of a Needle? Moving Beyond the Metabolic Syndrome

I have written a great deal both on this blog and in scholarly articles, about insulin resistance and the insulin resistance and metabolic syndromes.

You will have noticed that I’ve always used the term insulin resistance syndrome.

This is not a matter of semantics. For years now I’ve been worried about the splitting that’s been going on in the field: we currently have six sets of definitions of the metabolic syndrome. And apart from the fun of going to all those conferences in exotic parts of the world, you have to ask what’s been achieved by these ever more divisive attempts to “define” the medical consequences of insulin resistance.

The American Diabetes Association has begun to promote the concept of “cardiometabolic risk.” The Association has established a national Cardiometabolic Risk Initiative (CMRI) to stress the association between diabetes, heart disease and stroke. The idea of introducing this umbrella term is to help people better understand and manage all diabetes and cardiovascular risk factors, and to side-step some of the controversy surrounding the definition of insulin resistance or metabolic syndrome and which cluster of variables are in and out.

A new Cardiometabolic Risk (CMR) Calculator to help us evaluate an individual’s risk of diabetes or vascular disease should be available by the end of the year.
The formula already includes factors such as:
1.    Body mass index
2.    Waist circumference ratio
3.    Fasting plasma glucose
4.    HDL-cholesterol
5.    LDL-cholesterol
6.    Triglycerides
7.    Apolipoprotein B
8.    Blood pressure
9.    C-reactive protein
10.  Age
11.  Sex
12.  Race/ethnic origin
13.  Family history
14.  Tobacco use

Part of the reason for this new initiative is the discovery that pre-diabetes, or impaired fasting glucose, where plasma glucose levels are 100-125 mg/dl, is associated with a high prevalence of cardiovascular disease risk factors such as obesity, hypertension and dyslipidemias.

The person who first proposed the insulin resistance syndrome, a.k.a. syndrome X, a.k.a. metabolic syndrome, is Gerald Reaven who first recognized the syndrome in a landmark paper in 1988. He recently gave a lecture entitled; “Insulin Resistance Versus Metabolic Syndrome: Different Names, Different Concepts, Different Goals.” I am in complete agreement with his basic proposition, which is that insulin resistance explains the clustering of all of the components that make up the metabolic syndrome. So Gerry’s position is that there’s no point in trying to make a diagnosis of metabolic syndrome: everything is due to insulin resistance.

So instead of wasting time and resources in trying to diagnose metabolic syndrome, it is much better to understand the pathophysiology: what is going on at the molecular level, how these processes produce risk factors, and whether we can predict others. We should identify and treat each of the underlying processes and the complications of insulin resistance. If we are going to have a syndrome, it should be called insulin resistance syndrome.

And let’s stop these academic debates and get on with the job at hand: there is a 600% variation in peoples’ ability to have insulin transport glucose into cells. More than half the US population is destined to develop at least some degree of insulin resistance, so we need to look for better ways to identify people who have it, and to apply the principles of integrated medicine to keeping them healthy.

Technorati tags: Insulin resistance Insulin resistance syndrome Metabolic syndrome Cardiovascular disease Hypertension Inflammation Hyperlipidemia Weight gain Integrated medicine

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

Another Controller of Appetite and Weight

We recently discussed the role of cytokines in modulating appetite and energy balance. Now a study in mice has shown that animals deficient in interleukin-18 (IL-18) develop a voracious appetite, very marked obesity and insulin resistance. The insulin resistance is secondary to the obesity that was induced by increased food intake and occurred in the liver as well as muscle and fat.

When the little creatures were given recombinant IL-18 their food intake returned toward normal.

Only recently discovered, IL-18 is an important regulator of innate and acquired immune responses. The fact that a modulator or immunity and inflammation has a key role in feeding and in energy metabolism shows us once again just how closely all these systems are tied together. You lose weight when you are sick or depressed because the body is battling the illness. As you recover, the body needs to replace everything that was lost and re-establish your resilience. These systems don’t just exist in humans, they are found in all mammals and even some birds and fish. So they have evolved over millions of years and we need to be very careful about tinkering with these complex systems. Or of allowing stress or environmental toxins to compromise these protective mechanisms.

This finding may well pave the way not just for new pharmacological approaches to weight management, but also to some non-pharmacological approaches.

Technorati tags: Cytokines Weight management Insulin resistance Interleukin-18 Inflammation

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!

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