Richard G. Petty, MD

Testing for Diabetes in Children

Diabetes mellitus can be a devastating illness, especially when it comes on suddenly in a child or adolescent. In young people it is usually so-called Type 1, or insulin-dependent diabetes, an autoimmune disease in which the immune system attacks the insulin-producing beta cells in the pancreas. The disease can have a major impact on the whole family, and sometimes people forget the way in which it can affect siblings whose needs often need to be subordinated to the needs of the newly diagnosed young person.

And here is an important point: even when it appears suddenly, the disease process may have been going on for some time before the clinical symptoms appear. By the time that blood glucose levels begin to rise, it usually implies that the damage to the insulin-producing cells in the pancreas has reached a critical point, and the chance of recovery is low. Anything that we can do to prevent the disease from progressing to the point of producing symptoms would be immensely helpful, and that starts with early recognition before the pancreatic damage has reached critical.

Although we now understand a great deal about the interplay of genetic, environmental and immunological factors that may lead to the illness, this knowledge has so far not helped us very much. There has been a tremendous need to try and identify the early stages of the disease, but that goal has been elusive.

In a study published in the Journal of Immunology researchers from the University of Queensland's Diamantina Institute for Cancer, Immunology and Metabolic Medicine, are developing a simple test that may predict whether a child will develop Type 1 diabetes. They have identified a cellular pathway known as NF-kappa B that is activated in certain blood cells – monocytes and dendritic cells - of people with Type 1 diabetes.

In healthy people monocytes remain quiescent unless they are activated by an infection or other stressor. Then the NF-kappa B pathway gets activated.

In people with Type 1 diabetes things work the other way round: monocyte NF-kappa B was already activated in the blood, and when exposed to infection the pathway shut down. This tells us that there is a problem of immune control that may cause diabetes to develop in children. It is this monocyte abnormality that will hopefully form the basis of a diagnostic test.

This work is assuming more urgency since there are several trials of diabetes vaccines underway, and if successful, it may become possible to identify and intervene in children at risk of Type 1 diabetes before it occurs.

In addition, understanding why the immune system loses control before the disease starts should open up a number of new options for prevention and treatment.

Judah Folkman R.I.P.

I just heard that Judah Folkman just passed away at the age of 74. That is a name that is not widely known outside the scientific world, although a couple of years ago an excellent book –Dr. Folkman’s War - was written about him and his work.

His major work and his enduring legacy was in the field of angiogenesis: the production of new blood vessels. In the 1960s he came up with the idea that a way to kill tumors was to starve them of the blood supply that they need to survive. He was initially ridiculed, but history is now proving him correct. I got to know him twenty years ago after publishing a paper in which I described the discovery of a growth factor that is involved in the production of new blood vessels at the back of the eye in people with diabetes. Judah was very supportive and we had many good discussions about the potential role of angiogenesis not only in tumors and diabetic retinopathy, but also in diseases like rheumatoid arthritis and psoriasis.

Last November, at the 12th Annual Society for Neuro-Oncology Meeting in Dallas, researchers from the University of Virginia and several other leading brain tumor centers in the United States presented data on the successful use of an inhibitor of angiogenesis in the treatment of glioblastoma multiforme (GBM), the most common form of primary brain cancer. It is hard to treat, and if it recurred after surgery, radiation and/or chemotherapy there was often not much to be done.

Building on Judah’s work, they wanted to see if they could inhibit vascular endothelial growth factor (VEGF) that has an important role in the disease. VEGF fosters the growth of a tumor by stimulating the growth of new blood vessels to feed it. According to earlier studies, bevacizumab (BV) (Avastatin), a humanized monoclonal antibody that specifically targets VEGF, in combination with irinotecan (also called CPT-11) could have a role in recurrent glioblastoma multiforme. The researcher was an attempt to establish the clinical benefit of BV, both alone and in combination with CPT-11, in a multicenter, randomized phase II trial.

The results were very promising, substantially exceeded the pre-specified thresholds set for this work.

They looked at 6-month progression-free survival (PFS) defined as no clinical or MRI tumor growth and the objective response rate (ORR), which measures tumor shrinkage. Secondary endpoints included safety and survival. Response assessments were conducted by an independent radiographic facility that did not know which patients had been treated. All patients were followed for 24 weeks to determine efficacy and safety.

When taking BV, 35.6 percent of patients on average had a 6-month survival with no progression of their cancer, and an objective response rate of 21.2 percent on average.

The combination of BV and CPT was even more effective, with results of 51 percent and 34.1 percent, respectively.

The investigator group found similar results when they evaluated the patients. Those results showed that 44.7 percent of patients on average had a 6-month survival with no progression of their cancer, and an objective response rate of 38.8 percent on average. The combination therapy yielded results of 60.9 percent and 46.3 percent, respectively.

The surviving patients have remained in the study and are still being treated and followed, so we shall be seeing some longer-term results in the future.

In the United States bevacizumab has already been approved for the treatment of metastatic colon cancer and most forms of metastatic non-small cell lung cancer.

This is very encouraging research and a fitting tribute to a genuine medical pioneer.

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.

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.

It's Not the Food, It's the Size of the Plate

I grew up in a culture where the aftermath of the Great Depression and the Second World War meant that every child was expected to eat everything on their plates. That created a bit of a problem when I first moved to the United States: my conditioning led me to try and eat every morsel of those huge American portions. Fortunately I quickly noticed the impact on my waistline.

I love simple but practical and important experiments. I have just read about some very nice research from the University of Calgary in Alberta, Canada that fits the bill. It appears that simply using plates and cereal bowls with markers for proper portion sizes can help obese patients with diabetes lose weight. As a result, some can even decrease their use of glucose-controlling medications, according to a report in the Archives of Internal Medicine.

Between 1960 and 2000, the proportion of U.S. adults who were obese increased from 13.4% to 30.9%.  There is clearly an association between type 2 diabetes and obesity although it is not quite as simple as saying that obesity causes diabetes, at least not until the obesity becomes extreme. But we have known for half a century that calorie restriction may improve blood sugar control in diabetics, partially by contributing to weight loss.

The enormous increase in obesity has closely paralleled the explosion of portion sizes of both food and soft drinks.

The researchers conducted a six-month controlled trial of commercially available portion control plates and bowls in 2004. The plates were divided into sections for carbohydrates, proteins, cheese and sauce, with the rest left open for vegetables. The sections approximately totaled an 800-calorie meal for men and a 650-calorie meal for women. The cereal bowl was designed to allow a 200-calorie meal of cereal and milk. The subjects consisted of 130 obese patients with diabetes with an average age 56, half of whom were randomly assigned to use the plate for their largest meal and the bowl when they ate cereal for breakfast. The other half of the participants received usual care, which consisted of dietary assessment and teaching by dieticians.

At the end of the six-months, 122 patients remained in the study. Individuals using the portion-control dishes lost an average of 1.8 percent of their body weight, while those receiving usual care lost an average of 0.1 percent. A significantly larger proportion of those using the dishes - 16.9 percent vs. 4.6 percent - lost at least 5 percent of their body weight.

In addition, at the end of the six months, 26.2% needed a decrease in their diabetes medications compared with 10.8% in the control group.

These results are important: a 5% weight loss has been shown to be clinically significant in terms of decreasing morbidity and mortality associated with obesity-linked disorders.

Simple, straightforward and very practical.

Try it!

T’ai Ch Ch’uan and Your Feet

One of the worries about getting older is that aging can adversely affect our balance and increases the chance that we can slip and fall. This is even more of a problem in people with loss of sensation in the soles of the feet due to diabetic peripheral neuropathy and other diseases. T’ai Chi Ch’uan has previously been shown to improve balance in healthy elderly adults.

A new study from the Biomedical Engineering Program, Milwaukee School of Engineering, Milwaukee, Wisconsin was just published in the journal Diabetes Technology and Therapeutics. 

The aim of the study was to see if T’ai Chi improved both balance and sensory perception in the soles of the feet in healthy elderly adults and elderly adults with diabetes and sensory loss in the feet. Eighteen elderly people with a mean age of 73.1 years were tested for sensation and balance before t’ai chi training and again after 6 months of weekly sessions. Participants were grouped by their initial scores on tests of sensory perception, in order to calculate the effects of t’ai chi on sensory perception.

Plantar (soles of feet) sensation results showed that all the participants showed significant improvement in sensory ability with the 6 months of t’ai chi training. All groups also had a general improvement in all balance measures, with the greatest improvement seen in those subjects with large sensory losses. Hemoglobin A1c measurements – a standard way of estimating control of blood glucose - also decreased as a result of the intervention.

The study was small, but the effectiveness of t’ai chi training as a method of improving plantar sensation and balance in elderly adults with sensory loss, with and without diabetes, was impressive.

Another one of those things that is supposed to be impossible!

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.

T’ai Chi Ch’uan and Diabetic Health

Regular readers will know that I am a great fan of t’ai chi ch’uan and qigong. I have been recommending them to people for years and even taught it for a while.

I have also been very interested in metabolic problems, particularly insulin resistance and diabetes.

So I was intrigued to see a study  from Taiwan that was just sent to me.

The trial involved thirty-two people with type 2 diabetes mellitus who participated in three hour-long tai chi sessions once a week for 12 weeks. The conclusions were that practicing t’ai chi might help improve one component of immune function and also improve the control of blood glucose.

The researchers found statistically significant reductions in levels of glycosylated (glycated) hemoglobin in the blood of participants, indicating improved long-term blood glucose control. Glycosylated hemoglobin or HbA1c reflects the average blood glucose over the last 8-12 weeks, implying that the improvement must have been quite swift.

They also found increased numbers of regulatory and killer T cells. This may be important: people with diabetes are at considerably increased risk of getting infections.

It is even more impressive that the study was published in the journal Diabetes Care, that is known for its exacting standards.

If you or a loved one has diabetes, you may want to think about taking up t'ai chi.

Good luck!

Avandia and Heart Attacks: Hold Your Horses

The report in today’s New England Journal of Medicine about an apparent association between Avandia (rosiglitazone) and heart attacks made the front page of USA Today.

While it is an important study, it is important that we don’t go overboard until we have a little more information.

There is a key principle that we have looked at before: one study is rarely enough to prove that a thing is so. The scientific method is based on the principle of falsifiability: now that this data has been published it is up to scientists and investigators to try and disprove the finding.

The analysis in the New England Journal suggests that the risk of a heart attack increases by 43% for patients taking rosiglitazone compared to control groups, and the risk of death by heart attack by 64%. This data comes from the so-called “A Diabetes Outcome Prevention Trial” (ADOPT). This is one of three studies on the topic. The Diabetes Reduction Assessment with Ramipiril and Rosiglitazone Medication (DREAM) study that involved over 5,000 patients was published in the Lancet last September. This study showed small increases in cardiovascular events compared to controls, which were not statistically significant. The other key finding of the DREAM study was that it reduced the risk of progression of pre-diabetes to type 2 diabetes by 62%. That is important because it may mean that we need much longer studies: diabetes increases the risk of heart disease year after year. ADOPT involved more than 4000 patients, with the only significant relevant finding an excess of congestive heart failure episodes for rosiglitazone-treated patients compared with people who received the older diabetic medicine, glyburide (22 compared with nine events).

So there may be a signal there, but before stopping the medicine, we need to remember that the numbers of patients who developed problems is small. Obviously big enough if you are one of them, but the risk is still not that high given the high rates of heart diseases in people with diabetes.

There is another study on the horizon: The Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes (RECORD) trial, which is a phase III trial specifically designed to analyze cardiovascular events connected to use of rosiglitazone. The study that hit the front page is a meta-analysis, and even the authors admitted that there were some weaknesses in it. Though it is a personal choice that people have to make with their clinicians, many experts think that we can wait for the results of the third study so that we can make some sensible decisions.

And for the record, I have no connections with the manufacturer of Avandia, GlaxoSmithKline.

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.

 

Linking Depression, Diabetes and Alzheimer’s Disease

It has been known for many years that Alzheimer's disease and depression are associated with type 2 diabetes. Good control of blood glucose may reduce the risk of developing Alzheimer’s disease and depression, while treating depression may improve metabolic control.

Decreased levels of brain-derived neurotrophic factor (BDNF) have also been implicated in the pathogenesis of Alzheimer's disease and depression, and animal models have suggested that BDNF may play a role in insulin resistance.

So a group of scientists at The Centre of Inflammation and Metabolism, Department of Infectious Diseases at the University of Copenhagen in Denmark, decided to see whether BDNF plays a role in human glucose metabolism.

In the first study they looked at 233 people and found that BDNF was inversely associated with fasting plasma glucose, but not with insulin. In a second smaller study they did what are known as hyperglycemic and a hyperinsulinemic-euglycemic clamp studies, that allowed them to look at the relationships between BDNF, glucose and insulin. What they found was that output of BDNF from the brain was inhibited when blood glucose levels were elevated.

So it seems that low levels of BDNF accompany impaired glucose metabolism. Decreased BDNF may be a factor involved not only in dementia and depression, but also in type 2 diabetes, and it may be the missing link that explains the way in which the three conditions cluster together in epidemiological studies

This link between a chemical produced in the brain and diabetes is not altogether unexpected. The French physiologist Claude Bernard demonstrated that stimulation of the fourth ventricle of the brain caused glucose to rise, and it was later found that opiates put into this region of the brain could do the same thing.

This study reinforced the close links between metabolism and the brain, and gives us another reason for recommending that as we get older we must ensure that out glucose remains stable and that we do not become depressed.

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.

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.

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.

Chiropractic Treatment and Diabetes?

There is an interesting, thought still preliminary, article in the Journal of Vertebral Subluxation Research about the possibility that chiropractic manipulation may be able to make a valuable contribution to an overall program of wellness to help people with diabetes.

There is a case report of an insulin-requiring person with type 2 diabetes, whose diabetes stabilized as he had a short course of chiropractic manipulation. I've seen many such cases with acupuncture and homeopathy as well as osteopathic and chiropractic manipulation. But it has always been very difficult to tell if there was a causal relationship.  Diabetes is such a variable group of illnesses that something as simple as stress reduction or a person sleeping better can both help normalize glucose levels, as least for a while.

What I really liked about the article was the measured tone: the editor makes it clear that it's an interesting observation but that it's still early days. Nothing so irritates people in conventional medicine than wild grandiose claims that some treatment or other can cure everything.

The editor also calls for more research, and I totally agree. I've spent the last 25 years trying to get research moving in the fields of complementary, alternative and Integrated Medicine, and we have already had a decent level of success in getting many projects funded and completed.


“The simple exercise of stretching helps to counter the congestions, compressions, and adhesions which obstruct the flow of the vital force through the spinal column with its sixty-two branching nerves and thus to regain energy. This truth of the need of spine-loosening movement is instinctively known by every dog and cat, every lion and tiger, for they apply it immediately after awakening from sleep. The back, the legs, and even paws are bent and stretched and even rolled by them in this natural exercise.”
--Paul Brunton (English Spiritual Teacher and Author, 1898-1981)

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.)

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!"

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.

Multiple Sclerosis and Vitamin D

I have commented before that the increasing rates of multiple sclerosis as we move away from the equator has lead to speculation that it might have something to do with lack of sunlight and therefore reduced production of vitamin D in the skin.

A lack of vitamin D may also explain the increased rates of both type 1 and type 2 diabetes, as well as cluster headache at higher latitudes.

Vitamin D is not a single vitamin, but is instead a group of fat-soluble prohormones as well as the metabolites and analogues of these substances. There are two major forms of vitamin D: D₂ (or ergocalciferol) and D₃ or cholecalciferol. Vitamin D₃ is produced in skin exposed to sunlight, specifically ultraviolet B radiation. Very few foods are naturally rich in vitamin D, and most vitamin D intake is in the form of fortified products including milk and cereal grains.

It used to be that we all made plenty of Vitamin D simply by being outside in the sun, but our time outside has been steadily falling since the beginning of the Industrial Revolution, and there are the increasing concerns about exposure to sunlight and some skin cancers.

Vitamin D is involved in many critically important chemcial reactions in the body, and Vitamin D receptors are found in cells in most organs in the body, including the brain, heart, skin, gonads, prostate, and breast. Apart from its effects on regulating calcium and phosphorus, Vitamin D is involved in maintaining the integrity of cell membranes and in modulating the immune system. There is some evidence that a modest increase in Vitamin D intake may reduce the risk of colon, breast and ovarian cancers.

There is a risk of overdosing with Vitamin D. The U.S. Dietary Reference Intake Tolerable Upper Intake Level (UL) of vitamin D for childern and adults is 50 micrograms/day (2000 IU/day). In adults, a daily intake of 2500 μg/day (100,000 IU) can, over a period of weeks and months, produce toxicity  and, if taken for years, as little as 50 to 75 μg/day (2000 to 3000 IU) can produce toxicity.

In this week's issue of the Journal of the American Medical Association, there is an important report that endorses everything that we have been saying. Researchers from several prominent institutions in the United States have examined the hypothesis that higher levels of 25-hydroxyvitamin D are associated with a lower risk of multiple sclerosis.

The study confirmed the hypothesis: the risk of multiple sclerosis (MS) fell as blood levels of the vitamin rose.

The researchers uncovered 257 cases of MS among more than seven million military personnel who had given blood samples to the US Department of Defense.

Amongst white personnel, there was a 41% decrease in MS risk for every 50 nanomoles per litre increase in 25-hydroxyvitamin D, the key form of the vitamin found in the blood.

Those whose vitamin level was in the top 20% had a 62% lower risk of MS than those whose level was in the bottom 20%.

The researchers found no such association among black and hispanic personnel, but this could be a reflection of the smaller size of these sample groups.

This new research ties in with other work that has shown that Vitamin D supplements can prevent or favourably affect the course of a disease similar to MS in mice, as well as evidence that if you live in the Northern Hemisphere, being born in May is associated with a lower risk of MS than if you were born in the winter. If you are born in May, your mother will probably have been exposed to more sunlight - and therefore have produced more Vitamin D - during the later part of pregnancy when the final development of the nervous system takes place. Or alternatively you may have had a heathy dose of sunlight in the weeks immediately after your birth.

It is most likely that the Vitamin D helps by modulating the immune system and suppressing autoimmune reactions caused by specialised T helper 1 cells attacking myelin, the insulating material that sheathes most nerves. It is these attacks that are thought by most experts to play a key role in the development of MS.

If confirmed, the finding suggests that many cases of MS could be prevented or its severity reduced by increasing our levels of Vitamin D.

The data also confirm a point that we have made before: we should not be aiming to "boost" our immune systems, but to "modulate" them.

If you see an advertisement for some potion that is supposed to boost your immune system to help you ward off colds, the flu or something more serious, be suspicious: if the seller does not know the  difference between boosting and modulating, it would be best to move on.

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.

Consequences

We have a new little kitten and this morning, despite trying to keep her in the house, she scooted outside and then ran into the local feline bully. The poor little creature came in with a nasty scratch on her ear, and perhaps the understanding that the world can sometimes be a scary place. We had tried to advise and guide her, put sadly she had to learn for herself that there can be unpleasant consequences from running outside.

Similary we all want the best for our children and the people around us, but sometimes we can do them harm if we don’t help them understand the consequences of their actions.

We teach children how to cross the road, and later on, how safely to drive a car and deal with dangerous or exploitative people. We can’t live their lives for them, but we can try to help them understand the consequences of their actions.

Sometimes this important gift fails to materialize when a child or other loved one is struggling with a chronic illness.

Let me explain.

During my clinical career I dealt with two groups of clinical problems in which the biggest difficulty was not diagnosis, but helping people to stay on the treatment that they needed. The two problems were diabetes and psychiatric illnesses. By treatment, I certainly don’t just mean taking medicines: I mean being able and willing to follow a course of action.

There are dozens of reasons why people decide against taking the treatment that they need, whether it’s surgery, medication, psychotherapy or homeopathic remedies.

• Some people don’t see the point of treatment: they are happy as they are even if the illness is causing unseen damage
• Others just forget their treatment
• Others don’t like the side effects, or they are frightened that they may get side effects
• People worry about stigma and about being seen as somehow different
• There are even a few who like being ill: not just the experience of, say, having lots of extra energy, but being cared for and looked after. I have known people who have spent 40+ years in bed, sometimes with quite minor problems.
• Some just deny that they are ill: The extent of the denial can be amazing.

I saw an article on the BBC this morning about a young woman who believes that she went blind from the complications of diabetes because she “rebelled” as a teenager and was probably in denial.

It reminded me of a young woman whom I was once treating. Her metabolic control was becoming worse and worse. She was getting blurred vision and she was rapidly gaining weight. Her mother became extremely indignant when I asked – very, very gently - if the young woman might be pregnant. The patient and her mother vehemently denied the possibility. Less than a month later - on Christmas Eve - I had to arrange for the teenager to have emergency laser therapy on her eyes for severe diabetic retinopathy. Four weeks later she gave birth to a healthy, but very large baby girl. Both mother and daughter were in denial until the very end, and mother did not want to help the daughter face the consequences of failing to treat her diabetes or the pregnancy.

I’d like to give you two other examples of failing to face consequences.

In the first, a family saw me on television and asked me to see their son. He had a major neurological illness, did not want to take medicine, and It turned out that he had already seen some of my colleagues in my department. The parents wanted me to force him into taking medicine.

The second involved someone with attention deficit disorder (ADD) who could not remember to take her treatment or to follow through with any of the therapies that we recommended. Her parents wanted us to treat her. After a while it became impossible, because she had no interest in being treated.

But here is the point. The young man with the neurological illness had something progressive. He could not yet be declared legally incompetent, but he could not see that without treatment he would become very sick. The young woman with ADD also had a potentially progressive illness and was on a slippery slope. Not that the ADD was becoming worse, but because the behavioral consequences of the illness were leading her into more and more risky behaviors.

In each case the parents wanted doctors and other therapists to “Do something.” Yet in each case the parents were probably the only people who could help their kids.

What do I mean by that? Some parents enable their children to avoid the consequences of refusing treatment. I asked the young man’s family what they did if he refused his medications? The answer was that they yelled at him. Yelling helps nobody. But they were aghast when I suggested that his treatment should be linked to having “privileges” at home.

If he truly genuinely needs help, and he can’t see it, sometimes the best way forward is for the person to have to face some consequences.

Whether or not he took his treatment, he might get yelled at, but after that he could go to his wing of the house, watch TV, play on his computer and order food. No consequences. I suggested linking TV watching to participation in treatment. The family would not countenance it. They wanted to displace all the responsibility onto other people who should tell him what to do. Yet they had unwittingly sabotaged every attempt at treatment in several countries.

Treatment is a matter of discussion and agreement. And yes, of course, mentally competent people have a right to turn down treatment. But if they cannot see the consequences of their folly, then family and friends may be the only people with the leverage to help them.

Every one of us has wants and needs. If someone is stuck, then those wants and needs can help us to help them. This isn’t a matter of being coercive: it is sheer practicality.

The young man with the neurological problem saw no need for treatment because his every wish was being fulfilled: he even had servants waiting upon him. The young woman with ADD was probably not safe to be driving around in a car, yet her parents gave her one and paid for the gas and insurance anyway. They did not link treatment with providing all those things. So she saw no need to be treated.

Nobody wants to mean to a person suffering from an illness, but sometimes we need to mobilize all the resources that we have to help a person. It is entirely a matter of being pragmatic. The person saying, “Force my son to take his medicine,” is obviously speaking out of frustration. No clinician can or should do such a thing. Confrontation will scuttle any chance of setting up a therapeutic alliance with someone.

We do have some techniques for helping people. One very promising approach that we have been using is called motivational interviewing, and there are others. But even those will have little value unless people can see the advantages of treatment and the consequences of not being treated.

The best way of staying motivated to do something like stop smoking or manage your weight is to combine the advantages of taking action with the disadvantages of staying where you are.

If you know someone who has a real problem and is refusing help, ask if there is anything that you can do help motivate them to face the consequences of what they are doing. It can sometimes be the kindest and most loving thing that you can do for someone.

Diabetes in Indigenous Peoples

The BBC is today carrying a story BBC NEWS | Health | Diabetes 'threat' to indigenous. about a report presented at a diabetes conference in Melbourne, Australia.

Those of us in the metabolic field have been acutely aware of the burgeoning problem of abdominal obesity and Type 2 (non-insulin dependent) diabetes in many of the indigenous peoples of Asia, the Pacific, Australia and the Americas, in part a consequence of Western diets and sedentary lifestyles: Diabetes was unknown in the Pacific before World War II.

The combination of genes for insulin resistance, that were valuable during evolution, with extraordinary environmental changes is the culprit.

There are up to eight million new cases of diabetes across the world each year and it is predicted that around 250 million people will be affected by 2050.

The main reason for being so worried about the diabetes is not the disturbance in glucose itself, but the complications of Type 2 diabetes that include an increased risk of heart disease, stroke, eye and kidney disease.

Some experts are predicting that the scourge of diabetes could wipe out some indigenous groups. On the other hand, urgent action now could quickly reverse the trend.

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.

Shock Waves and Diabetes

A psychiatrist friend once called me to say that he knew that he had to change his job. He was in the second year of his Freudian training analysis, and as he was driving to work he experienced a severe pain in the back. He told me that it felt as if someone had put a knife in his back. This, he told me, was a psychosomatic reflection of the mean back stabbing environment in which he was working. “Tell me more about the pain,” I said. “Just like a knife,” he said, “it’s the most obvious example of my body telling me what’s going on here.” I suggested that he should come over for me to give him a physical check up, but he was having none of it.

The following day he passed a large kidney stone.

It’s important to listen to your body, and to try and understand its message. It’s also important to respect every aspect of your being: physical, psychological, social, subtle and spiritual. A physical pain may be telling you about something in your environment or it may just be telling you that there’s something wrong with your body. Sigmund Freud once famously remarked that “Sometimes a cigar is just a cigar.”

I was reminded of this story as I was reviewing a new report about an association between the use of sound waves – lithotripsy - to shatter kidney stones and the eventual development of diabetes. Approximately 10 percent of men and 5 percent of women under the age of 70 will experience a kidney stone.

Surgery for kidney stones used to be horribly traumatic. As a very young student and junior doctor I assisted in more than one operation to remove them. The invention of the lithotripter – a device that uses ultrasound to break up stones, so that they can be passed out of the body – was a big advance. Though the treatment itself is far from being painless, it is much better than major surgery, It is a shame to learn that the treatment is not as innocuous as we thought. This is important, because about 1 million people in the United States have had shock wave lithotripsy (SWL).

In a study published in the May issue of the Journal of Urology, researchers at the Mayo Clinic followed up on a group of 630 patients who had been treated with SWL in 1985. The Mayo was one of the first centers to use the technique, the hospital keeps wonderful records, and so it was one of the few places in the world where it was possible to follow people 19 years after treatment.

Almost 60 percent of the patients responded to a questionnaire and were matched to an equal number of patients whose kidney stones had been treated by some other method. Among the SWL group, 16.8 percent had developed diabetes, compared with 6.7 percent of the control group, and 36.4 percent had high blood pressure compared with 27.9 percent of the control group. According to the study, the development of hypertension was related to the treatment of stones in both kidneys, while the onset of diabetes bore a relationship to the number of shocks administered and the intensity of the treatment.

This makes sense: the kidneys are key controllers of blood pressure, and it has long been known that stones, inflammation, infection or vascular disease in the kidneys can cause elevated blood pressure. Perhaps the treatment scars the kidneys. And it is not surprising that sound waves powerful enough to shatter a stone might also cause damage to the tissues through which they are passing; which include the pancreas.

These findings will need to be replicated, particularly with newer model lithotripters. But even before that, I’m sure that the criteria for gets the treatment will be modified, and it will also be necessary to re-think how the treatment is done. As an example, instead of shooting one powerful burst of sound waves at the stone, it may be necessary to fire several low intensity burst from different directions that all crisscross in the vicinity of the stone.

For now, if you are one of the unlucky ones who gets a kidney stone, discuss this new research with your doctor before having lithotripsy. And if you have access to a good acupuncturist, naturopath or homeopath, ask them if they have had any success in treating kidney stones, and if “Yes,” whether they would be prepared to work with your physician to help you.

Laughter is The Best Medicine

“Time spent laughing is time spent with the gods.”
--Japanese Proverb

In the book and movie Anatomy of an Illness, Norman Cousins reported how he overcame a sever arthritic condition with a combination of huge doses of vitamin C, together with a positive mental attitude and hours of laughing at Marx Brothers movies. He wrote that, "I made the joyous discovery that ten minutes of genuine belly laughter had an anesthetic effect and would give me at least two hours of pain-free sleep. When the pain-killing effect of the laughter wore off, we would switch on the motion picture projector again and not infrequently, it would lead to another pain-free interval."

I’ve had a longstanding interest in the vascular endothelium, the single layer of cells that line blood vessels. Some very small blood vessels consist only of endothelial cells. These cells form the interface between the blood and the tissues, and they are involved in many disease processes. They are involved in diabetic vascular disease, arteriosclerosis, inflammation, many infections, and they play a role in the spread of tumors. There is some new evidence that laughter is good for you in more ways than one.

Investigators from University of Maryland School of Medicine found that watching a funny movie had a healthy effect on blood vessel function, allowing them to expand and contract more effectively in response to changes in blood flow. But watching a mentally stressful movie, like a war drama, may have the opposite effect, causing the vascular endothelial cells to narrow and restrict blood flow. On average, artery diameter increased by 22% during laughter and decreased by 35% during mental stress.

This work follows on from earlier research that showed an inverse association between sense of humor and coronary heart disease: people who laughed a lot seemed less likely to suffer form heart disease.

There is a very nice review article available online that confirms what is intuitively obvious humor and laughter may have a positive influence on health and on the outcome of many diseases.

There may be something to the old saying, "You don't stop laughing because you grow old; You grow old because you stop laughing.”

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.

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

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

The Passing of the Crazy Diamond

You may have heard of the passing of Syd Barrett, one of the founding members and creative drivers of Pink Floyd. He was only 60 years old.

His extraordinary creativity is well known: his fingerprints were all over the early performances and albums, and he was a muse to a generation of performers. I remember everyone’s consternation as his behavior became progressively more erratic between 1967 and 1968. I was very young then, but we all loved the music.

Some blamed his psychological meltdown on his consumption of prodigious amounts of LSD and all manner of other trendy chemical amusement aids. But in hindsight, he was probably suffering from a psychotic illness, and he was either self-medicating, or the drugs pushed him over the edge. Without doing a full evaluation, I could not say for sure. Although it’s now a moot point, several things make me think that he had a psychotic illness:
1.    His startling type of creativity before and in the early stages of his illness.
2.    There are clues suggesting that he already had problems before become obviously unwell.
3.    The chronicity of his problems are not at all like drug-induced psychosis. I saw a man in Australia who told me that all his years of psychosis were the result of a single “bad trip” in the 1960s. Unlikely.
4.    He suffered for years from diabetes mellitus. Diabetes may be as much as twice as common in people suffering from schizophrenia and bipolar disorder, and also in their first-degree relatives. (England’s first chess grandmaster, Tony Miles, who sadly had a psychotic episode in the late 1980s, also struggled with diabetes for many years, and died at the age of only 46.)

Why does any of this matter now?

If you ever see a young person abusing drugs, be aware that it is not necessarily that he or she is being impulsive or has just fallen in with a bad crowd. It may be that they are self-medicating.

People with major mental illnesses are at increased risk of many other physical illnesses, not all of which are a result of poor lifestyle choices. If you in contact with someone struggling with mental illness, anything that you can do to help them look after their physical health is all to the good.

And finally, a favorite song of mine that was written about Syd. According to legend, by a strange coincidence he arrived at the Abbey Road studio un-announced, at very time that the song was being recorded. It was nice that he was well enough to come and listen.

Remember when you were young, you shone like the sun.
Shine on you crazy diamond.
Now there's a look in your eyes, like black holes in the sky.
Shine on you crazy diamond.
You were caught on the cross fire of childhood and stardom,
blown on the steel breeze.
Come on you target for faraway laughter, come on you stranger,
you legend, you martyr, and shine!

You reached for the secret too soon, you cried for the moon.
Shine on you crazy diamond.
Threatened by shadows at night, and exposed in the light.
Shine on you crazy diamond.
Well you wore out your welcome with random precision,
rode on the steel breeze.
Come on you raver, you seer of visions, come on you painter,
you piper, you prisoner, and shine!

Technorati tags: Syd Barrett Pink Floyd Psychotic illness Diabetes mellitus Substance abuseSelf-medication 

Systemic Psychiatry

“Once a disease has entered the body, all parts which are healthy must fight it: not one alone, but all. Because a disease might mean their common death. Nature knows this; and Nature attacks the disease with whatever help she can muster.”
--Paracelsus (a.k.a. Theophrastus Phillippus Aureolus Bombastus von Hohenheim, Swiss Physician and Alchemist, 1493-1541)

It is usually a mistake to try and look at an illness in isolation.

We are all human beings, and physical challenges affect the whole organism, as well as our mind, our relationships and our spiritual connections.

There is currently a very hot area of research that is still unknown to most people: even to most people working in psychology and psychiatry. This hot new area proposes that schizophrenia, bipolar disorder, major depressive disorder and autistic spectrum disorders, are disturbances affecting the whole body, but with prominent effects in the brain and on emotion and behavior. This may help provide one part of the explanation for why people struggling with chronic mental illness - and their relatives - suffer from an array of physical illnesses that cannot be explained by stress or poor lifestyle choices alone.

You can find a brief review with a stack of references here.

This idea of psychiatric problems being generalized systemic disturbances that have their primary effects on the brain and on behavior is important to the general themes of this blog. We are always interested in looking beyond the obvious causes, to a dynamic integrated vision of a person that includes every part and every dimension of his or her being. If we want to help people recover from illness, to triumph over adversity, and to use challenges as springboards to transcend themselves and the limits placed upon them, it is only possible if we take account of the whole person.

Perhaps we can reduce mental illnesses to disturbances in cell membranes or a few chemicals in the brain. But I do not think so. It is more accurate for us to be thinking about a perturbation or disturbance in the Informational Matrix that underlies the subtle systems of the body, that in turn support the biochemical reactions that provide the structure for the external expression of life itself.

We live in very interesting times.

“Good timber does not grow with ease. The stronger the wind the stronger the trees.”
--Willard J. Marriott (American Businessman and Founder of Marriott Hotels, 1900-1985)

Technorati tags: Schizophrenia Bipolar disorder Diabetes mellitus Phospholipid Cell membrane Systemic illness Informational matrix 

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

A Breakthrough in the Pharmacological Treatment of Diabetic Retinopathy

One of the most distressing complication of diabetes is damage to the retina of the eyes. It is more likely to occur in people with poor metabolic control, but no diabetes sufferers seem to be totally immune from it. But there is no question, that in contrast to some diabetic complications, the level of blood glucose is closely related to the risk of getting retinopathy.In people of working age living in the Western world, diabetes is the number one cause of blindness, and blindness is twenty times more common in people with diabetes than in those without it.

It is such a major problem, that I had the privilege of spending several years working on the problem at the Royal Postgraduate Medical School in London, and diabetic retinopathy was a key part of my doctoral dissertation.

So if something new turns up, I always prick up my ears.

Well, we do seem to have something new. The trouble has been that there are complex mechanisms underlying the effects of diabetes on causing complications like retinopathy. At the American Diabetes Association's 66th Annual Scientific Sessions in Washington, DC Eli Lilly announced on June 11th, that a study headed by Aaron Vinik of The Strelitz Diabetes Institute at the Eastern Virginia Medical School, in Norfolk, Virginia of a new medicine called ruboxistaurin, almost halved the rate of the development of diabetic retinopathy over a two year period. This is astonishing, though it is important to point out that the medicine did not abolish the problem, and it was funded by the manufacturer. The medicine works by a completely new mechanism. In people with diabetes, high levels of glucose are one of the triggers of a cascade of chemical reactions in the cells of the retina, that turn on a chemical messenger called protein kinase C-β.

Though this is only a first study, and the medicine does not help with diabetic neuropathy, this is a very promising finding. Not least because most of us have failed to achieve much benefit from unorthodox medicine. I have colleagues who tell me that they have helped people with retinopathy with homeopathy and different kinds of electrical stimulation, but I’m just not sure how good those other treatments are. My guess is that if they were really effective, that independent research foundations would be falling over themselves to do research on them. But I could be convinced otherwise!

Ruboxistaurin, added to psychological, social, subtle and spiritual approaches is already looking like a very promising option for preventing problems.

Technorati tags: Diabetes mellitus Diabetic retinopathy Protein kinase C ruboxistaurin Integrated medicine

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,

A Rainy Day Question

“Millions long for immortality who do not know what to do on a rainy Sunday afternoon.”---Susan Ertz (a.k.a. J.R. McCrindle, Anglo-American Novelist, 1894-1985)

I was reminded of this quip while reading some new material about the progress being made in aging research. Speaking at the annual meeting of the American Association for the Advancement of Science in St. Louis, biologist Shripad Tuljapurkar who holds the Dean and Virginia Morrison Professor of Population Studies at Stanford University highlighted some of the issues surrounding the extension of human life-span. This is something that I have been tracking closely for over twenty years, since it was shown that the cells of people with diabetes mellitus age more quickly when placed in tissue culture, even if they are away from the high glucose of the diabetic environment. There is a link between premature aging and diabetes.

It is widely known in the scientific community that there has been a great deal of progress on aging research, much of it done behind the closed doors of pharmaceutical companies. According to Professor Tuljapurkar between 2010 and 2030, the modal, or most common, age of death will increase by 20 years if anti-aging therapies come into widespread use. This projected increase is based on some sophisticated modeling, and reflects a life-span growth rate that is five times faster than the current rate. If accurate, this would increase the modal age of death in industrialized countries such as the United States from roughly 80 years to 100.

So back to the question: if you suddenly discovered that you were going to have an extra thirty years of healthy life, what would you do with it?

I really do suggest that you start thinking about that. Assuming that you have enough money to live a decent life, what would you do with that extra twenty years? Would you:

1. Enjoy spending more time with younger members of the family?

2. Learn some new skills?

3. Make new friends?

4. Travel?

5. Read those books you always meant to?

6. Become more involved in spiritual pursuits?

7. Find a new way of serving others?

    8. Sit in front of the television?

What plans or aspirations do you have that you want to add to this list?

But then I have another question for you: if your answers included any of the points from 1-7, why not do them right now? What exactly is stopping you from doing all those things today?

Technorati tags: living, dreams, meaning, purpose

The Four Percent Solution

In this week’s edition of the Journal of the American Medical Association, is a study of 11,701 American over the age of 50, who participated in a national health survey in 1998 funded by the National Institute on Aging. The researchers analyzed participants' outcomes during a four- year follow-up and examined the health characteristics that seemed to predict death within four years.

These were the questions that were asked, and this is a bit like golf: you want to have the lowest score possible. Zero would be best. The score is supposed to tell you your chance of dying within the next four years.

1. Age: 60-64 years old = 1 point; 65-69 = 2 points; 70-74 = 3 points; 75-79 = 4 points; 80-84 = 5 points; 85 and older = 7 points.

2. Male or Female: Male = 2 points.

3. Body-Mass Index: Less than 25 (normal weight or less) = 1 point. (BMI = weight in pounds divided by height in inches squared, multiplied by 703.)

4. Diabetes: 2 points.

5. Cancer (excluding minor skin cancers): 2 points.

6. Chronic lung disease that limits activities or requires oxygen use at home: 2 points.

7. Congestive heart failure: 2 points.

8. Cigarette smoking in the past week: 2 points.

9. Difficulty bathing/showering because of a health or memory problem: 2 points.

10. Difficulty managing money, paying bills, keeping track of expenses because of a health or memory problem: 2 points.

11. Difficulty walking several blocks because of a health problem: 2 points.

12. Difficulty pushing or pulling large objects like a living room chair because of a health problem: 1 point.

Score:

• 0 to 5 points = less than a 4 percent risk of dying;
• 6-9 points = 15 percent risk;
• 10-13 points = 42 percent risk;
• 14 or more points = 64 percent risk.

So what should we make of this?

The first thing is that the study is just looking at the physical aspect of life. It asks nothing about diet or family history. It also says nothing about psychological and spiritual factors that can buttress health and well-being.

So what should it mean if somebody gets a high score? Does it mean that they should expect the end and stop reading long novels? Absolutely not! A high score should be a very good indicator that you should have a talk with your health care provider and get to work on all the reversible factors on the list. And as I have pointed out before, a positive psychological outlook and regular spiritual practice have been shown to extend the length and quality of your life.

It is not given to us to know the length of our lives and plenty of people live on and on despite breaking all the rules while others die young despite a lifetime of temperance. I had an aunt who smoked heavily throughout her adult life, yet lived to be well over ninety, while one of my former students died of lung cancer in his thirties, having never smoked a single cigarette.

Genes and lifestyle are important in determining our life span, but so are the quality and integrity of our relationships, our own sense of meaning and purpose, the clarity of the subtle systems of the body and our spirituality.

So use this study not as a death sentence, but as a wake-up call.

Technorati tags: health quiz, aging, longevity