Aug
01
2004

Too Much Fat Fuels Metabolic Syndrome

In a review article for physicians from the St. Michael’s Hospital of the University of Toronto (see reference below) Dr. Monge outlined some of the newer human research where links were found between the lining of the blood vessels and the hormones produced by fat cells that lead to the complications of the metabolic syndrome. In obese people there is a cluster of conditions such as high blood pressure, high blood sugar, high cholesterol, lipid abnormalities and high insulin levels, which is known as “metabolic syndrome”. Another name that was used for this condition in the 1990’s was “syndrome of insulin resistance”.

Dr. Monge pointed out that blood vessel health depends on the fine balance between two opposing forces. On the one hand there is a system that leads to blood vessel spasm, blood clotting, growth promoting, inflammation causing and oxidizing. On the other hand there is a system that is responsible for blood vessel relaxation, growth inhibition, blood clot dissolving, inhibiting inflammation and antioxidant activity. Complex changes occur in our metabolism when we put on pounds and accumulate too much fat. It is important to realize that fat is not just sitting there, but is composed of highly active fat cells that respond to insulin and growth factors and in turn produce a number of hormones and factors that affect the cells that are lining the blood vessels. Inflammatory cytokines are produced by fat cells that attack the blood vessels by producing atheromatous plaques, causing them to accumulate fat again and help in the processes that lead to rupture of the plaques.

Too Much Fat Fuels Metabolic Syndrome

Too Much Fat Fuels Metabolic Syndrome

The end result is that the deadly interplay between the fat cells and the endothelial cells lining the blood vessels tips the balance between the two systems mentioned above to the point where heart attacks and strokes suddenly occur.

There are two complex pathways that are involved in this process and that are linked to what was stated above. One crucial aspect of this involves nitric oxide, a small molecule that is normally produced by the endothelial lining cells and that is needed for normal circulation of the heart muscle, skeletal muscles and internal organs. This protective system is where much of the derangement of normal metabolism occurs with regard to the metabolic syndrome.

Dr. Monge pointed out that with these newer insights into the complex metabolic changes associated with the metabolic syndrome in obese people, there will be very practical results in the near future. Anti-inflammatory medications are already being utilized and some of the anti-diabetic medications have been shown to reduce the risk of heart attacks. It is hoped that sensitive tests will be developed to measure the hidden endothelial dysfunction at a time when preventative steps are still effective or early intervention can be done.

More info on the metabolic syndrome: http://nethealthbook.com/hormones/metabolic-syndrome/

Reference: Metabolic Syndrome Rounds (April 2004): J.C. Monge “Endothelial Dysfunction and the metabolic syndrome”

Last edited Oct. 26, 2014

May
01
2004

Chronic Inflammation Causes Cancer, Heart Attacks And More

When the Time Magazine devotes 7 full pages in the March 22, 2004 issue to the topic of inflammation as the source of most of the diseases of the Western World, you know that something important is happening in medicine. Christine Gorman and Alice Park have summarized some of the groundbreaking research of the past few years in this article. I will report about this article here, but also include direct links regarding some of the relevant research the authors have mentioned including some of the key links regarding the metabolic syndrome, which was not mentioned in the article.

Since the beginning of the obesity wave in North America it has become obvious that a cluster of diseases such as heart attacks, strokes, Alzheimer disease, cancer of the colon, multiple sclerosis, arthritis and others have also become more frequent. Dr. Paul Ridker, a cardiologist at Brigham and Women’s Hospital, was one of the pioneers of investigating inflammation as a possible cause and the common denominator of these diverse illnesses. He noticed that certain patients got heart attacks although their blood LDL cholesterol levels (the “bad” cholesterol) were normal. The theory at that time was that all patients who would develop heart attacks would come from a high-risk group of patients with elevated LDL cholesterol. The problem was that 50% of patients with heart attacks had normal LDL cholesterol levels. Dr. Ridker suspected that the C-reactive protein (CRP), which is found to be elevated in the blood of rheumatoid patients, would be somehow involved in the disease process of hardening of the arteries before a heart attack would occur. CRP is produced by the liver cells and by the lining cells of arteries in response to a general inflammatory reaction in the body. Examples of this would be rheumatoid arthritis patients and patients with autoimmune diseases, where CRP levels can be readily measured with a blood test. Dr. Ridker found that there was a very good correlation between the CRP level and the degree of inflammation as well as the risk for developing heart attacks and strokes. Further investigation by others confirmed that CRP levels were perhaps more important than LDL levels in predicting impending heart attacks. This is so, because CRP is the body’s substance in the blood stream that would be responsible for breaking up LDL containing deposits (plaques) in the walls of the arteries, which leads to heart attacks in the heart and to strokes in the brain.

Chronic Inflammation Causes Cancer, Heart Attacks And More

Chronic Inflammation Causes Cancer, Heart Attacks And More

Other investigators found that CRP was only one link in a complex chain of events that includes inflammatory substances (cytokines) from the fat cells as well as insulin and insulin-like growth factors from the metabolic syndrome. Leptins are also a factor as has been discussed under this link.
Dr. Steve Shoelsen from the Joslin Diabetes Center in Boston has developed a mouse model for the metabolic syndrome. These mice will produce huge amounts of inflammatory substances in their fatty tissue in response to any inflammatory process that is started in them. Anti-inflammatory drugs such as the statins or metformin, it is hoped, will be shown conclusively to dampen the inflammatory process and prevent heart attacks, strokes and diabetes as well as cancer, Alzheimers disease and arthritis. Heart disease has already been shown to be improved by anti-inflammatory drugs. Asthma is an inflammatory disease of the small bronchial tubes, which can be stabilized with the anti-inflammatory drug Avastin.

What can we do as consumers to prevent some of those life-threatening diseases? By reducing our weight through calorie restriction on a low-glycemic diet we can help to reduce the insulin-like hormone substances of the fatty tissue. Regular exercise of at least 30 minutes of a brisk walk daily or the equivalent of other sports activities will half our risk for colon cancer and many other cancers. A diet rich in fruits and vegetables as well as fish and fish oils will reduce the amount of free radicals in our system cutting down on the circulating inflammatory substances. This prolongs life, prevents all of the major diseases of modern civilization and leads to longevity as the study of the Okinawa diet has shown.

Based on an article in the Time Magazine, March 22, 2004 edition, page 54 to 60.

Here is a chapter on arteriosclerosis from the Net Health Book, which explains inflammatory changes of the arterial wall:

http://nethealthbook.com/cardiovascular-disease/heart-disease/atherosclerosis-the-missing-link-between-strokes-and-heart-attacks/

Last edited October 26, 2014

Feb
01
2004

Kidney Disease, Another Complication Of Metabolic Syndrome

The metabolic syndrome is a new disease entity that is known to be associated with obesity. In order to make the diagnosis of metabolic syndrome at least 3 of the 5 components listed in the table under this link (hypertension, hypertriglyceridemia, low high-density lipoprotein cholesterol level or LDL cholesterol, high glucose level, abdominal obesity) have to be present.

Dr. Jing Chen and colleagues of Tulane University School of Medicine in New Orleans, La., published an analysis of the Third National Health and Nutrition Examination Survey in the Feb.3, 2004 edition of the Annals of Medicine. Patients with chronic kidney disease were identified in this study where 3, 4 or 5 of the metabolic syndrome criteria were positive. Two criteria for chronic kidney disease were measured:

1. if there was a significant reduction of the filtration capacity of the kidney.

2. if there was critical leakage of blood protein into the urine.

Kidney Disease, Another Complication Of Metabolic Syndrome

Kidney Disease, Another Complication Of Metabolic Syndrome

Depending on how advanced the metabolic syndrome was (all 5 criteria of metabolic syndrome positive versus only 3 or 4) there was a higher or lower risk of developing chronic kidney disease.

I have depicted the results of this study in bar graph form here. It shows clearly that chronic kidney damage occurs in a dose-response curve pattern depending on how severe the degree of the metabolic syndrome is.

Risk of developing kidney disease with various degrees of severity of the metabolic syndrome
 Kidney Disease, Another Complication Of Metabolic Syndrome1

With 5 factors of the metabolic syndrome present the risk to develop reduction in filtration capacity of the kidneys is almost 6-fold. This is 3-fold higher than in a person with a milder degree of metabolic syndrome where only two factors are present. Such a person would only have a 2-fold risk for developing chronic kidney damage (dark blue shaded bars in graph). A dipstick urine test can measure protein in urine, which is an alternative way to measure kidney damage due to the metabolic syndrome. These values followed a very similar dose-response curve (light blue shaded bars in graph). The authors of this study believe that the kidney damage inflicted by the metabolic syndrome is different from that caused by high blood pressure or by diabetes. Future studies will have to establish whether this type of kidney damage can be repaired by treating the metabolic syndrome with a low glycemic, calorie restricted diet coupled with exercise.

Based on an article published in: Ann Intern Med 2004:140:167-174.

Last edited December 8, 2012

Jan
03
2004

Any Diet A Winner Research Says

 

Dr. Michael Dansinger reported at a recent annual meeting of the American Heart Association about a study where he compared the effect of 4 major diet plans on the lowering of risk factors for heart disease.

Dr. Dansinger is the director of obesity research at the Tufts New England Medical Centre’s Atherosclerosis Research Lab in Boston. Originally, the objective was to see whether any of the following four diets investigated would be superior: the Atkins diet, the Ornish diet, the Zone diet and the Weight Watchers diet. In the table below there are links for each of these diet plans. Briefly, the Atkins diet is a high protein/low carbohydrate diet; the Ornish diet is a vegetarian/low-fat diet; the zone diet is a low-glycemic load/balanced protein/low fat diet; weight watchers is a calorie restricted diet.

160 obese patients were divided into 4 groups and assigend to one of these four diet plans. They were instructed in the type of diet plan they were to follow in 4 couselling sessions in the beginning of the weight loss program. The participants ranged in age from 22 to 72 years of age (average age 50) and had on average starting weight of 220 lbs.

Any Diet A Winner Research Says

Any Diet A Winner Research Says

They were to follow the diet plan for 2 months strictly and were allowed to follow less supervised for another 10 months. To the surprise of the research team under Dr. Dansinger they all lost about the same amount of weight (average of weight loss 10 lbs or 5% of body weight), in other words they were all successful with any of these programs and none was superior. Below are the results in modified tabular form.

Dr. Dansinger indicated that the focus would now have to shift from “which is the best diet plan” to “which is the best diet plan for a particular patient”. The doctor should attempt to fit the weight loss programs that fit patients’ food preferences best and that patients can easiest fit into their lifestyle. This will hopefully lead to the lowest dropout rate. This trial showed that the Zone diet and the Weight Watchers diet had the least dropout rates. But those who stayed on the Atkins or Ornish diet were successful with their weight loss program also, as these may have been fitting these patients best.

Comparison of various diets with regard to weight loss effectiveness
Diets that
were compared:
Reduction of
heart risk (Framingham score):
Dropout rates
over 1 year:
Atkins diet
12.3% 48%
Ornish diet 6.6% 50%
Zone diet 10.5% 35%
Weight Watchers
diet
14.7% 35%

In other words, if the one diet plan does not work satisfactorily, try another one. The common denominator with all food plans was some form of calorie restriction despite all of the differences.

Based on The Medical Post, Dec. 16, 2003 (p. 15).

Here is a link to the Net Health Book’s weight loss and diet chapter.

Last edited December 8, 2012

Dec
01
2003

Fat Cells Secrete Hormones That Raise Blood Pressure

Fat cells are known to secrete a number of substances that affect the lining of the arteries and that are also known to be associated with the metabolic syndrome. One of the observations that physicians were aware of for some time is that aldosterone, a hormone from the adrenal glands, is often elevated in patients with high blood pressure and obesity or people who are overweight.

Dr. Ehrhart-Bornstein and her group from the University Medical Center, Heinrich Heine University of Düsseldorf in Germany investigated this interaction between fat cell metabolites and the cells of the adrenal cortex in more detail. They used a tissue culture model with human adrenocortical cells (NCI-H295R). To their surprise they found two separate hormone factors that were produced by fat cells and that showed in the tissue culture system a 7-fold increase in aldosterone hormone release. As aldosterone is a mineralocorticoid hormone they called these new releasing hormones mineralocorticoid-releasing factors. Further characterization of these factors demonstrated that one was of a higher molecular structure and was heat-sensitive, the other one was smaller in size and was more heat resistant. Each factor alone lost much of the aldosterone releasing activity, but when recombined they had 93% of the original action. Synthesis of messenger RNA inside the adrenocortical cells was stimulated by a factor of 10-fold from the action of the mineralocorticoid-releasing factors. Other hormones were also somewhat stimulated such as release of cortisol by a 3-fold increase and DHEA by a 1.5-fold increase. Other known substances from fat cells were entirely ineffective in this testing system.

Fat Cells Secrete Hormones That Raise Blood Pressure

Adipose cells secreting aldosterone releasing factor

When asked how this new research might fit in with the observation that loss of fat through calorie restriction has a beneficial effect on high blood pressure, the authors commented that with less fat storage in fat cells during weight loss the production of mineralocorticoid-releasing factors would go down significantly and aldosterone would be released at a much lower rate thus decreasing blood pressure through the aldosterone/angiotensin/renin mechanism.

Nov. 12, 2003 paper on which this write-up is based: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC283571/

Last edited October 26, 2014

Aug
01
2003

Newly Detected Hormone May Help Obesity

At a recent meeting of the Endocrine Society in Philadelphia new findings by British researchers were presented regarding hormone interactions with weight problems.

Dr. Simon Aylwin, a consultant from the King’s College Hospital in London, England, presented data showing that peptide hormone PYY levels were much lower in patients who were significantly obese versus normal weight controls.

As Dr. Stephen Bloom’s research group from Imperial College, London, UK had shown earlier, with a meal rich in calories the gut produces the PYY hormone in a way that with higher amounts of calories in food consumed more of the hormone PYY is secreted into the blood stream. The new information that was discussed at the meeting of the Endocrine Society was the fact that these hormone signals are registered in the hypothalamic tissue, a part of the brain situated just above the pituitary gland. It has been known for a long time that weight is regulated by a satiety centre in the hypothalamus. Now it has been appreciated that there are at least two or more pathways of registering weight related hormone signals: one being the gut related PYY hormone that tells the brain that enough food was consumed in a meal, and secondly leptin hormone signals where the hormone leptin is secreted from the fatty tissues in the body, which tells the satiety centre of the brain that not as much food needs to be consumed when our weight has reached a certain threshold.

Newly Detected Hormone May Help Obesity

Newly Detected Hormone May Help Obesity

Dr. Aylwin measured PYY hormone levels in a number of different groups of patients such as in patients who were obese, in patients who had gastric bypass surgery done and in a group who only had gastric banding done. They observed that the group who had bypass surgery done had a higher than normal response of PYY hormone release as a response to a meal. This enabled them to adhere to low calorie meals without any hunger pangs and this group of patients did well in terms of weight control on the longterm.

In contrast to this the group with gastric banding had a flat response curve to the stimulus of a meal with respect to the PYY hormone as did patients with obesity. The low PYY levels in response to meals likely explains why these patients continue to eat too much making their weight loss efforts more difficult.

Dr. Aylwin explained that with future research efforts new forms of medications could be developped that mimic the effects of the PYY hormone leading to satiety and allowing patients to control their weight easier. Dr. Linda Fish, an endocrinologist from the University of Minnesota, mentioned that for excessive obesity with a body mass index of more than 45 the only effective therapy right now would be the invasive gastric bypass procedure. With an anologue type medication that would have the same effect as the PYY hormone, many patients might be able to have persistent weight loss with these new medications allowing them to lose weight persistently without bypass surgery. However, results of this type of research likely would take about 10 years before a new drug would be available to the public.

This summary is based on an article in the July 15, 2003 issue of the Medical Post (page 50) as well as on the newsdesk article entitled “Obesity-is it all in the mind?” in The Lancet Neurology Volume 2, Number 1, January 2003.
Link to related topic (nasal spray for obesity).

Last edited December 9, 2012

Jul
01
2003

Obesity And Metabolic Syndrome

In the June 10, 2003 edition, following page24, of The Medical Post there was a minisymposium on obesity and the metabolic syndrome (also known as the “syndrome of hyperinsulinism”).

Four specialists had a discussion about this topic: Dr. Ehud Ur (endocrinologist, Dalhousie University, Halifax, N.S., Canada), Dr. Robert Dent (Director of the Weight Management Clinic, Ottawa Hospital, Ont.), Dr. Dominique Garrel (Director of Department of Nutrition and endocrinologist, University of Montreal, Quebec), and Dr. Arya Sharma (Prof. of Medicine, McMaster University, Hamilton, Ont.).

Introduction:

Obesity is now a health threat that about 25% of the North American population is suffering from. There is still a lot of discussion what the exact criteria should be, but the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III) has simplified the detection of the metabolic syndrome.

Obesity And Metabolic Syndrome

Obesity And Metabolic Syndrome

The experts agree that when three or more of the criteria mentioned in this table are positive the person would be considered to have metabolic syndrome.

There is a wide age-related variety: in one study only 7% had metabolic syndrome in the age group of 20 to 29. The same study found 40% of study participants had the metabolic syndrome in the age group of 70 years and older. It is thought that too many calories coupled with too little activity over a longer period of time, perhaps coupled in some people with a genetic tendency to develop metabolic syndrome, leads to an accumulation of abdominal (so-called”visceral”) fat.

Because fat cells have their own hormone systems (leptins etc.) there is a change of metabolism including an elevation of the insulin level with associated loss of “insulin sensitivity”. So, the more obese a person becomes, the less effective insulin becomes in transporting blood sugar through cell walls. At the same time the liver metabolism is changing with the good cholesterol (HDL) being less produced and the bad cholesterol (LDL) being overproduced. The liver will produce a different mix of coagulation factors, which leads to a tendency to form clots in the veins of the legs and in the lungs. As the pancreatic capacity for insulin production gets exhausted over a period of time, the patient eventually develops type 2 diabetes mellitus. Due to the risk of the coronary arteries clogging up with the cholesterol changes and the accelerated hardening of arteries from diabetes, the risk for getting severe heart attacks in obese people with the metabolic syndrome when compared to a normal weight population is about 4-fold.

Elements leading to the diagnosis of “metabolic syndrome”
Finding: Comments:
abdominal obesity waist circumference more than 102 cm in men or more than 88 cm in women
elevated triglyceride level level of 150 mg/dl or higher
low HDL cholesterol level under 40 mg/dl in men or under 50 mg/dl in women
elevated blood pressure systolic or diastolic blood pressure exceeding 130/85 mm Hg
high fasting blood glucose level fasting glucose higher than 110 mg/dl

Treatment of metabolic syndrome:

The experts agreed that a reduction of only 5% to 10% of the body weight through a sensible combination of a mild exercise program (e.g. walking 30 to 45 minutes every day) and a calorie reduced food intake will make a significant difference in terms of normalization of the body chemistry. It is my estimate that perhaps 70% to 90% of all cases of obesity and metabolic syndrome can be treated this way.

However, the remaining cases should continue to see their physician and be followed like the doctor would follow someone who has high blood pressure. There are two types of medications available and they have nothing to do with the Phen-Fen diet pills from not too long ago that were found to cause pulmonary hypertension. These new diet pills are fairly safe and show weight loss results provided the patient co-operates with regard to a modified to low fat diet and some degree of regular exercise.

1. Sibutramine (brand name: Meridia) is a specific brain hormone inhibitor in the area where the appetite zone is located (serotonine and norepinephrine reuptake inhibitor). This medication helps the patient by experiencing satiety sooner so that the patient does not feel deprived despite less calorie consumption.

It is the medication of choice for those who tend to eat a lot. Like with other anti-depressants side-effects are a dry mouth, heart rate increases and sleep loss (insomnia).

2. Orlistat (brand name: Xenical) inhibits fat uptake at the level of the gastrointestinal wall (gastrointestinal lipase inhibitor). This leads to an inhibition of fat absorption by about 30%. The patient needs to keep the fat intake down to about 2 oz. (=60 gm) per day. If the patient consumes more fat, the side-effect of orlistat will be flatulence, abdominal cramps and diarrhea. If the patient is on a strict low fat diet, there would not be enough fat in the gut for the medication to be effective.

At this point it is not known how long the patient should be on such weight loss medication, if this was the chosen route. The experts felt that 1 year would be reasonable, but that the patient should be observed by the treating physician and it may be necessary after some intermission to go for another year of therapy all the way attempting to permanently change eating and exercise habits as an ongoing maintenance program.

Here is a link to another reference about the metabolic syndrome (syndrome of insulin resistance).

Last edited December 9, 2012

 

Dec
02
2002

Obesity (Excessive Weight) A Predictor Of High Risk For Stroke

In the Dec.9th issue of the Archives of Internal Medicine an important follow-up from the US Physicians’ Health Study was published. It examined the effect of obesity on the development of stroke later in life. 21,414 male physicians of the US have been followed now for 12.5 years in this study. At present there were 747 strokes (631 ischemic, 104 hemorrhagic, 12 others).

They found that the rates of strokes were in direct relation to the amount of excessive weight, in other words the higher the weight, the higher the risk to develop a stroke. It did not matter what kind of stroke it was (ischemic stroke or hemorrhagic stroke), a body mass index above 30 was always associated with a 1.9-fold risk to develop a stroke when compared to normal weight controls (body mass index less than 25). This risk of obesity was independent from other risk factors such as diabetes, high cholesterol or high blood pressure. Dr. Kurth from the Brigham and Women’s Hospital, Boston, said that this finding is very significant in view of the fact that many young adults in the US are either overweight or obese and they will be exposed to this risk for a longer period of time inreasing the risk to develop strokes even further. He hopes that physicians will concentrate on treating obesity more aggressively preventing a stroke. In industrial countries strokes are the main cause of disability and are on the third place on the list of causes of death.

Obesity (Excessive Weight) A Predictor Of High Risk For Stroke

Obesity (Excessive Weight) A Predictor Of High Risk For Stroke

(This info based on: Arch Intern Med 2002;162:2557-2562.)

Other information about strokes can be found through this link: http://www.nethealthbook.com/articles/cardiovasculardisease_strokeandcerebralaneurysm.php

Last edited December 10, 2012

Oct
18
2002

Work Stress Is A Killer…More Than 2-Fold Over A Period Of 25 Years

In mid October 2002 the British Medical Journal(BMJ 2002;325:p.857-860) published a paper by Dr. Mika Kivimäki from the University of Helsinki where 812 healthy factory workers were followed for about 25 years. The issue was whether stress from work would have negative consequences, which could be measured in terms of cardiovascular disease. Various risk groups were defined from low stress to high stress.

Low stress jobs were classified as people who often had more training, more responsibilities, better salaries, physically less strenuous jobs with more job security. High stress jobs involved the opposite(high demand/low job control/low salary/no job security). Depending on which subgroups of high versus low risks were compared, the investigators found a 2.2 to 2.4-fold increase of strokes and heart attacks due to cardiovascular disease.The team measured other cardiovascular risk factors. They found a significant increase of cholesterol in the high stress job group after 5 years. After 10 years there was a marked weight gain in the stressed group with obesity becoming much more frequent. The authors noted that this likely led to a change of metabolism in the sense of hyperinsulinism, which is known to cause high cholesterol levels and leads to hardening of the arteries with heart attacks and strokes.

Work Stress Is A Killer...More Than 2-Fold Over A Period Of 25 Years

Work Stress Is A Killer…More Than 2-Fold Over A Period Of 25 Years

Visit these useful related links to chapters of my free Internet based Nethealthbook:
Hyperinsulinism or syndrome of insulin resistance:
http://www.nethealthbook.com/articles/hormonalproblems_diabetesmellitus.php

Heart disease:
http://www.nethealthbook.com/articles/cardiovasculardisease_heartdisease.php

Stroke:
http://nethealthbook.com/cardiovascular-disease/stroke-and-brain-aneurysm/hemorrhagic-stroke/

Last edited October 25, 2014