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

 

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Jun
01
2003

Hormones After Menopause (HRT) Not For Everybody

Lately there have been several review articles published in the medical literature about hormone replacement therapy (HRT) after menopause for women. A number of longterm follow-up studies have shown that HRT with a combination of estrogen and progesterone hormones is associated with a higher risk of stroke, heart attacks, blood clots and pulmonary embolism. The WAVE trial has recently shown that estrogen replacement does not lead to protection from heart disease or strokes, however exercise and weight loss (from calorie restriction) does.

Two more recent studies add to the story: the one is a study showing that urinary incontinence (=bladder leakage) is much worse on estrogen replacement (HRT) than without it. The other study showed that estrogen replacement leads to dementia of the Alzheimers type.

Here are the details: Dr. Jodi Steinauer (University of California at San Francisco) reported about the findings during the American College of Obstetrics and Gynecology meeting at New Orleans. The study was designed to see whether estrogen/progestin hormone replacement would improve bladder function with aging. Episodes of urine loss when coughing, sneezing or running (urinary incontinence) were observed by the 1208 women from the HERS trial (Heart and Estrogen/Progestin Replacement Study) who were followed along for 4 years. The women were either given a hormone tablet (estrogen/progestin) or a “fake” pill with no hormones (placebo pill). To the surprise of the investigators the opposite of what was expected happened: The HRT group did much worse than the placebo group.

Hormones After Menopause (HRT) Not For Everybody

Hormones After Menopause (HRT) Not For Everybody

After one year urinary incontinence was up 2 to 3-fold in the HRT group and after 4 years this number was up 3 to 5-fold. Of the women who did not have stress incontinence in the beginning, only 38% of the placebo group developed it over 4 years, whereas in the HRT group 54% developed it. The authors concluded that HRT replacement therapy in menopause should be avoided (reported in The Medical Post, page 1 and 86, May 13, 2003).

Recently a new study (JAMA 2203;289:2651-62) showed that dementia was double the rate in older postmenopausal women on HRT than in the placebo group. 4532 postmenopausal women aged 65 years or older from the Women’s Health Initiative’s memory study (“WHIMS”) were followed by researchers for 4 years. The HRT therapy consisted of Prempro (Premarin and Provera). None of the women had dementia in the beginning of the study. After 4 years 21 of the placebo group had developed it (age related), the Prempro group developed 40 dementia cases. It is unclear why the HRT group had developed dementia, but the authors of the study theorize that perhaps a series of mini-strokes would be responsible for this.

In summary, it appears now with more evidence from the literature that HRT should only be given to postmenopausal women in a few selected patients under close medical supervision, but that the majority of women likely should not take it. Osteoporosis can be prevented by regular brisk walks, dietary changes with fat reduction and avoidance of refined sugar etc. as another powerful tool to achieve longevity. Keep in mind that these “hormone” replacement trials were regarding Premarine and Provera, both products of the drug industry. The body reads these hormone-like susbstances as estrogen-like substances and gets an overdose with the regular dosaging. Only bio-identical hormones in the right mix will be heart and brain protective and will work against osteoporosis. In short, the study described above was done with the wrong “hormones” and should have been done with bio-identical hormones. In menopause there are all kinds of reasons why a woman should use bioidentical hormones to return to her previous hormone balance, but it needs to be supervised by a knowledgeable physician with experience in this.

Read the truth about bio-identical hormone replacement under the “menopause” link below.

Here is a link to “menopause”: http://www.nethealthbook.com/articles/menopause.php

Last edited December 9, 2012

Apr
01
2003

Menopause And Perimenopause In Women

In the February 19, 2003, issue of The Journal of the American Medical Association there was an extensive review of the topic of menopause and the time before and after menopause, called “perimenopause”.

The authors, Dr. Lori A. Bastian, from Duke University, and colleagues critically reviewed 1,246 articles on this topic and identified 16 studies that were accepted as being reliable regarding the review of this topic.

They were interested in finding menopause symptoms, signs and blood tests that would be reliable in terms of assessing whether a woman would be approaching menopause or would be in menopause. The result was that no single test or symptom was reliable, but that a number of tests and symptoms in combination were very helpful.

Menopause And Perimenopause In Women

Menopause And Perimenopause In Women

They measured reliability by “likelihood ratios (LRs)”. What this means is that any value above 1.0 is significant, but the higher the number, the more reliable and important is this fact or sign. I summarized the findings in table form below.

Results of a Review Study on Menopause in Women
(modifed according to Feb.19, 2003, issue of The Journal of the American Medical Association)
Findings:
Likelihood ratio (LR): Comments (by Dr. Ray Schilling):
self assessment of going through the transition 1.83 this is based on the effects of the changing hormones on the woman and how she feels it
is affecting her
symptoms of hot flashes 3.10 lack of estrogen from ovaries leads to a lability of the skin blood vessels with increased skin perfusion as well as stimulation of the sweat glands
night sweats 1.90
sleep pattern is changed and there is a loss of the day / night rhythm of skin perfusion
vaginal dryness 2.64 due to lack of estrogen
high follicle-stimulating
hormone levels
3.06 feedback from estrogen missing, which stimulates the hypothalamus of the brain to produce more
FSH hormone
low inhibin levels 2.05 this is a newer test, which is more specific than the FSH test and also has some importance in fertility work-ups
Self-assessment of perimenopausal status 0.25 this is not a reliable test as it is below 1.0. It was included to show how good the other tests are in comparison

The authors concluded that there is no need for blood tests for menopause diagnosis in a woman, if several points of the first 4 findings are positive (top part of the table).

Here is a link regarding menopause.

Last edited December 9, 2012

Mar
01
2003

Testosterone For Male Menopause (Andropause)

At a recent continuing education meeting at the University of Calgary in Alberta/Canada, which was reported in the Jan. 14, 2003 edition of the Medical Post, Dr. Norman Wong (professor of medicine, biochemistry and molecular biology) reviewed the symptoms, investigations and treatment modalities available for men who experience andropause (the male equivalent of menopause). They are as follows (my summary in table form).

Here is a link to the ADAM questionnaire regarding andropause by Dr. Morley, a geriatrician at the St. Louis Unversity in Missouri. If you answer “yes” to question #1 and #7 (sexual dysfunction or lack of sex drive) or if you answer “yes” to any three of the other total of 10 questions, you should see your physician and ask for a testosterone blood test.

What should you know about testosterone blood tests? What counts is the free testosterone or bioavailable testosterone. Dr. Ronald Swerdloff, professor of internal medicine and endocrinology at the UCLA School of Medicine in Torrance, California, stated at this conference that testosterone production decreases with aging, but is actually also one of the causes of aging. Testosterone levels decrease 1% to 2% every year from the age of 30 onwards. However, the sex hormone binding protein (SHBP) can buffer these changes for a certain period of time, if the SHBP is binding less testosterone thus keeping the free or biologically available testosterone relatively stable for a number of decades or years. Often, however, the andropausal men who need testosterone replacement have high SHBP levels. Nobody knows why some men have problems earlier than others. So, if the free testosterone serum level is low (and the LH and FSH hormones are low or normal) this means that this man likely should have testosterone replacement therapy, if there are also clinical signs and symptoms of hormone deficiency.

Testosterone For Male Menopause (Andropause)

Testosterone For Male Menopause (Andropause)

As can be seen from this link to menopause in women , the pituitary hormones LH and FSH, which are also known as gonadotropins, should be high to indicate that the feedback mechanism between the estrogen (or in the male the testosterone) no longer suppresses the production of these gondotropins. The fact that this mechanism is lost in most older men shows that the hormone deficiency is likely much more profound than a simple deficiency, it may actually be indicative of the aging process of the hormone glands themsevles. The good news though is that with a simple testosterone patch this can be fixed. Your doctor can discuss this further with you.

Other possibilities are injections every 3 to 4 weeks with a Depot-testosterone hormone preparation or tablets. However, with the tablets the problem is that this will get metabolized in the liver and higher amounts of hormone are required to overcome the liver barrier. Liver cancer has been reported in a small percentage of men taking tablets for a long period of time (I do not like testosterone tablets for this reason). Prostate cancer is the other worry and regular PSA tests and prostate exams should be done by your doctor. As no controlled trials have been done yet regarding the safety of longterm testosterone replacement in andropausal men, Dr. Swerdloff recommended to replace only in the lower dose range to the point where the free testosterone serum values are just barely normalized and the clinical signs and symptoms disappear. Overtreatment should be avoided.

Andropause symptoms (male menopause)
Symptoms: Comments:
loss of sex drive (libido) testosterone, which is the male hormone produced by the testicles, is needed for a normal sex drive
erectile dysfunction
(impotence)
inability to have sustained erections
loss of male characteristics loss of male type hair distribution, deep voice, muscle mass etc.
fatigue and depression brain hormones dysbalanced from low testosterone levels
decrease in muscle mass, increase in fat mass lack of testosterone responsible for muscle loss and change in bone metabolism
oligospermia or azoospermia too little sperm count or no sperm present

Addendum Nov. 2, 2012: At the 19th Annual World Congress Anti-Aging and Aesthetic Medicine in Las Vegas (December 8-10, 2011) Dr. Abraham Morgentaler, a Harvard trained urologist explained that with bio-identical testosterone replacement there is no longer any concern about prostate or liver cancer with long-term use. It has been one of the “medical myths” that has been around.

See also link to andropause/male menopause from the Net Health Book.

Last edited December 9, 2012

Feb
01
2003

CRP Test Better Than Cholesterol Test

At the 75th Annual Scientific sessions of the American Heart Association in Chicago several presentations centered around the use of the C-reactive protein test to evaluate risks for heart attacks, strokes and the risk of restenosing after doing a cardiac procedure to reopen stenosed coronary arteries.

I have previously reported about the use of the C-reactive protein (CRP) test in a review regarding Dr. Paul Ridker’s study in the New England Journal of Medicine.

This study is ongoing and is known under the name “Women’s Health Study”. He followed a large group of women and found that an increase of the CRP was closely associated with heart attacks. Other investigators found now that an increase of CRP is closely linked with obesity, with the metabolic syndrome (also known under “insulin resistance”) and hormone replacement therapy.

CRP Test Better Than Cholesterol Test

CRP Test Better Than Cholesterol Test

There appears to be a pivotal shift among cardiologists in that it is now clear that inflammation seems to be at the center of the process of hardening of the arteries, not just in a few cases, but in everybody who has heart disease.  Below I  summarized some of the features of CRP in a table.

C-reactive protein (CRP) and risk for heart disease
Facts: Comments:
CRP is produced by the endothelial cells that line the arteries CRP is intimately involved with arteriosclerosis. It has been identified as the culprit, which produces hardening of the arteries together with LDL cholesterol
CRP interferes with nitric oxide release from the endothelial cells, which is required for normal function this leads to a dysfunction of the lining of the arteries, atheromatous plaque formation and it stimulates scavenger cells, called macrophages, to take up LDL. CRP also causes plaque destabilization and clotting
these factors elevate CRP: obesity, the metabolic syndrome, hormone replacement in menopause with artificial hormones, but NOT with bio-identical hormones
these factors lower CRP: low carbohydrate diet, exercise, statins, rosiglitazone (Avandia), lowering of insulin

There will be a lot of information coming out in the next few years. Two major trials have been started where patients with a normal cholesterol, but an abnormally high CRP, will be followed along.

The JUPITER trial will look at the effect of treating these patients with rosuvastatin (brand name: Crestor). About 15,000 patients will be enrolled in this trial and followed for about 4 years. The Canadian 4R trial (Risk Reduction with Ramipril in patients with high CRP) uses ramipril (brand name: Altace) for 12 weeks to see whether it reduces CRP levels. Much more research is needed, but the doctors already know enough about CRP to state that it is a major player when it comes to hardening of arteries. They also know that LDL cholesterol is not outdated, as both LDL cholesterol and CRP play important roles in this process.

Based on a cardiology update in the Medical Post, Dec. 31, 2002, page 17 to 19.

Comments on Dec. 10, 2012: The 4 R Canadian study showed a tendency towards a lowering of CRP with Ramipril, but it was statistically not significant due to numbers that were too low and the observation period was not long enough. The Jupiter trial had to be abandoned after two years as there was concern of diabetes being caused by Crestor and because the effect of prevention of heart attacks was not seen early enough (the number of treatments required before a beneficial effect could be seen was too high). Here is a review why  rosuvastatin (brand name: Crestor) should be approached with caution.

Here are other links to related topics that won’t have serious side-effects:

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

Two things will lead to a normal weight (as you likely have heard before):

Proper nutrition…http://www.nethealthbook.com/articles/nutrition.php

…and proper exercise (fitness): http://www.nethealthbook.com/articles/fitness.php

Last edited December 10, 2012

Nov
01
2002

WAVE Trial Failed To Show Benefits Of Estrogen (Premarine) And Vitamins

Dr. David D. Waters of the University of California at San Francisco reported in Chicago at the American Heart Association’s Scientific Session 2002 about the WAVE trial. This stands for “Women’s Angiographic Vitamin and Estrogen” trial.

The results of this study were simultaneously published in the Journal of the American Medical Association(JAMA 2002;288:2432-2440). It was a “carefully designed randomized study” where 423 women with established blood vessel damage to their hearts (established by angiography) were put on a therapy and then followed for an average of 2.8 years. Essentially the question was whether or not estrogen (Premarine) and vitamins (Vit.E and C) would have a protective effect on the blood vessels. Surprisingly the worst outcome was in the group with estrogen replacement and vitamins. The placebo group (=no estrogen, only vitamins) had the lowest death rate. The authors felt that the beneficial effect of estrogen (speak “Premarine”) on heart vessels could not been verified in this study. The take home message to the physicians at the conference was that they should concentrate on lowering the known risk factors: weight reduction, blood pressure control, cholesterol lowering and increasing exercise. Estrogen should be given in low doses (Premarine 0.625mg per day) only to those women who are symptomatic with hot flashes, but not to every postmenopausal woman.

WAVE Trial Failed To Show Benefits Of Estrogen (Premarine) And Vitamins

WAVE Trial Failed To Show Benefits Of Estrogen (Premarine) And Vitamins

NOTE : This group of postmenopausal women is a selection of women more likely suffering from hyperinsulinism with a higher rate of cardiovascular disease (and also arthritis and possibly a higher risk for cancer as well). The most logical therapy for these women is to work on weight loss, to increase exercise and to change their diet to a zone diet as this is known to lower cholesterol. Hoping to cure these women with estrogen or vitamin manipulation alone does not make “medical common sense” to me. Also, those women who had not had a hysterectomy were not dealt with as a separate group, although they were put on medroxyprogesterone acetate (Prempro). This is called a “confounding bias” and should have been openly discussed, which it was not. This means the WAVE trial made waves, but it was not a properly designed randomized study.

You may want to read these useful related links to chapters of my free Internet based Nethealthbook: For links to arteriosclerosis, heart attacks and strokes see this link: http://nethealthbook.com/cardiovascular-disease/heart-disease/atherosclerosis-the-missing-link-between-strokes-and-heart-attacks/
For a link to hyperinsulinism follow this link:
http://www.nethealthbook.com/articles/hormonalproblems_diabetesmellitus.php

Last edited October 25, 2014