Health for life

People who are “apple-shaped” — with fat more concentrated around the abdomen — have long been considered more at risk for conditions such as heart disease and diabetes than those who are “pear-shaped” and carry weight more in the buttocks, hips and thighs.

But new research conducted at UC Davis Health System published in The Journal of Clinical Endocrinology and Metabolism provides further evidence that the protective benefits of having a pear-body shape may be more myth than reality. The journal article posted online January 10 and will appear in the March 2013 print edition.

The UC Davis study found that fat stored in the buttock area — also known as gluteal adipose tissue — secretes abnormal levels of chemerin and omentin-1, proteins that can lead to inflammation and a prediabetic condition know as insulin resistance in individuals with early metabolic syndrome.

Metabolic syndrome ers to a group of risk factors that occur together, doubling the risk for heart disease and increasing the risk for diabetes at least five-fold. Risk factors include having a large waistline, low levels of high-density lipoproteins (HDL), or “good” cholesterol, high blood pressure as well as high fasting blood sugar ( insulin resistance) and high triglyceride levels. According to the Centers for Disease Control and Prevention, metabolic syndrome affects 35 percent of American adults over age 20.

“Fat in the abdomen has long been considered the most detrimental to health, and gluteal fat was thought to protect against diabetes, heart disease and metabolic syndrome,” said Ishwarlal Jialal, lead author of the study and a professor of pathology and laboratory medicine and of internal medicine at UC Davis. ”But our research helps to dispel the myth that gluteal fat is ‘innocent.’ It also suggests that abnormal protein levels may be an early indicator to identify those at risk for developing metabolic syndrome.”

The UC Davis team found that in individuals with early metabolic syndrome, gluteal fat secreted elevated levels of chemerin and low levels of omentin-1 — proteins that correlate with other factors known to increase the risk for heart disease and diabetes. High chemerin levels, for example, correlated with high blood pressure, elevated levels of C-reactive protein (a sign of inflammation) and triglycerides, insulin resistance, and low levels of HDL cholesterol. Low omentin-1 levels correlated with high levels of triglycerides and blood glucose levels and low levels of HDL cholesterol.

“High chemerin levels correlated with four of the five characteristics of metabolic syndrome and may be a promising biomarker for metabolic syndrome,” said Jialal. “As it’s also an indicator of inflammation and insulin resistance, it could also emerge as part of a biomarker panel to define high-risk obesity states. The good news is that with weight loss, you can reduce chemerin levels along with the risk for metabolic syndrome.”

To conduct the study, Jialal and colleagues recruited 45 patients with early metabolic syndrome — defined as having at least three risk factors for metabolic syndrome including central obesity, hypertension, mild increases in glucose levels not yet in the diabetic range (<126 mg/dl), hyperlipidemia without cardiovascular disease or diabetes. A control group of 30 subjects had less than two risk factors for metabolic syndrome, with normal glucose and triglyceride levels. Both groups were matched for gender and age.

Complete blood counts, lipid profiles and blood glucose, blood pressure and C-reactive protein levels were measured in all participants. Levels of four proteins secreted by adipose tissue — chemerin, resistin, visfatin and omentin-1 — were also measured in plasma and in subcutaneous fat samples from gluteal tissue.

The researchers found that chemerin levels were increased and omentin-1 levels were decreased in both plasma and gluteal fat of subjects with metabolic syndrome compared to those in the control group. The abnormal levels of these two proteins were also independent of age, body mass index and waist circumference.

“Future large epidemiological studies should focus on evaluating the role of chemerin as a biomarker for the development of diabetes and cardiovascular disease in metabolic syndrome,” Jialal said.

AstraZeneca and Ardea Biosciences today presented results from a large study of allopurinol, a treatment commonly used to lower uric acid in patients with gout. The LASSO (Long-term Allopurinol Safety Study evaluating Outcomes in gout patients) study was a multinational, 6-month, open, prospective observational study involving 1,735 patients with gout and was designed to evaluate the safety and efficacy of medically appropriate doses of allopurinol. Results of the LASSO study showed no new safety signals with allopurinol doses of approximately 300mg/day. The study also revealed that at the time of last dose fewer than half (43%) of patients taking allopurinol achieved the target serum uric acid (sUA) level of <6.0 mg/dL, the level recommended by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR). Results of the LASSO study were presented today at the ACR Annual Meeting in San Diego, CA.

Allopurinol, the most commonly used treatment to lower blood uric acid levels in gout, is a generic treatment that has been available for more than 50 years. It is a xanthine oxidase inhibitor, a class of drugs intended to reduce the bodys production of uric acid. Allopurinol is recommended at doses between 100mg and 900mg per day, depending upon disease severity. The LASSO study encouraged investigators to increase, or titrate, the dose of allopurinol over the six months of the study to a medically appropriate dose. There was a high rate of adherence to therapy (97% across doses) and the most commonly used dose was 300mg. Approximately 45% of patients finished on the same dose as their baseline dose. Results show that even among patients titrated to final doses above the most commonly used dose of 300mg/day, approximately 46% did not reach target sUA levels of <6.0 mg/dL.

"Gout is a painful form of arthritis that is often misunderstood and inadequately treated. The LASSO study demonstrates that many patients with gout fail to reach the recommended treatment goal," said study co-author Nicola Dalbeth, MD of the University of Auckland. "Failing to reach the recommended sUA target leaves patients with gout at risk for further disease progression and long-term consequences of gout."

The results of this large, multinational, prospective observational study of gout are consistent with published literature confirming many patients do not reach sUA targets with allopurinol therapy as currently used.

Specific findings from LASSO include:

- The study revealed no new safety signals with allopurinol (approximately 300mg/day).
- There were no cases of allopurinol hypersensitivity syndrome in this study.
At the time of last dose 43% of all patients in the study achieved target sUA levels of <6.0 mg/dL.
- Of patients in the study at final doses above 300mg/day, approximately 54% achieved target sUA levels of <6.0 mg/dL.
- Gout is the most common form of inflammatory arthritis with a prevalence of 8 million in the U.S. Gout is commonly misrepresented as a lifestyle disease. While diet can contribute to elevated levels of uric acid, the majority of uric acid is produced by the bodys naturally occurring processes, and gout is most often caused by the inefficient excretion of uric acid by the kidneys.
- In patients with gout, abnormally high levels of uric acid in the blood known as hyperuricemia lead to deposition of needle-like crystals in joints and soft tissues throughout the body, causing inflammation. Hyperuricemia results when the kidneys do not efficiently remove enough uric acid, or when the body produces too much. A persons genetics play a significant role in their risk of developing gout. The most common symptom of gout is extremely painful arthritis. Over time, the deposits of uric acid crystals may lead to joint damage, visible nodules called tophi, and impaired quality of life. Additionally, gout has been associated with serious health problems including cardiovascular disease, diabetes and kidney damage.

I hate to say I told you so.  But I did.  Like a million times.  Yet, the fear of cholesterol continues.  What is it?  Is it the Lipitor ads?  Is it your cholesterol-phobic doctor, determined to get your cholesterol under 200 mg/dl at all cost?  Whatever it is, its about time we stopped worrying so damn much about high cholesterol.  This new study, entitled "Is the use of cholesterol in mortality risk algorithms in clinical guidelines valid?  Ten years prospective data from the Norwegian HUNT 2 study.", shows us why.  Did anybody hear anything about this one in the media??  I didnt think so, not with a catchy title like that.  At least now the 3 people that read my blog will be aware of it.  The researchers followed 52,087 Norwegians aged 20-74 who were free of cardiovascular disease (CVD) for 10 years, then assessed the relationship of total cholesterol with total mortality, CVD mortality, and ischemic heart disease mortality (IHD).  (Just to be clear, CVD mortality signifies deaths from any disease of the cardiovascular system, while ischemic heart disease ers only to diseases involving restricted blood flow to the heart.)  Lets jump straight into the data then, shall we?  And another note:  since this study comes from Europe, the units for blood cholesterol are shown in mmol/L, rather than the mg/dL that we are used to.  The researchers classified the participants into four groups, based on their blood cholesterol.  Here are the converted unit values in mg/dL for the four groups...  <193, 193-229, 230-269, and >270


First, the least shocking data.  This graph compares the association between cholesterol levels and death from ischemic heart disease.  For the men, it looks like theres not much variation.  Deaths from heart disease rose slightly along with cholesterol levels, but nothing dramatic.  Women, on the other hand, yielded a much more interesting result.  Clearly, by a LARGE margin, cholesterol below 193 mg/dL was most predictive of death from heart disease.  All other groups, including the group with cholesterol over 270 mg/dL, showed significantly lower risk.  Yes, seriously.  On to the next graph!




This one here shows the association between cholesterol and cardiovascular disease, or CVD, which includes heart disease with stroke and any other disease of the cardiovascular system.  Again, lets begin with the men.  The lowest risk appears to lie in those with total cholesterol between 193 and 229 mg/dL, but a close second is the next range up, from 230 to 269.  If you know your erence ranges, you know that anything over 200 is considered dangerous.  Does anybody ever bother to check why this is considered dangerous, or do we just accept it without question??  Clearly, the data from this study suggests that a cholesterol level in men between 193 and 269 is optimal for CVD prevention.  As for women... oops, looks like they screwed up the data there!  They must have it backwards!  Except they dont... yes, the data shows that if youre a woman, the higher your cholesterol is, the lower your risk of death from CVD.  Id repeat it, but Ill be doing that again shortly.  Read on to all-cause mortality!


Here we are, all-cause mortality... the only statistics that really matter.  Deaths from IHD or CVD are cool, but not nearly as cool as all-cause mortality.  This one cuts through the bullshit.  Its not your risk of dying from one disease that really matters, its your risk of dying overall.  So, for men... the group with the HIGHEST risk of dying overall had the LOWEST cholesterol (below 193 mg/dL).  Even those with a cholesterol level over 270 fared better.  The sweet-spot, protective level here was shown to be 193-229, a level that, based on the current erence ranges, will likely get you prescribed a statin drug for being too high!  Its just not right I tell ya.  And for the women, we see another complete inverse relationship between blood cholesterol and all-cause mortality.  High cholesterol appears to be protective for the ladies!  Maybe I could incorporate that into a pickup line somehow... but I digress.

So, does this prove anything?  No.  Not really.  Although it happens to be in accordance with what I believe, its all just observation.  But this isnt the only study to show this kind of trend, just the most recent; there are at least 20 others like it if you just follow that link.  And it certainly makes a strong case for women... having low cholesterol, in the healthy erence range, mind you, just appears to be straight up deadly!  Despite the studys inability to conclusively prove anything, that didnt stop the researchers from letting loose a little on the drug industry.  And I quote from the conclusion of the paper... "Many individuals who could otherwise call themselves healthy struggle conscientiously to push their cholesterol under the presumed danger limit, coached by health personnel, personal trainers, and caring family members.  Massive commercial interests are linked to drugs and other remedies marketed for this purpose."  That may not seem so harsh, but for a group of researchers to say this and imply that massive commercial interests are wrongly influencing the clinical guidelines... thats a pretty strong statement.  And I agree wholeheartedly.  The guidelines need to be reassessed.

What does this mean, though, if having high cholesterol isnt a bad thing?  What are the implications?  Well, for one, maybe it will get people off these ridiculous statin drugs.  But even more significant, to me, are the implications for saturated fat consumption.  These days, everyone just "knows" saturated fat is bad.  But if I asked you, could you tell me why?  The standard answer is, because saturated fat raises your blood cholesterol.  Well... um... so what?  If you step outside of this cholesterol=bad paradigm for a while, things start to look a bit different.  What else is known about saturated fat?  Well, if you eat more of it, it makes up more of your cell membranes, and its highly resistant to oxidative damage.  So thats good, it protects your cells.  And... short-chain saturated fats like butyric acid, found in butter, are burned perentially as fuel and promote proper immune function.  And... saturated fats enhance calcium absorption, along with all the fat-soluble vitamins (A, D, E, K).  And dont forget, if youre a woman, having high cholesterol appears to be beneficial.  Wait a minute... could saturated fat be... healthy!?  So much for a French paradox...