metabolic syndrome

Fat but Fit? Research on Obesity and Health

lborkowski — Tue, 28 Sep 2010 16:45:31 +0000

Fat but Fit? Research on Obesity and Health

Peter Janiszewski at Obesity Panacea has posted a fascinating series on the issue of people who are obese but metabolically healthy. We worry about rising rates of obesity because obesity increases the risk for health problems like diabetes and cardiovascular disease -- but what if that's not universally true? And if it turns out that some obese people aren't at an increased risk of chronic diseases, should they still be urged to lose weight?

The first post in the series introduces the definitions of "obese" and "metabolically healthy":

To date, countless epidemiological studies have shown that as you move from a normal weight (BMI = 18.5-24.9 kg/m2) towards overweight (BMI = 25-29.9kg/m2) and obesity (BMI â¥ 30 kg/m2) the risk of many diseases increases exponentially.

... Today it is believed that approximately 25-30% of obese individuals Â¬remain metabolically healthy (normal blood glucose, blood lipids, blood pressure, and cytokine profile) despite their excess weight.

Janiszewski notes that there are no established criteria for "metabolically healthy," so studies using different criteria may find different percentages of the obese population to meet this description. It's also good to keep in mind that while the BMI cutoffs are useful for studying population health (e.g., tracking the percentage of the population with BMIs of 30+), they're not necessarily the best indicator for determining whether any given individual is at an ideal weight (e.g., athletes may have high BMIs because they have lots of muscle mass, not because they have high body-fat percentages).

With those caveats in mind, what does research tell us about the health of obese individuals with different metabolic health status?

In the second post, Janiszewski describes two studies that divided research subjects into groups based on their BMI categories and the presence or absence of metabolic syndrome. Researchers tracked their subjects for more than a decade and recorded the development of diabetes and cardiovascular disease. Both studies found that subjects who were overweight or obese were not at increased risk for developing CVD; one found no increased risk for diabetes, and the other found obesity in the absence of metabolic abnormalities to be "a relatively weak risk factor" for developing diabetes.

From those two studies, it sounds like an overweight or obese person might be able to stave off health problems by remaining metabolically healthy. Exercise is a great way to reduce the risk of developing metabolic syndrome - so, as some put it, fitness may be just as important fatness.

The third post raises a caution for those of us who might feel justified in hitting the doughnuts after a vigorous workout. Janiszewski talks to researchers Jennifer Kuk and Christopher Ardern, whose study (published recently in Diabetes Care) looked at death rates among the overweight and obese and found that death rates are higher for obese individuals, regardless of whether they're metabolically healthy or not. (Kuk also notes that they used a more strict definition of "metabolically normal," which suggests that only about 6% of obese individuals are metabolically healthy.) Kuk reports on what they found about causes of death:

80% of the deaths in the metabolically-healthy obese were due to cancer and 'other' causes. Other causes are likely traumatic injuries, which highlights an important point. Obese individuals are less likely to survive a trauma as compared to normal weight individuals despite similar injuries. This is related to longer transport times due to their higher body weight, and difficulty assessing and treating the injuries due to their increased size. Further, they are less likely to see their physicians regularly, which may be in part why cancer is generally diagnosed in obese individuals at later stages. Thus, this study fits in line with the idea that these individuals are not more likely to develop these metabolic diseases, but still die from other causes.

Based on this research, it does sound like everyone who's obese should be advised to lose weight. But, Janiszewski asks, what if weight loss can actually be detrimental to health? His fourth post describes a study that followed obese women, 20 of whom were metabolically healthy and 24 of whom were deemed metabolically at-risk based on their insulin sensitivity (sensitivity to insulin is good). After a six-month medically supervised weight loss period, in which all women lost significant amounts of body weight, researchers evaluated subjects' insulin sensitivity. The metabolically at-risk group showed a 26% increase in insulin sensitivity - but, the counter-intuitive finding was that insulin sensitivity in the metabolically healthy subjects actually dropped 13%. This surprising finding has yet to be corroborated, Janiszewski reports, and I'd like to see a study with a larger sample size take on this issue.

Janiszewski's fifth post describes a study he and his colleagues conducted (which has just been published in Diabetes Care) to examine this same question with a somewhat different study design. They looked at both women and men, used different weight loss intervention (diet alone, exercise alone, and both), and assessed changes in body composition, blood lipids, and other variables. Their 63 metabolically healthy obese subjects and 43 metabolically unhealthy obese subjects engaged in their assigned interventions for 3-6 months. They actually found that insulin sensitivity improved in both groups, and the improvement was similar for the groups using different interventions.

Janiszewski reaches a familiar conclusion: "All obese individuals have something to gain from a modest 5-10% weight loss." Given that so many people try and fail to achieve sustainable weight loss, though, it's also helpful to see that regular exercise can reduce the risk of metabolic syndrome and, consequently, the risk of cardiovascular disease and perhaps diabetes. That risk reduction might not translate to longer lives, but it can certainly improve quality of life.

The whole series is well worth a read; you can start here with Part 1.

lborkowski Tue, 09/28/2010 - 12:45

Tags

obesity

Research

metabolic syndrome

metabolically healthy

obesity

Research

The obesity "epidemic" can be plausibly framed as a moral panic to blame health insurance cost increases on deficient people who get sick. The BMI is an early 19th century construct, the canonical ranges for overweight and obese

http://www.morris.umn.edu/~sungurea/introstat/history/w98/Quetelet.html

appear arbitrary. Body fat, which can now be conveniently measured, would be a more plausible measure of adiposity. Best outcomes for mortality, I think, are among the "overweight," while underweight (and I would guess low normal weight) is a risk factor.

I'm not in favor of "obesity." It's not aesthetic and is associated with specific health conditions. But I question whether "normal" weight is realistic. There's a literature on the adverse effect of body image concerns on mental health of women, but the ideals posed by media promoted actors and models are mostly underweight or borderline.

If the main causes of higher death rates are that it's taking longer to transport obese patients, and longer to assess some of their injuries, maybe the problem isn't with the patients but with the health care system.

There is nothing inevitable about the capabilities of medical hardware; yes, paramedics are humans with finite capacities, but a lot of the time that transport involves moving someone onto a wheeled bed, which can be made strong enough for large patients. I'd also like to see comparisons between transport times for, say, women weighing between 160-225 pounds and no more than 5'8" high, and men of the same range of weights with heights between 5'3" and 6'6". There is enough documented anti-fat prejudice among health professionals (not necessarily worse than in the population at large, but that's a significant amount), leading to delays in treatment when patients are at the doctor and asking for treatment, that I suspect it's delaying treatment and transport of emergency patients as well.

At least some of the "difficulty assessing and treating" might be addressed by better medical education: if a lot of your patients are fat, you should learn how to assess their injuries, not just those of thin to average-weight people. And some are hardware issues, yes: but again, if that many of your patients are more than X circumference, the hardware should be made to handle that.

Anecdotal, but it stuck with me: a friend of mine, years ago (before I knew her) was stabbed by a robber. On her way into the ER, the surgeon told her that because she was fat, she was likely to die on the table. There is no conceivable medical reason for telling a patient that. Even if it had been true, she wasn't going to go on a diet pre-surgery, and believing you're going to die doesn't improve outcomes. After the surgery, her doctor told her that the only reason she had lived long enough to reach the OR was that she was fat: her body fat had kept the knife from damaging a vital organ.

A surgeon who expects his fat patients to die might not make as much of an effort for them. A triage team that believes that might treat thinner people first, rather than "waste" resources. And time matters in trauma care.

I call BS on the idea that obese people are disadvantaged in traumas- it depends on what kind of trauma. They are MUCH better off if they get shot or stabbed in the torso than someone of a lower weight. I would imagine body fat to be useful when surviving a fall (depending on how you land, of course).

I've attended countless traumas, and outside of extreme situations the team has *always* been able to do their assessment. They are probably referring to the log roll portion of things.

I bet that it has more to do with how crappy overweight people are treated in hospitals. Everyone, from doctors to CNAs, complain and deride those patients for being overweight. Doctors can dismiss many problems based on the patient's weight when it isn't warranted. Patients who are people of color or women die in hospitals more too, because of the social attitudes of their care providers. Was this adjusted for in any way?

The definition of obesity seems to vary geographically.

When I lived in Southern California about a decade ago, I was 5'5" and 145 lbs. My primary care doc told me I had some vastly increased chance of getting breast cancer if I didn't get my weight down under 130 lbs. (Oddly enough, she didn't discuss type II diabetes, heart disease, etc.)

A few years later, I moved to Northern California. One possible side effect of a medication was weight loss. I weighed about 150 lbs by then (and wasn't more muscular), and my doctor warned me that if I lost any weight, she'd have to take me off that med, as I was in danger of becoming underweight. Now that I'm about 165 lbs, my current doctor suggested it might be a good idea to get back to 150 lbs.

In any case, all my doctors urged healthier diet and more exercise.

CA anonymous - good to see that your doctor actually discussed exercise with you. For how many chronic diseases can be partially prevented by exercise I am amazed that I have never been asked by primary physician whether I was physically active (did he assume because I am thin?) and that none of the questionnaires about medication, family history, and previous illness ever address this issue. While BMI is a controversial metric for health, physical activity level is not controversial, yet one is clearly more obsessed about than the other. Why is that?

There are definitely concerns about how medical professionals treat obese patients. I expect they come into play more often in primary care, as described in this Washington Post article. In their article on obesity and mortality risk, Kuk and Ardern write, "Obese individuals are more likely to die from traumatic incidences" and cite this study by Viano, Parenteau, and Edwards, which found:

Based on the simple model, the relative injury risk (r) for an increase in body mass is given by: r = (1 + Î m / m)0.5. For a given stature, an obese occupant (BMI = 30-35 kg/m2) has 54-61% higher risk of injury than a normal BMI occupant (22 kg/m2). Matched pairs showed that obese drivers have a 97% higher risk of fatality and 17% higher risk of serious injury (MAIS 3+) than normal BMI drivers. Obese passengers have a 32% higher fatality risk and a 40% higher MAIS 3+ risk than normal passengers. Obese female drivers have a 119% higher MAIS 3+ risk than normal BMI female drivers and young obese drivers have a 20% higher serious injury risk than young normal drivers.

The study also references findings from other research:

Obesity influences injury risks in motor vehicle crashes. Mock et al. (2002) found the risk of fatal injury increased with body mass index (BMI). In contrast, Wang et al. (2003) found the risk of abdominal injury decreased with body fat. Other studies have shown relationships between obesity and injury (Whitlock et al., 2003; Reiff et al., 2004).

Zhu et al. (2006) analyzed the effect of BMI on fatally injured occupants using the 1997-2001 National Accident Sampling System-Crashworthiness Data System (NASS-CDS). Linear regression showed a correlation between BMI and the risk of fatality in male occupants. For males, velocity and type of collision were significant factors, while occupant age, seatbelt use, and airbag deployment were not. For females, obesity did not affect the risk of fatality. Since the effect of obesity in motor vehicle crashes has not been more fully described in the literature, further analysis was conducted of NASS-CDS field accident data from 1993 to 2004 to compare injury risks for obese and average weight occupants using matched pair analysis (Evans, 1986; Cummings et al., 2003a, 2003b).

These are all specific to car crashes, which are the leading cause of injury deaths in the US. It sounds like obese vehicle occupants may be more likely to receive serious or fatal injuries during vehicle crashes in the first place.

Pocket Science - when enslaved bacteria go bad, gut microbes and fat mice, and stretchy beards of iron

edyong — Fri, 05 Mar 2010 08:35:04 +0000

Pocket Science - when enslaved bacteria go bad, gut microbes and fat mice, and stretchy beards of iron

The Not Exactly Pocket Science experiment continues after the vast majority of people who commented liked the pilot post. I'm really enjoying this, for quite unexpected reasons. It's forcing me to flex writing muscles that usually don't get much of a workout. Writing short pieces means being far more economical with language and detail than usual. It means packing in as much information as possible while still keeping things readable. And it means blitz-reading papers and writing quickly without losing any accuracy.

One quick note before the good stuff: last time, a few people suggested that I put each NEPS item in a separate post, but the majority preferred multiple items per post. For now, I'm keeping it that way because otherwise, the longer pieces would be diluted by the smaller ones. We'll see how that works for the foreseeable future.

Rising DAMPs - when enslaved bacteria turn our bodies against themselves

Our immune systems provide excellent defence against marauding hordes of bacteria, viruses and parasites, using sentinel proteins to detect the telltale molecules of intruders. But these defences can be our downfall if they recognise our own bodies as enemies.

All of our cells contain small energy-supplying structures called mitochondria. They're descendents of ancient bacteria that were engulfed and domesticated by our ancestor cells. They've come a long way but they still retain enough of a bacterial flavour to confuse our immune system, should they break free of their cellular homes. An injury, for example, can set them free. If cells shatter, fragments of mitochondria are released into the bloodstream including their own DNA and amino acids that are typical of bacteria. Qin Zhang showed that trauma patients have far higher levels of such molecules in their blood than unharmed people. Our white blood cells have sentinel proteins that latch onto these molecules and their presence (incorrectly) says that a bacterial invasion is underway.

This discovery solves a medical mystery. People who suffer from severe injuries sometimes undergo a dramatic and potentially fatal reaction called "systemic inflammatory response syndrome" or SIRS, where inflammation courses through the whole body and organs start shutting down. This looks a lot like sepsis, an equally dramatic response to an infection. However, crushing injuries and burns can cause SIRS without any accompanying infections. Now we know why - SIRS is caused by the freed fragments of former bacteria setting off a false alarm in the body. The technical term for these enemies within is "damage-associated molecular patterns" or DAMPs.

Reference: Nature DOI:10.1038/nature08780

Different gut bacteria lead to mice to overeat

On Wednesday, I wrote about the hidden legions residing up your bum - bacteria and other microbes, living in their millions and outnumbering your cells by ten to one. These communities wield a big influence over our health, depending on who their members are. Matam Vijay-Kumar found that different species colonise the guts of mice with weakened immune systems, and this shifted membership is linked to metabolic syndrome, a group of obesity-related symptoms that increase the risk of heart disease and type 2 diabetes.

Vijay-Kumar's mice lacked the vital immune gene TLR5, which defends the gut against infections. Their bowels had 116 species of bacteria that were either far more or less common than usual. They also overate, became fat, developed high blood pressure and became resistant to insulin - classic signs of metabolic syndrome. When Vijay-Kumar transplanted the gut menagerie from the mutant mice to normal ones, whose own bacteria had been massacred with antibiotics, the recipients also developed signs of metabolic syndrome. It was clear evidence that the bacteria were causing the symptoms and not the other way round.

Vijay-Kumar thinks that without the influence of TLR5, the mice don't know what to make of their unusual gut residents. They react by releasing chemicals that trigger a mild but persistent inflammation. These same signals encourage the mice to eat more, and they make local cells resistant to the effects of insulin. Other aspects of the metabolic syndrome soon follow. The details still need to be confirmed but for now, studies like this show us how foolish it is to regard obesity as a simple matter of failing willpower. It might all come down to overeating and inactivity, but there are many subtle reasons why an individual might eat too much. The microscopic community within our guts are one of them.

Read an amazing take on this from Carl Zimmer at the Loom and a previous post from me

Reference: Science DOI:10.1126/science.1179721

The stretchy iron-clad beards of mussels

For humans, beards are for catching food, looking like a druid, and getting tenure. But other animals have beards with far more practical purposes - mussels literally have beards of iron that they use as anchors. The beard, or byssus, is a collection of 50-100 sticky threads. Each is no thicker than a human hair but they're so good at fastening the mussels to wave-swept rocks that scientists are using them as the inspiration for glue. So they should. The byssus is a marvel of bioengineering - hard enough to hold the mussel in place, but also stretchy enough so that they can extend without breaking.

The mussel secretes each thread with its foot, first laying down a protein-based core and then covering it in a thick protective layer that's much harder. When Matthew Harrington looked at the strands under a microscope, he saw that the outer layer is a composite structure of tiny granules amid a looser matrix. The granules consist of iron and a protein called mfp-1, heavily linked to one other - this makes the byssus hard. The matrix is a looser collection of the same material, where mfp-is 1 heavily coiled but easy to straighten - this lets the byssus stretch. The granules have a bit of give to them but at higher strains, they hold firm while the matrix continues extending. If cracks start to form, the granules stop them from spreading.

It's unclear how the mussel creates such a complicated pattern, but Harrington suggests that it could be deceptively simple - changing a single amino acid in the mfp-1 protein allows it to cross-link more heavily with iron. That's the difference between the tighter granular bundles, and the looser ones they sit among.

More from Eric Bland at Discovery News and stories of bioengineering from me, including triple-armoured snails, shatter-proof teeth and sharp squid beaks.

Reference: Science DOI:10.1126/science.1181044

Cause of dinosaur extinction ~~revealed~~ confirmed

Sixty-five million years ago, the vast majority of dinosaurs were wiped out. Now, a new paper reveals the true cause of their demise - legions of zombies armed with chaingu... wait... oh. Right. An asteroid. You knew that.

More from Mark Henderson at the Times

Reference: Science DOI:10.1126/science.1177265

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edyong Fri, 03/05/2010 - 03:35

I just wanted to say that I prefer the multiple articles per post for two main reasons:

1) It forces me to look at research I might otherwise avoid since it's already right in front of me to read. Sort of like a newspaper or magazine. I use a feed reader so I'll avoid articles that don't catch my attention.

2) I read from my iPod, so multiple posts in one place is much more convenient. It makes it much more likely for me to read each article.

Further, I'm still loving the pocket science. Great for those of us that are super-busy, want to keep up on interesting finds, but don't have the time to get into a full article.

once again I am glad I have this site bookmarked. Some really fun stuff there! Thank you for spending the time that you do on this blog.

Re: gut bacteria. So does this mean obesity might be contagious after all? :)

I like this pocket science experiment.

I think the longer format is much better. Quality before quanity. Either way, however, you're doing a great job.

I hear you, Steve, and I feel largely the same. If I had infinite time on my hands, I'd give everything the full treatment. The short format does allow me to cover stories that I don't actually have much to say about but I thought were worth a mention. For example, I didn't really have much more to write about the mussel beards than the three paragraphs above. In previous months, I'd have just ignored it.

As I said in the pilot post, if I suspect that the Pocket Science posts are compromising the quality of the longer pieces, I'll cut back or stop them.