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Personalized Prevention, Part III: Applying the Model to Obesity

April 2, 2012

Weight loss (or gain) = calories in minus calories out.  Simple, right?  Well actually, not as any person who has gained a few pounds and can’t shed them will attest.  It seems as we grow older, our metabolism slows. There is also good evidence that once we put on weight, our body re-adjusts to ‘defend’ (that’s a word scientists use) that new weight. Stated another way, if you gain 10 pounds, then lose 10, your body goes into a state where various hunger hormones are secreted more often than they’d be in the case of someone who never gained the 10 lbs. Tara Parker-Pope covered this wonderfully in a recent NY Times Magazine article called The Fat Trap.

But actually that’s only true for some of us.  Those of you who were around to witness the amazing performance of Robert DeNiro in Raging Bull (1980) know he gained 50 lbs to play the character of Jake LaMotta in his later life.  After the film, DeNiro lost the weight promptly and easily.  He can be seen as slim and trim playing a priest in True Confessions  (1981) not long after. Even if you look at modern-day pictures of DeNiro (e.g. in Little Fockers 2010), he is no where near as heavy as he was when he played the senior LaMotta 30 years before.

Ok, now are you convinced that it is more complicated than simple calories in vs. calories out?

In Personalized Prevention, Part I, I reviewed the concept of connected health as phenotypic mapping and started a discussion of how one type of data might inform our use of the other.  In Part II, I discussed the psychology of engagement as applied to connected health interventions.  In this post, I want to use obesity as an illustration of how it might practically work.  I am not going to cover the public health story on obesity (how we live in a time of calorie excess and a dearth of opportunities to be active).  I know some of you will have that top of mind and may wonder why its not mentioned.  Yes, we’re all growing a bit more overweight as time goes on due to this trend. In general, we’d all benefit from eating more plants, more colorful foods, less animal-based food, less processed food and finding ways to be more active.  Today, I want to talk though about how the genetics of obesity may be able to help us create segments of the population that may respond differently to connected health interventions. Also, response to connected health interventions may be a trigger to prompt genetic testing.

Although I am not an expert on genetics, I have studied up on the genetics of obesity as I am giving at talk at BioIT, May 25, at the BIO meeting in Boston.  We are a long way off from having exact obesity genotypes the way we now do for certain cancers and the like.  But the genetics argue that we can distinguish at least 5 genotypes:

  • Thrifty genotype: low metabolic rate and insufficient thermogenesis
  • Hyperphagic genotype: poor regulation of appetite and satiety and propensity to overfeed
  • Sedens genotype: propensity to be physically inactive
  • Low lipid oxidation genotype: propensity to be a low lipid oxidizer
  • Adipogenesis genotype: ability to expand complement of adipocytes and high lipid storage capacity

Imagine a world where we knew this information before or shortly after birth.  Could you envision someone with either the thrifty genotype or the sedens genotype being targeted for an exercise program involving activity monitoring and customized motivational tools as were discussed in Parts I and II? If we got to these folks when they were young, do you think we’d have the ability to reorient their lifestyle choices for the better?

One example worthy of consideration is the partnership we have with the Boston Public Schools to encourage activity in children from some of our underserved schools.  I blogged on this some time ago.  The 2011 program was such a success that we’ve expanded it this year, and we are just launching the spring 2012 program.  The children who took part last year shared numerous stories about how wearing a smart pedometer, getting weekly feedback and participating in a classroom competition on activity helped them become more aware of how active they are, encouraged them to be more active and even bring the culture of activity into their homes.

When people are on a connected health program,  we can determine at an individual and at a population level who is active and who is not responding to the program. Imagine that we could take those data and compare them with genetic data to elicit finer and finer comparisons.

I am wildly enthusiastic about personalized connected health, about the opportunities to combine genetic and phenotypic data to gain insights about individuals and about personalized prevention.

24 Comments leave one →
  1. Tom permalink
    April 2, 2012 9:05 pm

    Kind of like teaching humanoids thousands of years ago that there’s fat in theose bones and this s how you get it. Most young emulate their local experience, let’s make i better.

  2. April 2, 2012 9:09 pm

    indeed. thanks

  3. April 3, 2012 1:42 am

    Activity is so important! Check out this great video by Dr. Mike Evans that puts the importance of exercise in a totally new perspective:

  4. April 3, 2012 8:51 am

    There is an ironic consequence here – some people are born to be fat. Perhaps we can move further as a species by accepting that.

    Today young people have an ideal for their bodies. It is the slim variant – nothing needs to change. However I wonder what is happening with the people who fail to be slim?

    When I went to China twenty odd years ago being fat was an aspiration. Now the aspiration is towards slim so we need to swim with that current. Still, it seems, some people will continue to be fat however much they try.

    I agree with Joe that we have a lot to gain by informing people of their metabolism when we can do so reliably. Equally we should improve our understanding for people who are genetically inclined to be overweight – the costs of the frustrated fatties who cannot help themselves extend beyond healthcare.

  5. April 3, 2012 9:32 am

    I appreciate your comments

    • April 3, 2012 2:57 pm

      Fascinating genotypes. Are there a group of genes that are affected? Is Leptin gene involved in the genotypes you list? Thanks, Vandana Bhide, MD (Mayo Clinic)

  6. April 3, 2012 3:43 pm

    I’ve attached the reference. it was an editorial from 2007.

    Bouchard C, The biological predisposition to obesity: beyond the thrifty genotype scenario. International Journal of Obesity (2007) 31, 1337–1339

  7. April 3, 2012 10:22 pm

    (somehow this didn’t get sent from yesterday)

    Thanks so much for sharing blog, link & video. I love that you are partnering with Boston Public Schools!

    I was fortunate to hear Phil McKinney, former VP/CTO of HP speak at Startupism2012 today. “Ask a question, for example, what is half of 13? But don’t stop at the first answer, everyone has the same answer, move on to the next answer, there is more than one answer. Discoverability is key to innovation.”

    After his Keynote, I was able to ask him about health, education, and technology before he was mobbed. He has been asked by the U.S. Education Dept to help them innovate, for example, this link gives you an idea of his focus: HOW to create killer innovations –

    But as the crowd surged forward, I stepped away, not because I was less passionate than others, but because I felt I was already past the first answer. I hold Phil in the highest esteem but he doesn’t have the same experience/context I have…for example, he home-schooled his children, I’ve kept mine in school but changed around which school to ensure the environment was the one I thought best to enable their success, in being forced to stay at school, I’ve had to research every school I felt realistic enough to commute to and that challenge defines my perspective. I’ve read somewhere that nationally 10% of children attend private schools, where I live over 30% attend private.

    I agree that genotype screening is a good thing, but when is early intervention early enough? In the 1960’s Todd Risley and Betty Hart went into preschools to provided early intervention but their initial positive momentum declined after a certain point, undeterred, they assessed children from 7-9 mos old…

    No, this wasn’t a study on obesity, but I do feel there is a connection between mind and body that we tend to ignore. I agree with speaker/authors Dr. John Ratey: “Spark: The Revolutionary New Science of Exercise and the Brain” and Dr. Daniel Amen: “Change Your Brain, Change Your Body: Use Your Brain to Get and Keep the Body You Have Always Wanted,” that there is a connection between mind and body, health and well-being.

    I hear many argue that electronics and technology are to blame for the increases in ADHD. Phil mentioned today was Autism Awareness Day and we talked about the new U.S. statistic that 1 in 88, 1 in 54 boys have autism costing $137 billion per year –

    Technology for certain has changed us but it has been a systemic evolution of progress towards efficiency. Our brains and bodies are always looking to optimize opportunity. The Bridges’ bodies are more efficient…they need less calories to hold onto fat. I think Risley & Hart were onto something but here’s my thought…just-in-time intervention is important, to keep us on track but it needs to focus on what Dr. Daniel Kahneman termed as System 2 vs System 1 issues., which I think you may be getting at with emotion sensors.

    I truly believe technology has the ability to extend our capabilities and enable us to overcome our natural limitations…it’s looking beyond the first answer, the first system.

    I would love to build a fitness program leveraging technology at my kids’ schools…let me know if this is possible! I’m am all about the possibilities ; )

  8. April 4, 2012 8:31 am

    thanks for all of your thoughtful, rich comments and links! I’m a fan of Kahneman too. reading “Thinking Fast and Slow” right now.

  9. April 5, 2012 12:49 pm

    Very interesting article. As a physician running medically supervised weight management programs, I see the genetic variations amongst the individuals. Very enlightening to have the genetics validated.

  10. April 6, 2012 9:27 am

    its early going, but I have high hopes that the field will mature and allow for hyper segmentation and very personalized health improvement plans.

  11. mikailov permalink
    April 8, 2012 9:48 am

    Really great post!! As a soon to be resident in the Partners program I also look forward to working with early intervention programs in school systems. There is definitely great area of opportunity in this population segment to involve lightweight and thoughtful technology as it relates to healthy behavior

  12. April 8, 2012 12:29 pm

    Loki me up when you get to town (or sooner).

  13. April 9, 2012 9:52 am

    Interesting to read the comments. I think we can make a big step forward when we can say “overweight is bad but it is not necessarily your fault. When your genes are against you there are still things you can do to lengthen your life.”

  14. goftedahl permalink
    April 24, 2012 2:21 pm

    Between my 26+ years of practicing internal medicine, and the last 10 years as Chief Knowledge Officer at the Institute for Clinical Systems Improvement, I’ve had the opportunity to consider the causes and effects of obesity, both from a physiological standpoint, but also from the psychological impact often seen in those who are obese. In fact, I supervised a weight loss clinic for over 7 years, while in practice, and was struck at the time, by the widely different stories, experiences, and frustrations seen in many of those whom I saw.

    This post resonates in that it begins to “destigmatize” the condition of obesity, which is commonly seen–through exhortations for “more will power”, “working harder,” “having more pride in your appearance”– and many more which have permeated our environment.

    Beginning to understand the genomic considerations, with their concomitant associated neurohormonal and protein differences, much like we need to consider in mental health issues, is critical. Eric Topol, MD, in his recent book, The Creative Destruction of Medicine, has similar questions and issues with the impact of our present knowledge or lack thereof in addressing specific issues. While there are many concerns with the impact of genomic information becoming easily accessible, it may be the one step to the “democratization” of health care for our patients which we need.

    Additionally, as we learn more about human behavior, decision making, and the illogical aspect often times seen, the information such as presented by Daniel Kahneman in Thinking: Fast and Slow, as well as many other books, such as Incognito by Daniel Eagleman, Nudge by Thaler and Sunstein, Predictably Irrational and The Upside of Irrationality by Daniel Ariely, How We Decide by Jonah Lehrer, to name a few, should be considered as we battle “system 1 vs. system 2” issues.

    I also see your recognition of the need to move our previously bounded medical thinking into the community, and recognize the relatively small part of our citizen’s lives that we in the health care community can impact, and the need to consider truly different approaches if we are to truly achieve a healthier tomorrow for our citizens. Great piece, and I look forward to reading more.

  15. April 24, 2012 5:38 pm

    Thank you for your wisdom and commentary. I am also a fan of Eric’s book and of Kahnemann’s work!!

  16. Marc Newman permalink
    April 25, 2012 2:48 pm

    Great posts. I know it’s early but finding ways to make knowledge from genomics actionable is vital. We are individuals and we deal with our genomes – consciously or not – by making choices in diet, exercise, lifestyle, behavior that ultimately can mitigate or accelerate our risks. It’s tough to change behavior, just look at the success of Weight Watchers. For those with genomic risks for obesity, how many will change their behavior to deal with it?

    Having said that, I then think of the population as a whole. You have to be struck by the rapid growth of obesity in just a few decades. Makes me think there’s more to this than just calories and perhaps we’re just eating the wrong things. See Gary Taubes’ “Good Calories, Bad Calories.” To have nearly half the US population at risk for T2D is staggering. It’s particularly concerning because people are so used to T2D, they may not realize how (1) it’s a terrible disease and (2) it’s preventable. We may have individual risks but there seems to have been a change toward the wrong calories (too many carbs?) over time. It’s amusing at one level: I attended a briefing on genomics and obesity last week. The lunch contained chips, sandwich, a large cookie, and an apple. We all might have done better with just the apple.

    On the matter of public schools, I realize this is a more complex social issue with many kids lacking access to healthy food alternatives and safe areas to exercise. But why must we allow candy bars to be sold in school vending machines? Why not try testing healthy alternatives? The kids may prefer it!

  17. April 25, 2012 5:45 pm

    There is something called the “obeseogenic environment, which is half the built environment (e.g. We have all of these technologies that obviate the need to expend calories) and the social environment which is all of the poor food choices we make. No question it’s easier than ever to be overweight, but it remains a fact that not everyone is or will be over weight.

  18. fswilhelm permalink
    May 4, 2012 5:14 pm

    As A TPA and health benefit plan payor, I am intersted in finding out this can be done across an employee group population without running afoul of the very strict GINA regulations.

  19. May 6, 2012 5:54 pm

    It’s a good question. I’m only slightly familiar with GINA, but if this concept shows its power, I have to believe there is a work around.

  20. June 15, 2012 4:00 pm

    Terrific posts! One change in the environment that might alter how we think about our eating and exercise patterns will be the introduction of ubiquitous video. As we learn more about how we trick our minds into ignoring what we unconsciously do that brings more calories in or burns fewer calories out, video evidence might help change our minds. The trend of introducing more video into both public and private spaces are pretty striking and it may be worth thinking about how this could effect the obesogenic environment.

    • June 17, 2012 10:05 am

      I quite agree that visualizations of all sorts, including video, are quite powerful at helping folks make associations that stick. these tools are particularly underutilized in healthcare.


  1. Personalized Prevention, Part IV « The cHealth Blog

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