Obesity, Metabolomics & Precision Medicine
Martin Hornshaw, PhD
Another year older, another year wiser, another Christmas has come and gone
Another year has passed. Another year older and perhaps another year wiser. We’ll see. At times like this we tend to look around us, take stock, and make grand New Year’s resolutions. Now that we’re a few weeks into 2017, how are yours holding up?
Like many of us over the holidays, Santa Claus will have had far too many treats. Just on his one-nightly travel through the UK, I estimate that he must have eaten approximately 10 to 20 million mince pies and a similar number of glasses of sherry. And, then it was on to the U.S. for milk and cookies on every hearth. Any way you look at it, that’s some serious overindulgence. Even magical beings need to look after their health. When I think that the average Christmas day lunch alone is typically the equivalent of a whole day’s calorific intake, then you can understand why Santa and so many of us might be in trouble.
An epidemic of obesity
You have no doubt heard and read lots about the problem of obesity in the Western world in recent years. Let’s look at the size and shape of that with some numbers. I am going to look at England (selfishly) and the U.S. First the U.S. In 2009-2010, more than two-thirds of adults were considered to be either obese or overweight1 with about half of those being obese. In 2013-2014, the percentage of adults aged 20 years and over who were either overweight or obese was nearly 71%, with those obese at approximately 38%2.
The fat man of Europe
The UK is known as ‘the fat man of Europe.’ Cheek! Specifically, for England in 20153, 27% of the adult population were obese, with 41% of adult men and 31% of women being overweight. So, the size and shape of obesity in the population of rich nations is basically big and round. Maybe not so jolly though, as we shall soon discuss. Today, obesity levels are more than three times what they were in 1980 when I had just become a teenager.
Why should we care about being obese or not?
Putting it simply, it is estimated that being obese removes nearly 10 years of your expected life span. That is not a happy statistic to read. Obesity is also associated with increased risks for many diseases, so the life you live if you are obese will also be considerably less healthy. In the time it took for me to go from a young teenager to a middle-aged man with teenage and younger children of my own (one generation), obesity levels have gone through the roof. It is no wonder that the medical community refers to our incidence of obesity in the West as epidemic.
Santa’s, my and your health
So, am I right to be worried about Santa’s health? Can he and we keep up this kind of over-eating coupled with overwork year after year? How might we keep tabs on signs of developing disease like diabetes, coronary artery disease, hyperlipidaemia and fatty liver disease? And, let’s not forget the big one: cancer. This kind of impact on health and life expectancy is no laughing matter.
Wake up! Snap out of it! Pay attention. What is happening to us?
For many of us, we happily go along living our lives, gaining weight slowly and exercising less as the years go by. Before we know it, we’re 10, 20, 30…% heavier than when we were young. Then something comes along - some ache or pain sends us to the doctor, who gives us a proverbial diagnostic slap in the face.
Perhaps your doctor gives you a health warning. Some of us will wake up and take action, but for others, perhaps even then, we feel that we cannot make the changes needed to regain our good health. It’s all too much. What if during that visit you gave a small blood sample to be analyzed by metabolomics (more about this shortly), which could tell you a great deal about your health? What if the doctor could say to you, “Looking at your blood results, you are almost certain to develop such-and-such a disease in the next five years and indeed are already showing the early signs of that. I want you to do the following to prevent or delay that.” That would be ideal, wouldn’t it? Preventing a disease before it even happens. That is what medicine should be all about.
What signs? What are these signs? Tell me!
Metabolites measured with metabolomics.
Metabolites are biochemicals that are a result of metabolism. An understanding of metabolism is important or even critical to our understanding of phenotype and changes to phenotype (healthy to unhealthy, for example), as metabolism is integral to good health. You will certainly know some metabolites such as glucose, vitamin B12 and cholesterol. These are made in our bodies (sometimes by our gut microbiome) or come from food, for example. There are thousands of metabolites that can potentially inform us about our health status, and looking at changes in the concentration of metabolites in blood can tell you about health or its lack. For example, recent studies have looked at lipid profiles with far more detail than would be possible in current clinical labs by using mass spectrometry to observe cardiovascular disease4 and diabetes5,6 and have identified clear signatures of illness.
We may have a technology that could help Santa, and you and me, get into better shape and perhaps live longer, healthier lives. It is early days yet, but looks promising. What I want to tell you about is metabolomics. In brief, metabolomics is the study of the complete set of metabolites (the metabolome) in an organism, organ, tissue, cell type, body fluid, etc.
The metabolome is not static like the genome, but is responsive to change, such as disease, diet and lifestyle. As such, it is a deeply interesting area for study in relation to health and illness. We can use this dynamic nature of the metabolome to our advantage to understand mechanisms of disease. From that, we can identify biomarkers that can be applied to prognosis, diagnosis and treatment response in personalized or precision medicine and ultimately change people’s lives for the better.
Precision medicine & metabolomics
I want to direct your attention to two videos relating to metabolomics in precision medicine. The first is of Dr. John Ryals, Metabolon’s CEO, describing metabolomics and how it is being used in “Metabolomics as a First-Line Phenotyping Tool.” Phenotyping here relates to the ability to measure phenotype (diseased/not diseased; responder to/non-responder to a pharmaceutical, for example) with measurements of metabolite levels using metabolomics. Based on the presence or absence of specific alleles in your genome, genomics can only make a prediction, with varying degrees of accuracy, on whether you may eventually develop a disease. It does not measure the actual phenotype. However, metabolomics does measure what is actually happening; it provides a picture of your current health status.
Just as interesting, but from a deeply personal perspective, is “Precision Medicine - Casey’s Story.” This video tells you about Casey, her mother and her brother Tanner and how cancer caused by the p53 gene mutation affected them. We’ve been monitoring Casey monthly for about three years, in collaboration with JCVI, TGen and UCSD, to identify biomarkers that may indicate early stages of cancer. We’re using our technology to pick up changes at “Stage 0” that may enable a more positive clinical outcome. It is ‘early days’ for this application of metabolomics, but it looks promising. Let’s hope it stays early for Casey.
Where is metabolomics heading in precision medicine?
Metabolon has a vast database of metabolites, knowledge of metabolism and proprietary informatics. We are currently developing a global health assessment product that may soon give clinicians unprecedented insight into an individual patient’s health. I hope to be able to give you more information about this soon.
Lifestyle choices for Santa
So, if I were a health professional what might I say to Santa? “Santa you live quite an unhealthy lifestyle. I'm concerned about you. First let’s check if my concerns are valid. We can detect early signs of insulin resistance by measuring certain metabolites with a test called Quantose IR®. Insulin resistance might well lead to type 2 diabetes if not addressed. If we determine that you are showing those signs, then we can act to stop or delay the onset of the disease.” Santa could use his Quantose IR score to help motivate him to kick-start (and stick with) his New Year’s resolution to lose weight and exercise more! It’s better to know that you are heading into a serious chronic disease while there’s still time to do something about it.
We are living in a world where the whole paradigm of medicine is shifting from impersonal to personal, unfocused to focused, and sometimes effective to always effective - at least, that is the dream or even the expectation of precision medicine. Metabolomics certainly has its part to play.
1. Data from the National Health and Nutrition Examination Survey 2009-2010.
2. Health, United States, 2015, table 53.
4. Stegemann et al, Circulation 2014; 129: 1821-1831
5. Rhee et al, J. Clin Invest 2016; 121: 1402-1411
6. Forouhi et al, Lancet Diabetes Endocrinol 2014; 2: 810-818