Follow me on

Rare Genetic Obesity May Be Less Rare Thank We Think

sharma-obesity-dna_moleculesharma-obesity-ras-hypothesis genes-rhythmMost of obesity is genetically complex in that it is generally attributable to a large number of genetic variants, each with a small effect size, all working together to promote genetic risk for obesity.

There are however rare obesity forms that are attributable to a single mutation on a single gene.

Now, an international consortium of researchers are trying to collect DNA samples from people who may seem to have one of these rare forms of monogenic obesity.

The Genetic Obesity Project, is a large genotyping study and registry on people with pro-opiomelanocortin (POMC) deficiency and leptin receptor (LEPR) deficiency obesity.

Both are exceptionally rare, although the researchers believe that they may be more common that generally believed (the true prevalence worldwide is unknown).

The Genetic Obesity Project is funded by Rhythm, a biopharmaceutical company developing a MCR4R agonist (setmelanotide) that can result in very substantial weight loss in patients with POMC deficiency (see my previous post on this).

POMC deficiency is characterised by severe, early-onset obesity, hyperphagia, and often adrenal insufficiency from ACTH deficiency. Weight gain continues rapidly, so that by the end of the first year of live, BMI is generally well above the 98th percentile. Red hair and fair skin are often (but not always) present. Occasionally, patients may also have central hypothyroidism from TSH deficiency, and adolescent-onset GH andFSH deficiency.

LEPR deficiency is characterised by severe, early-onset obesity and hyperphagia with impaired pubertal development with reduced secretion of thyrotropin and growth hormone.

More information including where to refer cases can be found here

@DrSharma
New Orleans

Comments

5th Canadian Obesity Summit – Four More Days To Submit Your Abstracts!

banff-springs-hotelEvery two years the Canadian Obesity Network holds its National Obesity Summit – the only national obesity meeting in Canada covering all aspects of obesity – from basic and population science to prevention and health promotion to clinical management and health policy.

Anyone who has been to one of the past four Summits has experienced the cross-disciplinary networking and breaking down of silos (the Network takes networking very seriously).

Of all the scientific meetings I go to around the world, none has quite the informal and personal feel of the Canadian Obesity Summit – despite all differences in interests and backgrounds, everyone who attends is part of the same community – working on different pieces of the puzzle that only makes sense when it all fits together in the end.

The 5th Canadian Obesity Summit will be held at the Banff Springs Hotel in Banff National Park, a UNESCO World Heritage Site, located in the heart of the Canadian Rockies (which in itself should make it worth attending the summit), April 25-29, 2017.

Yesterday, the call went out for abstracts and workshops – the latter an opportunity for a wide range of special interest groups to meet and discuss their findings (the last Summit featured over 20 separate workshops – perhaps a tad too many, which is why the program committee will be far more selective this time around).

So here is what the program committee is looking for:

  • Basic science – cellular, molecular, physiological or neuronal related aspects of obesity
  • Epidemiology – epidemiological techniques/methods to address obesity related questions in populations studies
  • Prevention of obesity and health promotion interventions – research targeting different populations, settings, and intervention levels (e.g. community-based, school, workplace, health systems, and policy)
  • Weight bias and weight-based discrimination – including prevalence studies as well as interventions to reduce weight bias and weight-based discrimination; both qualitative and quantitative studies
  • Pregnancy and maternal health – studies across clinical, health services and population health themes
  • Childhood and adolescent obesity – research conducted with children and or adolescents and reports on the correlates, causes and consequences of pediatric obesity as well as interventions for treatment and prevention.
  • Obesity in adults and older adults – prevalence studies and interventions to address obesity in these populations
  • Health services and policy research – reaserch addressing issues related to obesity management services which idenitfy the most effective ways to organize, manage, finance, and deliver high quality are, reduce medical errors or improve patient safety
  • Bariatric surgery – issues that are relevant to metabolic or weight loss surgery
  • Clinical management – clinical management of overweight and obesity across the life span (infants through to older adults) including interventions for prevention and treatment of obesity and weight-related comorbidities
  • Rehabilitation –  investigations that explore opportunities for engagement in meaningful and health-building occupations for people with obesity
  • Diversity – studies that are relevant to diverse or underrepresented populations
  • eHealth/mHealth – research that incorporates social media, internet and/or mobile devices in prevention and treatment
  • Cancer – research relevant to obesity and cancer

…..and of course anything else related to obesity.

Deadline for submission is October 24, 2016

To submit an abstract or workshop – click here

For more information on the 5th Canadian Obesity Summit – click here

For sponsorship opportunities – click here

Looking forward to seeing you in Banff next year!

@DrSharma
Edmonton, AB

Comments

Higher BMI In Identical Twins Increases Risk of Diabetes But Not Heart Attacks?

sharma-obesity-blood-sugar-testing1Increased BMI is often touted as a major risk factor for cardiovascular disease. However, this relationship is not as straightforward as most of us believe.

Now a study by Peter Nordström and colleagues, published in JAMA Internal Medicine, reports that a higher BMI in identical twins is associated with a greater risk for type 2 diabetes but not myocardial infarction or death.

The researchers looked at data from 4,046 monzygous twin pairs with discordant BMIs (difference >0.01 units) from the nationwide Swedish twin registry.

During a mean follow-up of 12 years, the rate of myocardial infarcts and deaths were similar in the twins with lower BMI compared to their higher BMI co-twin (5.0% vs. 5.2% and 13.6% vs. 15.6%, respectively).

This lack of difference remained true even when the researchers compared the extremes of BMI discordance and only considered twins with BMI greater than 30.

In contrast, both higher BMI and greater increase in BMI since 30 years before baseline was associated with greater risk of incident diabetes.

Given that diabetes is such a powerful risk factor for cardiovascular disease, one can only wonder why this did not translate into a higher cardiovascular risk in the higher weight twins.

One possible explanation, offered by the authors is that cardiovascular risk may have been well managed in these individuals thus minimizing any increased risk due to diabetes (or other BMI associated risk factors such as dyslipidemia or hypertension).

Indeed, it would probably have required a far larger group of twins (or much longer follow-up) to fully rule out higher cardiovascular risk in these twins.

Let us also not forget that BMI is a rather lousy measure of overall cardiovascular risk.

Thus, which the study is certainly compatible with the (genetics-independant?) role of higher BMI in the risk for diabetes, it certainly should not be interpreted as demonstrating that this increased risk in benign in terms of cardiovascular disease.

@DrSharma
Edmonton, AB

Comments

Non-Smokers Die of Lung Cancer and Teetotalers Die of Liver Cirrhosis

cause-effectIn all of my interactions with people who believe that the obesity epidemic is vastly overblown and that the links between excess body fat are imagined, I often hear the argument that obesity cannot “cause” [chose your health problem here] because “normal-weight” people can have [same health problem] too!

This is a rather naive argument, pretty much along the lines of, “Tobacco cannot cause lung cancer because non-smokers can get lung cancer too, or alcohol cannot cause liver cirrhosis because teetotalers get cirrhosis too”.

Or, “Drunk driving cannot cause road accidents, because non-drunk drivers get into accidents too”.

Or, “Flu vaccines don’t work, because vaccinated people get the flu too”.

I could go on….

What is missing in this perspective, is a very basic understanding of multiple cause and effect, as well as a fundamental understandings of probability and risk.

Firstly, almost all medical conditions can have more than one cause. Thus, although most lung cancer is by far attributable to smoking, it is also seen with exposure to asbestos, other environmental toxins, and of course sporadic mutagenesis.

Similarly, there are a multitude of reasons why someone may get liver cirrhosis, but, at least in Western societies, alcohol consumption is by far the number one cause of this problem.

And yes, some vaccinated people do catch the flu, but most vaccinated people don’t and when they do, it turns out to be less severe than it would have been without the vaccine.

So, just because “normal-weight” people can also have hypertension, diabetes, fatty liver disease, sleep apnea, osteoarthritis, gastroesophageal reflux, urinary incontinence, plantar fasciitis, and a host of other conditions, does not “prove” that excess weight does not also “cause” all of these conditions.

Yes, skinny people can have sleep apnea too but the overwhelmingly vast majority of sleep apnea is seen in people with excess weight – the same goes for virtually every obesity related health problem.

The other argument I often hear is that obesity cannot be the cause of [chose your health problem here] because not all people with obesity have [same health problem].

This argument is likewise stupid!

The fact that not every smoker dies of lung cancer, in no way “proves” that smoking does not cause cancer.

The fact that not everyone who regularly drinks a lot of alcohol gets a cirrhotic liver, does not disprove the link between alcohol and cirrhosis.

This is where we need to understand the basic concept of risk and probability.

When a certain factor (e.g. excess body fat) increases the risk of a certain condition, it does not mean that everyone exposed to that factor ends up with the condition. It just means that the risk for that condition is vastly higher.

Now let’s add a further level of complexity to the concept of risk, because, as we know, body fat is not body fat is not body fat is not body fat!

Whether or not my body fat actually causes any health problem, depends on a wide range of factors ranging from my underlying genetic predisposition (e.g. for diabetes, hypertension, etc.), my fat location (subcutaneous vs. ectopic), the cellular structure of my fat (hypertrophic vs. hyperplastic), fat-tissue inflammation, and probably countless other factors.

Add to this, that risk for obesity related conditions can be substantially modified by other factors including physical fitness, healthy diets, positive body image, good mental health – it is easy to understand why defining “sick” and “healthy” simply based on a measurement (direct or indirect) of body fat makes no sense.

Thus, we need to ensure that the medical term “obesity” is not used to label everyone above a certain (arbitrary) BMI cutoff.

Rather, we should reserve the medical term “obesity” only for the condition where excess or abnormal body fat directly impairs the health of a given individual (the actual WHO definition of obesity!).

Someone with the exact same amount of body fat (or even more), who does not experience any health impairment should not be referred to as having “obesity” – that person is just “fat” (a word that really needs to be destigmatised!).

Personally, I couldn’t care less about how “fat” anyone is. Only when “fat” becomes “obesity” does it become a medical issue.

@DrSharma
Edmonton, AB

Comments

Arguments For Calling Obesity A Disease #8: Can Reduce Stigma

sharma-obesity-hypothalamusNext, in this miniseries on arguments for and against calling obesity a disease, I turn to the issue of stigma.

One of the biggest arguments against calling obesity, is the fear that doing so can increase stigma against people living with obesity.

This is nonsense, because I do not think it is at all possible for anything to make stigma and the discrimination of people living with obesity worse than it already is.

If anything, calling obesity a disease (defined as excess or abnormal body fat that impairs your health), could well serve to reduce that stigma by changing the narrative around obesity.

The current narrative sees obesity largely as a matter of personal choice involving poor will power to control your diet and unwillingness to engage in even a modest amount of regular physical activity.

In contrast, the term ‘disease’ conjures up the notion of complex biology including genetics, epigenetics, neurohormonal dysregulation, environmental toxins, mental health issues and other factors including social determinants of health, that many will accept are beyond the simple control of the individual.

This is not to say that other diseases do not carry stigma. This has and remains the case for diseases ranging from HIV/AIDS to depression – but, the stigma surrounding these conditions has been vastly reduced by changing the narrative of these illnesses.

Today, we are more likely to think of depression (and other mental illnesses) as a problem related to “chemicals in the brain”, than something that people can pull out of with sheer motivation and will power.

Perhaps changing the public narrative around obesity, from simply a matter of motivation and will power, to one that invokes the complex sociopsychobiology that really underlies this disorder, will, over time, also help reduce the stigma of obesity.

Once we see obesity as something that can affect anyone (it can), for which we have no easy solutions (we don’t), and which often requires medical or surgical treatment (it does) best administered by trained and regulated health professionals (like for other diseases), we can perhaps start destigmatizing this condition and change the climate of shame and blame that people with this disease face everyday.

@DrSharma
Edmonton, AB

Comments