Arya M. Sharma, MD

As regular readers will be well aware, our recent publications on the Edmonton Obesity Staging System clearly show that BMI alone is a rather poor measure of mortality risk associated with excess weight.

Thus, according to our analyses of the NHANES population, 20-30% of obese individuals (Stage 0/1) had virtually no increased mortality risk even over the almost 20 year observation period, compared to Stage 2/3 individuals, who had substantially increased risk. Conversely, even in the ‘overweight’ category (BMI 25-30), almost 50% of individuals had a mortality risk as high of that of obese Stage 2/3 individuals.

This means that indications for obesity treatment based on BMI alone will overtreat a substantial number of obese individuals, who may have little benefit in terms of mortality, and miss an even greater number of individuals, who may well benefit from such treatments.

These observations are directly relevant to yesterday’s post on the findings of the SOS study.

As readers will recall, not only was there no relationship between BMI levels and cardiovascular outcomes in the SOS population but the overall cardiovascular risk of these participants - despite the majority being ’severely’ obese - was surprisingly low. In fact, the annual risk for experiencing an adverse cardiovascular outcome for SOS participants was well under 1% per year!

This risk level is highly reminiscent of the overall risk of Stage 0 obese individuals in our NHANES analyses.

Thus, it is readily apparent why it took almost 15 years to demonstrate any cardiovascular benefit of bariatric surgery in the SOS study - clearly this was a very ‘low-risk’ obese population.

Contrast this to the almost 3% annual cardiovascular event rate for the participants in the SCOUT trial, which, by definition, consisted exclusively of Stage 2/3 individuals. In this population, it took less than 3.5 years of even very modest weight-loss (3 to 10 kg) to significantly reduce cardiovascular outcomes.

But did surgery prove more beneficial in higher-risk participants in the SOS trial? It certainly did!

In fact, the only predictor of greater benefit of having bariatric surgery in the SOS paper proved to be having an elevated plasma insulin level - a rather crude marker of insulin resistance. It is fair to assume that these participants were in fact those with higher obesity Stages (elevated fasting insulin levels alone, would already suggest at least Stage 1 obesity).

The importance of this difference is reflected in the numbers-needed-to-treat (NNT): as low as 21 in participants with baseline plasma insulin concentrations above the median (>17.0 mU/L) and as high as 173 in individuals below or at the median (≤17.0 mU/L) insulin concentration.

This essentially means that you would need to operate only 21 patients with Stage 1+ obesity to ’save’ one life (over 15 years) but 173 Stage 0 patients for the same benefit. It does not take a financial genius to figure out that from a ‘cost-per-life-saved’ perspective, operating on Stage 1+ patients is a ‘no-brainer’ whereas operating on Stage 0 patients would (and should) probably raise some eyebrows (especially in a publicly funded healthcare system).

Thus, as we have argued before (and argued by Livingstone in an editorial accompanying the SOS paper in JAMA), it is high time we fully appreciate the “inadequacy of BMI as an indication for bariatric surgery” and begin adopting more sophisticated criteria (such as those of the Edmonton Obesity Staging System) to ensure that this treatment is available to those who are likely to benefit the most.

AMS
London, UK

Padwal RS, Pajewski NM, Allison DB, & Sharma AM (2011). Using the Edmonton obesity staging system to predict mortality in a population-representative cohort of people with overweight and obesity. CMAJ : Canadian Medical Association journal = journal de l’Association medicale canadienne, 183 (14) PMID: 21844111

Livingston EH (2012). Inadequacy of BMI as an indicator for bariatric surgery. JAMA : the journal of the American Medical Association, 307 (1), 88-9 PMID: 22215170

Earlier this week, I posted on an analysis of the SCOUT trial, in which we found a clear and significant ‘dose-response’ relationship between moderate weight loss (3-10 Kg) and reduced cardiovascular outcomes (including death) in the over 10,000 high-risk participants in this trial.

So far, the only data showing a reduction in overall mortality with weight loss comes from studies looking at the effects of bariatric surgery, such as the ongoing Swedish Obese Subjects (SOS) study, which just published its latest findings in the Journal of the American Medical Association (JAMA).

In this paper, Lars Sjöström and colleagues from the University of Gothenburg, Sweden, specifically examine the relationship between bariatric surgery, weight loss, and cardiovascular events in the SOS study.

Some readers may recall that the SOS study is an ongoing, nonrandomized, prospective, controlled study conducted at 25 public surgical departments and 480 primary health care centers in Sweden of 2010 obese participants who underwent bariatric surgery and 2037 contemporaneously matched obese controls who received usual care. Inclusion criteria were age 37 to 60 years and a body mass index of at least 34 in men and at least 38 in women. Surgery patients underwent gastric bypass (13.2%), banding (18.7%), or vertical banded gastroplasty (68.1%), and controls received usual care in the Swedish primary health care system.

In the present analysis, bariatric surgery was associated with an almost 50% reduction in the number of cardiovascular deaths (28 events among 2010 patients in the surgery group vs 49 events among 2037 patients in the control group) over the almost 15 years of follow-up. Similarly, there was an almost 35% reduction in the number of total first time (fatal or non-fatal) cardiovascular events (myocardial infarction or stroke, whichever came first) in the surgery group (199 vs. 234 events).

Notably, however, the investigators found no significant relationship between cardiovascular outcomes and baseline BMI or the magnitude of weight loss. This is in contrast to the SCOUT study, where we found a clear ‘dose-response’ relationship between the amount of weight lost and the reduction in cardiovascular outcomes.

Several factors may explain this lack of ‘dose-response’ relationship in the SOS study.

For one, the SOS population, despite being far more obese than the participants in the SCOUT trial, were at a much lower risk for cardiovascular complications. Thus, the annualised event rate per 1000 participants in the SCOUT trial population was more than four times that of the SOS trial (30 vs. 7). Thus, the SOS study, despite its size, duration, and heavier BMI of participants, may simply be underpowered to demonstrate a ‘dose-response’ relationship between the magnitude of weight loss and reduction in cardiovascular outcomes.

Another explanation for the lack of ‘dose response’ in the SOS vs. SCOUT trial could be related to the overall magnitude of weight loss. Thus, while average weight loss in the SCOUT trial was just under 5%, the average weight loss in SOS was about 20%. if, as many suspect, a moderate 5-10% weight loss is all it takes to significantly reduce cardiovascular risk, the average weight loss of 20% in SOS would obscure any ‘dose-response’ relationship, as all participants in SOS, so to say, were already on the highest effective ‘dose’ of weight loss.

Thus, by no means is it clear from the SOS study that losing 20% of your body weight through bariatric surgery is any better than losing just 5% of your body weight as far as cardiovascular outcomes are concerned (this is not denying any other potential benefits of bariatric surgery on diabetes, cancer, arthritis, sleep apnea, or quality of life).

Thus, in light of the recent SCOUT findings, the superiority of bariatric surgery to medical obesity treatment in reducing cardiovascular outcomes would indeed need to be demonstrated in a ‘head-to-head’ trial  - a study that is unlikely to be done anytime soon.

interestingly, the lack of relationship between baseline BMI and cardiovascular outcomes and the remarkably low overall incidence of cardiovascular complications in the SOS patients raises a number of other important issues regarding indications for surgery - a topic that I will save for tomorrow’s post.

AMS
Berlin, Germany

Sjöström L, Peltonen M, Jacobson P, Sjöström CD, Karason K, Wedel H, Ahlin S, Anveden Å, Bengtsson C, Bergmark G, Bouchard C, Carlsson B, Dahlgren S, Karlsson J, Lindroos AK, Lönroth H, Narbro K, Näslund I, Olbers T, Svensson PA, & Carlsson LM (2012). Bariatric surgery and long-term cardiovascular events. JAMA : the journal of the American Medical Association, 307 (1), 56-65 PMID: 22215166

In my continuing coverage from the World Diabetes Congress, I thought it may be appropriate to share with my readers the Global Diabetes Plan 2011-2012, recently released by the International Diabetes Federation.

The objectives of this ambitious plan are to

1) Improve health outcomes of people with diabetes - early diagnosis, cost effective treatment and self-management education can prevent or significantly delay devastating diabetes-related complications and save lives.

2) Prevent the development of type 2 diabetes - lifestyle interventions and socially responsible policies and market interventions within and beyond the health sector can promote healthy nutrition and physical activity and prevent diabetes.

3) Stop discrimination against people with diabetes - people with diabetes can play an important role in their own health outcomes and combating diabetes more generally. Supportive legal and policy frameworks, awareness campaigns and patient-centred services uphold the rights of people with diabetes and prevent discrimination.

The key strategy of the plan is to call on governments to implement National Diabetes Programmes - Comprehensive policy and delivery approaches enhance the organisation, quality and reach of diabetes prevention and care. It is feasible and desirable for all countries to have a national diabetes programme and successful models are already in place in some countries.

The hope is that this strategy will deliver the following results:

1) Strengthen institutional frameworks - strengthen UN and country-level leadership across multiple sectors to ensure coherent, innovative and effective global and national responses to diabetes, and achieve the best possible return on investment.

2) Integrate and optimise human resources and health services - re-orient, equip and build capacity of health systems to respond effectively to the challenge of diabetes through training and workforce devel- opment, particularly at primary care level.

3) Review and streamline supply systems - optimise the provision of essential diabetes medicines and technologies through reliable and transparent procurement and distribution systems.

4) Generate and use research evidence strategically - develop a prioritised research agenda, build research capacity and apply evidence to policy and practice.

5) Monitor, evaluate and communicate outcomes - use health information systems and robust moni- toring and evaluation to assess progress.

6) Allocate appropriate and sustainable domestic and international resources - achieve innovative, sustained and predict- able resourcing for diabetes, including Official Development Assistance (ODA) for low-and middle-income countries.

7) Adopt a whole of society approach - engage governments, the private sector and civil society (including healthcare workers, academia and people with diabetes) in working together to turn the tide on diabetes.

With regard to point 7, the report comes out very much in favour of engaging business and industry in an attempt to encourage:

- property developers to improve building design for physical activity and social inclusion.

- the food industry to support wide availability of nutritious and affordable food and bever- ages, reduce marketing of unhealthy food and to adopt socially responsible business policies and practices.

In fact, this afternoon (too late for this blog post), I will attend a debate on how such interactions with industry could work and perhaps, more specifically, whether or not an organization like the IDF (or for that matter any NGO) should accept funding from industry - including those, who may be deemed to be “part of the problem”.

As the Scientific Director and CEO of the Canadian Obesity Network, Canada’s only national non-profit organization dedicated to obesity prevention and management, which, despite enthusiastic public proclamations by health ministers on their intent to address the obesity problem, currently has no sustainable public funding, this topic is obviously of considerable interest.

I look forward to reporting, on what I hope will be an enlightening debate in tomorrow’s post.

AMS
Dubai, UAE

p.s. a copy of the IDF Global Diabetes Plan is available here

As regular readers will recall, this week I am attending the World Diabetes Congress - with well over 14,000 attendees, the largest ever world congress on this issue.

For readers, who are not familiar with the International Diabetes Federation (!DF), it may be worth pointing out that the IDF is an umbrella organization of over 200 national diabetes associations in over 160 countries. IDF’s national diabetes associations are divided into the following regions: Africa (AFR),Europe (EUR),Middle East and North Africa (MENA), North America and Caribbean (NAC),South and Central America (SACA), South East Asia (SEA) and Western Pacific (WP).

Thus, the IDF, which has been in operation since 1950, represents the interests of the growing number of people with diabetes and those at risk.

The mission of IDF is to:

“advance diabetes care, prevention and a cure worldwide.”

Its strategic goals are to:

Drive change at all levels, from local to global, to prevent diabetes and increase access to essential medicines.

Develop and encourage best practice in diabetes policy, management and education.

Advance diabetes treatment, prevention and cure through scientific research.

Advance and protect the rights of people with diabetes, and combat discrimination.

(interestingly, these goals are reminiscent of those of the Canadian Obesity Network, Canada’s National Obesity organization, with the difference perhaps that obesity is a much larger issue than just diabetes).

Amongst the many activities and resources provided by the IDF, one that readers may find of particular interest (and one that can be a great time waster for readers who are looking for new ways to procrastinate) is the interactive World Diabetes Atlas, now in its 5th edition (just released last month).

The atlas exemplifies just how many folks around the work (especially in South Asia) are affected by type 2 diabetes - interesting, an obesity map of the world would look almost identical, except that the numbers would be far greater (only about 15-20% of obese people actually go on to develop diabetes - but may well have other weight-related health problems).

One of the notable features of this congress is the massive industry exhibit - not quite as extensive as those at cardiology or oncology meetings but, by a significant magnitude of scale, larger than any industry exhibits seen at obesity meetings. This is of course because diabetes management (although never curative) is big business, with countless new classes of anti-diabetic drugs in the pharma pipelines to add to the many oral and injectable treatments that are already out there (not to mention the vast blood glucose monitoring and insulin pump industries).

While there is no doubt that these companies are providing excellent products and services that make the life of people with diabetes so much easier and help reduce the horrible risks of this condition, one can only wish that in the not too distant future, a similar arsenal of treatments and management tools may become available for those struggling with obesity and its myriad sequelae (EOSS 2-4).

While the hope is not to ‘cure’ obesity (I am not sure we can actually do that), having effective obesity treatments that fill the vast therapeutic gap between ‘eat-less-move-more’ and bariatric surgery are urgently needed.

Not only would this reduce the global burden of diabetes but hopefully also the global burden of the over 20 other chronic conditions that are strongly associated with excess weight (including many cancers).

Unfortunately, neither the current regulatory framework for new launching new obesity medications nor the necessary investment into training health professionals to better manage obesity or into research to find better treatments comes close to the actual size of the problem (just count how many Canadian medical schools actually have a chair in obesity - I know of two).

So although there is an appreciable number of talks and sessions on obesity (including the ones the I am giving and chairing), the focus of this congress is of course on managing diabetes and its complications.

Unfortunately, as I have said before, managing type 2 diabetes without addressing obesity is largely ‘palliative’ care.

Obviously, not a popular view at this conference.

AMS,
Dubai, UAE

This week I am attending the World Congress on Obesity, organized by the International Diabetes Federation.

As one would imagine, the program here is chock-full of talks on obesity - everything from the impact of excess weight on insulin resistance and diabetes risk to basic science talks on energy and appetite regulation.

This morning I will be presenting a 60 min course on obesity management in diabetes and later this week, I will be co-chairing a session on bariatric surgery.

At this moment I am sitting in a session on obesity in ethnic populations listening to talks on why, for e.g., the very concept of weight loss goes against many traditional cultures and indeed, losing weight or being skinny is neither socially desirable nor a sign of good health.

This of course, proves a challenge as type 2 diabetes becomes more rampant in these populations (like India, South America, Australian Aboriginals, etc.) where there is little interest in weight management as an important principle in diabetes prevention and management.

I certainly look forward to a most interesting week here in Dubai and learning more about diabetes and its management from my colleagues around the world.

AMS
Dubai, UAE