Dr. Sharma's Obesity Notes

Yesterday, I noted that, although in the short term, bariatric surgery may be the preferred treatment for individuals with diabetes, the vast majority of people with this condition will have little hope of ever being handed this ‘parachute’.

For most, medical management of diabetes will be the best they can hope for.

But hope they can - as shown in a report from the randomized controlled Look AHEAD trial (now in its 5th year) by Jack Rejiski and colleagues, published in the New England Journal of Medicine.

This paper reports the impact of the ongoing intensive lifestyle intervention, aimed at achieving and maintaining a ~7% weight loss together with increased physical activity, to a diabetes support-and-education program in over 10,000 overweight or obese adults between the ages of 45 and 74 years with type 2 diabetes.

At year 4, participants randomised to the lifestyle-intervention group had a relative reduction of 48% in the risk of loss of mobility, as compared with the support group. Both weight loss (approximately 6.5%) and improved fitness (as assessed on treadmill testing) were significant mediators of this effect.

Thus, as the authors conclude, even modest weight loss together with improved fitness slowed the decline in mobility in overweight adults with type 2 diabetes even over this rather short four years of the study.

While these results may appear modest in the light of yesterday’s report on surgical outcomes, let us remember, that we are here talking about a study with over 10,000 participants, compared to the just over 200 participants in the surgical trials (not to mention the remarkably longer follow-up of this ‘lifestyle’ study).

This is the reality of the situation - while surgery can ever only be a solution for a vanishingly small proportion of the over 300 million people living with diabetes today, the lifestyle interventions of the Look AHEAD trial, with its significant and clinically meaningful outcomes, could indeed be offered to virtually anyone, who should happen to develop this condition.

Let us also remember, that much of the infrastructure and personnel that would need to be put in place to assure the long-term outcomes of bariatric surgery, are not all that different from what would be needed to better manage diabetes.

AMS
Edmonton, Alberta

Rejeski WJ, Ip EH, Bertoni AG, Bray GA, Evans G, Gregg EW, Zhang Q, & Look AHEAD Research Group (2012). Lifestyle change and mobility in obese adults with type 2 diabetes. The New England journal of medicine, 366 (13), 1209-17 PMID: 22455415

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In 2003, Gordon Smith and Jill Pell from the University of Cambridge, UK, published a thought-provoking paper in the British Medical Journal, on the effectiveness of parachute use to prevent death and major trauma related to gravitational challenge.

Despite an exhaustive search of the medical literature, they were unable to identify any randomised controlled trials of parachute interventions to avoid death as a result of plummeting earthward from a great hight.

Notably, the researchers pointed out (rather harshly, perhaps) that,

“As with many interventions intended to prevent ill health, the effectiveness of parachutes has not been subjected to rigorous evaluation by using randomised controlled trials. Advocates of evidence based medicine have criticised the adoption of interventions evaluated by using only observational data. We think that everyone might benefit if the most radical protagonists of evidence based medicine organised and participated in a double blind, randomised, placebo controlled, crossover trial of the parachute.“

I remind readers of this paper in the context of two randomised controlled trials (one from the US, the other from Italy) on the effect of bariatric surgery on the resolution of type 2 diabetes recently published in the New England Journal of Medicine.

Without going into details of the trials or their findings, it suffices to point out that both studies turned out to be overwhelmingly favourable to surgery.

Thus, at 12 months, the US study found a glycated hemoglobin level of 6.0% or less in only 12% (5 of 41 patients) in the medical-therapy group versus 42% (21 of 50 patients) in the gastric-bypass group and 37% (18 of 49 patients) in the sleeve-gastrectomy group.

Even more remarkably, the Italian investigators noted no ‘remission’ of diabetes in the medical-therapy group versus 75% in the gastric-bypass group and 95% in the biliopancreatic-diversion group.

Why do I compare the results of these two studies to the use of parachutes? Because, to anyone who is even remotely aware of the outcomes of bariatric surgery in patients with type 2 diabetes, these results are neither unexpected nor earth-shattering (pardon the pun).

Thus, I am as unimpressed by the results of these two studies, as I would have been, had they compared the ‘remission’ of obstructive sleep apnea in patients on CPAP versus bariatric surgery.

Indeed, the question was never whether or not bariatric surgery can lead to short-term (or even longer-term) ‘remission’ of type 2 diabetes compared to medical treatment - the latter, is neither aimed at nor even expected to lead to remission of diabetes - conventional medical treatment merely offers to ‘manage’ diabetes, not ‘cure’ it.

That, however, is not at all the point.

No, the questions that are really of interest when it comes to surgery in patients with diabetes are very different indeed.

1) How long does the ‘remission’ last?

2) What happens to diabetes in those, where diabetes, despite surgery, does not improve?

3) Does remission really translate into reduced diabetes complications including premature death?

4) How do the long-term complications of surgery compare to the long-term complications of diabetes?

5) How much of this improvement in diabetes is simply attributable to weight loss and how much to other mechanisms that may not require any weight loss at all?

I especially raise the last question, as it (again) turns out that neither preoperative BMI nor weight loss predicted the improvement in hyperglycemia after these procedures.

But the real question is now for health systems.

Even if surgery turns out to be the only ‘effective’ treatment and thus perhaps declared by some to be considered as the ‘first-line’ treatment for type 2 diabetes, what proportion of the world’s 300 million people living with diabetes would likely ever benefit from this treatment option? Even at 1,000,000 operations a year, it would only take about 300 years to do everyone.

Even if all bariatric surgery currently performed were limited to individuals with diabetes, current global capacity at perhaps 500,000 operations a year, addresses less than 2% of the annual global burden of this condition.

A 150% increase in availability of bariatric surgery will still leave 95% of people with diabetes untreated.

Thus, the real question for health services is to determine which 5% of people living with diabetes should be the ones to most benefit from surgery - a question left unanswered by these studies.

No doubt, for the fortunate few, surgery may provide some (temporary?) respite from diabetes.

But for those, who do not have the option of jumping off the troubled plane with a parachute, the only realistic option may be to hang on and hope for a soft landing.

AMS
Edmonton, Alberta

Hat tip to Francis Finucane for reminding me of the parachute study.

Schauer PR, Kashyap SR, Wolski K, Brethauer SA, Kirwan JP, Pothier CE, Thomas S, Abood B, Nissen SE, & Bhatt DL (2012). Bariatric Surgery versus Intensive Medical Therapy in Obese Patients with Diabetes. The New England journal of medicine PMID: 22449319

Mingrone G, Panunzi S, De Gaetano A, Guidone C, Iaconelli A, Leccesi L, Nanni G, Pomp A, Castagneto M, Ghirlanda G, & Rubino F (2012). Bariatric Surgery versus Conventional Medical Therapy for Type 2 Diabetes. The New England journal of medicine PMID: 22449317

Regular readers will be aware that there is a rather poor relationship between the total amount of body fat and health, which, indecently, is why I am not a big fan of the term ‘healthy weight’ and why we had to come up with the Edmonton Obesity Staging System.

In fact, we have known for a long time that it is visceral fat or the fat deposited ‘ectopically’ in organs like the liver, pancreas, heart, or skeletal muscle that tends to cause the cardiometabolic problems.

Indeed, there are good reasons to believe that the safest place to store any excess calories is in your subcutaneous or skin fat.

This notion is once again supported by new data by Smith and colleagues published in the latest issue of the Journal of Clinical Endocrinology and Metabolism, suggesting that skin fat may, at least in women, reduce the risk of developing diabetes.

Thus, data from the The INternational Study of Prediction of Intra-abdominal adiposity and its RElationships with cardioMEtabolic risk/Intra-Abdominal Adiposity (INSPIRE ME IAA), a cross-sectional computed tomography imaging study with data collected from 4144 (51.8% men) in 29 countries, shows that while cardiovascular disease increased with visceral adiposity tertles, diabetes risk was inversely related with subcutaneous adipose tissue in women [0.76] and not associated with type 2 diabetes in men [0.97].

Good enough to remind us that using rather crude measures of obesity like weight, BMI, or even total body fat, is certainly not enough to decide on who needs obesity treatment and who doesn’t.

AMS
Washington, DC

Smith JD, Borel AL, Nazare JA, Haffner SM, Balkau B, Ross R, Massien C, Alméras N, & Després JP (2012). Visceral Adipose Tissue Indicates the Severity of Cardiometabolic Risk in Patients with and without Type 2 Diabetes: Results from the INSPIRE ME IAA Study. The Journal of clinical endocrinology and metabolism PMID: 22337910

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Dr. med. Jens Ringel

Since my first publication in 1987, I have authored or co-authored well over 300 peer-reviewed papers, about half of which are on topics related to obesity. This year, I thought I would dedicate my Saturday posts to reviewing some of these papers and sharing the stories behind them. If nothing else, it may point readers to some of the topics that have found my interest me over the years.

The first of my obesity papers to come up in a PubMed search is that of my MD-doctoral student Jens Ringel, published in Biochem Biophys Res Commun (1999), looking at a common genetic variant of the peroxisome proliferator activated receptor-gamma (PPARg), a nuclear receptor, that regulates adipocyte differentiation and possibly lipid metabolism and insulin sensitivity.

In this study, we specifically examined the allelic frequencies of the missense C –> G mutation at codon 12 of this gene, which results in the substitution of proline with alanine (Pro12Ala) in subjects with type 1 (n = 522) and type 2 (n = 503) diabetes compared to that in healthy controls (n = 310) and found no differences between these groups. There was also no significant relationship between dyslipoproteinemia or obesity and the PPARg Pro12Ala genotype.

Thus, these findings did not support the hypothesis that this genetic variant is strongly associated with diabetes, obesity, or dyslipidemia in patients with type 1 or type 2 diabetes mellitus and we concluded that this genetic marker is therefore unlikely to serve as a clinically useful predictor of these disorders in Caucasian patients with diabetes mellitus.

In hindsight such an assumption may appear rather naive, given that today we know that it takes far larger sample sizes (10s of thousands of subjects) and far more sophisticated analyses to stand even a remote chance of identifying genes for complex diseases. But back in 1999, when this paper was published, many of us were churning out papers looking at single nucleotide polymorphisms (SNPs) of candidate genes in a few hundred samples.

According to Google Scholar, this paper has been cited 134 times, so I guess someone did find this study of interest after all.

AMS
Edmonton, Alberta

Ringel J, Engeli S, Distler A, & Sharma AM (1999). Pro12Ala missense mutation of the peroxisome proliferator activated receptor gamma and diabetes mellitus. Biochemical and biophysical research communications, 254 (2), 450-3 PMID: 9918859

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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