The short answer, for the vast majority of Canadians, would simply be, “no one”.

Last year, the Canadian Obesity Network undertook a representative survey to examine how Canadians manage their weight.

It turns out that over 65% of overweight Canadians have never talked to a licensed health professional (family doctor, dietitian, pharmacist, etc.) about losing weight. The same is true for over 40% of Canadians, who meet the clinical definition of obesity, i.e. have a BMI greater than 30.

This may probably be as well, because most health professionals are in fact ill-equipped to support individuals struggling with excess weight. Although, health professionals often cite lack of time and resources as the main reason for not broaching the topic, I suspect that the key problem is simply a lack of knowledge and training in weight management.

As I have said before, most health professionals have little more than a layman’s understanding of the complex socio-psycho-biology of energy homeostasis and have virtually no formal training in even the basics of behavioural, medical or surgical management of excess weight.

Add to this an (un)healthy dose of anti-weight prejudice and discrimination and it is probably no surprise why anyone who has ever solicited weight management advice from their health professional is more likely to receive simplistic slogans along the lines of “eat less and move more”, than a meaningful analysis of the problem with a personalized evidence-based management plan.

Indeed, weight management plans too often follow along the lines of well-meant but often ineffective diet or exercise recommendations, that virtually always fail to address the actual root of the problem (see my post - overeating is a symptom).

It should hardly come as a surprise when simply providing an impulsive overeater with a diet plan proves to be about as effective as providing a drinking plan to an alcoholic.

In contrast, teaching time-management skills to people who regularly fall back on fast food for lack of time or offering stress management classes to people who use food as a coping strategy may well be far more effective than simply educating them on healthy choices or handing them recipe books.

Of course patients can always turn to the billion-dollar weight-loss industry, that peddles everything from magical weight loss supplements to crash diets. While some of these program may well be better than others, there is no way a consumer can tell which of these many products and services are likely to be effective or just a waste of money.

Even if patients “successfully” lose weight with any of these products or services, this is rarely more than temporary “symptomatic” relief with a one-in-twenty chance of weight regain within weeks or months of stopping the program.

Rarely do these products or services truly diagnose and address the root cause of the problem - that would require far more than a cursory “one-size-fits-all” business model and is unlikely to deliver the same lucrative profits.

Perhaps, it is time to promote a better public understanding of the many societal and individual level drivers of excess weight and it certainly appears high time health professionals and health care systems seriously took on the challenge of addressing the greatest health problem of our times.

When the problem is excess weight, not helping patients deal with this issue is simply palliative care.

AMS
Edmonton, Alberta

Today, the New England Journal of Medicine publishes the results of the Sibutramine Cardiovascular OUTcome (SCOUT) trial - a study in over 10,000 high-risk individuals with excess weight.

Over the past eight years, I have had the privilege of being on the Executive Steering Committee of this largest ever randomised controlled trial of obesity treatment.

The SCOUT trial examined the effect of the serotonin and norepinephrine reuptake inhibitor sibutramine plus lifestyle intervention versus placebo and lifestyle intervention alone in 10,744 overweight or obese subjects, 55 years of age or older, with preexisting cardiovascular disease, type 2 diabetes mellitus, or both, who successfully completed a six-week run-in phase on sibutramine.

The primary end point was the time from randomisation to the first occurrence of a primary outcome event (nonfatal myocardial infarction, nonfatal stroke, resuscitation after cardiac arrest, or cardiovascular death).

Unfortunately, individuals, randomised to the sibutramine arm of the study, despite signifiicantly greater weight loss, had a 16% higher relative risk (11.4% vs. 10.0%) for a primary endpoint. This was largely accounted for by higher rates of nonfatal myocardial infarction and nonfatal stroke were 4.1% and 2.6% in the sibutramine group and 3.2% and 1.9% in the placebo group.

Fortunately, there was no increased risk of fatal events.

Given that the SCOUT participants were essentially an “off-label” high-risk population (in fact largely patients, in whom the current label specifically does not recommend the use of this agent) , one needs to be careful in extrapolating these findings to “on-label” patients, who tend to generally have much lower risk profiles.

In fact, as a colleague once aptly put it, prescribing sibutramine, may perhaps not be unlike prescribing vigorous exercise, which can potential kill someone with pre-existing heart disease, but may well be quite beneficial and well-tolerated in younger low-risk individuals.

Apart from the subjects in the SCOUT trial being an essentially “off-label” populations, it is perhaps also worth noting that in this trial, patients were advised to continue on sibutramine irrespective of wether or not they actually lost any weight.

While this was feature of the study design was meant to test for potential, non-weight loss related benefits of sibutramine, this is certainly very different from clinical practice, where it is most unlikely that anyone taking a weight-loss drug would continue taking it without at least some discernible weight loss.

Obviously, without the benefits of weight loss, simply taking a drug that can (in the same manner as other SNRIs) increase heart rate and blood pressure, certainly may ultimately cause more harm than benefit.

However, before concluding that sibutramine itself (as suggested by an accompanying editorial) is a “flawed” drug, it would be important to consider the alternatives - which for most patients in reality means continuing weight gain with the eventual prospect of facing bariatric surgery (currently widely seen as the only effective treatment for obesity).

While “hard” endpoints are clearly relevant and important in the long-term, my clinic is full of patients who desperately need help in the short term, especially given their failure, despite best efforts, to control their weight with diet and lifestyle alone. They are clearly more concerned about their back pain, their sleep apnea and their poor quality of life than they are of dying of heart disease somewhere in the remote future.

Fortunately, in clinical practice it is relatively easy to predict both weight loss response as well as any unacceptable increases in blood pressure or heart rate within the first weeks of starting treatment with sibutramine. Indeed, the SCOUT trial did not reveal any unexpected or irreversible “side effects” of this compound - both the increase in heart rate and any increase in blood pressure is quickly reversed after stopping the drug.

As blogged recently, given the heterogeneity of obesity, I neither expect to see 100% of my patients respond to any given drug, not do I expect everyone to tolerate a given substance. Even if a new treatment for obesity turns out to be safe and effective for only 15% of obese patients, we are still talking about millions who would stand to benefit from such a treatment.

Yes, there is always a potential for “misuse” in that people who should not be taking a given drug may chose to do so. Unfortunately, I doubt that there will ever be an anti-obesity drug that will be safe enough to be widely misused or abused.

As much as we may have a responsibility to prevent the wrong people from using treatments that may potentially harm them, we have a far greater responsibility of making treatments that work accessible to those for whom they may clearly have a favourable risk-benefit ratio.

Let us not forget that for many patients battling obesity, the current choices are either drowning in a mire of essentially ineffective and unregulated “weight loss” products or ultimately opting for the far riskier path of obesity surgery.

AMS
Chicago, IL

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Disclosure: I have received consulting and speaking honoraria from Abbott Laboratories, the makers of sibutramine.

Yesterday, on my last day at the 2010 ESC meeting in Stockholm, I attended a session on incretins.

As regular readers of these pages will recall, the term incretins refers to a group of gut hormones that elicit a wide range of biological actions affecting ingestive behaviour, gut function and metabolic control.

Michaela Diamant from the University of Amsterdam, The Netherlands, talked about the importance of the incretin GLP-1 as a determinant of the attenuated insulin response to a meal seen in patients with type 2 diabetes.

There are currently two approaches to harnessing the effects of this system to better treat diabetes:

1) by blocking DPP-IV, the major degrading enzyme of GLP-1, with “gliptins”

2) the direct administration of long-acting GLP-1 analogues (e.g. exenatide, liraglutide).

While both approaches have been shown to significantly improve glycemic control, GLP-1 analogues are of particular interest, as they also promote clinically relevant weight loss, thereby further reducing HbA1c levels. Current GLP-1 analogues require daily injections, but longer-acting forms that can be injected at weekly intervals are under development.

Gliptins, which, although not associated with notable weight loss, are at least weight neutral, a clear advantage compared to other antidiabetic agents (with the exception of metformin).

Oliver Schnell, Munich, Germany, discussed the cardiovascular effects of GLP-1 analogues. He pointed out that fluctuations in glucose levels has been associated with increased CV mortality, something that GLP-1 analogues can perhaps help prevent.

Not only do GLP-! analogues not cause hypoglycemia, but, by virtue of their effects on delaying gastric emptying and improving insulin secretion, they may significantly blunt the glucose variability seen with conventional diabetes treatments. Thus, studies using continuous glucose monitoring show decreased fluctuations in glucose levels over the course of a 24 hour time period.

In addition, the weight loss seen with GLP-1 analogues is associated with improvements in other CV risk factors including lipids and blood pressure.

GLP-1 receptors have also been identified on vascular endothelial cells and GLP-1 infusions appear to improve endothelial function in patients with type 2 diabetes. There is also some preliminary data from animal studies to suggest that GLP-1 may improve post-ischemic ventricular function and a reduction in infarct size. A small study in patients with heart failure, GLP-1 infusion were observed to promote cardiac ejection fraction and improve physical function.

It appears that there are both GLP-1 receptor dependent and receptor independent effects of GLP 1.

Despite these putative positive effect, whether or not GLP-1 based therapies will provide cardiovascular benefits that go beyond glucose control remains to be seen.

AMS
Stockholm, Sweden

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Yesterday, at the ongoing 2010 European Society of Cardiology, I attended as session focussing on the potential role of excess fat tissue that may surround blood vessels or the heart. Regular readers will recall, that the role of these fat depots have been a focus of my interest in past years.

A new study by Olga Lamacchia and colleagues from the University of Foggia, Italy, published online in Nephrology Dialysis and Transplantation, suggests that increased fat deposition around the kidneys may also pose a risk marker for the development of chronic kidney disease in patients with type 2 diabetes.

The researchers performed a cross-sectional study in 151 patients with type 2 diabetes that included measurements of kidney function, blood flow and ultrasound assessment of the fat surrounding their kidneys.

Despite adjustment for both BMI and waist circumference, the amount of para- and perirenal fat predicted increases in renal resistance index and reduced glomerular filtration rate.

Furthermore, in subjects with waist circumference above the diagnostic values of metabolic syndrome kidney function significantly and progressively declined across tertiles of para- and perirenal fat thickness.

As explanations for this phenomenon, the authors discuss the potential role of increased intra-abdominal pressure of visceral obesity, direct physical compression of the kidneys, or mechanisms related to the secretion of adipokines and other factors by the surrounding fat tissue that may affect kidney function.

For anyone familiar with kidney anatomy, it may also be of interest to recall that as fat deposition grows within the renal sinus, compression of various renal structures, especially of the inner medulla that, unlike the entire kidney, is not protected by the fibrous capsule, may occur. Increases in renal interstitial fluid hydrostatic pressure tends to compress the medullary vasa recta and tubules, reducing blood and tubular flow through the distensible loop of Henle, which could ultimately result in greater fluid, sodium and urate reabsorption.

As my colleagues and I have previously suggested for epicardial fat, the authors suggest that measurement and recording of peri-renal fat should perhaps also be part of routine renal ultrasound assessments.

Although this recommendation, may be a bit premature, the study nevertheless adds to the continuing literature demonstrating that in obesity and the accumulation of excess fat it is not just the “how much” but rather the “exactly where”, that ultimately determines the development of certain weight-related health problems.

AMS
Stockholm, Sweden

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Lamacchia O, Nicastro V, Camarchio D, Valente U, Grisorio R, Gesualdo L, & Cignarelli M (2010). Para- and perirenal fat thickness is an independent predictor of chronic kidney disease, increased renal resistance index and hyperuricaemia in type-2 diabetic patients. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association PMID: 20798120

I am currently attending the 2010 Scientific Meeting of the European Society of Cardiology, here in Stockholm.

In a session on diabetes and heart disease, Mamas Mamas from the University of Manchester, UK, reported that abnormal glucose tolerance (pre-diabetes or diabetes) is found in about 50% of unselected heart failure patients.

Importantly, only a small fraction of patients will have abnormal fastng glucose, suggesting that glucose tolerance tests are essential to determine abnormal glucose disposition in patients with heart disease.

Insulin resistance, in part due to decreased exercise capacity, may also be exacerbated in heart failure patients.

Longitudinal studies confirm the negative prognostic relevance of abnormal glucose tolerance in with a 35% increased risk in cardiovascular death with each 1% increase in HbA1c levels.

However, Mamas also noted that while the Diabetes Prevention Program, showed a marked reduction in the progression to diabetes with lifesyle intervention in individuals with pre-diabetes, the findings from this study did not suggest any reduction in heart failure or cardiovascular deaths.

Indeed, despite the wide recognition that diabetes is an important risk factor for heart disease, data on the prevention or improvement in cardiac function with diabetes treatment remains rather disappointing.

On a similar note, Clyde Yancy, Baylor University Medical Center, Dallas, TX, spoke on the issue of diabetic cardiomyopathy.

As Yancy pointed out, diabetic cardiomyopathy defined as significantly impaired cardiac function in diabetic patients in the absence of epicardial vascular disease, left-ventricular hypertrophy, valvular disease, or other causes of cardiomyopathy, makes it largely a diagnosis of exclusion.

The association between diabetic cardiomyopathy and diabetic retinopathy suggests that microvascular abnormalities may play a role.

However, there may also be direct metabolic effects of dysglycemia and hyperinsulinemia, resulting in lipotoxicity and generation of oxidative stress leading to apoptosis and fibrosis. This may well explain the findings of left-ventricular remodeling, myocardial fibrosis, collagen and lipid deposition with altered compliance and diastolic dysfunction, seen in patients with diabetic cardiomyopathy.

Animal studies show that increased glucose levels can increase expression of box-1 protein, involved in pro-inflammatory defense mechanisms. Blocking this response may, thus, prove a novel approach to preventing and treating cardiomyopathy.

This is important because, as noted previously by Mamas (and other speakers in this session), current anti-diabetic treatments do not appear to have the expected beneficial effects on heart function or macrovascular disease in patients with diabetes.

In the context of obesity management it is therefore perhaps important to recall the fact that one of the most impressive findings from bariatric surgery studies, is the remarkable reduction (upto 80%) of diabetes related mortality - something conventional diabetes treatments have yet to demonstrate.

Whether similar benefits can be seen with more moderate weight loss of course remains to be seen, nevertheless, it is certainly increasingly apparent that simply controlling blood glucose levels in patients with diabetes may not be the answer.

AMS,
Stockholm, Sweden