Although, in the end I spent less than 24 hrs in the Emirates, one of the highlights of attending the 1st International Abu Dhabi Diabetes Conference, was the opportunity to once again hear David Cummings (Seattle) speak about how bariatric surgery can lead to the remission of type 2 diabetes. Cummings’ talk certainly provided plenty of food for thought on my long flight back to Canada.

As outlined in a newly released Diabetes Surgery Position Statement published in the latest issue of the Annals of Surgery, surgical approaches may well prove to be the treatment of choice in carefully selected patients with poorly controlled type 2 diabetes and a BMI greater than 30.

While the authors of the Statement emphasize the need for more clinical trials to investigate the future role of surgery in diabetes treatment, they also call for further investigations on the mechanisms of surgical control of diabetes (which are far from being fully understood).

Although weight loss itself clearly plays a significant role in the reversal of diabetes generally seen with bariatric surgery, with gastric bypass surgery, this reversal of diabetes often precedes the weight loss and there are likely neuroendocrine consequences to allowing food to bypass the duodenum that may substantially affect glucose metabolism (including regeneration of pancreatic beta-cells).

Thus, a better understanding of exactly how gastrointestinal surgery “cures” diabetes, will hopefully also open new avenues for pharmacological treatments that can mimic the effects of surgery in these patients.

Indeed, certain gut-hormones, which are known to be dramatically affected by gastric bypass surgery (e.g. GLP-1), have already been shown to have a beneficial effect both on diabetes and weight management (e.g. liraglutide).

Health professionals who want to learn more about this topic should consider attending the upcoming First Canadian Summit Metabolic Surgery for Type 2 Diabetes to be held in partnership with the Canadian Obesity Network and the Canadian Diabetes Association at the Hôtel Le Centre Sheraton, Montréal, May 6-7, 2010.

To watch a recent episode of 60 Minutes on CBS, which features interviews with Cummings and others discussing the surgical approach to type 2 diabetes, click here.

Very much appreciate hearing from my readers on their thoughts regarding whether or not diabetes surgery (vs. lifelong medications or injections) will significantly change how we treat diabetes in the future.

AMS
Edmonton, Alberta

Arab Food Pyramid

When we think of the global obesity epidemic, we tend to conjour up images of of US-Americans, literally hefting along excess pounds as they go about their lives across America. We may also recall that Canada and most other Western countries have a problem.

But, interestingly, nowhere is the obesity problem as big as in the countries of the Gulf Region and the Middle East (exceeded perhaps only by populations on remote Oceanic islands).

According to the United Arab Emirates global school-based student health survey (GSHS) 2005 fact sheet, over 30% of 13-15 year olds exceed the 85th percentile for body weights. The adult population (though it is hard to find accurate statistics) apparently does not fare much better.

Why, you may wonder, am I interested in this?

Because tonight I am heading out from Munich to speak on Saturday at the 1st International Abu Dhabi Diabetes Conference, in the United Arab Emirates.

Although the conference focusses on diabetes, it is obvious that the prime driver of the diabetes epidemic in that region of the world (as elsewhere) is the obesity crisis.

It is therefore not surprising that the organisers have opted to include sessions on obesity assessment and management (although most of the conference of course focusses on diabetes management, which I have often described as “palliative care”).

As should be obvious to anyone who has recently visited the UAE, population-based prevention measures in a society that spends most of its time indoors (I would too when it’s 40-50 degrees C outside) and enjoys food as one of the only officially endorsed “vices” (there are tough restrictions on alcohol, gambling and other worldly “pleasures”), is lilkely to be challenging if not simply impossible.

Given that the Arab susceptibility to obesity appears similar to other Asians in that they appear more prone to abdominal obesity with all its dire metabolic consequences, diabetes may in fact be the least of their worries.

I look forward to attending the meeting and learning more about the Arab “diabesity” epidemic from my friends and colleagues in the Emirates.

AMS
Munich, Germany

Of course, obesity is associated with a wide range of health problems like high blood pressure, diabetes, arthritis, or reflux disease, all of which may all require pharmacological treatment. But this is not what this post is about.

Rather, this post is actually about the question whether or not larger patients need higher doses of medications to have an optimal treatment effect.

This topic was recently discussed by Matthew Falagas and Drosos Karageorgopoulos in a Lancet article that specifically addresses the issue of dose adjustments for antimicrobial agents in larger patients.

As the authors point out, body size is routinely considered in the optimization of drug therapy in oncology, anaesthetics and pediatrics. However, there remains a paucity of data on the optimal dosing of pharmacological agents for most of the drugs we use in clinical practice.

Thus, although regulatory agencies regularly demand special pharmacokinetic studies in children, elderly prople and patients with renal or hepatic impairment, no such studies are demanded for obese or even severely obese patients.

Requiring such studies would at least make theoretical sense as, conceivably, obesity can affect drug absorption, distribution, metabolism and clearance. Furthermore, it is obvious that body composition can particularly affect the disposition of lipophilic compounds. Obese patients are also likely to have comorbiditiesthat can affect these parameters (e.g. fatty liver disease) and are much more likely to be on multiple medications that can make drug-drug interactions problematic.

In short, as pointed out by Falgas and Karageorgopoulos the one-size-fits-all strategy for antimicrobial agents (and other drugs?) may well be outdated and require much more consideration than has been given to this issue in the past.

AMS
Winnipeg, Manitoba

Despite the wide-spread concern about the health impact of the childhood obesity epidemic, there is actually not much data that directly shows how this excess weight may affect mortality.

Such data is now available at least for native American kids, from a study by Paul Franks (National Institutes of Health, Phoenix, AZ) and colleagues, just published in the New England Journal of Medicine.

The researchers analysed data from a cohort of 4857 American Indian (Pima or Tohono O’odham Indian) children without diabetes (mean age, 11.3 years) born between 1945 and 1984.

During a median follow-up period of around 24 years, death rates from endogenous causes among children in the highest quartile of BMI were more than double those among children in the lowest BMI quartile.

Similarly, rates of death from endogenous causes among children in the highest quartile of glucose intolerance were 73% higher than those among children in the lowest quartile and childhood hypertension was significantly associated with a 60% increased risk of premature death from endogenous causes.

Thus, at least in native Americans, childhood obesity is a significant risk factor for premature death - certainly a warning for those who believe that early obesity is something you can simply grow out of.

Given the raging epidemic of childhood obesity amongst the First Nations, Inuit, and Métis populations in Canada, these data should certainly prompt decisive action to address obesity amongst its native peoples.

AMS
Edmonton, Alberta

Obesity is often described as a state of low grade inflammation. Activated macrophages (white blood cells) in adipose tissue play an important role in this inflammatory response by secreting a number of pro-inflammatory molecules (cytokines) that can promote the development of insulin resistance and other complications of obesity.

Previous studies have shown that the “glitazone” class of antidiabetic agents can suppress inflammatory macrophage activation and can also increase the expression of an DGAT1 (triacylglycerol (TG) synthesis enzyme acyl CoA:diacylglycerol acyltransferase 1), an enzyme that makes it easier for fat cells and macrophages to store excess fat.

Now a paper by Suneil Koliwad and colleagues from the Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA, published in this weeks’ issue of the Journal of Clinical Investigation, provides further evidence that increasing activity of DGAT1 in adipocytes and macrophages may protect animals from the pro-inflammatory effects of obesity.

The researchers found that although mice overexpressing DGAT1 in both macrophages and adipocytes were more prone to weight gain, they did not show signs of the inflammatory response commonly seen with diet-induced obesity.

Through a series of experiments, the researchers were able to establish that DGAT1 is indeed necessary to protect against this inflammatory response, thereby raising the question of wether stimulation of this enzyme may also protect against the complications of obesity in humans.

Thus, although this research may not lead to new ways of preventing or reducing obesity, it may open new avenues for attenuating some of the health consequences related to excess weight.

AMS
Copenhagen, Denmark