Arya M. Sharma, MD

Yesterday, I discussed the strong interest in trying to understand why exactly bariatric surgery leads to an often dramatic improvement (if not resolution) of type 2 diabetes.

Additional insights into this topic comes from Marzieh Salehi and colleagues in a paper just published in Diabetes.

The paper takes advantage of the fact that some patients undergoing gastric bypass (GB) surgery experience significantly increased insulin secretion following a meal, sometimes even resulting in clinically significant hypoglycaemia.

In order to test the hypothesis that this increase in insulin secretion is in part mediated by the incretin glucagon-like peptide 1 (GLP-1), asymptomatic individuals with previous GB, 10 matched healthy nonoperated control subjects, and 12 patients with recurrent hypoglycemia after GB were examined with and without administration of the GLP-1 receptor antagonist exendin-(9-39).

Blocking GLP-1 significantly reduced postprandial insulin secretion in GB patients than in the non-surgical controls. However, in the hypoglycaemic GB patients, GLP-1 appeared to account for about 45% of increased insulin secretion, not much more than in the non-hypoglycemic surgical subjects.

Glucagon was suppressed similarly by hyperglycemia in all groups but rose significantly after the meal in surgical individuals but remained suppressed in nonsurgical subjects. GLP-1 receptor blockade increased postprandial glucagon in both surgical groups.

As the authors conclude,

“Increased GLP-1-stimulated insulin secretion contributes significantly to hyperinsulinism in GB subjects. However, the exaggerated effect of GLP-1 on postprandial insulin secretion in surgical subjects is not significantly different in those with and without recurrent hypoglycaemia.”

This means that additional factors are probably involved in the hypoglycaemic response seen in some GB patients.

As pointed out in an accompanying editorial by Jens Juul Holst, however, these findings may be more difficult to interpret due to several features of the study design used by Salehi and colleagues. Thus, without going into too many methodological details, there are questions about whether or not the approach used in this study fully explored (or rules out) the role of GLP-1 in the hypoglycaemic response.

Nevertheless, the study certainly supports the notion that increased secretion of GLP-1 following GB surgery, together with other mechanisms including secretion of other enteric hormones, quicker passage of food through the small bowel, reduction in liver fat, and weight loss in general, may all play a role in the substantial glycemic improvements seen with GB surgery in patients with type 2 diabetes.

Thus, while administration of GLP-1 analogues can potentially mimic some of the euglycemic effects of bariatric surfer, it is unlikely that injections of GLP-1 analogues alone will likely result in the same dramatic effects seen with GB surgery.

On the other hand, even if GLP-1 analogues can only deliver some of the potential benefits seen with surgery, I am sure that many patients would likely prefer forgoing some of the benefits in favour of a simple daily injection.

AMS
Edmonton, Alberta

Hat tip to Richard Lehner for alerting me to these articles.

Salehi M, Prigeon RL, & D’Alessio DA (2011). Gastric bypass surgery enhances glucagon-like Peptide 1-stimulated postprandial insulin secretion in humans. Diabetes, 60 (9), 2308-14 PMID: 21868791

Holst JJ (2011). Postprandial insulin secretion after gastric bypass surgery: the role of glucagon-like Peptide 1. Diabetes, 60 (9), 2203-5 PMID: 21868790

Regular readers of these pages, will by now know that bariatric surgery is by far the most effective and reliable treatment for severe obesity.

However, how exactly bariatric surgery works, continues to be an intense field of medical and experimental research.

Last year, this was the topic of the 13th Bariatric/metabolic International Symposium of the Merck Frosst/CIHR Research Chair in Obesity at Laval University, the proceeding of which have now been published in a supplement to the International Journal of Obesity.

As pointed out by Keith Sharkey, from the University of Calgary, in an accompanying editorial,

“surgeries are remarkably effective in reducing weight over a sustained period of time, and they also have significant beneficial effects on glucose homeostasis. Interestingly, the metabolic benefits of these surgeries frequently occur before significant weight loss.”

Studies in this supplement use animal models to reveal the neurohumoral mechanisms underlying weight loss and improved glucose homeostasis after experimental bariatric surgery.

Not only do these rodent models of bariatric surgery show that food reward is altered and that the proximal gut is important in the control of energy balance and glucose homeostasis, but these studies provide important insights into the molecular and neuronal mechanisms of these effects.

Of course, from my perspective, the hope is that there findings will eventually lead to pharmaceutical approached to treating severe obesity that will eventually put bariatric surgeons out of business.

Till then, we must accept that surgical treatment is far more effective for managing severe obesity in patients, who urgently need treatment, than any conservative ‘Eat-Less-Move-More’ approaches have to offer.

Of course, preventing the obesity in the first place would be even better, but that certainly does not solve the problem of the tens of thousands, who cary 100s of excess pounds and have few, if any, other options to deal with their considerable excess weight and related health problems.

AMS
Edmonton, Alberta

Sharkey KA (2011). Animal models of bariatric/metabolic surgery shed light on the mechanisms of weight control and glucose homeostasis: view from the chair. International journal of obesity (2005), 35 Suppl 3 PMID: 21912385

As not everyone may have a chance during the week to read every post, here’s a roundup of last week’s posts:

• Should We Outsource Obesity Treatments To Weight Watchers?
• Alberta’s Obesity Initiative: Not Just Diet and Exercise
• Is There Any Path For Approval of Anti-Obesity Drugs?
• GLP-1 Receptor Agonists, Obesity and Psoriasis
• Bariatric Surgery For Osteoarthritis of Hips and Knees?

Have a great Sunday! (or what’s left of it)

AMS
London, UK

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Osteoarthritis in hips and knees is a common progressive disease leading to joint pain and severe disability. It is a complex multifactorial condition leading to damage of cartilage, deposition of subchondral bone matrix and release of pro-inflammatory cytokines.

One of the most common risk factors for osteoarthritis is carrying around excess weight. In fact, no matter what the root cause of the problem (trauma or otherwise), weight loss has consistently been shown to reduce pain (for e.g. each lb lost takes about four pounds off each knee).

So the question arises, whether bariatric surgery should be used more commonly in obese patients with osteoarthritis in hips or knees.

In a paper authored by Richdeep Gill and other colleagues, just published in Obesity Reviews, we report our findings from a systematic review of the literature on bariatric surgery and osteorarthritis.

A comprehensive search of electronic databases using broad search terms revealed a total of 400 articles, including six studies, which met our criteria for inclusion in our qualitative analysis.

Although there was a clear trend towards improvement of hip and knee osteoarthritis in hips and knees following bariatric surgery, the data consists largely of case series.

Thus, it may well be time to conduct a large randomized controlled trial to determine whether or not bariatric surgery should perhaps be routinely considered as a means to better manage hip or knee osteoarthritis in patients with severe obesity.

AMS
Edmonton, Alberta

Gill RS, Al-Adra DP, Shi X, Sharma AM, Birch DW, & Karmali S (2011). The benefits of bariatric surgery in obese patients with hip and knee osteoarthritis: a systematic review. Obesity reviews : an official journal of the International Association for the Study of Obesity PMID: 21883871

Regular readers may recall previous posts in which I commented on the significant impact (both good and bad) that undergoing bariatric surgery can have on personal relationships.

This topic is extensively dealt with in an article by Katherine Applegate and Kelli Friedman (Duke University) published in Bariatric Nursing.

As the authors point out patients can encounter diverse relationship issues as they consider, undergo, and live with bariatric surgery.

These problems can stem from the patients’ and their partners’ expectations, the patients’ increase in energy, their enhanced confidence, and changes in appearance.

Other common concerns include changes in sexual intimacy and beliefs about the stability of the relationship and risk of divorce.

Although overall, there is considerable research showing that most patients will report improvements in
relationship satisfaction and weight-related sexual quality of life after surgery, problems can occur and health professionals should certainly be aware of and well able to counsel their patients on these issues.

As always, it is best to communicate these issues professionally and accurately and help patients recruit support and obtain psychological counseling when needed.

I’d certainly like to hear from any of my readers on how they have dealt with such issues or have counselled their clients about these problems.

AMS
Hamburg, Germany