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Role Of GLP-1 In The Resolution of Diabetes After Gastric Bypass Surgery



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

3 Comments

  1. Dr. Sharma, do you know if anyone has proposed this surgery for the young Alzheimer’s patient? Or possibly a longitudinal study to determine how many who have had the surgery, and are loyal to post surgery discipline, go on to develop Alzheimers or any other form of dimentia?

    If the psoriasis plaque can be dissolved/resolved, what effect will the surgery have on the amyloid plaques?

    And on another note, how many stage one or stage two patients will go on to develop dimentia?

    Thanks for educating us and bringing this work on GLP-1 into the public health stream.

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  2. GLP-1 antagonists would be interesting to have available for a trial treatment for patients with severe refractory hypoglycemia post gastric bypass, as this can prove difficult to manage with currently available options.

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