Greater glucose transport, insulin sensitivity reported after gastric bypass

Issue: January 2009

Whole body insulin sensitivity and muscle glucose transport values were greater in patients after gastric bypass compared with weight-matched controls in a new study.

Researchers conducted the cross-sectional, controlled study to assess the effects of gastric bypass and mechanisms explaining improved insulin sensitivity. Patients were separated into four groups: lean (BMI ,<25; n=93); weight-matched controls (BMI 25 to 35; n=310); morbidly obese (BMI >35; n=43); and postsurgery (BMI=30; n=40).

Greater values of insulin sensitivity and glucose transport in postsurgery patients compared with weight-matched controls suggested that “improved insulin sensitivity after gastric bypass is due to something other than, or in addition to, weight loss,” the researchers wrote. They postulated that improved insulin sensitivity is related to reduced inhibitor of kB kinase B activity and enhanced muscle insulin signaling.

Insulin-receptor substrate 1-pSer³¹² was lower among patients after gastric bypass compared with morbidly obese patients and weight-matched controls. Postsurgery patients also had higher inhibitor kBalpha compared with morbidly obese patients and weight-matched controls, which indicated reduced inhibitor of kB kinase B activity, according to the researchers.

“We interpret these findings to suggest that the improvement in insulin sensitivity is not a result of weight loss, but is more likely related to bypass of the foregut. Based on our results, we believe that IRS 1-Ser³¹² phosphorylation is a potential cause for the insulin resistance seen in the weight-matched and morbidly obese compared with the lean group, and that gastric bypass appears to result in reduced IRS 1-Ser³¹² phosphorylation to levels similar to lean controls,” the researchers wrote.

They implicated inhibitor of kB kinase B as potentially responsible for phosphorylating IRS 1-Ser³¹². “We find that bypass surgery may indirectly result in reduced inhibitor of kB kinase B activity in human skeletal muscle,” they wrote. – by Katie Kalvaitis

J Clin Endocrinol Metab. 2008;93:4656-4663.

This is just the beginning of determining the mechanistic impact of bariatric surgery. This complex study helps provide insight into defining the link between insulin resistance and metabolic risks in the morbidly obese person. The bottom line is gastric bypass could be or may be one of the best therapies for improving diabetes control in morbidly obese patients. Previously, it was felt that patients' diabetes improved secondary to weight loss; individuals with type 2 diabetes who lose weight will improve insulin sensitivity. But the question is — is it weight loss alone or is it something else? This paper attempts to define the 'something else.' Not only were the researchers able to demonstrate improved insulin sensitivity in the post-surgery group, but that insulin sensitivity improved to a level equivalent to that of a lean person. In addition, unlike the weight-matched obese controls, the post-surgical subjects did not demonstrate the same relationship of BMI and insulin sensitivity that is typically seen in people who are losing weight. Therefore, there must be some other mechanistic/molecular processes that allow glucose regulation to correct even better than with weight loss alone. I believe this paper does demonstrate that there is an advantage in the post-surgery patient to an even better improvement in glucose regulation.

However, there is still a link missing: we don't know how the changes to the intestinal anatomy translate to molecular changes at the level of the muscle.

As an aside, there is some work going on now looking at gastric bypass in the obese patient — not morbidly obese — to see if the surgery will bring about the same positive effects on glucose regulation without the same degree of weight loss. This will be the next step in verifying the findings of these researchers.

– Dara P. Schuster, MD

Associate Professor of Internal Medicine and Associate Medical Director
Ohio State University Medical Center