Gastric Bypass Surgery Improves Insulin Sensitivity

"The improvement in insulin sensitivity is much greater than would be predicted from weight loss alone," Dr. G. Lynis Dohm from East Carolina University, Greenville, North Carolina, stated.  "This seems to suggest to us that the surgery itself (maybe by bypassing part of the gut) has put into play a mechanism that regulates insulin sensitivity."

Dr. Dohm and colleagues investigated gastric bypass surgery-induced increases in insulin sensitivity at the whole body and muscle level and attempted to determine the mechanism behind these increases. Four groups of patients were evaluated: 93 lean patients, BMI 25 to 35; 43 morbidly obese subjects; and 40 post-gastric bypass surgery patients.

Patients who underwent gastric bypass surgery had an insulin sensitivity that was 361% higher than the morbidly obese patients and 47% higher than weight-matched groups, the authors report, and their insulin sensitivity did not differ significantly from lean individuals, despite having a higher BMI.

Similarly, basal and insulin-stimulated muscle glucose transport after surgery was comparable to that in the lean group and greater than that in the morbidly obese and weight-matched groups.

"This was unexpected because we had predicted that insulin resistance might only have an effect on insulin-stimulated glucose transport," the investigators say.

Serine phosphorylated insulin receptor substrate (IRS)-1 levels and inhibitor of kappaB kinase beta (IKK-beta) activity were lower after gastric bypass surgery than in the weight-matched patients, the researchers note, suggesting that IRS-1 serine phosphorylation is a potential cause for insulin resistance in weight-matched and morbidly obese patients.

"There is a strong link between storage of fat inside muscle and insulin resistance," Dr. Dohm explained. "We believe that fat may be activating IKK-beta (and probably other kinases) to cause insulin resistance."

"We are continuing these studies in muscle cells in culture," Dr. Dohm added. "By taking muscle biopsies for lean and obese patients we can culture myoblasts that proliferate. We then differentiate them into myocytes, which resemble the muscle cells of interest. We can then incubate the myocytes in activators and inhibitors to try to dissect the actual cause and effect."

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