Mechanisms of Diabetes Control After Weight Loss Surgery

Obesity and type 2 diabetes (T2DM) are increasing in the US. One third of patients seeking
bariatric surgery have T2DM. Although all surgeries result in significant weight loss and
often 'cure' the T2DM, the rapid onset and the magnitude of the benefits of gastric bypass
(GBP) on T2DM has thus far baffled clinical scientists. Limited data suggest that the
improvement in T2DM after GBP occurs very rapidly, and may not be wholly accounted for by
weight loss. Secretion of incretins (gut peptides secreted in response to meals which enhance
insulin secretion) is impaired in T2DM and improves after GBP, possibly due to the specific
anatomical changes after this surgery. While some determinants of impaired insulin secretion,
such as glucotoxicity, improve equally after diet or surgical weight loss, the improvement in
the incretin effect after GBP might be specific to this surgery. The aim of this study is to
determine whether the magnitude of the incretin effect on insulin secretion is greater after
GBP than after an equivalent diet-induced weight loss. We will compare, in obese patients
with diabetes, randomized to very low calorie diet or to GBP, the effect of an equivalent
weight loss on the incretin effect (difference in insulin secretion after comparable oral and
intravenous (IV) glucose loads). As more obese diabetic patients undergo GBP, understanding
the mechanisms that produce improvement in their diabetes is increasingly important.