Reduced Gluconeogenic Amino Acids Following Bariatric Surgery Are Associated with Resolution of the Diabetic State

Dustin M Bermudez, MD, John R Pender, MD, William H Chapman, MD, G. L Dohm, PhD, Walter J Pories, MD

Department of Surgery, Brody School of Medicine, East Carolina University

Introduction:
We hypothesize that the root of the rapid resolution of diabetes following bariatric surgery is altered metabolism of the gluconeogenic amino acids. There are 13 gluconeogenic amino acids but glutamate, aspartate and alanine predominate.

Methods and Procedures:
Following IRB approval, 18 patients who underwent an antecolic, antegastric roux-en-y gastric bypass were included in this study. Following two weeks of a low calorie diet (Optifast), serologic testing was performed approximately 1 week preoperatively and 1 week and 3 months postoperatively. Patients were stratified prior to surgery as either “obese, non-diabetics” or “obese diabetics” based on fasting hyperglycemia in accordance with American Diabetes Association guidelines. Quantification of metabolites was performed using mass spectrometry.

Results:
The levels of aspartate and glutamate were elevated in diabetic patients preoperatively compared to controls but were significantly reduced postoperatively at 1 week and 3 months in diabetic patients undergoing gastric bypass (p<0.05). Levels were signifcantly decreased 3 months postoperatively in obese non-diabetics. Alanine levels were not elevated prior to surgery but dropped significantly compared to lean patients at 7 days and 3 months in both diabetics and obese non-diabetics (p<0.05).

Conclusions:
The mechanism for resolution of diabetes following bariatric surgery remains a mystery. Our data demonstrate that the root of this altered physiology may be due to decreased levels of highly gluconeogenic amino acids thus altering the degree of gluconeogenesis that occurs at baseline and thus stemming the tide of subsequent fasting hyperglycemia.