Mechanisms of type 2 diabetes resolution after Roux-en-Y gastric bypass  Dariush Elahi, Ph.D., Panagis Galiatsatos, M.D., Atoosa Rabiee, M.D., Rocio Salas-Carrillo, M.D., Amin Vakilipour, M.D., Olga D. Carlson, Ph.D., Franca S. Angeli, M.D., Ph.D., Richard P. Shannon, M.D., Josephine M. Egan, M.D., Dana K. Andersen, M.D.  Surgery for Obesity and Related Diseases  Volume 10, Issue 6, Pages 1028-1039 (November 2014) DOI: 10.1016/j.soard.2014.07.011 Copyright © 2014 American Society for Bariatric Surgery Terms and Conditions

Fig. 1 Schematic of the procedure for combined hyperglycemic-euglycemic clamp and hyperglycemic clamp, coupled with tracer methodology and GLP-1 (7–36) amide infusion. Abbreviations: GLP-1 = glucagon-like peptide-1; IV = intravenous. Surgery for Obesity and Related Diseases 2014 10, 1028-1039DOI: (10.1016/j.soard.2014.07.011) Copyright © 2014 American Society for Bariatric Surgery Terms and Conditions

Fig. 2 Plasma glucose (top panel), insulin (middle panel), and active GLP-1 (7–26) amide (bottom panel) profiles of STM before and at 1, 3, 6, 9, 12, and 15 months after RYGB. Times when STM was administered are indicated by symbols in the middle panel and n for each test is provided in Table 1. Abbreviations: Pre = presurgery; GLP-1 = glucagon-like peptide-1. Surgery for Obesity and Related Diseases 2014 10, 1028-1039DOI: (10.1016/j.soard.2014.07.011) Copyright © 2014 American Society for Bariatric Surgery Terms and Conditions

Fig. 3 Plasma glucose profiles (top panel) during the combined hyperinsulinemic-euglycemic clamps and hyperglycemic clamps before surgery (circles) and at 12 months after surgery (triangles). The bottom panel represents the glucose infusion rates during presurgery and postsurgery clamps. The shaded area from 0 to 120 minutes indicates the period when insulin was infused, and the area from 240 to 300 minutes when GLP-1(7–26) amide was infused. Abbreviations: Pre = presurgery; GLP-1 = glucagon-like peptide-1. Surgery for Obesity and Related Diseases 2014 10, 1028-1039DOI: (10.1016/j.soard.2014.07.011) Copyright © 2014 American Society for Bariatric Surgery Terms and Conditions

Fig. 4 Plasma insulin levels during the combined hyperinsulinemic-euglycemic clamps and hyperglycemic clamps before surgery and at 1, 3, 6, and 12 months after surgery. Because of robust insulin response during GLP-1 (7–36) amide infusion, it is necessary to have an expanded insulin scale, which makes it difficult to discern the first-phase insulin response during the hyperglycemic clamps at 0 to 10 minutes. Abbreviation: Pre = presurgery. Surgery for Obesity and Related Diseases 2014 10, 1028-1039DOI: (10.1016/j.soard.2014.07.011) Copyright © 2014 American Society for Bariatric Surgery Terms and Conditions

Fig. 5 First- and second-phase insulin responses during the first hour of the hyperglycemic clamp when only glucose was infused. Abbreviation: Pre = presurgery. Surgery for Obesity and Related Diseases 2014 10, 1028-1039DOI: (10.1016/j.soard.2014.07.011) Copyright © 2014 American Society for Bariatric Surgery Terms and Conditions

Fig. 6 Rates of glucose metabolism, insulin response, and M/I when both glucose and GLP-1 (7–36) amide were infused during the hyperglycemic clamp (90–120 minutes). Asterisks indicate P<.05 compared with presurgery values (Table 2). Abbreviations: M = metabolism; I = insulin response; M/I = metabolism/insulin. Surgery for Obesity and Related Diseases 2014 10, 1028-1039DOI: (10.1016/j.soard.2014.07.011) Copyright © 2014 American Society for Bariatric Surgery Terms and Conditions

Fig. 7 Hepatic glucose production rates before surgery and 1 and 3 months after surgery. Ra was completely suppressed by 3 months during the hyperinsulinemic-euglycemic clamps and at all subsequent visits. Abbreviations: pre = presurgery; Ra = rate of glucose appearance. Surgery for Obesity and Related Diseases 2014 10, 1028-1039DOI: (10.1016/j.soard.2014.07.011) Copyright © 2014 American Society for Bariatric Surgery Terms and Conditions