SSAT - Gastric Emptying, Ensuing GLP-1 Release and Insulin Sensitivity After Partial Pancreaticoduodenectomy: Improved Glycemic Control in Cases Without Pylorus Preservation (Whipple Procedure)

Gastric Emptying, Ensuing GLP-1 Release and Insulin Sensitivity After Partial Pancreaticoduodenectomy: Improved Glycemic Control in Cases Without Pylorus Preservation (Whipple Procedure)
Johannes Miholic^*¹, Marlene Wewalka², Stefan Harmuth¹, Jens J. Holst³
¹Department of Surgery, Medical University of Vienna, Vienna, Austria; ²Gastroenterology, Department of Internal Medicine III - Medical University of Vienna, Vienna, Austria; ³The Panum Institute, Dept. of Medical Physiology, University of Copenhagen, Copenhagen, Denmark

OBJECTIVE: Investigate the relationship between gastric emptying, postprandial GLP-1 and insulin sensitivity after pancreaticoduodenectomy (PD). BACKGROUND. Abnormal glucose regulation is highly prevalent in patients with pancreatic neoplasm, and resolves in some after PD, the cause of which is unclear. The procedure is carried out with pylorus preservation (PPPD) or with distal gastrectomy (Whipple procedure). Accelerated gastric emptying, and ensuing enhanced release of glucagon-like peptide-1 (GLP-1) conceivably play a role in glucose metabolism after PD. Any procedure associated with accelerated gastric emptying might improve glycemic control. It was the purpose of this study to shed light on the relationship between gastric emptying, GLP-1 and glycemic control after PPPD and the Whipple procedure. METHODS. A 75 g oral glucose tolerance test was carried out in tumor free subjects, 13 having undergone PPPD, and in 13 after the Whipple procedure (Table1). Gastric emptying was measured by the paracetamol absorption method. Plasma concentrations of glucose, insulin, GLP-1, and paracetamol were measured at baseline, 10, 20, 30 60, 90, 120, 150, and 180 minutes. Homeostasis model assessment-estimated insulin resistance (HOMA-IR) and oral glucose insulin sensitivity were calculated from glucose and insulin concentrations. RESULTS. Patients with Whipple procedure as compared to PPPD had accelerated gastric emptying (p=0.01) which correlated with early (0-60 min.) integrated GLP-1 (AUC30; r2=0.61; p=0.02) and insulin sensitivity (r2=0.41; p=0.026), and inversely with HOMA insulin resistance (r2=0.17; p=0.033). 2 of 13 Whipple patients (15%) as compared to 7 of 13 after PPPD (54%) had postload glucose concentrations (i.e. 120 minutes postmeal) ≥200 mg/dl (p<0.05). None of 13 (0%) after Whipple procedure but 4 of 13 (31%) after PPPD had fasting glucose concentrations ≥126 mg/dl (p<0.05). CONCLUSIONS. Gastric emptying was accelerated after Whipple procedure as compared to patients who have undergone pylorus preserving PD, resulting in higher postprandial GLP-1 concentrations and insulin sensitivity and improved glycemic control.

Whipple PPPD P-Value
Age(yr) 61(32-70) 62(48-66) NS
Interval (mo) 31(7-199) 19(5-107) NS
Gastr. Emptying (Integr.parac. 30 min) 495(309-860) 319(230-601) 0.01
Early integ. GLP-1(30min) 2880(920-9205) 1740(340-3215) 0.03
Fasting glucose (mg/dl) 91(75-123) 108(83-170) 0.02
Insulin resistance (HOMA-IR) 0.6(0.22-1.75) 0.8(0.6-5.8) 0.02
Insulin sensitivity (OGIS 180) 488(310-568) 406(265-500) 0.009

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