KATE VELTMAN Drug use changes after Whipple pancreaticduodenectomy

What is a Whipple procedure? Removal of the head of the pancreas, part of the bile duct, gallbladder, and duodenum Part of the stomach may or may not be removed Performed for:  Cancers in the pancreas, duodenum, bile duct, or ampulla  Chronic pancreatitis  Benign tumors of the head of the pancreas

Pancreatogenic diabetes Parameter Type I Juvenile-onset IDDM Type II NIDDM Type III Pancreatogenic KetoacidosisCommonRare HyperglycemiaSevereUsually mildMild HypoglycemiaCommonRareCommon Peripheral insulin sensitivity Normal or increased DecreasedIncreased Hepatic insulin sensitivity NormalNormal or increased Decreased Insulin levelsLowHighLow Glucagon levelsNormal or high Low

Diabetic goals and management A 1 C ≤ 7% Fasting plasma glucose 70 – 130 mg/dL Begin insulin therapy with A 1 C ≥ 8.5% Begin treatment with pancreatic enzymes There is no clear-cut guideline for treatment

ClassMedicationsMechanism of action SulfonylureasGlyburide; glimepiride; glipizide Stimulates insulin secretion in beta cells BiguanidesMetforminDecreases insulin resistance in the liver Glucagon-like peptide agonists Byetta; VictozaBinds GLP-1 receptors to enhance insulin secretion and decrease glucagon release ThiazolidinedionesPioglitazone; rosiglitazone Bind PPAR on the fat and vascular cells to reduce insulin resistance in the periphery α-Glucosidase inhibitorsAcarbose; miglitol Decrease post-prandial highs by delaying absorption of complex carbohydrates DPP-4 inhibitorsSitagliptin; saxagliptin Reduce post-prandial elevated glucagon and improve insulin response

ClassMedicationsMechanism of action SulfonylureasGlyburide; glimepiride; glipizide Stimulates insulin secretion in beta cells BiguanidesMetforminDecreases insulin resistance in the liver Glucagon-like peptide agonists Byetta; VictozaBinds GLP-1 receptors to enhance insulin secretion and decrease glucagon release ThiazolidinedionesPioglitazone; rosiglitazone Bind PPAR on the fat and vascular cells to reduce insulin resistance in the periphery α-Glucosidase inhibitorsAcarbose; miglitol Decrease post-prandial highs by delaying absorption of complex carbohydrates DPP-4 inhibitorsSitagliptin; saxagliptin Reduce post-prandial elevated glucagon and improve insulin response

Steatorrhea The presence of fat in stool Due to a lack of bile acids and decrease of pancreatic enzymes Impacts absorption of fats, which therefore impacts absorption of Vitamins A, D, E and K

Treatment of steatorrhea Diet changes  Start with 50 gm fats per day and increase  Avoid exceeding 100 gm fat per day  Small and frequent meals Drug therapy  Pancreatic enzymes  Includes lipase, protease and amylase  Begin at 500 U lipase/kg/meal and increase if symptoms persist  Max dose: 10,000 U lipase/kg/day OR 2,500 U lipase/kg/meal OR 4,000 U lipase/gm fat/day  Possibly H2 blocker or PPI NOTE: Can affect diabetic control!

Sources 1. Braga M, Cristallo M, De Franchis R, et al. Correction of malnutrition and maldigestion with enzyme supplementation in patients with surgical suppression of exocrine pancreatic function. Surg Gynecol Obstet. 1988;167(6): Cui YF, Andersen DK. Pancreatogenic diabetes: Special considerations for management. Pancreatology. 2011;11(3): Knop FK, Vilsbøll T, Larsen S, et al. Increased postprandial responses of GLP-1 and GIP in patients with chronic pancreatitis and steatorrhea following pancreatic enzyme substitution. American Journal of Physiology-Endocrinology And Metabolism. 2007;292(1):E324-E Slezak LA, Andersen DK. Pancreatic resection: Effects on glucose metabolism. World J Surg. 2001;25(4): USC Department of Surgery. Whipple operation. 20resection/whipple%20operation.html. Accessed November/03, resection/whipple%20operation.html Montgomery PA. Chapter 46. Pancreatitis. In: Talbert RL, DiPiro JT, Matzke GR, Posey LM, Wells BG, Yee GC, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. New York: McGraw-Hill; Accessed November 4, Doherty GM, Way LW. Chapter 26. Pancreas. In: Doherty GM, ed. CURRENT Diagnosis & Treatment: Surgery. 13th ed. New York: McGraw-Hill; Accessed November 4, Peter L, Jutta K, Lankisch PG. Pancreatic enzyme replacement therapy. Curr Gastroenterol Rep. 2001;3(2):