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Noninsulinoma Pancreatogenous Hypoglycemia Syndrome (NIPHS) and Mixed Meal Tests

Noninsulinoma Pancreatogenous Hypoglycemia Syndrome (NIPHS) and Mixed Meal Tests. Presented by: Michelle Gelfand Dietetic Intern. What is it?. NIPHS = hypoglycemia caused by hyper secretion of insulin by the pancreas but not caused by an insulinoma (tumor on the pancreas)

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Noninsulinoma Pancreatogenous Hypoglycemia Syndrome (NIPHS) and Mixed Meal Tests

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  1. Noninsulinoma Pancreatogenous Hypoglycemia Syndrome (NIPHS) and Mixed Meal Tests Presented by: Michelle Gelfand Dietetic Intern

  2. What is it? • NIPHS= hypoglycemia caused by hyper secretion of insulin by the pancreas but not caused by an insulinoma (tumor on the pancreas) • Pts have postprandial hypoglycemia (2-5 hrs after eating) and may have nesidioblastotisis • Nesidioblastotisis = hypertrophy of the islets cells of the pancreas

  3. Clinical Features • Can be a complication of bariatric surgery • Predominantly seen in males • Neuroglycopenic symptoms (BG < 55-50 mg/dL): dizziness, confusion, tiredness, difficulty speaking, weakness, lightheadedness, cloudy vision, shakiness, sweating, loss of consciousness (Goldman. 2011, Bantle et al. 2007)

  4. Theories of Why It Happens Post Bariatric Surgery • Changing the anatomy of the GI tract changes insulin secretion -> nutrients being absorbed rapidly • The islet cells increase and/or less apoptosis • Beta cells are hypertrophied before surgery and fail to regress after significant weight loss • Failure to adaptively decrease insulin secretion after surgery • Acquired phenomenon (McLaughlin et al. 2010, Meier et al. 2006)

  5. How is it diagnosed? • Whipple’s triad: hypoglycemia symptoms, low BG, and resolution when BG is raised • Majority have a negative 72-hour fast • Mixed meal tolerance test • Positive selective arterial calcium stimulation test (SACST) • CT, US • Pathology confirmation

  6. How is it treated? • Dietary modification: reduce carbohydrate intake (Service. 2012), high protein, low carbohydrate diet (VCU Patient Education Manual) • Meds: acarbose, octreotide, verapamil, & diazoxide (Service. 2012) & GLP-1 receptor antagonist (Salehi et al. 2014) • G-tube placement? (McLaughlin et al. 2010) • Reversal of gastric bypass surgery (Lee et al. 2013) Note: did not work • Partial or subtotal pancreatectomyif severe (Service. 2012)

  7. Diet after Bariatric Surgery • Lifelong • Focused on receiving adequate protein (60-80 g/day) • ½ cup servings at a time (some can eat more as time goes on) • Avoid refined carbohydrates/simple sugars (can cause dumping/weight gain) • No more than 5 g sugar on nutrition label • Beverages separated from meals (30 min before and 60-90 min after) • 1200 calories/day

  8. Diet after Bariatric Surgery (Cont.) - ASMBS Guidelines • One study highlighted that many patients are noncompliant with diet and exercise recommendations (Elkins et al. 2005)

  9. Mixed Meal Test • Many methodologies used in varying studies: - Ensure Plus/Ensure High Protein liquid meal (Salehi et al. 2014, Khoo et al. 2013, Lee et al. 2013) - Eggs, Canadian bacon or steak, and Jell-O (Della Man et al, 2013) - 75 g glucose in water, 40 g parmesan cheese, and eggs (Camastra et al. 2013) - High and low carbohydrate meal (1 of each) (Bantle et al. 2007) - Subject’s own meal (Goldman. 2011, Service. 2012)

  10. Conclusions/Summary • No established/standardized way to conduct a mixed meal test • Various treatment options, should be individualized, surgery only in severe cases • Post bariatric surgery patients should adhere to recommended lifelong diet • Can lead to severe consequences if not treated

  11. References • Aills, L., Blankenship, J., Buffington, C., Furtado, M., & Parrott, J. (2008). Allied health nutritional guidelines for the surgical weight loss patient. Surgery for Obesity and Related Disease, 4, 73-108. • Bantle, J.P., Ikramuddin, S., Kellogg, T.A., & Buchwalk, H. (2007). Hyperinsulinemic hypoglycemia developing late after gastric bypass. Obesity Surgery, 17(5), 592-594. • Camastra, S., Muscelli, E., Gastaldelli, A., Hoist, J.J., Astiarraga, B., Baldi, S., et al. (2013). Long- term effects of bariatric surgery on meal disposal and beta cell function in diabetic and nondiabetic patients. Diabetes, 62(11), 3709-3717. • Dalla Man, C., Piccinini, F., Basu, R., Basu, A., Rizza, R.A., & Cobelli, C. (2013). Modeling hepatic insulin sensitivity during a meal: validation against the euglycemic hyperinsulinemic clamp. American Journal of Physiology Endocrinology Metabolism, 304(8), 819-825. • Elkins, G., Whitfield, P., Marcus J., Symmonds R., Rodriguez J., & Cook T. (2005). Noncompliance with behavioral recommendations following bariatric surgery. Obesity Surgery, 15, 546–551. • Khoo, C.M., Muehlbauer, M.J., Stevens, R.D., Pamuklar, Z., Chen, J., Newgard, C.B., & Torquarti, A. (2013). Postprandial metabolite profiles reveal differential nutrient handling after bariatric surgery compared with matched caloric restriction. Annals of Surgery, 00(00), 1-7. • Lee, C.J., Brown, T., Magnuson, T.H., Egan, J.M., Carlson, O., & Elahi, D. (2013). Hormonal response to a mixed meal challenge after reversal of gastric bypass for hypoglycemia. Jounal of Clnical Endocrinology Metabolism, 98(7), 1208-1212. • McLaughlin, T., Peck, M., Holst, J., & Deacon, C. (2010). Reversible Hyperinsulinemic hypoglycemia after gastric bypass: A consequence of altered nutrient delivery. The Journal of Clinical Endocrinology and Metabolism, 95, 1851-1855. • Meier, J.J., Butler, A.E., Galasso, R., & Butler, P.C. (2006). Hyperinsulinemic hypoglycemia after gastric bypass surgery is not accompanied by islet hyperplasia or increased beta-cell turnover. Diabetes Care, 29(7), 1554-1559. • Salehi, M., Gastaldilli, A., & D’Alessio, D.A. (2014). Blockade of glucagon like peptide 1 recptor corrects postprandial hypoglycemia after gastric bypass. Gastroenterology, 146(3), 669-680. • Service, J.F. (2012). Noninsulinoma pancreatogenous hypoglycemia syndrome, Up To Date. Available from http://www.uptodateonline.com. • Service, J.F. (2013). Hypoglycemia in adults without diabetes mellitus: Diagnostic approach, Up To Date. Available from http://www.uptodateonline.com. • Valderas, J.P., Ahuad, J., Rubio, L., Escalona, M., Pollak, F., & Maiz, A. (2012). Acarbose improves hypoglycaemia following gastric bypass surgery without increasing glucagon-like peptide 1 levels. Obesity Surgery, 22(4), 582-586. • VCU Medical Center Obesity Surgery Program. Laparoscopic Gastric Bypass Surgery: Patient Education Manual. • Vella, A., Rizza R.A., & Service, J.F. (2011). Hypoglycemia and Pancreatic Islet Cell Disorders. In Goldman (Eds.), Goldman’s Cecil Medicine. (24th ed., pp. 1499-1505). Philadelphia, PA: Elsevier Saunders 

  12. Thank You Questions?

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