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)

• Pts have postprandial hypoglycemia (2-5 hrs after eating) and may have nesidioblastotisis

• Nesidioblastotisis = hypertrophy of the islets cells of the pancreas

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)

Theories of Why It Happens Post Bariatric Surgery

1. Changing the anatomy of the GI tract changes insulin secretion -> nutrients being absorbed rapidly

2. The islet cells increase and/or less apoptosis3. Beta cells are hypertrophied before surgery and

fail to regress after significant weight loss4. Failure to adaptively decrease insulin secretion

after surgery 5. Acquired phenomenon

(McLaughlin et al. 2010, Meier et al. 2006)

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

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 pancreatectomy if

severe (Service. 2012)

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

Diet after Bariatric Surgery (Cont.)Food Type Recommendation

Sugar, sugar-containing foods, concentrated sweets

Avoid

Carbonated beverages Avoid

Fruit juice Avoid

High-saturated fat, fried foods Avoid

Soft “doughy” bread, pasta, rice Avoid/delay

Tough, dry, red meat Avoid/delay

Nuts, popcorn, other fibrous foods Delay

Caffeine Avoid/delay in moderation

Alcohol Avoid/delay in moderation

• One study highlighted that many patients are noncompliant with diet and exercise recommendations (Elkins et al. 2005)

- ASMBS Guidelines

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)

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

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 

Thank You

Questions?