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 apoptosis
3. Beta cells are hypertrophied before surgery and
fail to regress after significant weight loss
4. 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 (6080 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
- ASMBS Guidelines
• One study highlighted that many patients are noncompliant
with diet and exercise recommendations (Elkins et al. 2005)
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
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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), 819825.
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?