Noninsulinoma Pancreatogenous Hypoglycemia Syndrome (NIPHS) and Mixed Meal Tests

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

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Clinical Features

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

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Theories of Why It Happens Post Bariatric Surgery

• Changing the anatomy of the GI tract changes
  insulin secretion -gt 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)

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How is it diagnosed?

• Whipples 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

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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)

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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

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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)

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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)
• - Subjects own meal (Goldman. 2011, Service.
  2012)

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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

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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,
  546551.
• 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., DAlessio, 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.uptodateonli
  ne.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.), Goldmans Cecil Medicine.
  (24th ed., pp. 1499-1505). Philadelphia, PA
  Elsevier Saunders 

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• Thank You
• Questions?