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Postprandial Hypoglycemia: Complication of Peptic Ulcer Surgery
Accepted Manuscript Title: Postprandial Hypoglycemia. Complication of Peptic Ulcer Surgery Author: Adnan Haider, James K Burks, HI Cheema, Angel Tejada PII: DOI: Reference:
S0002-9343(17)30683-6 http://dx.doi.org/doi: 10.1016/j.amjmed.2017.06.010 AJM 14159
To appear in:
The American Journal of Medicine
Please cite this article as: Adnan Haider, James K Burks, HI Cheema, Angel Tejada, Postprandial Hypoglycemia. Complication of Peptic Ulcer Surgery, The American Journal of Medicine (2017), http://dx.doi.org/doi: 10.1016/j.amjmed.2017.06.010. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Postprandial Hypoglycemia. Complication of Peptic Ulcer Surgery Adnan Haider MD, James K Burks MD, Cheema HI, MD, Angel Tejada, MD
Running Title: Dumping syndrome, Postprandial hypoglycemia, Incretins. Authors: Adnan Haider MD, James K Burks MD, Cheema HI, MD, Angel Tejada, MD Author’s address: [email protected] [email protected] [email protected] [email protected] Affiliations: Adnan Haider, MD (Texas Tech University Health Science center) James. K. Burks, MD (Texas Tech University Health Science center) Hira Cheema, MD (Texas tech University Health Science center) Angel Tejada, MD (Texas Tech University Health Science center)
Funding source: None
Clinical Significance: Recognition of hypoglycemia in nondiabetic patients can be challenging and expensive. History of upper G.I surgeries should alert the providers for a possibility of postprandial hypoglycemia. Five-hour post prandial testing is straightforward and relative inexpensive test that help in diagnosis.
Page 1 of 8
Establishing diagnosis is reassuring for the patient and can avoid other expensive tests. Avoidance of large carbohydrate meals and six small meals will help prevent such events.
Abstract Objective: Billroth II procedures (gastrojejunostomy with vagotomy) are seldom performed now, but were popular before the advent of histamine 2 (H2) receptor blockers and proton pump inhibitors (PPIs). Such procedures can be a cause of late postprandial hypoglycemia. Method: Formal evaluation, discussion of postprandial hypoglycemia. Results: We present a case of an 85-year-old man who presented to the Endocrinology clinic with a complaint of “fainting spells following large meals.” The patient previously had extensive evaluations by a neurologist and a cardiologist. Because of the history of Billroth II surgery and the description of his fainting spells, a five-hour glucose tolerance test was performed in the clinic using the foods that uniformly resulted in symptoms. This confirmed that the late dumping syndrome with associated hypoglycemia was the cause of his spells. Conclusion: Late dumping syndrome manifesting with hypoglycemia should be considered in the workup of patients with a history of prior gastric surgery and unusual postprandial symptoms. This case highlights the importance of an appropriate workup that can lead to avoidance of unnecessary testing in such patients. Keywords: Dumping syndrome, hypoglycemia, Incretins
Page 2 of 8
Case Presentation: An 85-year-old Caucasian male presented to the Endocrinology clinic for evaluation of near fainting spells. His spells were described in detail in a note that he had written. The typical spells were described as feeling lightheaded and nauseous; symptoms were especially bothersome in the morning and worse after eating biscuits and gravy. His spells had been present for ten years but were especially troublesome in the last few years. The patient described a spell about six years prior to his visit while visiting Florida. After eating a large breakfast, he went for a swim and lost consciousness in the pool necessitating help from paramedics. His heart rate and blood sugars at the time were noted to be low. The patient ended up having a pacemaker inserted for a possible sick sinus syndrome. His timolol eye drops were also stopped because it was thought that the beta blocker eye drops contributed to his spells by causing bradycardia. After stopping the medication, there was no improvement in the frequency or severity of his spells. His past medical history included the history of severe peptic ulcer disease for which he had Billroth II procedure performed in 1985. Other medical problems included anxiety, insomnia, and sick sinus syndrome. Postprandial hypoglycemia was considered in the differential. To confirm this diagnosis a 5-hour large carbohydrate meal test was scheduled. The patient had a normal B12, Methylmalonic acid, and 25hydroxy-vitamin D level. The patient was instructed to fast overnight (12 hours), and baseline labs (glucose, C-peptide, proinsulin, insulin levels) were drawn. A large meal (IHOP breakfast) was given to the patient. The patient had one large waffle, two pancakes, one hash brown, a total of 4 syrup packages, 10 ounces of Welch’s grape juice and a few sips of sweet tea. Blood sugars were drawn every hour for a
Page 3 of 8
total of 5 hours. Results are shown in table one. The patient was symptomatic at approximately 5 hours after breakfast and repeat labs were drawn. IV glucagon, 1 mg, was then given and repeat blood sugar 15-minutes post injection was 98 mg/dL with resolution of symptoms.
Discussion: Billroth II, more formally Billroth’s operation II is a procedure in which the lower part of the stomach (antrum) is removed and a loop of small bowel (jejunum) is brought up and joined to it (gastrojejunostomy).
Bariatric surgery for weight loss has enhanced our understanding and role of gastrointestinal hormones in controlling insulin release in the postprandial state. (7,5) Although uncommon now, Billroth procedures frequently performed in the 1970s for uncontrolled peptic ulcer disease should be considered in the differential of hypoglycemic spells in the appropriate clinical settings. (3) Patients who have undergone gastrectomy (partial or complete) or vagotomy may encounter various postoperative complications. One such complication is post-gastrectomy dumping syndrome, divided into early and late phase types. (6) Dumping syndrome is not a single disease but a constellation of symptoms that can be categorized as early and late dumping. (1) Physiologically in addition to secreting hydrochloric acid, gastrin, and intrinsic factor, the stomach also serves as a reservoir, storing up to 0.8-1.5 liters of food until food can be processed into the duodenum and lower intestinal tract. The stomach converts food into chyme, a semifluid mixture of ingested food and gastric secretions. The pylorus of the stomach and vasovagal reflex
Page 4 of 8
regulates slow emptying of chyme from the stomach into the small intestine at a rate suitable for proper digestion and absorption. (7) Bariatric and Billroth surgeries can affect the above functions of the stomach and vasovagal reflex resulting in rapid transit of a hyperosmolar load into the proximal small intestine leading to a rapid shift of fluid into the gut lumen and produces intestinal distention and contraction of plasma volume manifested as hypotension and increased sympathetic response. (3) The Early dumping syndrome occurs within the first hour of ingesting a meal and is characterized by nausea, abdominal pain, borborygmi, diarrhea, a sensation of heat, dizziness, desire to lay down. (7,2) Lethargy and sleepiness after meals are typical. Late dumping syndrome symptoms occur later and are attributed to hypoglycemia with tremors, cold sweats, difficulty in concentrating, and loss of consciousness. Late dumping syndrome symptoms occur 3 -4 hours after a meal and is an incretin driven hyperinsulinemia phenomenon. Rapid transit of hyperosmolar food will result in an exaggerated release of Incretins. Two incretins that play a significant role in insulin release are glucosedependent insulinotropic polypeptide (GIP) or gastric inhibitory peptide and glucagon like peptide (GLP). (4) Gut hormones are implicated in the reduction of appetite and weight loss after bariatric procedures. Postprandial polypeptide YY (PYY) and GLP -1 profiles start rising as early as two days after gastric bypass. Changes in appetite are evident within days after gastric bypass surgery. In patients with poor weight loss after gastric bypass associated with increased appetite, the postprandial PYY and GLP-1 responses are attenuated compared with patients with expected weight loss. After gastric bypass, 85% of patients with type 2 diabetes become normoglycemic, many within days of the operation and independent of weight loss, indicating gut hormone role in improving glucose-dependent Insulin release. (7) Billroth II surgery is results in an increase in PYY and GLP-1 release from the distal small intestine, especially in response to a large carbohydrate meal. Both PYY and GLP-1 causes glucose-dependent Insulin release.
Page 5 of 8
Vagotomy which is a critical part of gastric surgery can hamper the accommodation reflex of the stomach in response to a large meal leading to a rapid transit of unprocessed food into the small intestine. The combination results in delayed digestion and absorption of simple sugars into the blood stream and exaggerated GLP-1 mediated insulin release leading to postprandial hypoglycemia. The dumping syndrome has been reported to occur in approximately 20% of patients who undergo vagotomy with pyloroplasty, in up to 40% of the patient's after Roux-en-Y gastric bypass or sleeve gastrectomy, and in up to 50% of patients who undergo esophagotomy.
Conclusion:
The patient was reassured that these spells could be prevented by avoiding large carbohydrate meals and eating small meals throughout the day. Timolol eye drops were resumed. Pharmacologic treatment (Alpha-glucosidase inhibitor) was not started to avoid polypharmacy. The patient followed up in clinic three months after testing and is adherent to dietary and treatment plan. He denied any further fainting spells and his intraocular pressure is better following reinstitution of his timolol eye drops. References: 1. Mala T, Hewitt S. Dumping syndrome following gastric Surgery.2015 Jan 27;135(2):137-41 2. Pinatel Lopasso. Rev Gastroenterol Peru. Peptic ulcer: late complications of the surgical treatment. 1995 Sep-Dec;15(3):273-81. 3. Milkov G. Definition and classification of the late complications after gastric resection. Probl Khig. 1980;8:139-49.
Page 6 of 8
4. Yoshinori Yamashita. Gastrointestinal Hormones in Dumping Syndrome and Reflux Esophagitis after Gastric Surgery J. Smooth Muscle Res. 33: 3748. 5. W. W te Riele, J.M. Vogten, D. Boerma. Comparison of weight loss and Morbidity after Gastric Bypass and Gastric Banding. A single Center European Experience. Obesity Surgery (2008) 18:11-16 6. Rohof WO, Bisschops R, Tack J, Boeckxstaens GE. Postoperative problems 2011: fundoplication and obesity surgery. Gastroenterol Clin North Am. 2011 Dec;40(4):809-21 7. Carel W. le, Richard W, Merlin W. Gut hormones as Mediators of Appetite and weight loss After Roux-en-Y Gastric bypass. Annals of surgery, 2007;246:780-785.
Page 7 of 8
Table 1. Normal Lab values: C-peptide 1.1-4.4 ng/ml, Insulin 2.6- 24.9 (uIU/ml), Proinsulin 210pmol/L
Time
Symptoms
Labs. (Venous draw)
8AM(Fasting)
Capillary blood sugars 110
No symptoms
Glucose 89 C-Peptide 2.4 Insulin 5.6 Proinsulin 3.7
9AM 10 AM
206 307
11AM
118
12 Noon
40
No symptoms Felt lightheaded” Could take a nap” Bowel movement. Formed Incoherent, sweating
Glucose 25 C-Peptide 21.2 Insulin 146.8
Page 8 of 8
S0002-9343(17)30683-6 http://dx.doi.org/doi: 10.1016/j.amjmed.2017.06.010 AJM 14159
To appear in:
The American Journal of Medicine
Please cite this article as: Adnan Haider, James K Burks, HI Cheema, Angel Tejada, Postprandial Hypoglycemia. Complication of Peptic Ulcer Surgery, The American Journal of Medicine (2017), http://dx.doi.org/doi: 10.1016/j.amjmed.2017.06.010. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Postprandial Hypoglycemia. Complication of Peptic Ulcer Surgery Adnan Haider MD, James K Burks MD, Cheema HI, MD, Angel Tejada, MD
Running Title: Dumping syndrome, Postprandial hypoglycemia, Incretins. Authors: Adnan Haider MD, James K Burks MD, Cheema HI, MD, Angel Tejada, MD Author’s address: [email protected] [email protected] [email protected] [email protected] Affiliations: Adnan Haider, MD (Texas Tech University Health Science center) James. K. Burks, MD (Texas Tech University Health Science center) Hira Cheema, MD (Texas tech University Health Science center) Angel Tejada, MD (Texas Tech University Health Science center)
Funding source: None
Clinical Significance: Recognition of hypoglycemia in nondiabetic patients can be challenging and expensive. History of upper G.I surgeries should alert the providers for a possibility of postprandial hypoglycemia. Five-hour post prandial testing is straightforward and relative inexpensive test that help in diagnosis.
Page 1 of 8
Establishing diagnosis is reassuring for the patient and can avoid other expensive tests. Avoidance of large carbohydrate meals and six small meals will help prevent such events.
Abstract Objective: Billroth II procedures (gastrojejunostomy with vagotomy) are seldom performed now, but were popular before the advent of histamine 2 (H2) receptor blockers and proton pump inhibitors (PPIs). Such procedures can be a cause of late postprandial hypoglycemia. Method: Formal evaluation, discussion of postprandial hypoglycemia. Results: We present a case of an 85-year-old man who presented to the Endocrinology clinic with a complaint of “fainting spells following large meals.” The patient previously had extensive evaluations by a neurologist and a cardiologist. Because of the history of Billroth II surgery and the description of his fainting spells, a five-hour glucose tolerance test was performed in the clinic using the foods that uniformly resulted in symptoms. This confirmed that the late dumping syndrome with associated hypoglycemia was the cause of his spells. Conclusion: Late dumping syndrome manifesting with hypoglycemia should be considered in the workup of patients with a history of prior gastric surgery and unusual postprandial symptoms. This case highlights the importance of an appropriate workup that can lead to avoidance of unnecessary testing in such patients. Keywords: Dumping syndrome, hypoglycemia, Incretins
Page 2 of 8
Case Presentation: An 85-year-old Caucasian male presented to the Endocrinology clinic for evaluation of near fainting spells. His spells were described in detail in a note that he had written. The typical spells were described as feeling lightheaded and nauseous; symptoms were especially bothersome in the morning and worse after eating biscuits and gravy. His spells had been present for ten years but were especially troublesome in the last few years. The patient described a spell about six years prior to his visit while visiting Florida. After eating a large breakfast, he went for a swim and lost consciousness in the pool necessitating help from paramedics. His heart rate and blood sugars at the time were noted to be low. The patient ended up having a pacemaker inserted for a possible sick sinus syndrome. His timolol eye drops were also stopped because it was thought that the beta blocker eye drops contributed to his spells by causing bradycardia. After stopping the medication, there was no improvement in the frequency or severity of his spells. His past medical history included the history of severe peptic ulcer disease for which he had Billroth II procedure performed in 1985. Other medical problems included anxiety, insomnia, and sick sinus syndrome. Postprandial hypoglycemia was considered in the differential. To confirm this diagnosis a 5-hour large carbohydrate meal test was scheduled. The patient had a normal B12, Methylmalonic acid, and 25hydroxy-vitamin D level. The patient was instructed to fast overnight (12 hours), and baseline labs (glucose, C-peptide, proinsulin, insulin levels) were drawn. A large meal (IHOP breakfast) was given to the patient. The patient had one large waffle, two pancakes, one hash brown, a total of 4 syrup packages, 10 ounces of Welch’s grape juice and a few sips of sweet tea. Blood sugars were drawn every hour for a
Page 3 of 8
total of 5 hours. Results are shown in table one. The patient was symptomatic at approximately 5 hours after breakfast and repeat labs were drawn. IV glucagon, 1 mg, was then given and repeat blood sugar 15-minutes post injection was 98 mg/dL with resolution of symptoms.
Discussion: Billroth II, more formally Billroth’s operation II is a procedure in which the lower part of the stomach (antrum) is removed and a loop of small bowel (jejunum) is brought up and joined to it (gastrojejunostomy).
Bariatric surgery for weight loss has enhanced our understanding and role of gastrointestinal hormones in controlling insulin release in the postprandial state. (7,5) Although uncommon now, Billroth procedures frequently performed in the 1970s for uncontrolled peptic ulcer disease should be considered in the differential of hypoglycemic spells in the appropriate clinical settings. (3) Patients who have undergone gastrectomy (partial or complete) or vagotomy may encounter various postoperative complications. One such complication is post-gastrectomy dumping syndrome, divided into early and late phase types. (6) Dumping syndrome is not a single disease but a constellation of symptoms that can be categorized as early and late dumping. (1) Physiologically in addition to secreting hydrochloric acid, gastrin, and intrinsic factor, the stomach also serves as a reservoir, storing up to 0.8-1.5 liters of food until food can be processed into the duodenum and lower intestinal tract. The stomach converts food into chyme, a semifluid mixture of ingested food and gastric secretions. The pylorus of the stomach and vasovagal reflex
Page 4 of 8
regulates slow emptying of chyme from the stomach into the small intestine at a rate suitable for proper digestion and absorption. (7) Bariatric and Billroth surgeries can affect the above functions of the stomach and vasovagal reflex resulting in rapid transit of a hyperosmolar load into the proximal small intestine leading to a rapid shift of fluid into the gut lumen and produces intestinal distention and contraction of plasma volume manifested as hypotension and increased sympathetic response. (3) The Early dumping syndrome occurs within the first hour of ingesting a meal and is characterized by nausea, abdominal pain, borborygmi, diarrhea, a sensation of heat, dizziness, desire to lay down. (7,2) Lethargy and sleepiness after meals are typical. Late dumping syndrome symptoms occur later and are attributed to hypoglycemia with tremors, cold sweats, difficulty in concentrating, and loss of consciousness. Late dumping syndrome symptoms occur 3 -4 hours after a meal and is an incretin driven hyperinsulinemia phenomenon. Rapid transit of hyperosmolar food will result in an exaggerated release of Incretins. Two incretins that play a significant role in insulin release are glucosedependent insulinotropic polypeptide (GIP) or gastric inhibitory peptide and glucagon like peptide (GLP). (4) Gut hormones are implicated in the reduction of appetite and weight loss after bariatric procedures. Postprandial polypeptide YY (PYY) and GLP -1 profiles start rising as early as two days after gastric bypass. Changes in appetite are evident within days after gastric bypass surgery. In patients with poor weight loss after gastric bypass associated with increased appetite, the postprandial PYY and GLP-1 responses are attenuated compared with patients with expected weight loss. After gastric bypass, 85% of patients with type 2 diabetes become normoglycemic, many within days of the operation and independent of weight loss, indicating gut hormone role in improving glucose-dependent Insulin release. (7) Billroth II surgery is results in an increase in PYY and GLP-1 release from the distal small intestine, especially in response to a large carbohydrate meal. Both PYY and GLP-1 causes glucose-dependent Insulin release.
Page 5 of 8
Vagotomy which is a critical part of gastric surgery can hamper the accommodation reflex of the stomach in response to a large meal leading to a rapid transit of unprocessed food into the small intestine. The combination results in delayed digestion and absorption of simple sugars into the blood stream and exaggerated GLP-1 mediated insulin release leading to postprandial hypoglycemia. The dumping syndrome has been reported to occur in approximately 20% of patients who undergo vagotomy with pyloroplasty, in up to 40% of the patient's after Roux-en-Y gastric bypass or sleeve gastrectomy, and in up to 50% of patients who undergo esophagotomy.
Conclusion:
The patient was reassured that these spells could be prevented by avoiding large carbohydrate meals and eating small meals throughout the day. Timolol eye drops were resumed. Pharmacologic treatment (Alpha-glucosidase inhibitor) was not started to avoid polypharmacy. The patient followed up in clinic three months after testing and is adherent to dietary and treatment plan. He denied any further fainting spells and his intraocular pressure is better following reinstitution of his timolol eye drops. References: 1. Mala T, Hewitt S. Dumping syndrome following gastric Surgery.2015 Jan 27;135(2):137-41 2. Pinatel Lopasso. Rev Gastroenterol Peru. Peptic ulcer: late complications of the surgical treatment. 1995 Sep-Dec;15(3):273-81. 3. Milkov G. Definition and classification of the late complications after gastric resection. Probl Khig. 1980;8:139-49.
Page 6 of 8
4. Yoshinori Yamashita. Gastrointestinal Hormones in Dumping Syndrome and Reflux Esophagitis after Gastric Surgery J. Smooth Muscle Res. 33: 3748. 5. W. W te Riele, J.M. Vogten, D. Boerma. Comparison of weight loss and Morbidity after Gastric Bypass and Gastric Banding. A single Center European Experience. Obesity Surgery (2008) 18:11-16 6. Rohof WO, Bisschops R, Tack J, Boeckxstaens GE. Postoperative problems 2011: fundoplication and obesity surgery. Gastroenterol Clin North Am. 2011 Dec;40(4):809-21 7. Carel W. le, Richard W, Merlin W. Gut hormones as Mediators of Appetite and weight loss After Roux-en-Y Gastric bypass. Annals of surgery, 2007;246:780-785.
Page 7 of 8
Table 1. Normal Lab values: C-peptide 1.1-4.4 ng/ml, Insulin 2.6- 24.9 (uIU/ml), Proinsulin 210pmol/L
Time
Symptoms
Labs. (Venous draw)
8AM(Fasting)
Capillary blood sugars 110
No symptoms
Glucose 89 C-Peptide 2.4 Insulin 5.6 Proinsulin 3.7
9AM 10 AM
206 307
11AM
118
12 Noon
40
No symptoms Felt lightheaded” Could take a nap” Bowel movement. Formed Incoherent, sweating
Glucose 25 C-Peptide 21.2 Insulin 146.8
Page 8 of 8