Post-bariatric Surgery Hypoglycemia Research Articles

Postbariatric surgery hypoglycemia: Nutritional, pharmacological and surgical perspectives.

Post-bariatric hypoglycaemia (PBH) is a metabolic complication of bariatric surgery (BS), consisting of low post-prandial glucose levels in patients having undergone bariatric procedures. While BS is currently the most effective and relatively safe treatment for obesity and its complications, the development of PBH can significantly impact patients' quality of life and mental health. The diagnosis of PBH is still challenging, considering the lack of definitive and reliable diagnostic tools, and the fact that this condition is frequently asymptomatic. However, PBH's prevalence is alarming, involving up to 88% of the post-bariatric population, depending on the diagnostic tool, and this may be underestimated. Given the prevalence of obesity soaring, and an increasing number of bariatric procedures being performed, it is crucial that physicians are skilled to diagnose PBH and promptly treat patients suffering from it. While the milestone of managing this condition is nutritional therapy, growing evidence suggests that old and new pharmacological approaches may be adopted as adjunct therapies for managing this complex condition.

SAT661 Bypass-oma Or Medication-oma: A Clinical Dilemma About Hypoglycemia

Abstract Disclosure: C.A. Perez Hernandez: None. M.J. Pesantez Borja: None. Introduction With the ongoing worldwide obesity epidemic, the number of bariatric procedures rises every year. Although complications have decreased in the last 20 years, they can result in significant morbidity and mortality. Hypoglycemia is a complication that usually occurs 1-3 years after a Roux-en-Y gastric bypass, and is caused by increased postprandial incretin secretion. Although reported incidence is 0.1%, it is likely underdiagnosed and underestimated cause of hyper insulinemic hypoglycemia. Clinical Case A 33-year-old male with history of pancreatic cancer status post partial pancreatectomy and Roux-en-Y gastric bypass performed 10 years ago, and type 2 diabetes on insulin was admitted for severe persistent hypoglycemia refractory to treatment. He stopped using insulin 6 months ago after passing out while driving 1-2 hours postprandially. Only 2 hours after starting a 72-hour fasting test, the patient had a venous blood glucose of 39 mg/dl. Laboratory results showed: C-peptide:3.3, Insulin:9.3, cortisol:2.6, BHB: 0.5 and proinsulin:3.7; and negative sulfonylurea screening. Dotatate scan was unremarkable. He has started diazoxide, acarbose, octreotide and Everolimus with no improvement to his symptoms. Plan was to repeat the work up, however, the patient refused to cooperate. He also declined a Calcium stimulation test, endoscopic US and bariatric surgery reversal. Review of his imaging studies which, showed no signs of pancreatic surgery. When re-interrogated, medical history inconsistencies were noticed. Hypoglycemia episodes occurred exclusively after being transferred out of ICU, patient was placed in a one-to-one monitoring. During the night shift, he was found injecting himself an unknown medication via PICC line and several medications were found in his room. After being confronted by staff, the Patient left the AMA only to be readmitted the same day for hypoglycemia at another institution. Conclusion Our patient was diagnosed with Munchausen's syndrome, substance abuse and depressive disorder upon evaluation by psychiatry. It was found that 4 years prior to current admission, he completed a 72-hour fasting test in another hospital, without hypoglycemia episodes. However, due to concerns for insulinoma, his oncology team was contacted who reported never having seen the patient or diagnosing with pancreatic cancer. Also, patient was found self-injecting with an unknown medication, and when confronted, he left AMA just like he did while he was under our care. History of self-harm behavior and inconsistencies in medical history may call for atypical presentations of Post Bariatric Surgery hypoglycemia and should prompt a detailed anamnesis and psychiatric assessment. This case represents a clinical dilemma and illustrates the therapeutic challenges encountered with a patient diagnosed with post bariatric surgery hypoglycemia and Munchausen syndrome. Presentation: Saturday, June 17, 2023

FRI612 Tirzepatide For The Treatment Of Post-bariatric Surgery Hypoglycemia And Early Dumping Syndrome

Abstract Disclosure: E.F. Stortz: None. H.M. Lawler: Research Investigator; Self; VogenX. Background: Post-bariatric hypoglycemia (PBH) is a challenging condition with limited treatment options. Glucagon-like peptide 1 (GLP-1) receptor agonists have been used with mixed success. To our knowledge, there have been no reported cases of PBH treatment with dual incretin agonist medications. We describe a case in which tirzepatide was successfully used to improve both post-bariatric surgery hypoglycemia as well as symptoms of early dumping syndrome. Clinical Case: A 46-year-old woman with prediabetes presented with labile blood sugars, post-prandial hypoglycemia, and intermittent severe bloating with diarrhea shortly after eating meals. She had a past medical history of gastric banding 16 years ago, resulting in a 70 pound weight loss. Her post-operative course was complicated by post-meal retching and vomiting for many years. She subsequently had gastric band reversal with concurrent sleeve gastrectomy 2 years ago. While her vomiting improved, she experienced intermittent post-meal bloating and diarrhea. About 8 months after this surgery, she developed symptoms of hypoglycemia after meals, with glucometer readings of 30-49 mg/dL. Continuous glucose monitoring (CGM) for 1 week prior to therapy revealed a time in range (70-180 mg/dL) of 90%, 3-4% time above 180 mg/dL, and 6-7% time below 70 mg/dL. Dietary changes did not help improve hypoglycemic episodes or her dumping symptoms. She initially started tirzepatide 2.5mg weekly and noticed improvement in both symptoms. Her dose increased to 5mg weekly, and she had near complete resolution in her post-prandial hypoglycemia. Upon review of 1 week of CGM data, her time in range improved to 96% with 2% time above 180 mg/dL and 0% time below 70 mg/dL. Her glucose peak was 224 with a nadir of 72. Her early dumping symptoms also improved, occurring only with very high-carb meals. Conclusion: Many pharmacotherapies have sought to improve post-bariatric surgery hypoglycemia with limited success often significant side effects. The post-prandial peak of GLP-1 levels tends to be higher in patients after bariatric surgery compared to obese controls, possibly playing a role in the condition’s pathophysiology. Studies of glucose-dependent insulinotropic peptide (GIP) in patients after bariatric surgery exhibit mixed trends. Numerous case reports have shown successful treatment of PBH with GLP-1 receptor agonists, while other have shown no clear benefit. It is possible that dual incretin therapy may attenuate more of the post-prandial hyperinsulinemic-hypoglycemic response in ways that are incompletely understood and requires further investigation. Interestingly, this case showed that tirzepatide administration not only resulted near-resolution of post-prandial hypoglycemia, but it also improved this patients’ early dumping syndrome symptoms. Presentation: Friday, June 16, 2023

Relationship Between Symptom Perception and Postprandial Glycemic Profiles in Patients With Postbariatric Hypoglycemia After Roux-en-Y Gastric Bypass Surgery.

Post-bariatric surgery hypoglycemia (PBH) is a metabolic complication of Roux-en-Y gastric bypass (RYGB). Since symptoms are a key component of the Whipple's triad to diagnose nondiabetic hypoglycemia, we evaluated the relationship between self-reported symptoms and postprandial sensor glucose profiles. Thirty patients with PBH after RYGB (age: 50.1 [41.6-60.6] years, 86.7% female, BMI: 26.5 [23.5-31.2] kg/m2; median [interquartile range]) wore a blinded Dexcom G6 sensor while recording autonomic, neuroglycopenic, and gastrointestinal symptoms over 50 days. Symptoms (overall and each type) were categorized into those occurring in postprandial periods (PPPs) without hypoglycemia, or in the preceding dynamic or hypoglycemic phase of PPPs with hypoglycemia (nadir sensor glucose <3.9 mmol/L). We further explored the relationship between symptoms and the maximum negative rate of sensor glucose change and nadir sensor glucose levels. In 5,851 PPPs, 775 symptoms were reported, of which 30.6 (0.0-59.9)% were perceived in PPPs without hypoglycemia, 16.7 (0.0-30.1)% in the preceding dynamic phase and 45.0 (13.7-84.7)% in the hypoglycemic phase of PPPs with hypoglycemia. Per symptom type, 53.6 (23.8-100.0)% of the autonomic, 30.0 (5.6-80.0)% of the neuroglycopenic, and 10.4 (0.0-50.0)% of the gastrointestinal symptoms occurred in the hypoglycemic phase of PPPs with hypoglycemia. Both faster glucose dynamics and lower nadir sensor glucose levels were related with symptom perception. The relationship between symptom perception and PBH is complex, challenging clinical judgement and decision-making in this population.

Is there a link between post-bariatric surgery hypoglycemia and the increased risk of external-cause mortality?

Is there a link between post-bariatric surgery hypoglycemia and the increased risk of external-cause mortality?

Comparison of Hormonal Response to a Mixed-Meal Challenge in Hypoglycemia After Sleeve Gastrectomy vs Gastric Bypass.

Exaggerated postprandial incretin and insulin responses are well documented in postbariatric surgery hypoglycemia (PBH) after Roux-en-Y gastric bypass (RYGB). However, less is known about PBH after sleeve gastrectomy (SG). We sought to compare meal-stimulated hormonal response in those with PBH after SG vs RYGB. We enrolled 23 post-SG (12 with and 11 without PBH) and 20 post-RYGB (7 with and 13 without PBH) individuals who underwent bariatric surgery at our institution. PBH was defined as plasma glucose less than 60 mg/dL on 4-hour mixed-meal tolerance test (MTT). Islet and incretin hormones were compared across the 4 groups. Participants (N = 43) were on average 5 years post surgery, with a mean age of 48 years, mean preoperative body mass index of 48.4, 81% female, 61% White, and 53% post SG. Regardless of PBH, the SG group showed lower glucose, glucagon, and glucagon-like peptide 1 (GLP-1) responses to MTT and similar insulin and glucose-dependent insulinotropic polypeptide (GIP) responses compared to the RYGB group. Among those with PBH, the SG group following the MTT showed a lower peak glucose (P = .02), a similar peak insulin (90.3 mU/L vs 171mU/L; P = .18), lower glucagon (P < .01), early GLP-1 response (AUC0-60 min; P = .01), and slower time to peak GIP (P = .02) compared to PBH after RYGB. Among individuals with PBH, those who underwent SG were significantly different compared to RYGB in meal-stimulated hormonal responses, including lower glucagon and GLP-1 responses, but similar insulin and GIP responses. Future studies are needed to better understand the differential contribution of insulin and non-insulin-mediated mechanisms behind PBH after SG vs RYGB.

Evaluation and Management of Patients Referred for Post-Bariatric Surgery Hypoglycemia at a Tertiary Care Center.

Following bariatric surgery, patients can develop non-specific symptoms self-described as hypoglycemia. However, confirming hypoglycemia can be technically challenging, and therefore, these individuals are frequently treated empirically. This study aimed to describe what diagnostic evaluation and therapeutic interventions patients referred for post-bariatric surgery hypoglycemia undergo. Retrospective observational cohort study of patients with a history of bariatric surgery was evaluated for post-bariatric surgery hypoglycemia in a tertiary referral center from 2008 to 2017. We collected demographic and bariatric surgery information, clinical presentation of symptoms referred to as hypoglycemia, laboratory and imaging studies performed to evaluate these symptoms, and symptom management and outcomes. A total of 60/2450 (2.4%) patients who underwent bariatric surgery were evaluated in the Department of Endocrinology for hypoglycemia-related symptoms. The majority were middle-aged women without type 2 diabetes who had undergone Roux-en-Y gastric bypass. Thirty-nine patients (65%) completed a biochemical assessment for hypoglycemia episodes. Six (10%) had confirmed hypoglycemia by Whipple's triad, and four (6.7%) met the criteria for post-bariatric surgery hypoglycemia based on clinical and biochemical criteria. All patients were recommended dietary modification as the initial line of treatment, and this intervention resulted in most patients reporting at least some improvement in their symptoms. Eight patients (13%) were prescribed pharmacotherapy, and two patients required additional interventions for symptom control. In our experience, evaluation for hypoglycemia-related symptoms after bariatric surgery was rare. Hypoglycemia was confirmed in the minority of patients. Even without establishing a diagnosis of hypoglycemia, dietary changes were a helpful strategy for symptom management for most patients.

Postbariatric Surgery Hypoglycemia and Nutritional Deficiencies: Long-Term Follow-Up

Background: The aim was to assess the long-term impact of laparoscopic sleeve gastrectomy (LSG) on weight loss, postload hypoglycemia, and nutritional status of 25-OH-vitamin D, cyanocobalamin, albumin, creatinine, ferritin, and hemoglobin. Methods: A prospective, longitudinal analysis of collected data from 60 sleeve gastrectomy patients was performed on a 5-year follow-up period. Results: Therapeutic success rate (excess body mass index loss ≥60%) was 80% at 5 years. The prevalence of postload hypoglycemia increased progressively, reaching a maximum at 1 year (20.3%) and then drop out to 0% at 5 years postoperatively. Glycemic profile and insulin resistance improved significantly from the 1st month postoperatively, remaining stable thereafter, whereas the C peptide had a decreasing trend throughout the study period. Prevalence of nutritional deficiencies at baseline, 1 month, 3 months, 1 year, and 5 years postsurgery were specifically for cyanocobalamin (0%, 3.3%, 15.5%, 27.1%, and 30.0%), vitamin D (21.7%, 48.3%, 63.8%, 76.3%, and 85%), and albumin (0%, 16.7%, 1.7%, 1.7%, and 11.7%, respectively). Ferritin and hemoglobin levels showed a significant drop in the 1st month postoperative and remain stable afterward, whereas creatinine decreased significantly after the 1st year postoperative in comparison with preoperative. Conclusions: LSG was effective in terms of weight loss, insulin sensitivity, and glycemic profile improvement, but with the risk of nutritional deficiencies and postload hypoglycemia.

Continuous glucose monitoring reveals glycemic variability and hypoglycemia after vertical sleeve gastrectomy in rats

ObjectivePost–bariatric surgery hypoglycemia (PBH) is defined as the presence of neuroglycopenic symptoms accompanied by postprandial hypoglycemia in bariatric surgery patients. Recent clinical studies using continuous glucose monitoring (CGM) technology revealed that PBH is more frequently observed in vertical sleeve gastrectomy (VSG) patients than previously recognized. PBH cannot be alleviated by current medication. Therefore, a model system to investigate the mechanism and treatment is required. MethodsWe used CGM in a rat model of VSG and monitored the occurrence of glycemic variability and hypoglycemia in various meal conditions for 4 weeks after surgery. Another cohort of VSG rats with CGM was used to investigate whether the blockade of glucagon-like peptide-1 receptor (GLP-1R) signaling alleviates these symptoms. A mouse VSG model was used to investigate whether the impaired glucose counterregulatory system causes postprandial hypoglycemia. ResultsLike in humans, rats have increased glycemic variability and hypoglycemia after VSG. Postprandial hypoglycemia was specifically detected after liquid versus solid meals. Further, the blockade of GLP-1R signaling raises the glucose nadir but does not affect glycemic variability. ConclusionsRat bariatric surgery duplicates many features of human post–bariatric surgery hypoglycemia including postprandial hypoglycemia and glycemic variability, while blockade of GLP-1R signaling prevents hypoglycemia but not the variability.

SYMPTOMATIC AND ASYMPTOMATIC HYPOGLYCEMIA POST THREE DIFFERENT BARIATRIC PROCEDURES: A COMMON AND SEVERE COMPLICATION.

Background: The prevalence of post-bariatric surgery hypoglycemia (PBH) remains unclear due to diagnostic criteria variability, types of bariatric procedures and possible unawareness. Objective: To determine the frequency, pattern and severity of symptomatic and asymptomatic hypoglycemia in subjects post three different bariatric procedures performed >1 year before evaluation and a group of obese subjects before surgery. Design and Setting: Observational cohort study. Fifty-one consecutive patients participated: post Roux-en-Y gastric-bypass (RYGB) (n=16), post omega-loop gastric-bypass (OLGB) (n=12), post sleeve-gastrectomy (SG) (n=15), obese subjects before surgery (controls) (n=8). Hypoglycemic events (glucose ≤54 mg/dL) and severe hypoglycemia (glucose ≤40 mg/dL) were evaluated by symptoms' questionnaire, mixed-meal tolerance test (MMTT) and continuous glucose monitoring (CGM). Results: According to questionnaires, meal-related complaints were reported in 11 (26%) of the surgical group and in one control subject. During MMTT, 88%, 82% and 67% experienced hypoglycemia in RYGB, OMGB and SG groups, respectively, vs. none of the controls (P<0.001). Severe hypoglycemia occurred in 38%, 45% and 7% in RYGB, OMGB and SG groups, respectively (P=0.025), but only 10 of the total operated patients (24%) reported any symptoms. During CGM, fasting hypoglycemic events occurred more in RYGB and OLGB vs. SG group: 55%, 63% and 17% respectively (P=0.036). Conclusions: PBH is very common after RYGB, OMGB and SG and can be severe especially following bypass procedures. Our results show that hypoglycemia occurs not only postprandially but also in the fasting state, especially following bypass procedures. In most cases, there were no specific complaints, possibly leading to its underestimation.

389-P: Comparison of Hormonal Response to a Mixed-Meal Challenge in Individuals with Hypoglycemia after Sleeve Gastrectomy vs. Gastric Bypass

Objective: Exaggerated post-prandial incretin and insulin responses are well-documented in post-bariatric surgery hypoglycemia (PBH) after Roux-en-Y gastric bypass (RYGB). However, less is known about PBH after sleeve gastrectomy (SG). Thus, we sought to compare meal-stimulated hormonal response in those with PBH after SG vs. RYGB. Methods: We enrolled 20 RYGB (7 with and 13 without PBH) and 23 SG (12 with and 11 without PBH) who underwent bariatric surgery at our institution. PBH was defined as a postprandial interstitial or plasma glucose &amp;lt;55 mg/dl on continuous glucose monitor (5-days as outpatient, Dexcom) or 4-hour mixed meal tolerance test (MTT). Plasma samples from MTT were used to measure glucose, insulin, glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP). We used Kruskal Wallis Test to compare the difference in glucose or hormones across 4 groups (with and without PBH after SG or RYGB). Results: Participants (N=43) were on average 5 years since surgery, with mean age of 50 years, mean preoperative BMI of 48 kg/m2, 81% female, 61% Caucasian, 53% post SG. There were no differences in fasting glucose (p=0.38) or fasting insulin (p=0.34) across the 4 groups. Among those with PBH, the SG group showed a lower peak glucose (131.8 mg/dl, p&amp;lt;0.01), similar nadir glucose (59.6 mg/dl, p=0.18), peak insulin (68.7 mU/L, p&amp;lt;0.01) and peak GLP-1 (15.3 pM, p&amp;lt;0.01) and differed in overall hormonal response (AUC 0-240min) with lower insulin (3956.1 mU/L/min, p&amp;lt;0.01), lower GLP-1 (2498.9 pM/min, p&amp;lt;0.01) and higher GIP (51335.4 pM/min, p=0.05) compared to RYGB with PBH group. Conclusion: Among those with PBH, the SG group showed less glycemic excursion and different hormonal profiles including lower insulin, GLP-1 and higher GIP responses to MTT compared to the RYGB group. Future studies are needed to better understand the differential contribution of insulin and non-insulin mediated mechanisms behind PBH after SG vs. RYGB. Disclosure C. Lee: Consultant; Self; XOMA Corporation. Research Support; Self; Eiger BioPharmaceuticals. T. Brown: None. M. Schweitzer: Consultant; Self; Ethicon, Inc. T. Magnuson: None. J. Clark: None. Funding National Institutes of Health

2109-P: Symptomatic and Asymptomatic Hypoglycemia following Three Different Bariatric Procedures Is a Frequent and Severe Complication

Background: Post-bariatric surgery hypoglycemia has been previously reported. However, its prevalence remains uncertain due to variability of diagnostic criteria, types of bariatric procedures and possible lack of awareness. Objective: To determine the frequency and severity of symptomatic and asymptomatic hypoglycemia in persons following 3 different surgical procedures ≥ 1 years before evaluation, and a group of non-operated obese persons. Design and Setting: Observational cohort study conducted at an out-patient clinic. Fifty-one consecutive individuals were enrolled: post Roux-en-Y gastric bypass (RYGB) (n=16), post omega loop gastric bypass (OLGB) (n=12), post sleeve gastrectomy (SG) (n=15), obese persons prior to surgery (controls) (n=8). Hypoglycemic events (blood glucose ≤ 54 mg/dL) and severe hypoglycemia (blood glucose ≤ 40 mg/dL) were evaluated by: symptoms' questionnaire, mixed meal tolerance test (MMT) and continuous glucose monitoring (CGM). Results: According to questionnaires, meal-related complaints were reported in 11 (26%) of the surgical group and 1/8 of controls. During MMT, 88%, 82% and 67% experienced hypoglycemia in the RYGB, OLGB and SG groups respectively, vs. none in the controls (P &amp;lt; 0.001). Severe hypoglycemia occurred in 38%, 45% and 7% of the RYGB, OLGB and SG groups respectively, (P= 0.025) but only 10 of the total operated group (24%) reported any symptoms. During CGM, fasting hypoglycemic events occurred more in the RYGB and OLGB vs. the SG group: 55%, 63% vs.17% respectively, (P= 0.036). Conclusions: Post-bariatric surgery hypoglycemia is a very common phenomenon after 3 types of bariatric surgery and can be severe especially following bypass procedures. Intriguingly, our results show that hypoglycemia occurs not only in postprandial but also in fasting state, especially following bypass procedures. In many cases there were no specific complaints that may lead to underestimation of this serious complication. Disclosure H. Knobler: Advisory Panel; Self; AstraZeneca, Novo Nordisk A/S. L. Lazar: None. S. Sapojnikov: None. G. Pines: None. E. Mavor: None. V. Ostrovsky: None. T. Schiller: Advisory Panel; Self; Novo Nordisk Inc., Sanofi-Aventis. T. Zornitzki: None.

MON-183 Comparison of Continuous Glucose Monitor versus Meal Tolerance Test for Detection of Post-Bariatric Surgery Hypoglycemia

Objective: Post-bariatric surgery hypoglycemia (PBH) is an emerging metabolic complication thought to be due in part to an exaggerated insulin response to a meal. We sought to compare the ability of continuous glucose monitor (CGM) versus meal tolerance test (MTT) in detecting PBH. Methods: Among the participants who underwent bariatric surgery at our institution and completed the hypoglycemic symptoms (hypo-sx) survey, we enrolled 20 Roux-en-Y gastric bypass (RYGB, 10 with and 10 without hypo-sx) and 21 sleeve gastrectomy (SG, 10 with and 11 without hypo-sx) patients. Participants wore the CGM (Dexcom, San Diego, CA) for 72-120 hours at home and additionally underwent a MTT during a research visit. Hypoglycemia was defined as postprandial (within 5 hours of eating) interstitial or plasma glucose <55 mg/dl on CGM or MTT. We used Chi-square test to compare the difference in hypoglycemia detected by CGM alone vs CGM and MTT. Results: A total of 41 participants completed both the CGM and MTT on average 5.5 years since surgery, with mean age of 51 years, mean preoperative BMI of 49 kg/m2, 81% female, 61% Caucasian, 51% post SG, ; 49% had high suspicion for hypoglycemia on prior hypo-sx survey. Of those, 22 participants (54%) had postprandial hypoglycemia on CGM versus 10 (24%) on MTT. Only 4 participants reported hypo-sx during MTT. Compared to the 8 participants who had hypoglycemia on both tests, the 14 participants who had postprandial hypoglycemia on CGM only were similar in clinical characteristics including age, gender, ethnicity, type of surgery, time since surgery, hypo-sx survey response and preoperative BMI. Conclusions: Asymptomatic postprandial hypoglycemia was common in post-bariatric patients regardless of surgery type and previous response to hypo-sx survey. Assessments that rely on hypoglycemic symptoms or MTT may not adequately capture PBH. Future studies should consider CGM to assess the true prevalence and impact of PBH.

Validation of the Use of Electronic Medical Records for Identification of Post-gastric Bypass Hypoglycemia Cases.

We sought to validate an algorithm designed to identify patients with post-gastric bypass hypoglycemia (PGBH) using clinician chart review. We conducted a chart review study of non-diabetic patients who underwent Roux-en-Y gastric bypass (RYGB) at our institution from 2004 to 2013. The electronic medical record (EMR) algorithm was based on any post-operative glucose <60mg/dl, diagnosis of hypoglycemia, or medication use for treatment of PGBH and identified 158 charts as PGBH and 1048 charts without PGBH. Two clinicians independently reviewed a random selection of 80 cases and 80 control charts and determined the presence or absence of PGBH by searching the chart using keywords and reviewing laboratory results, medications, and clinic notes. Of the 160 charts reviewed, the EMR algorithm agreed with the chart review for 130 (accuracy = 80%, 95% CI = 75-87%) with sensitivity of 89% (95% CI = 83-96%) and specificity of 86% (95% CI = 78-93%). We improved the algorithm's accuracy to 90% by limiting the search to data obtained 3months or more following RYGB. The EMR algorithm has high sensitivity, specificity, and accuracy to identify post-gastric bypass hypoglycemia within our patient cohort. The use EMR-based algorithms may be a useful tool for future research to improve our understanding of epidemiology and risk factors for post-bariatric surgery hypoglycemia.

Continuous Glucose Monitoring in Patients With or Without Symptoms of Hypoglycemia after Bariatric Surgery

Objective: Hypoglycemia after bariatric surgery is an increasingly recognized metabolic complication. We sought to determine the sensitivity and specificity of a prior hypo-sx survey in detecting post-bariatric surgery hypoglycemia (PBSH) using a continuous glucose monitor (CGM). Methods: Among the patients who underwent bariatric surgery at our institution and completed the hypo-sx survey, we enrolled 13 Roux-en-Y gastric bypass (RYGB, 7 with and 6 without hypo-sx) and 19 sleeve gastrectomy (SG, 9 with and 10 without hypo-sx) patients. Patients wore the CGM (Dexcom, San Diego, CA) for 72-120 hours at home. Hypoglycemia was defined as postprandial interstitial glucose (IG)&amp;lt;54 mg/dl. We used Kruskal Wallis test to compare the difference in hypoglycemia across groups. Results: A total of 19 patients (59%) had hypoglycemia (Table 1), with a mean low glucose of 46.8 mg/dl. Two patients reported hypo-sx. The prevalence of hypoglycemia did not differ by the type of surgery (69% vs. 53%) or the presence of hypo-sx by survey (63% vs. 56%). The survey had a specificity of 53.8% and sensitivity of 52.6% for measured PBSH. Conclusions: Asymptomatic postprandial hypoglycemia was common in post-bariatric patients regardless of surgery type. Assessments that focus on hypoglycemic symptoms may not adequately capture PBSH. Future studies should consider CGM to assess the true prevalence and impact of PBSH. Table 1. Baseline Characteristics and Results from continuous glucose monitoring on post-bariatric surgery patients who were categorized as with or without symptoms of hypoglycemia based on their survey responsesRYGB with Hypo-sx (N=7)RYGB without Hypo-sx (N=6)SG with Hypo-sx (N=9)SG without Hypo-sx (N=10)P ALLP RYGB vs SGP With vs Without Hypo-sxMean Age, years52.9 (5.1)52.0 (10.0)41.9 (11.3)44.8 (11.9)% Female67%56%89%82%% Caucasian71%67%33%60%Time since surgery (years)7.3 (3.2)4.8 (1.3)4.7 (0.7)4.2 (0.8)Percent Patients with Postprandial Hypoglycemia (N)71% (5)67% (4)56% (5)50% (5)Total Average IG (mg/dl, SD)97.0 (6.7)103.5 (12.5)93.0 (8.1)96.9 (6.4)0.3730.2270.228Average Minimum IG (mg/dl, SD)47.7 (10.9)45.8 (9.7)46.4 (5.6)47.0 (9.9)0.8570.7440.429Postprandial Minutes/day IG &amp;lt;54 mg/dl (SD)9.5 (12.7)4.7 (4.9)3.0 (3.9)11.3 (25.1)0.8020.3370.955Abbreviations: SD: standard deviation , RYGB: Roux-en-Y gastric bypass, Hypo-sx: hypoglycemic symptoms, SG: sleeve gastrectomy, IG: interstitial glucose, Postprandial: within 3 hours of eating Disclosure C. Lee: None. T. Brown: Advisory Panel; Self; Merck &amp; Co., Inc. M. Schweitzer: Consultant; Self; Ethicon US, LLC.. T. Magnuson: None. J. Clark: None.

Clinical features of symptomatic hypoglycemia observed after bariatric surgery

BackgroundLiterature directly looking at post–bariatric surgery hypoglycemia consists mostly of small case series. The rate, severity, and outcomes of treatment in a large bariatric population are less characterized. ObjectiveTo determine the rate of post–bariatric surgery hypoglycemia, its clinical features and management outcomes over a 13-year period at our institution. SettingAn academic center in the United States. MethodsPatients who underwent bariatric surgery at a single academic center between 2002 and 2015 and had a postdischarge glucose level of ≤70 mg/dL were studied. ResultsOf 6024 patients who underwent bariatric procedure, 118 patients (2.0%) had a postoperative glucose level ≤70 mg/dL. Eighty-three patients (1.4%) had symptomatic hypoglycemia. The known underlying causes of symptomatic hypoglycemia included postprandial hyperinsulinemic hypoglycemia (n = 32, 38%), infection (n = 8, 10%), diabetic medications (n = 8, 10%), and poor oral intake (n = 8, 10%). Overall, 9 patients required intervention for nutritional supplementation including enteral (n = 9) and intermittent parenteral (n = 2) nutrition. No patients required reversal of their bariatric surgeries or pancreatic resection for management of hypoglycemia. The majority of the symptomatic patients had resolution of their symptoms (n = 76, 92%). Thirty-two patients had postprandial hypoglycemia with a median onset of hypoglycemia after bariatric surgery of 790 days (interquartile range 388–1334). All 32 patients with postprandial hypoglycemia had dietary adjustment and 53% received pharmacotherapy, which resulted in complete resolution of hypoglycemia (n = 29, 91%) and resolution with minimal disability (n = 3, 9%). ConclusionThe rate of symptomatic hypoglycemia and postprandial hypoglycemia after bariatric surgery were 1.4% and .5%. The majority of patients were successfully managed with dietary counseling, nutritional intervention, and occasionally pharmacotherapy. No surgical reversal or pancreatic procedures were performed.

Stable Liquid Glucagon: Beyond Emergency Hypoglycemia Rescue.

Glycemic control is the mainstay of preventing diabetes complications at the expense of increased risk of hypoglycemia. Severe hypoglycemia negatively impacts the quality of life of patients with type 1 diabetes and can lead to morbidity and mortality. Currently available glucagon emergency kits are effective at treating hypoglycemia when correctly used, however use is complicated especially by untrained persons. Better formulations and devices for glucagon treatment of hypoglycemia are needed, specifically stable liquid glucagon. Out of the scope of this review, other potential uses of stable liquid glucagon include congenital hyperinsulinism, post-bariatric surgery hypoglycemia, and insulinoma induced hypoglycemia. In the 35 years since Food and Drug Administration (FDA) approval of the first liquid stable human recombinant insulin, we continue to wait for the glucagon counterpart. For mild hypoglycemia, a commercially available liquid stable glucagon would enable more widespread implementation of mini-dose glucagon use as well as glucagon in dual hormone closed-loop systems. This review focuses on the current and upcoming pharmaceutical uses of glucagon in the treatment of type 1 diabetes with an outlook on stable liquid glucagon preparations that will hopefully be available for use in patients in the near future.

When Hyperinsulinemia Is Not Insulinoma: A Case of Recurrent Post-Prandial Hypoglycemia Following Roux-en-Y Gastric Bypass Surgery

Introduction: Roux-en-Y gastric bypass (RYGB) surgery is currently one of the most popular procedures to aid weight loss. Recently, hypoglycemia associated with gastric bypass surgery has been described as a potential complication. We present a case of refractory hypoglycemia after RYGB that necessitated partial pancreatectomy. Case presentation: A 44 year old female with past medical history significant for RYGB ten years ago presented to the hospital with recurrent episodes of postprandial dizziness and near-syncope. She denied any flushing or diaphoresis during these spells. Physical examination was unremarkable. Laboratory data revealed serum glucose of 66 mg/dl with intermittent drop down to 37 mg/dl. Serum insulin level was 8 μU/ml and C peptide level was 3.6 ng/ml. Serum sulfonylurea screen was negative. Computed tomographic (CT) abdomen did not show any pancreatic mass. Endoscopic ultrasound to assess pancreatic anatomy was not feasible in the setting of prior gastric bypass surgery. Dietary modification by decreasing carbohydrate content did not ameliorate her symptoms. A trial of acarbose, diazoxide and somatostatin was unsuccessful. The patient's persistent symptoms necessitated readmission and continuous 5 % Dextrose infusion to prevent hypoglycemia. Since all medical options were exhausted, the patient underwent distal pancreatectomy. Histopathology showed hyperplastic pancreatic islets with amyloid deposits (Fig 1,2) that varied in size. Post operatovely, the patient had resolution of hypoglycemia (figure 3).Figure: Histologic examination of the pancreas demonstrating hyperplastic pancreatic islets containing amyloid deposits staining positively with Congo red.Figure: Histologic examination of the pancreas demonstrating hyperplastic pancreatic islets.Figure: A pictorial representation of our patient's serum glucose during the hospital course. Arrow depicts the time of pancreatectomy and discontinuation of dextrose infusion.Discussion: The prevalence of post bariatric surgery hypoglycemia has been reported as < 1%. It was first described by Service et al. in 2005. In contrast to dumping syndrome, which is noted soon after the surgery and improves with time, post RYGB hypoglycemia presents several months to years after surgery. Its hallmark feature is severe postprandial neuroglycopenia, which is characteristically absent in dumping. Current research suggests that after RYGB, food intake and rapid gastric emptying triggers an excessive rise in glucose, which stimulates GLP-1 secretion with subsequent excess insulin secretion. Other potential mechanisms include enhanced beta cell function and dysregulated insulin secretion. Diagnosis requires documentation of Whipple's triad, elevated serum insulin >3 μU/ml, C peptide > 0.6 ng/ml, negative sulfonylurea screen and negative pancreatic imaging. Most patients respond well to low carbohydrate diet. Medications to decrease postprandial hyperinsulinemia including alpha-glucosidase inhibitors, calcium channel blockers, diazoxide and somatostatin, have had inconsistent results. Patients with persistent hypoglycemia that is not responsive to diet and/ or medical treatment may benefit from pancreatectomy (partial or total). Reversal of gastric bypass has been proposed to alleviate resulting hypoglycemia, but results have not been promising. With increasing use of RYGB to treat obesity, physicians may encounter an increasing incidence of post bariatric surgery hypoglycemia. Additional research is needed to further elucidate its pathophysiology that may open up new avenues for management.

Weight regain in patients with symptoms of post–bariatric surgery hypoglycemia

BackgroundWeight regain (WR) and symptoms of post–bariatric surgery hypoglycemia (PBSH) are metabolic complications observed in a subset of postbariatric patients. Whether hypoglycemic symptoms are an important driver of increased caloric intake and WR after bariatric surgery is unknown. ObjectiveThis study aims to determine whether patients with PBSH symptoms have greater odds for WR. SettingTertiary academic hospital. MethodsPatients who underwent Roux-en-Y gastric bypass or sleeve gastrectomy at our tertiary academic hospital from August 2008 to August 2012 were mailed a survey, from which weight trajectory and PBSH symptoms were assessed. Percent WR was calculated as 100×(current weight−nadir weight)/(preoperative weight−nadir weight) and was compared between dates of survey completion and bariatric surgery. The primary outcome was WR≥10%, as a reflection of the median WR among respondents. Multivariable logistic regression was used to determine clinical factors that indicate greater odds for WR≥10% at the P<.05 level. ResultsOf 1119 potential patients, 428 respondents (40.6%) were eligible for analysis. WR was observed in 79.2% (n = 339), while 20.8% (n = 89) experienced either weight loss or no WR at a mean of 40.6±14.5 months. Median WR was 10.8% (interquartile range, 5.6–19.4). Odds of WR≥10% was significantly increased in those who experienced PBSH symptoms (odds ratio [OR] = 1.66; 95% confidence interval [CI]: 1.04–2.65), reported less adherence to nutritional guideline (OR = 2.36; 95% CI: 1.52–3.67), and had a longer time since surgery (OR = 1.05; 95% CI: 1.03–1.07). ConclusionsWe found evidence that the presence of PBSH symptoms was associated with WR. Future studies should elucidate the role of hypoglycemia among other factors in post–bariatric surgery WR.

Hypoglycemia Following Bariatric Surgery: Our 31-Year Experience.

The purposes of this study are to identify the cumulative incidence of post-bariatric surgery hypoglycemia (PBSH), describe its symptomatology, and characterize treatment patterns at a large academic institution. All patients who underwent bariatric surgery at a single institution from 1985 to 2015 were identified using a clinical database, administrative billing data identified patients who were treated for hypoglycemia, and chart reviews were performed to make a diagnosis of PBSH based on Whipple's triad. PBSH cases were reviewed including patient diabetes history, symptomatology, and treatment measures. Univariate analyses were performed to identify correlations based on symptomatology, laboratory values, and treatments utilized. Ninety (2.6%) of 3487 patients were diagnosed with PBSH with preoperative median age of 43years, mean BMI of 50.0kg/m2, and median glycated hemoglobin of 6.0%. Median time-to-first hypoglycemic event was 40.6months. No factors were identified which predict symptom severity or resolution. The 24 (27%) patients who received pharmacotherapy to treat hypoglycemia were younger, had lower nadir blood glucose levels, and more frequent symptoms. Sixty-nine (79%) cases eventually resolved. PBSH onset and severity are highly variable. Successful management of these patients can prove difficult and should include dietary therapy, the selective use of pharmacotherapy and surgery, and the use of a multidisciplinary team including bariatric surgeons and endocrinologists.