Post-Bariatric Hypoglycemia in Individuals with Obesity and Type 2 Diabetes after Laparoscopic Roux-en-Y Gastric Bypass: A Prospective Cohort Study.

Post-bariatric hypoglycemia (PBH) is an increasingly recognized complication after metabolic bariatric surgery (MBS). The aim of this study is to investigate potential factors associated with PBH. A cohort of 24 patients with type 2 diabetes mellitus (T2DM) and body mass index (BMI) ≥40 kg/m2 who underwent laparoscopic Roux-en-Y gastric bypass (LRYGBP) was retrospectively investigated for PBH at 12 months. PBH was defined as postprandial glucose at 120 min below 60 mg/dL. Questionnaires based on the Edinburgh hypoglycemia scale were filled out by the participants. Glycemic parameters and gastrointestinal (GI) hormones were also investigated. Based on the questionnaires, five patients presented more than four symptoms that were highly indicative of PBH at 12 months. According to glucose values at 120 min, one patient experienced PBH at 6 months and four patients experienced it at 12 months. Postprandial insulin values at 30 min and 6 months seem to be a strong predictor for PBH (p < 0.001). GLP-1 and glucagon values were not significantly associated with PBH. PBH can affect patients with T2DM after MBS, reaching the edge of hypoglycemia. Postprandial insulin levels at 30 min and 6 months might predict the occurrence of PBH at 12 months, but this requires further validation with a larger sample size.

The Impact of Cholecystectomy in Patients with Post-Bariatric Surgery Hypoglycemia.

BACKGROUND: Metabolic surgery is the foremost treatment for obesity and its associated medical conditions. Nonetheless, post-bariatric hypoglycemia (PBH) emerges as a prevalent complication. PBH pathophysiology implicates heightened insulin and glucagon-like peptide 1 (GLP-1) levels, with bile acids (BA) contributing to GLP-1 release. A plausible association exists between cholecystectomy and PBH, which is attributed to alterations in BA metabolism and ensuing hormonal responses. The objective of this retrospective cohort study was to evaluate the impact of cholecystectomy on PBH pharmacological treatment, diagnostic timelines and metabolic parameters. MATERIALS AND METHODS: Patients diagnosed with PBH after bariatric surgery were evaluated based on their history of cholecystectomy. Demographic, anthropometric and clinical data were collected. Mixed meal tolerance tests (MMTT) results were compiled to assess metabolic responses. RESULTS: Of the 131 patients with PBH included in the study, 29 had prior cholecystectomy. The time to PBH diagnosis was similar across groups. Patients with prior cholecystectomy required higher doses of acarbose (p = 0.046), compared to those without prior cholecystectomy. Additionally, MMTT revealed higher insulin (t = 60 min: p = 0.010 and t = 90 min: p = 0.034) and c-peptide levels (t = 60 min: p = 0.008) and greater glycemic variability in patients with prior cholecystectomy (p = 0.049), highlighting the impact of cholecystectomy on glucose metabolism. CONCLUSION: Our study offers novel insights into PBH pharmacotherapy, indicating that PBH patients with a history of cholecystectomy require elevated doses of acarbose for symptom control than PBH patients without such surgical history. Furthermore, our findings underscore the pivotal role of hyperinsulinism in PBH aetiology, emphasizing the significance of the BA-GLP-1-insulin axis.

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.

Mixed Meal Tolerance Test Versus Continuous Glucose Monitoring for an Effective Diagnosis of Persistent Post-Bariatric Hypoglycemia.

Gastric bypass determines an increase in incretin secretion and glucose excursions throughout the day and may sometimes entail the development of severe post-bariatric hypoglycemia (PBH). However, there is no consensus on the gold standard method for its diagnosis. In this study, we evaluated the usefulness of a mixed meal tolerance test (MMTT) and continuous glucose monitoring (CGM) for the diagnosis of PBH, defined as glucose levels <54 mg/dL (3.0 mmol/L). We found that hypoglycemia occurred in 60% of patients after the MMTT and in 75% during CGM, and it was predominantly asymptomatic. The MMTT confirmed the diagnosis of PBH in 88.9%of patients in whom surgery had been performed more than three years ago, in comparison to 36.4% in cases with a shorter postsurgical duration. CGM diagnosed nocturnal asymptomatic hypoglycemia in 70% of patients, and daytime postprandial hypoglycemia in 25% of cases. The mean duration of asymptomatic hypoglycemia was more than 30 min a day. Patients with ≥2% of their CGM readings with hypoglycemia exhibited a higher degree of glucose variability than those with <1% of the time in hypoglycemia. Our results show that the MMTT may be a useful dynamic test to confirm the occurrence of hypoglycemia in a large number of patients with persistent and recurrent PBH during long-term follow-up after gastric bypass. CGM, on its part, helps identify hypoglycemia in the real-world setting, especially nocturnal asymptomatic hypoglycemia, bringing to light that PBH is not always postprandial.

Workup and Management of Recurrent Attacks of Post-bariatric Hypoglycemia in a Patient With Non-alcoholic Steatohepatitis.

Bariatric surgery is an established treatment option for patients with non-alcoholic fatty liver disease (NAFLD) as well as non-alcoholic steatohepatitis (NASH) and is said to effectively reduce hepatic inflammation as well as steatosis in these patients. However, bariatric surgery is associated with multiple complications, including nutritional deficiencies, malnutrition, post-bariatric hypoglycemia (PBH), anastomotic leaks, and bowel strictures. This case report describes a rare but significant complication of post-bariatric surgery hypoglycemia in a patient with NASH, which started almost six months after Roux-en-Y gastric bypass (RYGB) surgery. This 55-year-old male patient presented with recurrent episodes of severe hypoglycemia, which, on further work-up, were found to be predominantly nocturnal as well as occurring two to three hours after meals. We report the successful treatment of the patient with an unconventional approach using nifedipine and acarbose. Our findings emphasize the importance of careful evaluation of patients who have undergone bariatric surgery, as this complication can occur as early as six months following the bariatric surgery as well as several years after the surgery. Our case report highlights the need for early recognition, relevant workup, and appropriate management of resistant hypoglycemic events using calcium channel blockers and acarbose, thus adding to the existing literature on this topic.

Insulinoma Misdiagnosed as Post-bariatric Hypoglycemia: A Case Report and Review of the Literature.

Hypoglycemia is seen with increasing frequency after bariatric surgery. After the diagnosis of hypoglycemia has been clarified, malnutrition, drugs, hormone deficiencies, insulinoma, extra-islet tumors, post-bariatric hypoglycemia (PBH), early or late dumping syndrome, and nesidioblastosis should be considered in the differential diagnosis. A few case reports of insulinomas presenting after bariatric surgery have been reported in the literature. The coexistence of insulinoma and type 2 diabetes mellitus (T2D) is very rare. We herein report a clinical case of insulinoma presenting with severe hypoglycemia in a patient with a history of gastric transit bipartition. A patient with type 2 diabetes mellitus underwent gastric transit bipartition surgery due to the inability of medical therapy to provide adequate hyperglycemia control. After the operation, hypoglycemic symptoms appeared, and a reversal operation was performed, considering the diagnosis as PBH. After the reverse operation, the patient's hypoglycemia symptoms did not regress. The patient was admitted to our endocrinology clinic due to the persistence of hypoglycemia and symptoms such as fatigue, palpitation, and syncope. The patient's detailed anamnesis was examined, additional tests were performed, and the patient was diagnosed with insulinoma. The symptoms of hypoglycemia and the need for treatment for diabetes mellitus disappeared after the Whipple operation. This is the first case of insulinoma after gastric transit bipartition and subsequent reversal operations. In addition, the patient's diagnosis of diabetes mellitus makes this case unique. Although this is a very rare case, clinicians must be aware of it, especially if the patient has hypoglycemic symptoms during the fasting state.

Persistent post-bariatric-surgery hypoglycemia: A long-term follow-up reassessment.

BACKGROUND AND AIM: Post-bariatric-surgery hypoglycemia (PBH) is a serious complication of bariatric surgery (BS). In our previous study about three quarters of the patients developed PBH. However long-term follow-up data is lacking to determine whether this condition improves with time. The aim of the current study was to re-assess post-BS patients who participated in our previous study and determine whether there are changes in the frequency and/or severity of hypoglycemic events. METHODS AND RESULTS: Twenty-four post-BS, post Roux-en-Y gastric-bypass (RYGB = 10), post omega-loop gastric-bypass (OLGB = 9) and post sleeve-gastrectomy (SG = 5) individuals were reevaluated in a follow-up study 34.4 ± 4 months after their previous assessment and 67 ± 17 months since surgery. The evaluation included: a dietitian assessment, a questionnaire, meal-tolerance test (MTT) and a one-week masked continuous glucose monitoring (CGM). Hypoglycemia and severe hypoglycemia were defined by glucose levels ≤54 mg/dl and ≤40 mg/dl, respectively. Thirteen patients reported questionnaire meal-related complaints, mainly non-specific. During MTT, hypoglycemia occurred in 75% of the patients, and severe hypoglycemia in a third, but none was associated with specific complaints. During CGM, 66% of patients developed hypoglycemia and 37% had severe hypoglycemia. We did not observe significant improvements in hypoglycemic events compared to the previous assessment. Despite the high frequency of hypoglycemia, it did not necessitate hospitalizations or lead to death. CONCLUSIONS: PBH did not resolve within long-term follow-up. Intriguingly, most patient were unaware of these events which can lead to underestimation by the medical staff. Further studies are needed to determine possible long term sequela of repeated hypoglycemia.

Utility of Continuous Glucose Monitoring vs Meal Study in Detecting Hypoglycemia After Gastric Bypass.

CONTEXT: Gastric bypass (GB) increases postprandial glucose excursion, which in turn can predispose to the late complication of hypoglycemia. Diagnosis remains challenging and requires documentation of symptoms associated with low glucose and relief of symptom when glucose is normalized (Whipple triad). OBJECTIVE: To compare the yield of mixed meal test (MMT) and continuous glucose monitoring system (CGMS) in detecting hypoglycemia after GB. SETTING: The study was conducted at General Clinical Research Unit, Cincinnati Children's Hospital (Cincinnati, OH, USA). METHODS: Glucose profiles were evaluated in 15 patients with documented recurrent clinical hypoglycemia after GB, 8 matched asymptomatic GB subjects, and 9 healthy weight-matched nonoperated controls using MMT in a control setting and CGMS under free-living conditions. RESULTS: Patients with prior GB had larger glucose variability during both MMT and CGMS when compared with nonsurgical controls regardless of their hypoglycemic status. Sensitivity (71 vs 47%) and specificity (100 vs 88%) of MMT in detecting hypoglycemia was superior to CGMS. CONCLUSIONS: Our findings indicate that a fixed carbohydrate ingestion during MMT is a more reliable test to diagnose GB-related hypoglycemia compared with CGMS during free-living state.

Uncooked cornstarch for the prevention of hypoglycemic events.

Hypoglycemia is a pathological condition characterized by a low plasma glucose concentration associated with typical autonomic and/or neuroglycopenic symptoms, and resolution of these symptoms with carbohydrate consumption. Hypoglycemia is quite common in clinical practice, particularly in insulin-treated patients with diabetes and in other inherited or acquired conditions involving the regulation of glucose metabolism. Beyond symptoms that might strongly affect the quality of life, hypoglycemia can lead to short- and long-term detrimental consequences for health. Hypoglycemia can be prevented by appropriate changes in dietary habits or by relevant modifications of the drug treatment. Several dietary approaches based on the intake of various carbohydrate foods have been tested for hypoglycemia prevention; among them uncooked cornstarch (UCS) has demonstrated a great efficacy. In this narrative review, we have summarized the current evidence on the UCS usefulness in some conditions characterized by high hypoglycemic risk, focusing on some inherited diseases -i.e. glycogen storage diseases and other rare disorders - and acquired conditions such as type 1 diabetes, postprandial hypoglycemia consequent to esophageal-gastric or bariatric surgery, and insulin autoimmune syndrome. We also considered the possible role of UCS during endurance exercise performance. Lastly, we have discussed the dose requirement, the side effects, the limitations of UCS use, and the plausible mechanisms by which UCS could prevent hypoglycemia.

Hypoglycemia After Upper Gastrointestinal Surgery: Clinical Approach to Assessment, Diagnosis, and Treatment.

CONTEXT: Post-bariatric hypoglycemia (PBH) is an increasingly encountered complication of upper gastrointestinal surgery; the prevalence of this condition is anticipated to rise given yearly increases in bariatric surgical procedures. While PBH is incompletely understood, there is a growing body of research describing the associated factors, mechanisms, and treatment approaches for this condition. EVIDENCE ACQUISITION: Data are integrated and summarized from studies of individuals affected by PBH and hypoglycemia following upper gastrointestinal surgery obtained from PubMed searches (1990-2020). EVIDENCE SYNTHESIS: Information addressing etiology, incidence/prevalence, clinical characteristics, assessment, and treatment were reviewed and synthesized for the practicing physician. Literature reports were supplemented by clinical experience as indicated, when published data were not available. CONCLUSION: PBH can be life-altering and severe for a subset of individuals. Given the chronic nature of this condition, and sequelae of both acute and recurrent episodes, increasing provider awareness of both the condition and associated risk factors is critical for assessment, prompt diagnosis, treatment, and preoperative identification of individuals at risk.

Efficacy of Conversion of Roux-en-Y Gastric Bypass to Roux Jejuno-Duodenostomy for Severe Medically Refractory Postprandial Hypoglycemia.

Treatment of medically refractory postprandial hypoglycemia after Roux-en-Y Gastric bypass (RYGB) is often unsuccessful. Various operations have been described with poor results. We describe a novel procedure and retrospective review of 8 patients who underwent Roux jejuno-duodenostomy for postprandial hypoglycemic symptoms refractory to dietary modification and medications. Mean follow-up was 35 months. Complete resolution occurred in two of the patients, marked improvement in four, and no improvement in two. The mean frequency of hypoglycemic symptoms decreased from 30 to 7 episodes per week (p = 0.015). One complication was noted with no mortality. Mean weight decreased postoperatively by 0.8 kg (p = 0.93). Conversion to a Roux jejuno-duodenostomy appears to be a safe and effective treatment with maintenance of post-RYGB weight loss in most such cases.

Insights from the Impact of Meal Composition on Glucose Profile Towards Post-bariatric Hypoglycemia Management.

BACKGROUND/AIM: The need to improve post-bariatric hypoglycemia (PBH) diagnosis and clinical management is well recognized. Our aim was to evaluate the influence of meal nutritional composition on interstitial fluid glucose (IFG) profiles and symptom profile after Roux-en-Y gastric bypass (RYGB). METHODS: Seventeen subjects previously submitted to RYGB were allocated into two groups of symptomatic (n = 9) or control individuals (n = 8), according to spontaneous report of symptoms suggestive of hypoglycemia. Subjects were provided with a food and symptom diary (FSD) to record dietary intake and symptoms experienced, while using a flash glucose monitoring (FGM) system for 14 days. RESULTS: Postprandial symptom reports occurred in 70.5% of subjects (88.9% vs 50.0%, p = 0.0790, symptomatic vs control), although symptoms with concurrent IFG < 54 mg/dL and within 54 to 69 mg/dL were only observed in 31.9% and 4.8% of the events in the symptomatic vs control group, respectively (p = 0.0110). Daily glucose profiles, total energy, and macronutrients intake were not significantly different between the groups. However, nutritional composition of meals preceding reported symptoms had lower protein (3.2 g ± 1.0 g vs 7.7 g ± 0.5 g, p = 0.0286) or higher sugar (11.6 g ± 2.4 g vs 4.3 g ± 0.9 g, p = 0.0333) content. CONCLUSIONS: Postprandial symptoms are often in patients after RYGB. Concurrent hypoglycemia only occurs in up to a third of the symptomatic episodes being more frequent in patients that spontaneously reported complaints. Hypoglycemia is more likely to be triggered by meals with a low protein or high sugar content. These findings highlight the putative role of meal composition in eliciting PBH and reinforce the need to refine nutritional intervention.

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.

Implementation of Low Glycemic Index Diet Together with Cornstarch in Post-Gastric Bypass Hypoglycemia: Two Case Reports.

Post-bariatric hypoglycemia (PBH) is an increasingly recognized long-term complication of bariatric surgery. The nutritional treatment of PBH includes a high-fiber diet and the restriction of soluble and high-glycemic index carbohydrates; however, these measures are not always enough to prevent hypoglycemia. We evaluated the efficacy of uncooked cornstarch, a low-glycemic index carbohydrate characterized by slow intestinal degradation and absorption, in addition to a high-fiber diet, for the treatment of PBH. We report the cases of two young women suffering from severe postprandial and fasting hypoglycemia following Roux-en-Y gastric bypass (RYGB). The patients underwent Continuous Glucose Monitoring (CGM) before and 12⁻16 weeks after the administration of uncooked cornstarch (respectively 1.25 g/kg b.w. and 1.8 g/kg b.w.) in addition to a high-fiber diet. In both patients, CGM showed more stable glucose levels throughout monitoring, a remarkable reduction of the time spent in hypoglycemia (.