Postprandial Hyperinsulinemic Hypoglycemia Research Articles

Successful treatment of dumping syndrome with diazoxide in an infant with hypoplastic left heart syndrome.

Dumping syndrome is a rare but potentially serious condition that causes inappropriate postprandial hyperinsulinemia leading to hypoglycemia in children following gastrointestinal surgeries. While dietary modifications are often the first line of treatment, severe cases may require pharmacological intervention to prevent severe hypoglycemia. We present a case of successful treatment of dumping syndrome with diazoxide. A 2-month-old infant with left hypoplastic heart syndrome who underwent single ventricle palliation pathway and developed feeding intolerance that required Nissen fundoplication. Postprandial hypoglycemia was detected following the procedure, with glucose level down to 12 mg/dL, and the diagnosis of dumping syndrome was established. The patient was successfully managed with diazoxide, which effectively resolved postprandial hypoglycemia without any major adverse events. The patient was eventfully weaned off the medication at the age of 5 months. This case highlights the potential role of diazoxide in the management of pediatric patients with postprandial hyperinsulinemic hypoglycemia secondary to dumping syndrome. Dumping syndrome is a possible complication of gastrointestinal surgeries and should be suspected in children with abnormal glucose levels. Postprandial hyperglycemia should be monitored closely for significant subsequent hypoglycemia. Diazoxide might be considered as part of the treatment plan for dumping syndrome.

THU276 The Use of Continuous Glucose Monitors for Management of Postbariatric Hypoglycemia

Abstract Disclosure: S. Jani: None. S. Bao: None. Postprandial hypoglycemia is a known complication of bariatric surgery. Mixed meal tolerance test performed in these patients often revealed hypoglycemia 1-3 hours after meals. Recent clinical studies using continuous glucose monitors (CGM) have shown the incidence of postbariatric hypoglycemia is much higher than previously identified. In addition to diet modification and medication treatment, CGM has become a more popular and useful tool in managing severe cases. We present a case of using CGM to manage postbariatric hypoglycemia. A 47 year old female with prior history of class 3 obesity treated with sleeve gastrectomy presented with hypoglycemia 2.5 years after her bariatric surgery. She complained of headache, anxiety, dizziness, and fatigue during a routine clinic visit, two hours after consuming a carbohydrate rich meal with simple sugars. Blood glucose was obtained and revealed severe hypoglycemia (glucose 38 mg/dL). This prompted an urgent referral to endocrinology. Review of glucose trends revealed multiple instances of postprandial hypoglycemia. Further labs suggested a low likelihood for insulinoma with no fasting hypoglycemia and HA1C normal at 5.3%. Postprandial hyperinsulinemic hypoglycemia was suspected clinically. Dietary modification with multiple small meals consisting of high protein, fiber and complex carbohydrates was recommended. Additionally, she was started on Libre 2 CGM for monitoring and prevention of severe hypoglycemia. Review of her CGM data during follow up visit demonstrated very low incidence of hypoglycemia and absence of severe hypoglycemia. Over time with continued use of her CGM and low incidence of hypoglycemia, she did not require medical therapy. Postprandial hypoglycemia after bariatric surgery can be severe and lead to disabling neuroglycopenic symptoms. With increased utilization of bariatric surgery, these postoperative complications will likely become more prevalent. In a Swedish nationwide study, the prevalence of postbariatric hypoglycemia was close to 0.2% in a cohort of 5040 patients. However, a more recent prospective study with a two-year observation of 333 patients after bariatric surgery using 2-hour glucose tolerance test revealed much higher prevalence of severe postprandial hypoglycemia (25.6%). Hypoglycemia was highest after gastric bypass surgery (32.6%), followed by sleeve gastrectomy (22.6%). Currently, there is no official guideline on utilization of CGM in management of hypoglycemia in nondiabetic patients. This case highlights the role of CGM in managing postbariatric hypoglycemia. CGM provides continuous glucose data, trends and alerts that can be a critical tool for patients to monitor, anticipate and prevent hypoglycemic events. Additionally, the real time data provided by CGM’s can help clinicians identify high risk patients who may benefit from the addition of medications to treat hypoglycemia. Presentation: Thursday, June 15, 2023

1586-P: Post-OGTT Low Blood Glucose in Individuals with Metabolic Syndrome, Metabolic Phenotypes, and Metabolic-Associated Fatty Liver Disease

Introduction: Post-prandial low blood glucose (LBG) is usually associated with late postprandial hyperinsulinemia in metabolic syndrome (MetS), but have not been well studied. Objectives: We aimed to 1) characterize insulin/glucose metabolism associated with LBG post 75g OGTT in a sample of individuals with MetS; and 2) assess the association between MAFLD (≥ 5% liver fat at MRI) and LBG. Methods: Plasma glucose, insulin and c-peptide concentrations were measured on OGTT over 180 mins. Insulin sensitivity and secretion were assessed with the Oral Minimal Model. During OGTT, we defined glucose ≤ 50 mg/dl as LBG, glucose > 70 mg/dl as no LBG and glucose 51-70 mg/dl as undefined status and were excluded from this analysis. Results: Of 82 participants, 50 were included and 15 (18 %) experienced LBG. Of the 33 participants who underwent MRI, 48% had MAFLD. Median age and BMI were 59 [IQR: 49-74] years and 28 [IQR: 26-31] kg/m2 respectively. Women represented 70% (n=35) of participants and experienced less LBG (p=0.0002) than men. Individuals experiencing LBG had higher insulin sensitivity (p=0.02), higher ß cell function (p=0.03), earlier glucose peaks (p<0.0001) and lower c-peptide peaks (p=0.007) than those without LBG. MAFLD was not associated with more LBG (p=0.7), but was associated with a different insulin curve. LBG+MAFLD status was associated with higher and later c-peptide and insulin levels compared to LBG without MAFLD status. Conclusion: In contrary to our hypothesis, individuals with MetS without MAFLD experiencing glucose ≤ 50 mg/dl during OGTT displayed a healthier metabolic profile. However, individuals with MAFLD experiencing a LBG during OGTT had a glucose phenotype similar to the late post-prandial hyperinsulinemic hypoglycemia often found in prediabetes state and associated with worst metabolic parameters. This suggests that MAFLD may be an important feature of MetS associated with a different post-OGTT glucose metabolism. Disclosure T.Gignac: None. A.Morissette: None. A.Agrinier: None. C.Gagnon: Advisory Panel; Novo Nordisk, Other Relationship; Ascendis Pharma A/S, Research Support; Novo Nordisk. M.Vohl: None. A.Marette: Advisory Panel; Valbiotis, Amancia, Plexus, Acasti. A.Carreau: Advisory Panel; Novartis, Consultant; Valbiotis, Speaker's Bureau; Novo Nordisk Canada Inc.

The oral disposition index calculated from a meal tolerance test is a crucial indicator for evaluating differential normalization of postprandial glucose and triglyceride excursions in morbidly obese patients after laparoscopic sleeve gastrectomy.

To determine the normalization of postprandial blood glucose (PG) and triglyceride (TG) excursions in 30 morbidly obese patients with or without diabetes mellitus (DM) 1-year after they underwent a laparoscopic sleeve gastrectomy (LSG) vs. their pre-surgery data, we administered the 75-g oral glucose tolerance test (OGTT) and a meal tolerance test (MTT) using a 75-g glucose-equivalent carbohydrate- and fat-containing meal. The results were as follows; (i) Postoperative body-weight reduction was associated with DM remission and reduced multiple cardiometabolic risks. (ii) OGTT data showing postprandial hyper-insulinemic hypoglycemia in many post-surgery patients were associated with overdiagnosis of improved glucose tolerance. However, postoperative MTT data without hypoglycemia showed no improvement in the glucose tolerance vs. pre-surgery data. (iii) The disposition index (DI) i.e., [Matsuda index] × (Glucose-induced insulin secretion) was progressively worsened from normal glucose tolerance to DM patients after LSG. These post-surgery DI values measured by the MTT were correlated with 2h-plasma glucose levels and were not normalized in DM patients. (iv) The baseline, 2h-TG, and an increase in 2h-TG values above baseline were correlated with the insulin resistance index, DI, or HbA1c; These TG values were normalized post-LSG. In conclusion, the glucose tolerance curve measured by the MTT was not normalized in T2DM patients, which was associated with impaired normalization of the DI values in those patients 1-year after the LSG. However, the baseline TG and a fat-induced 2h-TG values were normalized postoperatively. The MTT can be used to assess normalization in postprandial glucose and TG excursions after LSG.

The efficacy of GLP-1RAs for the management of postprandial hypoglycemia following bariatric surgery: a systematic review.

Postprandial hyperinsulinemic hypoglycemia with neuroglycopenia is an increasingly recognized complication of Roux-en-Y gastric bypass and gastric sleeve surgery that may detrimentally affect patient quality of life. One likely causal factor is glucagon-like peptide-1 (GLP-1), which has an exaggerated rise following ingestion of carbohydrates after bariatric surgery. This paper sought to assess the role of GLP-1 receptor agonists (GLP-1RAs) in managing postprandial hypoglycemia following bariatric surgery. MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and Scopus were systematically and critically appraised for all peer-reviewed publications that suitably fulfilled the inclusion criteria established a priori. This systematic review was developed according to the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols (PRISMA-P). It followed methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions and is registered with PROSPERO (International Prospective Register of Systematic Reviews; identifier CRD420212716429). Postprandial hyperinsulinemic hypoglycemia remains a notoriously difficult to manage metabolic complication of bariatric surgery. This first, to the authors' knowledge, systematic review presents evidence suggesting that use of GLP-1RAs does not lead to an increase of hypoglycemic episodes, and, although this approach may appear counterintuitive, the findings suggest that GLP-1RAs could reduce the number of postprandial hypoglycemic episodes and improve glycemic variability.

Study protocol for a randomised, double-blind, placebo-controlled crossover trial assessing the impact of the SGLT2 inhibitor empagliflozin on postprandial hypoglycaemia after gastric bypass

IntroductionPostprandial hypoglycaemia after gastric bypass surgery (also known as postbariatric hypoglycaemia or PBH) is an increasingly encountered clinical problem. PBH is characterised by meal-induced rapid spikes and consequent falls in...

Postprandial hypoglycemia after upper gastrointestinal tract surgery: diagnosis and treatment (part 2)

The causes of postprandial hyperinsulinemic hypoglycemia (PHH) in patients who have under-gone an upper gastrointestinal tract surgery are still a matter of debate in the scientific community. Low postoperative body mass index, high postprandial beta-cell activity before the surgery, and younger age are all have been associated with higher PHH risk. It is hypothesized that the insulin-like growth factor-1 increases the tissue sensitivity to insulin and indirectly promotes the development of hypoglycemia. An increase in postprandial secretion of enteropancreatic hormones is still considered to be the main reason for PHH manifestation; however, a particular contribution has been ascribed to glycentin, which could be used as a marker of PHH risk in the future. At present, there are no clinical guidelines for the diagnosis of PHH. Undoubtedly, the first step in this direction should be the collection of the disease history. The provocative tests have been proposed for the detection of PHH. Today, the 72-hour fast test is still the gold standard in the diagnosis of hypoglycemia. However, most post-bariatric patients do not have fasting hypoglycemia, and insulinoma is extremely rare in this patient category. The use of a prolonged oral glucose tolerance test as the main method is associated with a risk of a false diagnosis, because about 12% of healthy individuals may have their glycemic levels at below 2.8 mmol/l. The mixed meal test has not been validated yet. The best results in the assessment of glucose variability have been obtained with “real time” continuous glucose monitoring the interstitial fluid for several days. The goal of PHH treatment is to reduce the stimulated insulin secretion. First of all, patients are advised to eat small meals consisting of carbohydrates with a low glycemic index in combination with proteins and lipids, with high fiber content. Should the nutritional modification be ineffective, it is possible to prescribe medical treatment, such as acarbose or somatostatin analogs. Diazoxide and slow calcium channel blockers can be used as the third line of therapy. A recent study has suggested that exogenous agonists of glucagon-like peptide-1 (GLP-1) receptors by stronger bonds with receptors, compared to those with endogenous GLP-1, could enhance glucagon response to hypoglycemia, thereby stabilizing glucose levels. In severe refractory PHH, reconstructive surgery and gastric banding are to be considered. If the expected decrease in insulin hypersecretion by reconstructive surgery is not achieved, partial or complete pancreatectomy remains the only possible approach to prevent hypoglycemia. However, due to the small number and short duration of the studies, effectiveness and safety of these techniques for PHH treatment have not yet been proven.

Postprandial hypoglycemia after upper gastrointestinal tract surgery: prevalence and pathophysiology (part 1)

Nowadays obesity is a major health problem worldwide. Surgery is the most promising treatment for morbid obesity. There are two types of bariatric procedures, one to reduce the food intake volume and the other to limit the absorption of nutrients. Despite the indisputable advantages of bariatric surgery for weight loss, it is necessary to remember the potential risk of severe complications, such as hypoglycemic syndrome at 2 to 3 hours after ingestion of rapidly absorbable carbohydrates manifested by adrenergic and neuroglycopenic symptoms. According to the literature, the prevalence of post-bariatric postprandial hyperinsulinemic hypoglycemia (PHH) varies from 10% to 75%. PHH in post-bariatric patients should be differentiated from the syndrome of non-insulinoma pancreatogenic hypoglycemia and from insulinoma; however, these diseases are described also in patients after bariatric surgery.The mechanisms of PHH as an outcome of shunting bariatric procedures are currently not fully clear. According to the recent studies, incretin hypersecretion in response to the accelerated flow of carbohydrates into the small intestine plays a leading role in the inappropriate excess production of insulin by the pancreas. In addition, there are hypotheses on a slower normalization of insulin production during more rapid bodyweight decrease and regression of insulin resistance, the role of alpha-cell dysfunction, disturbed negative feedback between insulin and ghrelin, compensatory hyperplasia and hypertrophy of the remaining enterocytes (including L-cells), changes in gut microflora, bile acids level and composition. A number of other mechanisms have also been proposed that require further studies.

Late complications of biliopancreatic diversion in an older patient: a case report

BackgroundIn the mid-seventies, biliopancreatic diversion became popular as weight-loss surgery procedure. This bariatric procedure combines distal gastric resection and intestinal malabsorption, leading to greater weight loss and improvement of co-morbidities than other bariatric procedures. Nowadays, biliopancreatic diversion has become obsolete due to the high risk of nutritional complications. However, current patients with biliopancreatic diversions are aging. Consequently, geriatricians and general practitioners will encounter them more often and will be faced with the consequences of late complications.Case presentationA 74-year old female presented with weakness, recurrent falls, confusion, episodes of irresponsiveness, anorexia and weight loss. Her medical history included osteoporosis, herpes encephalitis 8 years prior and a biliopancreatic diversion (Scopinaro surgery) at age 52. Cerebral imaging showed herpes sequelae without major atrophy. Delirium was diagnosed with underlying nutritional deficiencies. Biochemical screening indicated vitamin A deficiency, vitamin E deficiency, zinc deficiency and severe hypoalbuminemia. While thiamin level and fasting blood glucose were normal. However, postprandial hyperinsulinemic hypoglycemia was observed with concomitant signs of confusion and blurred consciousness. After initiating parenteral nutrition with additional micronutrient supplementation, a marked improvement was observed in cognitive and physical functioning.ConclusionsLong-term effects of biliopancreatic diversion remain relatively underreported in older patients. However, the anatomical and physiological changes of the gastrointestinal tract can contribute to the development of metabolic and nutritional complications that may culminate in cognitive impairment, functional decline and delirium. Therefore, it is warranted to evaluate the presence of metabolic disturbances and nutritional complications in older patients after biliopancreatic diversion.

Is Bariatric Surgery Brain Surgery?

Roux-en-Y gastric bypass (RYGB) reliably produces sustained weight losses, reduces circulating blood glucose, and lowers risk of type 2 diabetes (1). Accompanying these benefits, however, is symptomatic hypoglycemia, reported by up to one-third of post–bariatric surgery patients (2,3). In an estimated <1% of RYGB patients (4), postprandial hyperinsulinemic hypoglycemia causes severe symptoms including neuroglycopenia with significant morbidity. New mechanistic insights and treatment options for these patients are needed. Potential contributors include rapid glucose delivery into the bloodstream, improved β-cell function, and gut adaptations, but the role of the central nervous system (CNS) is an important and underdeveloped area of research (3). In their article in this issue of Diabetes , Almby et al. (5) investigate whether RYGB alters the brain response to hypoglycemia in humans—a topic with further relevance to the CNS contribution to RYGB’s modification of overall glucose homeostasis. Human neuroimaging studies document RYGB-induced changes in brain function and suggest reversibility of obesity-associated findings (6–8). Studies of cerebral metabolism measuring [18F]-fluorodeoxyglucose uptake by positron emission tomography (FDG-PET) show that brain glucose uptake is elevated in participants with obesity and partially reversed post-RYGB (6,7), but controlled studies of the cerebral metabolic response to insulin-induced hypoglycemia are lacking. Cerebral blood flow response to insulin-induced hypoglycemia assessed by arterial spin labeling (ASL) showed increased regional blood flow (vs. euglycemia) in the cortex, thalamus (9), and hypothalamus (10) in healthy adults. Almby et al. provide novel data on the effect of RYGB on brain response to hypoglycemia (5). Almby et al. included 11 participants that underwent, before and …

Symptomatic Hypoglycemia After Gastric Bypass: Incidence and Predictive Factors in a Cohort of 1,138 Consecutive Patients.

After Roux-en-Y gastric bypass (RYGB), postprandial hyperinsulinemic hypoglycemia (PPHH) is particularly critical because of the risk of trauma. The aim of this study was to assess the incidence and identify risk factors for symptomatic PPHH. Patients with RYGB were classified into moderate PPHH (MH) or severe hypoglycemia (SH), which is defined as patients with neuroglycopenic symptoms. Logistic multivariate linear regressions were performed to identify predictive factors for symptomatic PPHH and more specifically for SH with neuroglycopenic symptoms. Patients with diabetes and those with a follow-up shorter than 2 years were excluded. Among the 1,138 patients, 44.2% had at least one episode of hypoglycemia with a mean delay of 25.5 (21.3) months, 32.6% had MH, and 11.6% had SH. The annual incidence rate of SH was 2.5% the first year, 3.7% the second year, and 1.5% the third year. Independent predictive factors for higher risk of SH were: younger age (odds ratio [OR] = 1.01; 95% CI: 1.05-16.69; P = 0.0007), lower BMI after RYGB (OR = 1.61; 95% CI: 1.17-2.22; P = 0.0035), and maximal weight loss (OR = 1.04; 95% CI = 1.39-1.23; P = 0.0106), whereas higher preoperative BMI was protective (OR = 0.78; 95% CI: 0.64-0.95; P = 0.0112). This observational cohort study showed that the incidence of severe PPHH with neuroglycopenic symptoms after RYGB was higher than expected.

Minimally Invasive Conversion of a Gastric Bypass into Sleeve Gastrectomy for Postprandial Hyperinsulinemic Hypoglycemia.

The treatment of postprandial hyperinsulinemic hypoglycemia following gastric bypass surgery for obesity can be challenging despite dietetic and medical treatment and eventually surgical treatment remains the exclusive treatment to resolve the problem for the patient. In the following, the experience with a conversion surgery from a complicated Roux-en-Y gastric bypass to sleeve gastrectomy using the Da Vinci robotic system will be reported.

Canagliflozin: A New Therapeutic Option in Patients That Present Postprandial Hyperinsulinemic Hypoglycemia after Roux-en-Y Gastric Bypass: A Pilot Study

Introduction: Roux-en-Y gastric bypass (RYGB) is the most common surgical procedure for morbid obesity. However, it can present serious late complications, like postprandial hyperinsulinemic hypoglycemia (PHH). Recent data suggested an increase in intestinal SGLT-1 after RYGB. However, there is no data on the inhibition of SGLT-1 to prevent PHH in patients with prior RYBG. On this basis, we aimed to evaluate (a) the effect of canagliflozin 300 mg on the response to 100 g glucose overload (oral glucose tolerance test [OGTT]); (b) the pancreatic response after intra-arterial calcium stimulation in the context of PHH after RYGB. Materials and Methods: This is a prospective pilot study including patients (n = 21) with PHH after RYGB, matched by age and gender with healthy controls (n = 5). Basal OGTT and after 2 weeks of daily 300 mg of canagliflozin was performed in all cases. In addition, venous sampling after intra-arterial calcium stimulation of the pancreas was performed in 10 cases. Results: OGTT after canagliflozin showed a significant reduction of plasma glucose levels (minute 30: 161.5 ± 36.22 vs. 215.9 ± 58.11 mg/dL; minute 60: 187.46 ± 65.88 vs. 225.9 ± 85.60 mg/dL, p < 0.01) and insulinemia (minute 30: 95.6 ± 27.31 vs. 216.35 ± 94.86 mg/dL, p = 0.03; minute 60: 120.85 ± 94.86 vs. 342.64 ± 113.32 mIU/L, p < 0.001). At minute 180, a significant reduction (85.7%) of the rate of hypoglycemia was observed after treatment with canagliflozin (p < 0.00001). All cases presented normal pancreatic response after intra-arterial calcium administration. Conclusion: Canagliflozin (300 mg) significantly decreased glucose absorption and prevented PHH after 100 g OGTT in patients with RYGB. Our results suggest that canagliflozin could be a new therapeutic option for patients that present PHH after RYGB.

1793-P: C-Peptide Kinetics: The Van Cauter Population Model May Not Be Applicable to Post–Gastric Bypass Adults with Postprandial Hyperinsulinemic Hypoglycemia

Insulin secretion is key to understand postprandial hyperinsulinemic hypoglycemia (PHH), an increasingly recognized and potentially debilitating complication of gastric bypass (GB) surgery. To assess it noninvasively, the Oral C-peptide Minimal Model (OCMM) can be used. This requires to know C-peptide (CP) metabolic clearance rate (MCR) usually fixed to the values predicted by the Van Cauter (VC) population model, but this has never been assessed in PHH individuals. Here, the aim is to fill this gap. Two groups of post-GB adults with PHH underwent either a 75g oral glucose (11F/5M; age=43±8 y; BMI=28.2±7.1kg/m2) or a 60g mixed-meal (9F/3M; age=44±10y; BMI=27.4±3.9kg/m2) tolerance test with sampling for plasma glucose and CP over 3.5 and 3h, respectively. The OCMM was used to describe CP concentration with CP kinetics fixed to VC or estimated based on data (DB). Model performance was assessed by its ability to predict CP data. In both groups, the VC approach underestimated CP-peak and overestimated CP-tail, while the DB one well predicted CP data in all subjects (Figure 1A). As a consequence, MCR resulted significantly higher with DB than VC approach (Figure 1B). The present findings question the validity of the VC population model to predict CP kinetics in PHH patients and call for CP bolus experiments to develop a reliable kinetic model in this population. Disclosure M. Schiavon: None. D. Herzig: None. M. Hepprich: None. M.Y. Donath: Advisory Panel; Self; AstraZeneca, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Merck Sharp &amp; Dohme Corp., Novo Nordisk Inc., Roche Pharma, Sanofi-Aventis. C. Stettler: None. L. Bally: None. C. Dalla Man: Research Support; Self; Sanofi-Aventis Deutschland GmbH. Funding Italian Ministry of Education (232/2016); Swiss National Science Foundation (PCEGP3_186978); University of Padova

Hyperinsulinemic Hypoglycemia after Bariatric Surgery.

Postprandial hyperinsulinemic hypoglycemia (PHH) is one of the serious complications after bariatric surgery, it can lead life-threatening neuroglycopenic symptoms, such as seizures, disorientation, impairment of version and loss of consciousness without any premonitory. The presentation, prevalence, diagnosis, pathology and treatment are reviewed in this summary.

A519 Surgical treatment of postprandial hyperinsulinemic hypoglycemia after gastric by pass: is it efficient?

A519 Surgical treatment of postprandial hyperinsulinemic hypoglycemia after gastric by pass: is it efficient?

Postprandial hypoglycemia after gastric bypass surgery: from pathogenesis to diagnosis and treatment.

The Roux-en-Y gastric bypass surgery (RYGB) improves glucose control in majority of patients with type 2 diabetes. However, a minority group of individuals develop a life-threatening complication of hyperinsulinemic hypoglycemia. The goal of this review is to identify underlying mechanisms by which RYGB cause hypoglycemia and describe pathogenesis-driven strategies to diagnose and treat this condition. Gastric bypass leads to higher and earlier peak levels of glucose and lower nadir glucose after eating along with larger insulin and glucagon-like peptide 1 (GLP-1) secretion, resetting the balance between glucose appearance and clearance after this procedure. These weight-loss independent glycemic effects of RYGB have been attributed to changes in ingested glucose appearance as a result of rapid nutrient emptying from stomach pouch to the intestine and increased glucose clearance as a result of prandial hyperinsulinemia. The exaggerated effect of RYGB on postmeal glucose metabolism is a syndrome of postprandial hyperinsulinemic hypoglycemia manifesting in a group of individuals several years after this surgery. Affected patients have larger systemic appearance of ingested glucose and greater postmeal secretion of insulin and GLP-1 compared to those with history of RYGB without symptomatic hypoglycemia. Current evidence supporting a multifactorial model of glucose dysregulation among patients with hypoglycemia will be highlighted in this review. Hypoglycemia after RYGB is a life-threatening condition and likely represents the extreme glycemic phenotype of this procedure. Diagnosis is challenging and treatment options are limited.

HIPOGLUCEMIA HIPERINSULINÉMICA POSTPRANDIAL LUEGO DE LA CIRUGÍA BARIÁTRICA

La incidencia de complicaciones informadas luego de la cirugía bariátrica (CB) ha ido en aumento en relación con la epidemia de obesidad y el mayor número de procedimientos quirúrgicos realizados a nivel mundial. Entre las complicaciones, la hipoglucemia hiperinsulinémica postprandial (HHP) adquirió relevancia, aunque es una de las menos conocidas y comprendidas de la cirugía bariátrica (CB), frecuentemente inadvertida y por lo tanto subdiagnosticada. Se distingue de la hipoglucemia de ayuno en que su presentación es típicamente posterior a la ingesta, asociada a valores de hipoglucemia precedidos por hiperglucemia e hiperinsulinemia en sangre. Se caracteriza por el incremento de la variabilidad de la glucemia, con absorción acelerada, aumento y caída rápida de azúcar en sangre, por lo que comprende valores de hiper e hipoglucemia. Debe sospecharse cuando se detectan síntomas adrenérgicos o de neuroglucopenia postprandiales luego de la CB1.Ha sido considerada más frecuente luego del bypass gástrico en-Y-Roux (BGYR), pero también fue descripta asociada a otras técnicas quirúrgicas, como la derivación biliopancreática/switch duodenal (DBP/SD)2 y la gastrectomía vertical en manga (GVM), y de otras intervenciones que comprometen el píloro o el vaciamiento gástrico3. No se observó luego de la cirugía con banda gástrica ajustable, un procedimiento que no altera la anatomía gastrointestinal4-5.

Prevalence of hypoglycaemia in a random population after Roux-en-Y gastric bypass after a meal test.

ObjectiveRoux-en-Y gastric bypass (RYGB) is an effective way to induce sustainable weight loss and can be complicated by postprandial hyperinsulinaemic hypoglycaemia (PHH). To study the prevalence and the mechanisms behind the occurrence of hypoglycaemia after a mixed meal tolerance test (MMTT) in patients with primary RYGB.DesignThis is a cross-sectional study of patients 4 years after primary RYGB.MethodsFrom a total population of 550 patients, a random sample of 44 patients completed the total test procedures. A standardized mixed meal was used as stimulus. Venous blood samples were collected at baseline, every 10 min during the first half hour and every 30 min until 210 min after the start. Symptoms were assessed by questionnaires. Hypoglycaemia is defined as a blood glucose level below 3.3 mmol/L.ResultsThe prevalence of postprandial hypoglycaemia was 48% and was asymptomatic in all patients. Development of hypoglycaemia was more frequent in patients with lower weight at surgery (P = 0.045), with higher weight loss after surgery (P = 0.011), and with higher insulin sensitivity calculated by the homeostasis model assessment indexes (HOMA2-IR, P = 0.014) and enhanced beta cell function (insulinogenic index at 20 min, P = 0.001).ConclusionIn a randomly selected population 4 years after primary RYGB surgery, 48% of patients developed a hypoglycaemic event during an MMTT without symptoms, suggesting the presence of hypoglycaemia unawareness in these patients. The findings in this study suggest that the pathophysiology of PHH is multifactorial.

Successful management with GLP-1 agonists in postprandial hyperinsulinemic hypoglycemia after roux-en-y gastric bypass: clinical case descriptionand review of the literature

Successful management with GLP-1 agonists in postprandial hyperinsulinemic hypoglycemia after roux-en-y gastric bypass: clinical case descriptionand review of the literature