Postprandial plasma GLP-1 levels are elevated in individuals with postprandial hypoglycaemia following Roux-en-Y gastric bypass - a systematic review.

BACKGROUND AND AIMS: Bariatric surgery is the most effective treatment in individuals with obesity to achieve remission of type 2 diabetes. Post-bariatric surgery hypoglycaemia occurs frequently, and management remains suboptimal, because of a poor understanding of the underlying pathophysiology. The glucoregulatory hormone responses to nutrients in individuals with and without post-bariatric surgery hypoglycaemia have not been systematically examined. MATERIALS AND METHODS: The study protocol was prospectively registered with PROSPERO. PubMed, EMBASE, Web of Science and the Cochrane databases were searched for publications between January 1990 and November 2021 using MeSH terms related to post-bariatric surgery hypoglycaemia. Studies were included if they evaluated individuals with post-bariatric surgery hypoglycaemia and included measurements of plasma glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), insulin, C-peptide and/or glucagon concentrations following an ingested nutrient load. Glycated haemoglobin (HbA1c) was also evaluated. A random-effects meta-analysis was performed, and Hedges' g (standardised mean difference) and 95% confidence intervals were reported for all outcomes where sufficient studies were available. The τ2 estimate and I2 statistic were used as tests for heterogeneity and a funnel plot with the Egger regression-based test was used to evaluate for publication bias. RESULTS: From 377 identified publications, 12 were included in the analysis. In all 12 studies, the type of bariatric surgery was Roux-en-Y gastric bypass (RYGB). Comparing individuals with and without post-bariatric surgery hypoglycaemia following an ingested nutrient load, the standardised mean difference in peak GLP-1 was 0.57 (95% CI, 0.32, 0.82), peak GIP 0.05 (-0.26, 0.36), peak insulin 0.84 (0.44, 1.23), peak C-peptide 0.69 (0.28, 1.1) and peak glucagon 0.05 (-0.26, 0.36). HbA1c was less in individuals with hypoglycaemia - 0.40 (-0.67, -0.12). There was no evidence of substantial heterogeneity in any outcome except for peak insulin: τ2 = 0.2, I2 = 54.3. No publication bias was evident. CONCLUSION: Following RYGB, postprandial peak plasma GLP-1, insulin and C-peptide concentrations are greater in individuals with post-bariatric surgery hypoglycaemia, while HbA1c is less. These observations support the concept that antagonism of GLP-1 would prove beneficial in the management of individuals with hypoglycaemia following RYGB.PROSPERO Registration Number: CRD42021287515.

Transoral gastric outlet reduction for post-prandial hypoglycemia after Roux-en-Y gastric bypass.

BACKGROUND: Post-prandial hypoglycemia is an uncommon but disabling late complication of Roux-en-Y gastric bypass (RYGB). Most patients can be treated with dietary interventions and medications; however, some patients develop refractory hypoglycemia that may lead to multiple daily episodes and seizures. While RYGB reversal surgery is an effective treatment, complication rates are high, and patients inevitably experience weight regain. Transoral gastric outlet reduction (TORe) is a minimally invasive treatment that is effective for early and late dumping syndrome. However, prior studies have not distinguished the effectiveness of TORe specifically for patients with post-prandial hypoglycemia. This study aims to describe a single institution's experience of TORe for treating post-prandial hypoglycemia. METHODS: This is a case series of patients with prior RYGB complicated by post-prandial hypoglycemia who underwent TORe from February 2020 to September 2021. Pre-procedural characteristics and post-procedural outcomes were obtained. Outcomes assessed included post-prandial hypoglycemia episodes, dumping syndrome symptoms, and weight change. RESULTS: A total of 11 patients underwent TORe from 2020 to 2021 for post-prandial hypoglycemia. Three (27%) patients had a history of seizures due to hypoglycemia. All had been advised on dietary changes, and ten patients (91%) were on medications for dumping. All patients reported a reduction in post-prandial hypoglycemic events as well as the majority of dumping syndrome symptoms during an average follow-up time of 409 ± 125 days. Ten patients (91%) had experienced weight regain from their post-RYGB nadir weight. For these patients, the average total body weight loss 12 months post-TORe was 12.4 ± 12%. There were no complications requiring hospitalization. One patient experienced post-TORe nausea and vomiting requiring dilation of the gastrojejunal anastomosis with resolution in symptoms. CONCLUSION: TORe is a safe and effective treatment for post-prandial hypoglycemia and weight regain after RYGB in patients with symptoms refractory to medications and dietary changes.

Occult insulinoma with treatment refractory, severe hypoglycaemia in multiple endocrine neoplasia type 1 syndrome; difficulties faced during diagnosis, localization and management; a case report.

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN 1) syndrome is a rare, complex genetic disorder characterized by increased predisposition to tumorigenesis in multiple endocrine and non-endocrine tissues. Diagnosis and management of MEN 1 syndrome is challenging due to its vast heterogeneity in clinical presentation. CASE PRESENTATION: A 23-year-old female, previously diagnosed with Polycystic Ovarian Syndrome (PCOS) and pituitary microprolactinoma presented with drowsiness,confusion and profuse sweating developing over a period of one day. It was preceded by fluctuating, hallucinatory behavior for two weeks duration. There was recent increase in appetite with significant weight gain. There was no fever, seizures or symptoms suggestive of meningism. Her Body mass index(BMI) was 32 kg/m2.She had signs of hyperandrogenism. Multiple cutaneous collagenomas were noted on anterior chest and abdominal wall. Her Glasgow Coma Scale was 9/15. Pupils were sluggishly reactive to light. Tendon reflexes were exaggerated with up going planter reflexes. Moderate hepatomegaly was present. Rest of the clinical examination was normal. Laboratory evaluation confirmed endogenous hyperinsulinaemic hypoglycaemia suggestive of an insulinoma. Hypercalcemia with elevated parathyroid hormone level suggested a parathyroid adenoma. Presence of insulinoma, primary hyperparathyroidism and pituitary microadenoma, in 3rd decade of life with characteristic cutaneous tumours was suggestive of a clinical diagnosis of MEN 1 syndrome. Recurrent, severe hypoglycaemia complicated with hypoglycaemic encephalopathy refractory to continuous, parenteral glucose supplementation and optimal pharmacotherapy complicated the clinical course. Insulinoma was localized with selective arterial calcium stimulation test. Distal pancreatectomy and four gland parathyroidectomy was performed leading to resolution of symptoms. CONCLUSIONS: Renal calculi or characteristic cutaneous lesions might be the only forewarning clinical manifestations of an undiagnosed MEN 1 syndrome impending a life-threatening presentation. Comprehensive management of MEN 1 syndrome requires multi-disciplinary approach with advanced imaging modalities, advanced surgical procedures and long-term follow up due to its heterogeneous presentation and the varying severity depending on the disease phenotype.

Reversal to Normal Anatomy (With Sleeve Gastrectomy) for Severe Hypoglycemia.

Background. Laparoscopic Roux-en-Y gastric bypass (GBP) is an essential bariatric surgical procedure which is globally performed because of the associated effective weight loss and resolution of metabolic comorbidities, such as diabetes and dyslipidemia. Although some complications may occur, hypoglycemia is a rare complication, which can lead to lethal consequences. We aimed to describe the technical aspects and surgical results after reversal to normal anatomy (RNA). Methods. We conducted a retrospective data analysis including 16 patients who underwent laparoscopic RNA from 2011 to 2018. All data were archived in a prospective database. Previous bariatric surgery and postoperative outcomes were analyzed. Results. Sixteen patients underwent RNA, most of them after GBP, and 15 patients required sleeve gastrectomy. Among them, 80% were women; 5 patients presented with postoperative complications, such as colitis with intra-abdominal collection (n = 1), gastric leak (n = 2) treated with an endoprosthesis, mesenteric venous thrombosis (n = 1), and intra-abdominal bleeding (n = 1). Mean length of hospital stay was 5.93 (3-30). All patients recovered from their initial condition although 3 patients presented with mild hypoglycemia during follow-up. Seven patients regained weight (43.75%), and another 4 developed gastroesophageal reflux disease (25%). Conclusions. These laparoscopic RNA results are acceptable, indicating a clinical improvement in the hypoglycemic syndrome in all patients.

Postprandial hypoglycaemia after Roux-en-Y gastric bypass in individuals with type 2 diabetes.

AIMS/HYPOTHESIS: Postprandial hypoglycaemia (PPHG) is a complication of Roux-en-Y gastric bypass (RYGB) surgery in normoglycaemic individuals. In type 2 diabetes, RYGB improves glucose metabolism, but whether this improvement is related to the later development of PPHG is not known. We investigated the presence and mechanisms of PPHG in individuals with type 2 diabetes undergoing RYGB. METHODS: A total of 35 obese individuals with type 2 diabetes underwent an OGTT before and 24 months after surgery. PPHG was defined as a plasma glucose level of ≤3.3 mmol/l when not taking glucose-lowering agents. Insulin sensitivity was assessed by oral glucose insulin sensitivity index and beta-cell function by mathematical modelling of the plasma glucose, insulin and C-peptide concentrations. RESULTS: After surgery, PPHG occurred in 11 of 35 individuals who underwent RYGB. Before surgery, BMI was lower, glycaemic control less good and time of glucose peak earlier in the PPHG vs No PPHG group, and the duration of diabetes was shorter with PPHG (all p ≤ 0.05). In addition, insulin sensitivity was greater in the PPHG than No PPHG group (p = 0.03). After surgery, BMI and fasting glucose and insulin levels decreased similarly in the two groups; insulin secretion during the first hour of the OGTT increased more in the PPHG than No PPHG group (p = 0.04). Beta-cell glucose sensitivity increased more in individuals with PPHG than those without (p = 0.002). Over the same time interval, the glucagon-like peptide 1 (GLP-1) response was lower in individuals with PPHG before surgery (p = 0.05), and increased more after surgery. At 2 h after glucose ingestion in the OGTT, postsurgery plasma glucagon level was significantly lower in the PPHG than No PPHG group. CONCLUSIONS/INTERPRETATION: In morbidly obese individuals with type 2 diabetes, spontaneous PPHG may occur after bariatric surgery independently of a remission of diabetes. Before surgery, individuals had a shorter duration and were more insulin sensitive. Two years after surgery, these individuals developed greater beta-cell glucose sensitivity, and showed greater insulin and GLP-1 release early in the OGTT.

Multidisciplinary management of refractory insulinomas.

Insulinomas are predominantly benign (~90%), pancreatic neuroendocrine tumours characterized by hyperinsulinaemic hypoglycaemia. They usually present as a small (<2 cm), well-demarcated, solitary nodule that can arise in any part of the organ. Treatment for sporadic insulinomas is generally aimed at curative surgical resection with special consideration in genetic syndromes. Patients with significant hypoglycaemia can pose a difficult management challenge. In isolated cases where the patient is not medically fit for surgery or with metastatic spread, other treatment options are employed. Medical therapy with diazoxide or somatostatin analogues is commonly used first line for symptom control, albeit with variable efficacy. Other medical options are emerging, including newer targeted biological therapies, including everolimus (an mTOR inhibitor), sunitinib (a tyrosine kinase inhibitor) and pasireotide, a multisomatostatin receptor ligand. Pasireotide and everolimus both cause hyperglycaemia by physiological mechanisms synergistic with its antitumour/antiproliferative effects. Minimally invasive treatment modalities such as ethanol ablation are available in selected cases (particularly in patients unfit for surgery), peptide receptor radionuclide therapy (PRRT) can effectively control tumour growth or provide symptomatic benefit in metastatic disease, while cytotoxic chemotherapy can be used in patients with higher-grade tumours. This review considers the developments in the medical and other nonsurgical management options for cases refractory to standard medical management. Early referral to a dedicated neuroendocrine multidisciplinary team is critical considering the array of medical, oncological, interventional radiological and nuclear medical options. We discuss the evolving armamentarium for insulinomas when standard medical therapy fails.

Nutrient re-routing and altered gut-islet cell crosstalk may explain early relief of severe postprandial hypoglycaemia after reversal of Roux-en-Y gastric bypass.

BACKGROUND: Roux-en-Y gastric bypass is associated with an increased risk of postprandial hyperinsulinaemic hypoglycaemia, but the underlying pathophysiology remains poorly understood. We therefore examined the effect of re-routing of nutrient delivery on gut-islet cell crosstalk in a person with severe postprandial hypoglycaemia after Roux-en-Y gastric bypass. CASE REPORT: A person with severe postprandial hypoglycaemia, who underwent surgical reversal of Roux-en-Y gastric bypass, was studied before reversal and at 2 weeks and 3 months after reversal surgery using liquid mixed meal tests and hyperinsulinaemic-euglycaemic clamps. The nadir of postprandial plasma glucose rose from 2.8 mmol/l to 4.1 mmol/l at 2 weeks and to 4.4 mmol/l at 3 months after reversal. Concomitant insulin- and glucagon-like peptide-1 secretion (peak concentrations and area under the curve) clearly decreased after reversal, while concentrations of glucose-dependent insulinotropic polypeptide and ghrelin increased. Insulin clearance declined after reversal, whereas clamp-estimated peripheral insulin sensitivity was unchanged. The person remained without symptoms of hypoglycaemia, but had experienced significant weight gain at 15-month follow-up. DISCUSSION: Accelerated nutrient absorption may be a driving force behind postprandial hyperinsulinaemic hypoglycaemia after Roux-en-Y gastric bypass. Re-routing of nutrients by reversal of the Roux-en-Y gastric bypass diminished postprandial plasma glucose excursions, alleviated postprandial insulin and glucagon-like peptide-1 hypersecretion and eliminated postprandial hypoglycaemia, which emphasizes the importance of altered gut-islet cell crosstalk for glucose metabolism after Roux-en-Y gastric bypass.

Selective Arterial Calcium Stimulation with Hepatic Venous Sampling in Patients with Recurrent Endogenous Hyperinsulinemic Hypoglycemia and Metastatic Insulinoma: Evaluation in Five Patients.

Selective arterial calcium stimulation (SACST) with hepatic venous sampling was performed in 5 patients (3 female, 2 male; age range, 53-73 y) with recurrent endogenous hyperinsulinemic hypoglycemia caused by metastatic insulinoma between January 2004 and December 2014. The biochemical results of SACST confirmed functional hepatic metastases alone (n = 3), peripancreatic lymph-node and hepatic metastases (n = 1), and occult insulinoma in the pancreatic bed (n = 1), thereby helping to guide management. SACST may be useful to determine the extent of functional metastatic insulinoma, particularly within the liver, and may provide clinicians with additional information to help guide the multidisciplinary management of patients with recurrent endogenous hyperinsulinemic hypoglycemia.

The impact of glycaemic variability on the surgical patient.

PURPOSE OF REVIEW: Diabetes is the most prevalent long-term metabolic condition and its incidence continues to increase unabated. Patients with diabetes are overrepresented in the surgical population. It has been well recognized that poor perioperative diabetes control is associated with poor surgical outcomes. The outcomes are worst for those people who were not recognized as having hyperglycaemia. RECENT FINDINGS: Recent work has shown that preoperative recognition of diabetes and good communication between the clinical teams at all stages of the patient pathway help to minimize the potential for errors, and improve glycaemic control. The stages of the patient journey start in primary care and end when the patient goes home. The early involvement of the diabetes specialist team is important if the glycated haemoglobin is more than 8.5%, and advice sought if the preoperative assessment team is not familiar with the drug regimens. To date the glycaemic targets for the perioperative period have remained uncertain, but recently a consensus is being reached to ensure glucose levels remain between 108 and180 mg/dl (6.0 and 10.0 mmol/l). There have been a number of ways to achieve these - primarily by manipulating the patients' usual diabetes medications, to also allow day of surgery admission. SUMMARY: glycaemic control remains an important consideration in the surgical patient.

[Islet transplantation as a treatment for hypoglycemia unawareness syndrome. Evaluation of the pilot program and comparison with pancreas transplantation]. / Transplantace Langerhansových ostruvku v lécbe syndromu poruseného vnímání hypoglykemie. Vyhodnocení pilotního programu a porovnání s transplantací pankreatu.

Islet transplantation (ITx) started in 2005 in IKEM as a potentially safer alternative to pancreas transplantation (PTx), which so far had represented the method of choice in type-1 diabetic patients with conservatively intractable hypoglycemia unawareness syndrome. The aim of the study was to compare these two methods with regard to severe hypoglycemia elimination and to frequency of complications.Up to November 2015 a total number of 48 patients underwent ITx. The results from 22 patients with hypoglycemia unawareness were statistically analyzed. The mean number of transplanted islet equivalents was 12,096 (6,93316,705) IEQ/kg administered percutaneously in local anesthesia under radiological control to the portal vein. 44 patients underwent PTx from 1996. We evaluated glycated hemoglobin(HbA1c), insulin dose, fasting and stimulated C-peptide, frequency of severe hypoglycemia and complications. Medians (interquartile range) were analyzed using the Wilcoxon signed-rank test.One and two years after ITx, HbA1c decreased, C-peptide became significantly positive, insulin dose and frequency of severe hypoglycemia decreased and 18 % of ITx recipients were temporarily insulin-independent. Bleeding was present in 41 % of patients. One year after PTx, 73 % of patients were insulin and hypoglycemia-free, after two years 68 % of patients were insulin and hypoglycemia-free; graftectomy occurred in 20 % of recipients.Both methods led to restoration of insulin secretion and severe hypoglycemia elimination. PTx made more recipients insulin-independent at the cost of serious complications.

Reversal of Hypoglycemia Unawareness with a Single-donor, Marginal Dose Allogeneic Islet Transplantation in Korea: A Case Report.

Pancreatic islet transplantation is a physiologically advantageous and minimally invasive procedure for the treatment of type 1 diabetes mellitus. Here, we describe the first reported case of successful allogeneic islet transplantation alone, using single-donor, marginal-dose islets in a Korean patient. A 59-yr-old patient with type 1 diabetes mellitus, who suffered from recurrent severe hypoglycemia, received 4,163 islet equivalents/kg from a single brain-death donor. Isolated islets were infused intraportally without any complications. The immunosuppressive regimen was based on the Edmonton protocol, but the maintenance dosage was reduced because of mucositis and leukopenia. Although insulin independence was not achieved, the patient showed stabilized blood glucose concentration, reduced insulin dosage and reversal of hypoglycemic unawareness, even with marginal dose of islets and reduced immunosuppressant. Islet transplantation may successfully improve endogenous insulin production and glycemic stability in subjects with type 1 diabetes mellitus.

Insulinoma as rare cause of severe post-partum hypoglycemia.

Post-partum hypoglycemia in non-diabetic women is a rare condition. We report the exceptional case of a 38-year-old obese woman who experienced recurrent neuroglycopenia 3 weeks after delivery. Corresponding to severe hypoglycemia with blood glucose levels of <30 mg/dL, there was no suppression of insulin or C-peptide. Through endoscopic ultrasound we detected a hypoechoic lesion of 8 × 9 mm localized in the head of the pancreas. Thus, the diagnosis of insulinoma was most probable. Complete surgical enucleation of the insulinoma resulted in immediate and permanent resolution of hypoglycemia. The postoperative course was complicated by recurrent episodes of pancreatitis requiring endoscopic ultrasound-guided punctures of pseudocysts and temporary stenting of the pancreatic duct. In conclusion, insulinoma is a very rare, nonetheless important, differential diagnosis of post-partum hypoglycemia.

[TREATMENT OF A NEWBORN BABIES FOR AN ACUTE DISORDER OF THE BRAIN BLOOD CIRCULATION OF A HEMORRHAGIC TYPE].

A timely and adequate application of complex of conservative and surgical measures determines at large the result of treatment of a newbor babies, suffering perinatal intracranial hematoma. The treatment includes, besides neurosurgical manipulations and operations, providing of evacuation of the blood extrused, the intracranial pressure normalization, liquorocirculation restoration, correction of hemodynamical and metabolic disorders, antiedematous, membrane-stabilizing and anticonvulsant therapy. A control of metabolic disorders, as well as especially hypoglycemia, hypocalcemia, hypomagnesemia, hypopyridoxinemia constitutes a leading moment of the treatment

Magnitude and mechanisms of glucose counterregulation following islet transplantation in patients with type 1 diabetes suffering from severe hypoglycaemic episodes.

AIMS/HYPOTHESIS: Pancreatic islet transplantation stabilises glycaemic control in type 1 diabetes mellitus patients with neuroglycopoenia, despite them not achieving insulin independence because of limited graft function. However, the extent and underlying metabolic pathways of restored glucose counterregulation are unknown. We therefore compared systemic glucose turnover, including lactate gluconeogenesis (GN) and muscle glucose uptake, in individuals with type 1 diabetes who were transplant recipients with partial graft function (T1DM/ITx(+)), matched non-transplanted individuals with type 1 diabetes (T1DM/ITx(-)) and matched healthy non-diabetic individuals. METHODS: Participants (n = 12 in each group) underwent a euglycaemic and a hypoglycaemic (2.5-2.8 mmol/l) hyperinsulinaemic clamp (0.8 mU kg(-1) min(-1)) in a randomised crossover fashion. Systemic and skeletal muscle glucose and lactate kinetics were assessed using a combination of isotopic and forearm balance techniques. RESULTS: Whole-body glucose counterregulation, the difference in glucose infusion rates required to maintain the glycaemic goal between the hypoglycaemic and euglycaemic clamps, was improved in T1DM/ITx(+) (7.8 ± 1.3 µmol kg(-1) min(-1)) compared with T1DM/ITx(-) (0.3 ± 0.9 µmol kg(-1) min(-1)), but was ~45% lower than in controls (14.1 ± 2.1 µmol kg(-1) min(-1)). Increased endogenous glucose production (EGP) and decreased systemic glucose disposal accounted for 49% and 39% of glucose counterregulation in T1DM/ITx(+), respectively, compared with 60% and 36% in controls. Lactate GN increased in T1DM/ITx(+) (2.7 ± 0.4 µmol kg(-1) min(-1)) and controls (1.7 ± 0.5 µmol kg(-1) min(-1)), such that it accounted for 70% and 20% of the increased EGP, respectively. Skeletal muscle accounted for similar proportions of the decrease in systemic glucose disposal in controls (49%) and T1DM/ITx(+) (41%). CONCLUSIONS/INTERPRETATION: Partial islet graft function improves hypoglycaemia counterregulation by increasing EGP, largely via lactate GN and decreasing systemic glucose disposal. This may explain the reduction in severe hypoglycaemic events in T1DM/ITx(+) individuals. TRIAL REGISTRATION: ClinicalTrials.gov NCT01668485.

Histological insights into the pathogenesis of post-Roux-en-Y hyperinsulinaemic hypoglycaemia.

BACKGROUND: ß-cell hyperplasia has been implicated in the aetiology of post Roux-en-Y gastric bypass hyperinsulinaemic hypoglycaemia, but the pathogenesis of this condition is still unclear. CASE REPORT: We report a case of a 52-year-old man with post-Roux-en-Y gastric bypass hyperinsulinaemic hypoglycaemia who underwent distal pancreatectomy to alleviate his symptoms. Pancreatic histopathology showed chronic pancreatitis with a corresponding loss of exocrine tissue and islet retention. Amyloid deposition was found in pancreatic islets. These features are more typically associated with Type 2 diabetes. DISCUSSION: This case highlights the potential multifactorial pathogenesis of symptomatic hypoglycaemia after Roux-en-Y gastric bypass.

Hypoglycemia mediated by paraneoplastic production of Insulin like growth factor-2 from a malignant renal solitary fibrous tumor - clinical case and literature review.

BACKGROUND: Hypoglycemic episodes are infrequent in individuals without a history of diabetes mellitus or bariatric surgery. When hypoglycemia does occur in such individuals, an uncommon but important diagnosis to consider is non-islet cell tumor hypoglycemia (NICTH). We report a case of NICTH associated with paraneoplastic insulin-like growth factor-2 (IGF-2) production and review current relevant medical literature. CASE PRESENTATION: A 60 year old male with no relevant past medical history was referred to the endocrinology clinic with 18 month history of episodic hypoglycemic symptoms and, on one occasion was noted to have a fingerstick glucose of 36 mg/dL while having symptoms of hypoglycemia. Basic laboratory evaluation was unrevealing. Further evaluation however showed an elevated serum IGF-2 level at 2215 ng/mL (reference range 411-1248 ng/mL). Imaging demonstrated a large right suprarenal mass. A right nephrectomy with resection of the mass demonstrated a malignant solitary fibrous tumor. Post resection, the patient's IGF-2 levels normalized and hypoglycemic symptoms resolved. CONCLUSION: Due to the structural and biochemical homology between IGF-2 and insulin, elevated levels of IGF-2 can result in hypoglycemia. A posttranslational precursor to IGF-2 known as "big IGF" also possesses biologic activity. Review of recent reported cases of NICTH identified widespread anatomic locations and varied pathologic diagnoses of tumors associated with paraneoplastic production of IGF-2 causing hypoglycemia. Definitive management of hypoglycemia associated with paraneoplastic production of IGF-2 consists of resection of the tumor responsible for IGF-2 production. Accumulating literature provides a firm basis for routine IGF-2 laboratory evaluation in patients presenting with spontaneous hypoglycemia with no readily apparent cause.

Endogenous hyperinsulinemic hypoglycemia syndrome: surgical treatment.

BACKGROUND: The endogenous hyperinsulinemic hypoglicemia syndrome (EHHS) can be caused by an insulinoma, or less frequently, by nesidioblastosis in the pediatric population, also known as non insulinoma pancreatic hypoglycemic syndrome (NIPHS) in adults. The aim of this paper is to show the strategy for the surgical treatment of ehhs. MATERIAL AND METHODS: A total of 19 patients with a final diagnosis of insulinoma or NIPHS who were treated surgically from january 2007 until june 2012 were included. We describe the clinical presentation and preoperative work-up. Emphasis is placed on the surgical technique, complications and long-term follow-up. RESULTS: All patients had a positive fasting plasma glucose test. Preoperative localization of the lesions was possible in 89.4% of cases. The most frequent surgery was distal pancreatectomy with spleen preservation (9 cases). Three patients with insulinoma presented with synchronous metastases, which were treated with simultaneous surgery. There was no perioperative mortality and morbidity was 52.6%. Histological analysis revealed that 13 patients (68.4%) had benign insulinoma, 3 malignant insulinoma with liver metastases and 3 with a final diagnosis of SHPNI. Median follow-up was 20 months. All patients diagnosed with benign insulinoma or NIPHS had symptom resolution. CONCLUSION: The surgical treatment of EHHS achieves excellent long-term results in the control of hypoglucemic symptoms.

Glycemic variability and hypoglycemia before and after Roux-en-Y Gastric Bypass and Sleeve Gastrectomy - A cohort study of females without diabetes.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) lead to lower fasting glucose concentrations, but might cause higher glycemic variability (GV) and increased risk of hypoglycemia. However, it has been sparsely studied in patients without preoperative diabetes under normal living conditions. OBJECTIVES: To study 24-hour interstitial glucose (IG) concentrations, GV, the occurrence of hypoglycemia and dietary intake before and after laparoscopic RYGB and SG in females without diabetes. SETTING: Outpatient bariatric units at a community and a university hospital. METHODS: Continuous glucose monitoring and open-ended food recording over 4 days in 4 study periods: at baseline, during the preoperative low-energy diet (LED) regimen, and at 6 and 12 months postoperatively. RESULTS: Of 47 patients included at baseline, 83%, 81%, and 79% completed the remaining 3 study periods. The mean 24-hour IG concentration was similar during the preoperative LED regimen and after surgery and significantly lower compared to baseline in both surgical groups. GV was significantly increased 6 and 12 months after surgery compared to baseline. The self-reported carbohydrate intake was positively associated with GV after surgery. IG concentrations below 3.9 mmol/L were observed in 14/25 (56%) of RYGB- and 9/12 (75%) of SG-treated patients 12 months after surgery. About 70% of patients with low IG concentrations also reported hypoglycemic symptoms. CONCLUSIONS: The lower IG concentration in combination with the higher GV after surgery, might create a lower margin to hypoglycemia. This could help explain the increased occurrence of hypoglycemic episodes after RYGB and SG.

Refractory idiopathic non-insulinoma pancreatogenous hypoglycemia in an adult: case report and review of the literature.

CONTEXT: Non-insulinoma pancreatogenous hypoglycemia is a rare cause of spontaneous hypoglycemia in adults. The ideal diagnostic and therapeutic approach is still controversial, not least because most reported cases lack long-term follow-up. CASE REPORT: We describe the case of a 58-year-old woman, who was diagnosed with idiopathic non-insulinoma pancreatogenous hypoglycemia in 2001. After resection of 75% of the distal pancreas, she initially experienced no additional hypoglycemic episodes and did not suffer from diabetes mellitus. However, after one month, recurrent hypoglycemia occurred. After resection of the larger part of the remaining pancreatic tissue, the patient suffered from hypoglycemic as well as hyperglycemic episodes. Octreotide and diazoxide were not successful in preventing the hypoglycemic attacks, whereas continuous insulin therapy with an insulin pump helped to stabilize the blood glucose level temporarily. Finally, all remaining pancreatic tissue had to be removed. CONCLUSION: This long-term follow-up of non-insulinoma pancreatogenous hypoglycemia treatment in an adult patient indicates that lateral pancreatectomy may not be sufficient for permanent blood glucose control and emphasizes the need of follow-up data after subtotal pancreatectomy.

Adult onset nesidioblastosis treated by subtotal pancreatectomy.

CONTEXT: Nesidioblastosis is a rare cause of non insulinoma pancreatogenous hypoglycemic syndrome seen in adults. It is characterized by postprandial hypoglycemia with high insulin and C-peptide levels without any detectable pancreatic lesion. The definitive diagnosis can be made only on histopathological examination of the resected specimen. CASE REPORT: We report a case of a 50-year-old lady presenting with hypoglycemic attacks being misdiagnosed preoperatively as insulinoma and treated with enucleation leading to recurrence of symptoms after 6 months. Later medical therapy was tried which failed and patient needed subtotal pancreatectomy for resolution of symptoms. CONCLUSION: Nesidioblastosis should be suspected in patients with endogenous hyperinsulinemic hypoglycemia without any detectable pancreatic tumor on preoperative imaging.