Postprandial Hypoglycemia Research Articles

Comparison of patient characteristics between East Asian and non-East Asian patients with insulin autoimmune syndrome.

Insulin autoimmune syndrome (IAS) is the third most common cause of spontaneous hypoglycaemia in Japan but very rare in the rest of the world. We aimed to identify factors, which are associated with the occurrence of IAS and which may differ between East Asian and non-East Asian patients. A PubMed search using the search terms 'insulin autoimmune syndrome' and 'Hirata disease' revealed a total of 287 reports of IAS cases, including one previously unpublished own case. Mean age (±standard deviation) was 52 ± 19 years in East Asian and 54 ± 21 years in non-East Asian patients (p > .05). In both groups, there were more females. Mean body mass index was lower in East Asian than in non-East Asian patients (23.0 ± 4.3 vs. 27.1 ± 5.6 kg/m2 , p < .0001). Postprandial hypoglycaemia was more common in non-East Asian patients (p < .05). East Asian patients took more frequently antithyroid medications and non-East Asian patients angiotensin-converting enzyme (ACE) inhibitors (both p < .0001). Graves' disease and other autoimmune diseases were more frequently observed in East Asian patients (both p < .01). Parameters of glucose metabolism were comparable in both groups, independent of diabetes diagnosis (p > .05), except for insulin that was higher in East Asian compared to non-East Asian metabolically healthy patients (p < .01). Human leukocyte antigen (HLA)-DRB1*0406 was the most frequent HLA-type in East Asian patients (p < .0001), whereas DRB1*0403 and *0404 were more frequent in non-East Asian patients (both p < .05). Non-East Asian patients received more secondary treatments, including plasmapheresis and rituximab, whereas medication discontinuation was more common in East Asian patients (all p < .05). Outcome was similar in both groups (p > .05). Factors associated with IAS markedly differ between East Asian and non-East Asian patients, with autoimmune disorders, particularly Graves' disease, antithyroid medications, and HLA-DRB1*0406 more prevalent in East Asian patients and cardiovascular and plasma cell diseases, ACE inhibitors and HLA-DRB1*0403 more prevalent in non-East Asian patients.

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.

Prevalence of Post-Glucose Challenge Hypoglycemia in Adult Patients with Cystic Fibrosis and Relevance to the Risk of Cystic Fibrosis–Related Diabetes

The clinical relevance of fasting and post-prandial hypoglycemia in patients with cystic fibrosis (CF) is poorly characterized. Our aim was to characterize the prevalence of hypoglycemia in adult patients during oral glucose tolerance test (OGTT) screening and determine its impact on the risk of developing CF-related diabetes (CFRD).

A PID Control Algorithm for a Post-Prandial Hypoglycemic Clamp Study.

Post-prandial hypoglycemia occurs 2-5 hours after food intake, in not only insulin-treated patients with diabetes but also other metabolic disorders. For example, postprandial hypoglycemia is an increasingly recognized late metabolic complication of bariatric surgery (also known as PBH), particularly gastric bypass. Underlying mechanisms remain incompletely understood to date. Besides excessive insulin exposure, impaired counter-regulation may be a further pathophysiological feature. To test this hypothesis, we need standardized postprandial hypoglycemic clamp procedures in affected and unaffected individuals allowing to reach identical predefined postprandial hypoglycemic trajectories. Generally, in these experiments, clinical investigators manually adjust glucose infusion rate (GIR) to clamp blood glucose (BG) to a target hypoglycemic value. Nevertheless, reaching the desired target by manual adjustment may be challenging and possible glycemic undershoots when approaching hypoglycemia can be a safety concern for patients. In this study, we developed a PID algorithm to assist clinical investigators in adjusting GIR to reach the predefined trajectory and hypoglycemic target. The algorithm is developed in a manual mode to permit the clinical investigator to interfere. We test the controller in silico by simulating glucose-insulin dynamics in PBH and healthy nonsurgical individuals. Different scenarios are designed to test the robustness of the algorithm to different sources of variability and to errors, e.g. outliers in the BG measurements, sampling delays or missed measurements. The results prove that the PID algorithm is capable of accurately and safely reaching the target BG level, on both healthy and PBH subjects, with a median deviation from reference of 2.8% and 2.4% respectively.Clinical relevance- This control algorithm enables standardized, accurate and safe postprandial hypoglycemic clamps, as evidenced in silico in PBH patients and controls.

Spontaneous and iatrogenic hypoglycemia in cystic fibrosis

Spontaneous episodes of hypoglycemia can occur in people with cystic fibrosis (CF) without diabetes, who are not on glucose lowering medications. Spontaneous hypoglycemia in CF could occur both in the fasting or postprandial state (reactive hypoglycemia). The pathophysiology of fasting hypoglycemia is thought to be related to malnutrition and increased energy expenditure in the setting of inflammation and acute infections. Reactive hypoglycemia is thought to be due to impaired first phase insulin release in response to a glucose load, followed by a delayed and extended second phase insulin secretion; ineffective counterregulatory response to dropping glucose levels may also play a role. The overall prevalence of spontaneous hypoglycemia varies from 7 to 69% as examined with oral glucose tolerance test (OGTT) or with continuous glucose monitoring (CGM) under free living conditions. Spontaneous hypoglycemia in CF is associated with worse lung function, higher hospitalization rates, and worse clinical status. In addition, patients with CF related diabetes on glucose-lowering therapies are at risk for iatrogenic hypoglycemia. In this article, we will review the pathophysiology, prevalence, risk factors, clinical implications, and management of spontaneous and iatrogenic hypoglycemia in patients with CF.

POST-GASTRIC BYPASS HYPERAMMONEMIC ENCEPHALOPATHY: A RARE AND POTENTIALLY FATAL CAUSE OF ENCEPHALOPATHY IN THE ICU

TOPIC: Critical Care TYPE: Fellow Case Reports INTRODUCTION: In the US the prevalence of obesity has risen to 39.8% and affected about 93.3 million of US adults in 2015. Morbidly obese patients are increasingly pursuing bariatric surgery. While the benefits of bariatric surgery are numerous, it is important to recognize and understand the short term and long term postoperative complications. Hyperammonemic syndrome is an uncommon but severe complication of gastric bypass surgery. CASE PRESENTATION: A 43 year old woman with history of non-alcoholic fatty liver disease and history of prior gastric sleeve which was followed by Roux-en-Y Gastric Bypass (RYGB) surgery was admitted for shortness of breath and altered mental status. On hospital day number 10 patient was transferred to ICU for altered mental status, worsening hypoxia, retroperitoneal bleed and septic shock. Patient was subsequently intubated, given transfusions, placed on vasopressors, and given broad-spectrum antibiotics. After 72 hours her overall shock resolved and her ventilator requirements were minimal, but she remained in a comatose state. Initial workup including CT head and brain MRI were unremarkable. Initial routine EEG was consistent with low voltage delta frequencies which could be seen in the setting of severe encephalopathy. Ammonia level had risen to 169 umol/L, which was significantly elevated from prior level of 81 umol/L on admission (Table 1). In addition to aggressive treatment with lactulose and rifaximin, multiple supplements were added, including: Zinc, multivitamin, and L-carnitine. Subsequent EEG on ICU revealed myoclonic status epilepticus for which antiepileptic drugs were given. Repeat MRI of the brain revealed increased diffusion-weighted signal intensity within the cortex and subcortical white matter of suggesting hypoxic and anoxic brain injury. DISCUSSION: Hyperammonemic syndrome related to bariatric surgery is characterized by hyperammonemia, elevated plasma glutamine, hypoalbuminemia, reactive hypoglycemia, nutritional deficiencies of essential amino acids, and low zinc levels, in the absence of overt liver fibrosis or evidence of significant hepatocellular injury (1). The mortality rate approaches 50% and it tends to occur at a high rate in women (1). Patients may present with irritability, vomiting, ataxia, mental retardation, lethargy, and eventually alteration in consciousness and coma (1). There are multiple genetic and nongenetic hypothesized mechanisms (Table 2). Treatment strategies for hyperammonemia include: lactulose, rifaximin, repletion of deficient amino acids, zinc, micro nutrients, and prevention of seizures and cerebral edema (2). CONCLUSIONS: It is important to consider hyperammonemia related to bypass as a potential etiology for neurologic changes in patients with prior bypass, especially in the ICU setting where multiple etiologies can cause encephalopathy and hyperammonemia. REFERENCE #1: Fenves, A. et al. "Hyperammonemic Syndrome After Roux-En-Y Gastric Bypass." Obesity Journal. Volume 23. Number 4. 2015. REFERENCE #2: Krishnan P, Ramdas P, Landsberg. "Bariatric Surgery causing hyperammonemia." Cureus 11 (7): e5098. DOI 10.7759/cureus.5098. July 8, 2019 DISCLOSURES: No relevant relationships by SOHAIB KHAN, source=Web Response No relevant relationships by Jessica Nash, source=Web Response No relevant relationships by Mehul Patel, source=Web Response No relevant relationships by Mena Tawfik, source=Web Response

Dietary obesity and glycemic excursions cause a parallel increase in STEAP4 and pro-inflammatory gene expression in murine PBMCs.

The balance between pro-atherogenic and anti-atherogenic factors is very crucial in thedevelopmentof atherosclerotic lesions. Although the expression of the six-transmembrane epithelial antigen of the prostate 4 (STEAP4) in myeloid cells is known to be atheroprotective,there is not a single study reporting on the status of STEAP4 expression in circulating monocytes in the early stages of diet-induced obesity or in events of glycemic excursions. We induced glycemic spikes twice daily for a 1-week duration to rats fed on regular chow and western diet, and analyzed gene expression changes in the peripheral blood mononuclear cells (PBMCs).We also conducted experiments on RAW 264.7 cells to gain insight into some of our in vivo findings. Diet-induced obesity and glycemic excursions independently caused a significant increase in STEAP4 mRNA expression in PBMCs.This was also accompanied by an induction of a substantial number of pro-inflammatory cytokines, chemokines, and chemokine receptors.However, the combined effect of western diet and hyperglycemic spikes was subtle and non-additive.In the in vitro setting, either glucose spikes, persistent hyperglycemia,or a combination of palmitic acid and insulin resulted in a parallel increase in expression of STEAP4 and pro-inflammatory genes.This was, however, significantly abrogated with 4-octyl itaconate or attenuated by inhibitors of p38MAPK and NF-kB. STEAP4 expression in mononuclear cells is induced by increasing inflammation or oxidative stress.The observed increase in STEAP4 expression in circulating monocytes due to visceral obesity or glycemic excursions is a compensatory response. The online version contains supplementary material available at 10.1007/s13340-021-00542-1.

Постпрандіальний гіпоглікемічний синдром

Постпрандіальний гіпоглікемічний синдром, або реактивна гіпоглікемія, — вегетативні симптоми, такі як слабкість, втома, голод, нудота, серцебиття, занепокоєння, тремор, пітливість, що виникають через одну-дві години після прийому їжі. Синдром досить слабо висвітлений у літературі, більшість відомостей є розрізненими. Лабораторні критерії діагностики постпрандіальної реактивної гіпоглікемії досить контроверсивні, але більшість авторів схиляються до того, що це рівень глюкози крові нижче тощакової або ≤ 3,9 ммоль/л протягом двох годин після прийому їжі. Гіпоглікемія є результатом дисбалансу між надходженням глюкози в кров (від ендогенної продукції глюкози або екзогенної доставки) і використанням глюкози тканинами. Баланс між надходженням і витрачанням глюкози контролюється складною рівновагою глікорегулюючих гормонів. Інсулін, глюкагон і адреналін діють протягом кількох хвилин, а кортизол і гормон зросту — кілька годин. Це пояснює наявність негайних і відстрочених різноманітних ефектів: адренергічного, нейроглікопенічного, гастроінтестинального дискомфорту. Відомо, що в генезі постпрандіального синдрому лежать механізми, подібні до постгастректомічних у пацієнтів, оперованих з приводу морбідного ожиріння. Найбільш імовірним чинником формування реактивної гіпоглікемії є постпрандіальна гіперсекреція інсуліну під впливом глюкози і глюкагоноподібного пептиду (GLP-1), що є компонентом ентероендокринної системи, основна дія якого спрямована на цефалічну фазу формування насичення. Як у оперованих пацієнтів, так і у відносно здорових осіб симптоми виникають після прийому їжі, багатої простими вуглеводами. Симптоми досить ефективно лікуються прийомом їжі з вживанням вуглеводів із низьким глікемічним індексом і харчовими волокнами. При недостатності ефекту використовують препарати акарбози, інгібуючої α-глюкозидази тонкого кишечника, що є основним стимулом для секреції GLP-1. Таким чином, при епідемічній швидкості поширення ожиріння в умовах неадекватних харчових пріоритетів у дитячій популяції ймовірність значної поширеності постпрандіального синдрому досить вірогідна, що вимагає додаткового дослідження. При цьому зниження в раціоні простих вуглеводів може істотно поліпшити якість життя дітей із постпрандіальним дискомфортом.

Cardiovascular Adverse Outcomes as Challenges on Glycemic Variability Among Patients with Type 2 Diabetes on Intensive Insulin Therapy: The Role of Medical Nutrition Therapy with Automatic Snacking

The glycemic variability (GV) is the fluctuation of the blood glucose (BG) in relation to the daily mean BG or mean glycosylated hemoglobin (HbA1c). BG oscillations can be influenced by the type of food and timing of intake, activity, psychological condition (fear of hypoglycemia), and systemic hormonal cross-talking between insulin and glucagon. Pharmacologically, these BG oscillations can be affected by the regulators of insulin secretion like sulfonylurea and insulin. The increase in GV with very high and very low BG excursions has been associated with the development of macrovascular and microvascular complications among type 2 diabetes mellitus (DM) patients. Increased mortality has been demonstrated in the past among elderly patients on intensive insulin therapy due to severe hypoglycemia. Prompt intake of glucose has obviously compromised glycemic control and worsens the GV. Automatic snacking (AS) as a part of medical nutrition therapy (MNT) is the provision of snacks 2 h after meals which are taken even in the absence of hunger. This review will showcase our published papers among patients with type 2 DM where AS was instituted to obtain long-term glycemic control and prevent the occurrence of fatal postprandial hypoglycemia. Although, further research is needed, AS is a promising dietary management to address GV in type 2 DM patients on intensive insulin therapy.

Autoimmune hypoglycaemia: a narrative review from the laboratory perspective

: Whilst hypoglycaemia is common, autoimmune causes are relatively rare. Autoimmune causes of hypoglycaemia includes both insulin autoimmune syndrome (IAS), and type B insulin resistance syndrome (TBIR). IAS typically presents with post-prandial hypoglycaemia in adulthood and is characterised by inappropriately high plasma insulin, proinsulin and C-peptide concentrations during hypoglycaemia, with C-peptide:insulin molar ratios of <1, high insulin autoantibody titres and the presence of macroinsulin. TBIR typically presents with hyperglycaemia due to insulin resistance as a result of insulin receptor antibodies. TBIR may, however, also present with endogenous hyperinsulinaemic hypoglycaemia or hyperglycaemia-hypoglycaemia depending on the activating or inhibiting action of the insulin receptor antibodies. Very rarely, autoimmune hypoglycaemia may be due to insulin antibodies raised to therapeutic insulin or insulin-binding paraproteins with purported mechanisms similar to IAS in producing hypoglycaemia. This review summarises the pathophysiology and laboratory features of IAS and TBIR, and highlights the importance of considering these diagnoses in patients with hypoglycaemia associated with non-suppressed insulin levels, to prevent unnecessary pancreatic surgery.

Glucagon-like Peptide-1 Receptor as Emerging Target: Will It Make It to the Clinic?

The glucagon-like peptide-1 receptor (GLP-1R) is an emerging target due to its high expression in benign insulinomas as well as in islet cell hypertrophia/hyperplasia (nesidioblastosis) and pancreatic β-cells. In 2008, occult insulinomas were localized for the first time in men using the metabolically stable radiolabeled glucagon-like peptide-1 (GLP-1) agonist [Lys40(Ahx-DTPA-111In)NH2]-exendin-4 (111In-DTPA-exendin-4). Afterward, several radiopharmaceuticals for GLP-1R PET/CT imaging were synthesized and evaluated, for example, [Nle14,Lys40(Ahx-DOTA-68Ga)NH2]-exendin-4 (68Ga-DOTA-exendin-4), [Cys40(MAL-NOTA-68Ga)NH2]-exendin-4 (68Ga-NOTA-exendin-4), and [Lys40(NODAGA-68Ga)NH2]-exendin-4 (68Ga-NODAGA-exendin-4). Several prospective comparison studies provided evidence that GLP-1R PET/CT is significantly more sensitive than contrast-enhanced MRI (ceMRI), contrast-enhanced CT (ceCT), GLP-1R SPECT/CT, somatostatin receptor PET/CT, and SPECT/CT in the detection of benign insulinomas, and insulinomas in the context of multiple endocrine neoplasia type 1. As a result, the European Neuroendocrine Tumor Society guidelines recommend GLP-1R imaging or selective intraarterial calcium stimulation and venous sampling (ASVS) in patients for whom there is a clinical suspicion of having an insulinoma but who have a negative ceMRI/ceCT or negative endoscopic ultrasound. Furthermore, there is growing evidence that GLP-1R PET/CT can visualize and localize adult nesidioblastosis. This is clinically relevant as the distinction between focal and diffuse nesidioblastosis is critical in directing a therapeutic strategy in these patients. Prospective studies have proven the clinical relevance of GLP-1R imaging as it is often the only imaging modality able to localize the insulinoma or nesidioblastosis. It is therefore likely that this noninvasive imaging modality will replace the invasive localization of insulinomas using ASVS. More experimental indications for GLP-1R imaging include the diagnosis of an insulinoma/nesidioblastosis in patients with postprandial hypoglycemia after bariatric bypass surgery and monitoring β-cells in patients with brittle type 1 diabetes after islet-cell transplantation. We believe that these indications and possibly future indications will bring GLP-1R imaging to the clinic.

Age-dependent transition from islet insulin hypersecretion to hyposecretion in mice with the long QT-syndrome loss-of-function mutation Kcnq1-A340V

Loss-of-function (LoF) mutations in KCNQ1, encoding the voltage-gated K+ channel Kv7.1, lead to long QT syndrome 1 (LQT1). LQT1 patients also present with post-prandial hyperinsulinemia and hypoglycaemia. In contrast, KCNQ1 polymorphisms are associated with diabetes, and LQTS patients have a higher prevalence of diabetes. We developed a mouse model with a LoF Kcnq1 mutation using CRISPR-Cas9 and hypothesized that this mouse model would display QT prolongation, increased glucose-stimulated insulin secretion and allow for interrogation of Kv7.1 function in islets. Mice were characterized by electrocardiography and oral glucose tolerance tests. Ex vivo, islet glucose-induced insulin release was measured, and beta-cell area quantified by immunohistochemistry. Homozygous mice had QT prolongation. Ex vivo, glucose-stimulated insulin release was increased in islets from homozygous mice at 12–14 weeks, while beta-cell area was reduced. Non-fasting blood glucose levels were decreased at this age. In follow-up studies 8–10 weeks later, beta-cell area was similar in all groups, while glucose-stimulated insulin secretion was now reduced in islets from hetero- and homozygous mice. Non-fasting blood glucose levels had normalized. These data suggest that Kv7.1 dysfunction is involved in a transition from hyper- to hyposecretion of insulin, potentially explaining the association with both hypoglycemia and hyperglycemia in LQT1 patients.

51-OR: Driving Performance after Intake of Glucose vs. Aspartame in Patients with Postprandial Hypoglycemia following Gastric Bypass Surgery

Background: Due to the high rate of asymptomatic patients, the impact of postprandial hypoglycemia after bariatric surgery (PBH) on daily activities such as driving remains controversial. We sought to assess driving performance in patients with PBH.Methods: In a random single-blind crossover study, 10 active drivers with PBH (2 males, age 38±15years, BMI 27.2±4.6kg/m2, gastric bypass 5±2years ago) ingested 75g glucose (GLU) to induce hypoglycemia or aspartame (ASP). A simulator was driven during 10min before and at 20 (D1), 80 (D2), 125 (D3) and 140min (D4) after GLU/ASP, reflective of expected blood glucose (BG) increase (D1), decrease (D2), and hypoglycemia (D3 and D4). Seven driving features (traffic violations and high accelerations) were integrated in a Bayesian hierarchical regression model to assess altered driving performance in GLU vs. ASP.Results: Mean peak and nadir BG after GLU were 182±24 and 47±14mg/dl, respectively. BG was stable after ASP (85±4mg/dl). Driving performance differed between GLU and ASP at times of hypoglycemia (Figure 1), particularly D4, whereas no differences were found for D1 and D2. The posterior probability for impaired driving after GLU was 16% in D1, 82% for D2, 81% for D3 and 98% for D4.Conclusion: Our findings suggest impaired driving performance during PBH.View largeDownload slideView largeDownload slide DisclosureA. Tripyla: None. V. Lehmann: None. D. Herzig: None. J. Meier: None. N. Banholzer: None. M. Maritsch: None. S. Feuerriegel: None. F. Wortmann: None. L. Bally: None.FundingSwiss National Science Foundation (PCEGP3_186978, CRSII5_183569, PCEGP1_186932); Dexcom, Inc. (OUS-2020-014)

134-OR: Comparison of Glucose-Insulin Homeostasis in People with Postprandial Hypoglycemia after Gastric Bypass Surgery and Nadir Plasma Glucose &amp;lt;50 mg/dl vs. &amp;gt;50 mg/dl

Background: Mechanisms of postprandial hypoglycemia following gastric bypass (GB) surgery (PBH), remain incompletely understood. Thus, we aimed to assess the role of insulin secretion/beta-cell function (BCF), fractional hepatic insulin extraction (HE), insulin sensitivity (SI) and rate of glucose appearance (Ra) in patients with biochemically moderate and severe hypoglycemia. Methods: A total of 23 subjects with PBH (mean±SD age 41±12 years, BMI 28.1±6.1 kg/m2, 6.0±2.5 years since GB surgery) underwent an oral glucose tolerance test (75g of glucose), with frequent blood sampling for determination of glucose, insulin and C-peptide concentrations for up to 180minutes. Indices of BCF, HE, SI and Ra were calculated using the oral minimal model method and compared between subjects with nadir plasma glucose during the test below (severe hypo) and above 50mg/dL (moderate hypo). Results: Mean±SD nadir glucose was 43.3±6.0mg/dL in the severe hypo group and 60.1±9.1mg/dL in the moderate hypo group. Differences between the groups were found for indices of BCF, HE and Ra, whereas no significant differences were observed for SI (Figure 1). Conclusion: Present findings confirm three candidate mechanisms involved in PBH: increased BCF, diminished HE and faster Ra. Disclosure D. Herzig: None. M. Schiavon: None. A. Tripyla: None. V. Lehmann: None. J. Meier: None. S. Jainandunsing: None. C. Dalla man: Research Support; Self; Becton, Dickinson and Company, Sanofi-Aventis Deutschland GmbH. L. Bally: None. Funding Swiss National Science Foundation (PCEGP3_186978); Italian Ministry of Education, University and Research (Law 232/2016); University of Padova; Diabetes Center Berne

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 …

Severe postprandial hypoglycemia as a possible sequel of COVID-19

Severe postprandial hypoglycemia as a possible sequel of COVID-19

Glycemic Patterns Are Distinct in Post-Bariatric Hypoglycemia After Gastric Bypass (PBH-RYGB).

Severe hypoglycemia with neuroglycopenia, termed post-bariatric hypoglycemia (PBH). typically occurs postprandially, but it is also reported after activity or mid-nocturnally. To quantify glycemia, glycemic variability, and magnitude/duration of low sensor glucose (SG) values in patients with PBH after Roux-en-Y gastric bypass (PBH-RYGB). This retrospective analysis of data from an academic medical center included individuals with PBH-RYGB (n = 40), reactive hypoglycemia without gastrointestinal surgery (Non-Surg Hypo, n = 20), prediabetes (Pre-DM, n = 14), newly diagnosed T2D (n = 5), and healthy controls (HC, n = 38). Masked continuous glucose monitoring (Dexcom G4) was used to assess patterns over 24 hours, daytime (6 am-midnight) and nighttime (midnight-6 am). Prespecified measures included mean and median SG, variability, and percent time at thresholds of sensor glucose. Mean and median SG were similar for PBH-RYGB and HC (mean: 99.8 ± 18.6 vs 96.9 ± 10.2 mg/dL; median: 93.0 ± 14.8 vs 94.5 ± 7.4 mg/dL). PBH-RYGB had a higher coefficient of variation (27.3 ± 6.8 vs 17.9 ± 2.4%, P < 0.0001) and range (154.5 ± 50.4 vs 112.0 ± 26.7 mg/dL, P < 0.0001). Nadir was lowest in PBH-RYGB (42.5 ± 3.7 vs HC 49.0 ± 11.9 mg/dL, P = 0.0046), with >2-fold greater time with SG < 70 mg/dL vs HC (7.7 ± 8.4 vs 3.2 ± 4.1%, P = 0.0013); these differences were greater at night (12.6 ± 16.9 vs 1.0 ± 1.5%, P < 0.0001). Non-Surg Hypo also had 4-fold greater time with SG < 70 at night vs HC (SG < 70: 4.0 ± 5.9% vs 1.0 ± 1.5%), but glycemic variability was not increased. Patients with PBH-RYGB experience higher glycemic variability and frequency of SG < 70 compared to HC, especially at night. These data suggest that additional pathophysiologic mechanisms beyond prandial changes contribute to PBH.

An Atypical Presentation of a Patient With Postprandial Hypoglycemic Induced Seizures

Abstract Background: Insulinomas are exceptionally uncommon pancreatic islet cell neuroendocrine tumors. Typically, insulinoma induced hypoglycemia occurs exclusively in the fasting state in 73 percent, reported in a retrospective analysis of 237 patients, whereas 6 percent reported only postprandial symptoms. Clinical Case: A 53-year-old female with a history of rheumatoid arthritis, obesity, and prediabetes initially admitted for new onset seizures and recurrent spontaneous hypoglycemic episodes. She experienced recurrent, symptomatic, post-prandial, hypoglycemia daily for the past 8 years. Each episode was closely associated with a high carbohydrate meal, inducing a post-prandial hypoglycemia more consistently and more profoundly than intermittent fasting. Symptoms of lightheadedness, shakiness, and seizure were exacerbated by each carbohydrate meal. Initial labs revealed serum glucose of 35 mg/dl. After recovery with dextrose infusion, a brief fasting trial less than 24 hours was performed with no recurrence of hypoglycemia. However, a mixed meal study utilizing watermelon resulted in a postprandial serum hypoglycemia of 28 mg/dl, provoking a seizure within 30 minutes. During her hospitalization, recurrent hypoglycemia was found during the postprandial period rather than intermittent fasting periods requiring dextrose infusion and octreotide. A Hypoglycemia panel sent during the initial episode was consistent with endogenous hyperinsulinism (Serum glucose=35, Insulin level=24, Proinsulin=166, C-peptide=0.9, BHB=undetectable, Sulfonurea=negative). A subsequent CT of the abdomen/pelvis revealed a mass associated with the pancreatic tail, measuring 4.1 x 4.4 x 5.2 cm concerning for pancreatic malignancy. A fine needle aspiration followed by a distal pancreatectomy and splenectomy with histopathological and immuno-histochemical evaluation confirming a well differentiated (grade 1), 5.0 x 4.5 x 3.0 cm, neuroendocrine tumor (insulinoma). Her recovery, post-operatively, was complicated by an intraabdominal abscess, left pleural effusion, necessitating insulin therapy for hyperglycemia believed to be secondary to morbid obesity, weight gain, and insulin resistance. Hypoglycemic symptoms resolved, blood glucose normalized, and insulin therapy was weaned over the following 3 months and she remains on metformin to date with no evidence of recurrence. Conclusion: Although rare, an insulinoma should be considered in the differential diagnosis of any individual with recurrent episodes of frequent symptomatic hypoglycemia. The classical clinical manifestation of an insulinoma is a fasting hypoglycemia, with distinct episodes of autonomic symptoms. However, postprandial symptoms have been reported with increasing frequency. Here we present a case of surgically confirmed insulinoma with predominantly post-prandial hypoglycemia.

Metastatic Insulinoma Presenting With Post-Prandial Hypoglycemia

Background: Patients with an insulinoma, a type of pancreatic neuroendocrine tumor, typically present with fasting hypoglycemia (1). Occurrence of exclusively postprandial hypoglycemia as a result of a predominantly proinsulin-secreting metastatic neuroendocrine tumor is rare (2).Clinical Case: A 69-year-old man presented with episodes of postprandial blurry vision, sweating and confusion for the last two years that were becoming more frequent over the last several weeks. Self-monitoring of blood glucose at home revealed postprandial hypoglycemia (45-70mg/dl) and symptoms were consistent with Whipple’s triad. Continuous glucose monitoring over 14-days via Dexcom G6 showed no nocturnal or fasting hypoglycemia and revealed only postprandial hypoglycemia within one-two hours after meals. Laboratory measurements were performed at 8am in fasting state which revealed a blood glucose of 97mg/dl, insulin level 7.8 µIU/ml (2-21 µIU/ml), c-peptide 1.67 ng/ml (1.1-4.4 ng/ml) and elevated proinsulin level of 39 pmol/l (<8.0 pmol/l). An outpatient fast was conducted in the clinic, and when serum blood glucose dropped to 47mg/dL (21 hours after the initiation of the fast), insulin (6 µIU/ml) and c-peptide (2.0ng/ml) levels were detectable with an elevated proinsulin (20.8pmol/L) level. CT abdomen and pelvis showed a 1.6cm hyperenhancing lesion in the distal body of the pancreas. He underwent endoscopic ultrasonography with fine-needle aspiration, confirming the diagnosis of a pancreatic neuroendocrine tumor. Distal pancreatectomy and splenectomy were performed to resect the tumor which led to resolution of his symptoms. Pathology revealed a low grade well-differentiated neuroendocrine tumor with lymphovascular invasion and regional lymph node metastases.Conclusion: Pancreatic neuroendocrine tumor should be considered in post-prandial hypoglycemia, even in the absence of fasting hypoglycemia. Measuring proinsulin is essential in the diagnostic workup of insulinoma causing hypoglycemia

Management of Late Dumping Syndrome Induced Hypoglycemia With GLP-1R Agonist

Background: Late dumping syndrome is a prominent post-bariatric surgery side effect. Glucose-dependenthyperinsulinemia, induced by elevated gastric inhibitory polypeptide (GIP) and glucagon-likepeptide-1 (GLP-1) levels, leading to 2–3 hours post-prandial hypoglycemia. In literature, several managements are available: dietary changes, glucosidase inhibitor, andsomatostatin analogues. In case of failure of those strategies, partial or total pancreatectomy isindicated. Recently, management using GLP-1R agonists showed promising effect inmanagement of late dumping syndrome induced post-prandial hypoglycemia. (1)AimThe aim of this study was to investigate the effect of using GLP-1R agonists w/o low glycemicindex diet for treating dumping syndromes induced post-prandial hypoglycemia in post bariatricsurgery patients. Methods: A sample of 27 cases (25 females, 2 males) mean age 44.64, SD 10.2 of post-bariatric surgerywere managed using GLP-1R w/o low-glycemic index diet after being diagnosed with the latedumping syndrome induced post-prandial hypoglycemia for duration 1–3 years post-surgery. The27 were sent a survey of 13 questions related to their experience pre-and post-management plan. Results: Out of the 27 patients, 15 responded to the survey. The results showed 100% of the participantsdeveloped episodes of severe symptomatic late dumping syndrome with hypoglycemiasymptoms diagnosed after one and half years of their symptoms. 87% of them experiencedhypoglycemia post meals 2–3 hours.70 % of the participants got hypoglycemia more than 5episodes per week (less than 4.0 mmol/l) which was confirmed by blood glucose monitoring. After starting treatment with GLP-1R agonists with or without low-glycemic index diet, 87% ofthe participants reported that the hypoglycemia episodes were reduced. Out of those 87%participants 46% did not get any hypoglycemia episode and 54% of them experienced 1–2 timeshypoglycemia episodes. Conclusion: The results of the survey showed the successful reduction or prevention of late dumpinghypoglycemia episodes frequency post-bariatric surgery by GLP 1R agonist with or without lowglycemicindex diet.