Background & Aims Post-prandial glycemia excursions increase after gastric bypass surgery; this effect is even greater among individuals with recurrent hypoglycemia (blood glucose levels <50 mg/dL). These patients also have increased post-prandial levels of insulin and glucagon-like peptide 1 (GLP1). We performed a clinical trial to determine the role of GLP1 in post-prandial glycemia in patients with hyperinsulinemic hypoglycemia syndrome after gastric bypass. Methods Nine patients with recurrent hypoglycemia after gastric bypass (H-GB), 7 asymptomatic individuals with previous gastric bypass (A-GB), and 8 non-diabetic subjects who did not receive surgery (controls) were studied with a mixed-meal tolerance test (350 kcal) using a dual glucose tracer method on 2 days. On 1 day they received continuous infusion of GLP-1 receptor (GLP1R) antagonist, exendin-(9–39) (Ex-9), and on the other day, a saline control. Glucose kinetics and islet and gut hormone responses were measured before and after the meal. Results Infusion of Ex9 corrected hypoglycemia in all H-GB individuals. The reduction of post-prandial insulin secretion by Ex9 was greater in the H-GB group than other groups (H-GB, 50%±8%; A-GB, 13%±10%; and controls, 14%±10%) (P<.05). Meal-derived glucose (RaOral) was significantly greater among subjects who had undergone gastric bypass than controls, and in H-GB patients compared with A-GB subjects. Ex9 shortened the time to peak RaOral in all groups without any significant effect on the overall glucose flux. Post-prandial glucagon levels were higher among patients who had undergone gastric bypass than controls, and increased with Ex9 administration. Conclusions Hypoglycemia following gastric bypass can be corrected by administration of a GLP1R antagonist, which might be used to treat this disorder. These findings are consistent with reports that increased GLP1 activity contributes to hypoglycemia following gastric bypass. ClinicalTrials.gov number, NCT01803451

OBJECTIVEGastric bypass (GB) surgery is associated with postprandial hyperinsulinemia, and this effect is accentuated in postsurgical patients who develop recurrent hypoglycemia. Plasma levels of the incretin glucagon-like peptide 1 (GLP-1) are dramatically increased after GB, suggesting that its action contributes to alteration in postprandial glucose regulation. The aim of this study was to establish the role of GLP-1 on insulin secretion in patients with GB.RESEARCH DESIGN AND METHODSTwelve asymptomatic individuals with previous GB (Asym-GB), 10 matched healthy nonoperated control subjects, and 12 patients with recurrent hypoglycemia after GB (Hypo-GB) had pre- and postprandial hormone levels and insulin secretion rates (ISR) measured during a hyperglycemic clamp with either GLP-1 receptor blockade with exendin-(9–39) or saline.RESULTSBlocking the action of GLP-1 suppressed postprandial ISR to a larger extent in Asym-GB individuals versus control subjects (33 ± 4 vs.16 ± 5%; P = 0.04). In Hypo-GB patients, GLP-1 accounted for 43 ± 4% of postprandial ISR, which was not significantly higher than that in Asym-GB subjects (P = 0.20). Glucagon was suppressed similarly by hyperglycemia in all groups but rose significantly after the meal in surgical individuals but remained suppressed in nonsurgical subjects. GLP-1 receptor blockade increased postprandial glucagon in both surgical groups.CONCLUSIONSIncreased GLP-1–stimulated insulin secretion contributes significantly to hyperinsulinism in GB subjects. However, the exaggerated effect of GLP-1 on postprandial insulin secretion in surgical subjects is not significantly different in those with and without recurrent hypoglycemia.

Hypoglycemia, occurring after gastric bypass surgery, is challenging for patients and physicians alike. This review provides a systematic approach to diagnosis and treatment based on the underlying pathophysiology.

ImportanceSARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals.ObjectiveTo develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections.Design, Setting, and ParticipantsProspective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling.ExposureSARS-CoV-2 infection.Main Outcomes and MeasuresPASC and 44 participant-reported symptoms (with severity thresholds).ResultsA total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months.Conclusions and RelevanceA definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.

Among GB subjects with a clinical history of hypoglycemia, hyperinsulinemia is the result of inappropriate insulin secretion and reduced insulin clearance. In subjects with symptoms of postprandial hypoglycemia, insulin secretion is higher in the latter stages of meal glucose clearance, and despite elevated meal-induced glucagon, there is no further response to hypoglycemia. These abnormalities in islet function are most pronounced in subjects who report neuroglycopenic symptoms.