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Aims/hypothesis Roux-en-Y gastric bypass (RYGB) improves glycaemic control in part by increasing postprandial insulin secretion through exaggerated glucagon-like peptide (GLP)-1 release. However, it is unknown whether islet cell responsiveness to i.v. glucose, non-glucose (arginine) and incretin hormones, including GLP-1, is altered. Methods Eleven severely obese glucose-tolerant individuals underwent three hyperglycaemic clamps with arginine bolus and co-infusion of either GLP-1, glucose-dependent insulinotropic polypeptide (GIP) or saline before, and at 1 week and 3 months after RYGB. In addition, an OGTT was performed before and 3 months after surgery. Results After RYGB, insulin sensitivity improved at 1 week and 3 months, while insulin stimulation and glucagon suppression in response to the clamp with saline co-infusion were largely unaltered. The influence of i.v. GLP-1 and GIP on insulin and glucagon secretion was also unchanged postoperatively. In response to the postoperative OGTT at 3 months, insulin and GLP-1, but not GIP, secretion increased. Furthermore, the glucose profile during the OGTT was altered, with a substantial reduction in 2 h plasma glucose and a paradoxical hypersecretion of glucagon. Conclusions/interpretation After RYGB, insulin hypersecretion is linked to the oral, but not the i.v., route of administration and is associated with exaggerated release and preserved insulinotropic action of GLP-1, while both the secretion and action of GIP are unchanged. The results highlight the importance of increased GLP-1 secretion for improving postoperative glucose metabolism. Trial registration ClinicalTrials.gov NCT01559779.

BackgroundEarly dumping and post-bariatric hypoglycemia (PBH) are often addressed as two separate postprandial complications after Roux-en-Y gastric bypass (RYGB). The aim of the study was to evaluate the occurrence of early dumping in RYGB-operated individuals with PBH with and without treatment intervention.MethodsEleven RYGB-operated women with documented PBH each underwent a baseline liquid mixed meal test (MMT) followed by five MMTs preceded by treatment with: acarbose 50 mg for 1 week, sitagliptin 100 mg for 1 week, verapamil 120 mg for 1 week, liraglutide 1.2 mg for 3 weeks, and pasireotide 300 μg as a single dose. Repetitive venous blood sampling and continuous electrocardiogram recordings were performed at fasting and during a 3-h postprandial period.ResultsDuring the baseline MMT, there was a significant increase in HR (from 65 ± 2 to 90 ± 4 bpm, p < 0.0001) within 30 min after meal intake, while hypoglycemia occurred in the later postprandial period. The HR increase was accompanied by significant increases in serum albumin, plasma norepinephrine, blood glucose, serum insulin, and plasma GLP-1 concentrations. The postprandial HR changes were positively correlated with the changes in insulin and GLP-1 concentrations. Treatment with acarbose and pasireotide both reduced HR, plasma norepinephrine, and serum insulin, and pasireotide also decreased plasma GLP-1.ConclusionsRYGB-operated individuals with PBH also have large early postprandial HR increases, hemoconcentration, and sympathetic activation, consistent with early dumping. Moreover, hormone excursions associated with PBH appear to be related to measures of early dumping, suggesting a causal relationship between early dumping and PBH.Trial RegistrationNCT02527993

Post-bariatric hypoglycemia (PBH) can be a serious complication after Roux-en-Y gastric bypass (RYGB), and treatment with somatostatin analogs has been suggested. We investigated the acute effects of three different doses of pasireotide (75 μg, 150 μg, and 300 μg) on the postprandial glucose metabolism in five RYGB-operated individuals with PBH using a mixed meal test. All three doses prevented hypoglycemia but were associated with a notable increase in postprandial hyperglycemia. Moreover, all doses greatly diminished insulin, C-peptide, and glucagon-like peptide-1 responses. Considering its strong hyperglycemic potential, we suggest that pasireotide should be administered carefully in RYGB-operated individuals with PBH, and if necessary, a 75 μg dose seems sufficient to prevent hypoglycemia.

Aims/hypothesis Roux-en-Y gastric bypass surgery (RYGB) improves glucose tolerance in patients with type 2 diabetes, but also changes the glucose profile in response to a meal in glucose-tolerant individuals. We hypothesised that the driving force for the changed postprandial glucose profiles after RYGB is rapid entry of glucose into the systemic circulation due to modified gastrointestinal anatomy, causing hypersecretion of insulin and other hormones influencing glucose disappearance and endogenous glucose production. Methods We determined glucose absorption and metabolism and the rate of lipolysis before and 3 months after RYGB in obese glucose-tolerant individuals using the double-tracer technique during a mixed meal. Results After RYGB, the postprandial plasma glucose profile changed, with a higher peak glucose concentration followed by a faster return to lower than basal levels. These changes were brought about by changes in glucose kinetics: (1) a more rapid appearance of ingested glucose in the systemic circulation, and a concomitant increase in insulin and glucagon-like peptide-1 secretion; (2) postprandial glucose disappearance was maintained at a high rate for a longer time after RYGB. Endogenous glucose production was similar before and after surgery. Postoperative glucagon secretion increased and showed a biphasic response after RYGB. Adipose tissue basal rate of lipolysis was higher after RYGB. Conclusions/interpretation A rapid rate of absorption of ingested glucose into the systemic circulation, followed by increased insulin secretion and glucose disappearance appears to drive the changes in the glucose profile observed after RYGB, while endogenous glucose production remains unchanged. Trial registration ClinicalTrials.gov NCT01559792. Funding The study was part of the UNIK program: Food, Fitness & Pharma for Health and Disease (see www.foodfitnesspharma.ku.dk ). Funding was received from the Novo Nordisk foundation and the Strategic Research Counsel for the Capital Area and Danish Research Agency. The primary investigator received a PhD scholarship from the University of Copenhagen, which was one-third funded by Novo Nordisk.

To examine after gastric bypass the effect of peroral versus gastroduodenal feeding on glucose metabolism. A type 2 diabetic patient was examined on 2 consecutive days 5 weeks after gastric bypass. A standard liquid meal was given on the first day into the bypassed gastric remnant and on the second day perorally. Plasma glucose, insulin, C-peptide, glucagon, incretin hormones, peptide YY, and free fatty acids were measured. Peroral feeding reduced 2-h postprandial plasma glucose (7.8 vs. 11.1 mmol/l) and incremental area under the glucose curve (iAUC) (0.33 vs. 0.49 mmol . l(-1) . min(-1)) compared with gastroduodenal feeding. beta-Cell function (iAUC(Cpeptide/Glu)) was more than twofold improved during peroral feeding, and the glucagon-like peptide (GLP)-1 response increased nearly fivefold. Improvement in postprandial glucose metabolism after gastric bypass is an immediate and direct consequence of the gastrointestinal rearrangement, associated with exaggerated GLP-1 release and independent of changes in insulin sensitivity, weight loss, and caloric restriction.

Postprandial Diabetic Glucose Tolerance Is Normalized by Gastric Bypass Feeding as Opposed to Gastric Feeding and Is Associated With Exaggerated GLP-1 Secretion A case report Carsten Dirksen , MD 1 , Dorte L. Hansen , MD, PHD 1 , Sten Madsbad , DMSC 1 , Lisbeth E. Hvolris , MD 2 , Lars S. Naver , MD 2 , Jens J. Holst , DMSC 3 and Dorte Worm , MD, PHD 1 1 Department of Endocrinology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark; 2 Department of Gastroenterology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark; 3 Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark. Corresponding author: Carsten Dirksen, cardir{at}gmail.com . Abstract OBJECTIVE To examine after gastric bypass the effect of peroral versus gastroduodenal feeding on glucose metabolism. RESEARCH DESIGN AND METHODS A type 2 diabetic patient was examined on 2 consecutive days 5 weeks after gastric bypass. A standard liquid meal was given on the first day into the bypassed gastric remnant and on the second day perorally. Plasma glucose, insulin, C-peptide, glucagon, incretin hormones, peptide YY, and free fatty acids were measured. RESULTS Peroral feeding reduced 2-h postprandial plasma glucose (7.8 vs. 11.1 mmol/l) and incremental area under the glucose curve (iAUC) (0.33 vs. 0.49 mmol · l −1 · min −1 ) compared with gastroduodenal feeding. β-Cell function (iAUC Cpeptide/Glu ) was more than twofold improved during peroral feeding, and the glucagon-like peptide (GLP)-1 response increased nearly fivefold. CONCLUSIONS Improvement in postprandial glucose metabolism after gastric bypass is an immediate and direct consequence of the gastrointestinal rearrangement, associated with exaggerated GLP-1 release and independent of changes in insulin sensitivity, weight loss, and caloric restriction. Footnotes The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Received July 27, 2009. Accepted November 9, 2009. © 2010 by the American Diabetes Association.

Abstract Aim To investigate whether Roux-en-Y gastric bypass surgery (RYGB) – an in vivo model for normalisation of hyperglycaemia – improves carotid intima-media thickness (IMT) in patients with type 2 diabetes (T2D)/impaired glucose tolerance (IGT) and normal glucose tolerance (NGT). Methods Observational prospective study, 34 obese patients (T2D (n = 14)/IGT (n = 4), and NGT (n = 16)) were investigated before and six and 12 months after RYGB. Results Mean carotid IMT was significantly reduced 12 months after RYGB in patients with T2D/IGT (− 0.041 mm (95% CI − 0.069; − 0.012, p = 0.005)) but not in patients with NGT (− 0.010 mm (− 0.039; 0.020, p = 0.52)). The between-group difference was not significant (p = 0.13). Twelve months after RYGB, patients with respectively T2D/IGT and NGT demonstrated changes in weight: − 29.9 kg, p < 0.001/− 30.6 kg, p < 0.001, HbA1c: − 0.7%, p < 0.001/− 0.1%, p = 0.33, systolic blood pressure: − 2 mmHg, p = 0.68/− 10 mmHg, p = 0.01 and diastolic blood pressure: − 8 mmHg, p = 0.003/− 11 mmHg, p < 0.001. 80% of T2D patients terminated antihyperglycaemic medication. Conclusion Mean carotid IMT was significantly reduced 12 months after RYGB in patients with T2D/IGT which provides evidence to support that the earliest atherosclerotic changes in the arterial wall are reversible. Although numerically different from the changes observed in patients with NGT, the between-group difference was not statistically significant.

To investigate whether Roux-en-Y gastric bypass surgery (RYGB) – an in vivo model for normalisation of hyperglycaemia – improves carotid intima-media thickness (IMT) in patients with type 2 diabetes (T2D)/impaired glucose tolerance (IGT) and normal glucose tolerance (NGT). Observational prospective study, 34 obese patients (T2D (n=14)/IGT (n=4), and NGT (n=16)) were investigated before and six and 12months after RYGB. Mean carotid IMT was significantly reduced 12months after RYGB in patients with T2D/IGT (−0.041mm (95% CI −0.069; −0.012, p=0.005)) but not in patients with NGT (−0.010mm (−0.039; 0.020, p=0.52)). The between-group difference was not significant (p=0.13). Twelve months after RYGB, patients with respectively T2D/IGT and NGT demonstrated changes in weight: −29.9kg, p<0.001/−30.6kg, p<0.001, HbA1c: −0.7%, p<0.001/−0.1%, p=0.33, systolic blood pressure: −2mmHg, p=0.68/−10mmHg, p=0.01 and diastolic blood pressure: −8mmHg, p=0.003/−11mmHg, p<0.001. 80% of T2D patients terminated antihyperglycaemic medication. Mean carotid IMT was significantly reduced 12months after RYGB in patients with T2D/IGT which provides evidence to support that the earliest atherosclerotic changes in the arterial wall are reversible. Although numerically different from the changes observed in patients with NGT, the between-group difference was not statistically significant.

To assess if SARS-CoV-2 (COVID-19) systemic disease can be determined by available nucleoprotein assays, we compared the performance of three commercial SARS-CoV-2 nucleoprotein (N) assays in plasma. A total of 272 plasma samples collected in the period November–December 2021 were analyzed by the methods Simoa SARS CoV‐2 N Protein Advantage Kit [Quanterix Simoa], Solsten SARS-CoV-2 Antigen enzyme immunosorbent assay (ELISA) [Solsten ELISA], and Elecsys SARS‐CoV‐2 Antigen electrochemiluminescence immunoassay [Elecsys ECLIA]. Additionally, a dilution series of inactivated virus culture was analyzed by the three assays. The SARS CoV-2 PCR-status was not known for the patients. Linear correlation in the pairwise correlation between assays as well as linearity of dilution series of inactivated virus culture was estimated by Spearman score. Sensitivity and specificity were estimated by pairwise comparison. The three assays showed poor agreement on patient samples with regards to concentration. Performance on virus culture was excellent but with different level of detection (LOD). Positive vs negative results show comparable sensitivity and specificity of Quanterix Simoa and Solsten ELISA, with a higher LOD in Elecsys ECLIA and thus lower sensitivity and high specificity. N by all tested assays can be used as a marker for systemic COVID-19 disease.

Objective: To investigate associations between age, lifestyle and erectile dysfunction (ED) in the general population and to explore associations between age, lifestyle and contact with a general practitioner (GP) regarding ED. Design: Cross-sectional web-based questionnaire study. Setting: The general Danish population. Subjects: A randomly selected sample of 48,910 men aged 20 years and older. Main outcome measures: Prevalence of ED and probability of contacting a GP regarding ED. In logistic regression models we analysed associations between age, smoking status, alcohol consumption, body mass index (BMI), and self-rated physical fitness on both ED and GP contact. Results: A total of 22,198 men (47.6%) completed the question regarding ED. The overall prevalence of ED was 19.3%, varying from 2.3% among men aged 20-29 years to 55.3% among men aged 80 years and above. 31.8% of men reporting ED had contacted a GP regarding ED. Increasing age, current or former smoking, complete alcohol abstinence or alcohol consumption above seven units per week, high BMI, and poor self-rated physical fitness were significantly associated with reporting ED. The proportion of GP contacts was significantly associated with age. Overall, no significant associations between lifestyle and healthcare seeking were observed, although lower odds of GP contact were found when physical fitness was rated as poor. Conclusion: Reporting ED and GP contact were significantly associated with age. Furthermore, lifestyle was significantly associated with reporting ED, but largely not associated with healthcare seeking. These findings are important for future interventions aiming to improve diagnosis and treatment of ED. Key points Experiencing erectile dysfunction is frequent in the general population, especially among older men.   * In this large-scale national survey, age and lifestyle were significantly associated with reporting erectile dysfunction.   * Healthcare seeking with erectile dysfunction was significantly associated with age, but not with lifestyle.   * Diagnosis and treatment of erectile dysfunction might be challenged when erectile dysfunction does not lead to healthcare seeking.