Publications by authors named "Linda Hilsted"

71 Publications

Humoral response to two doses of BNT162b2 vaccination in people with HIV.

J Intern Med 2021 Nov 28. Epub 2021 Nov 28.

Viro-Immunology Research Unit, Department of Infectious Diseases, Section 8632, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark.

Background: People with HIV (PWH) are at increased risk of severe COVID-19. We aimed to determine humoral responses in PWH and controls who received two doses of BNT162b2.

Methods: In 269 PWH and 538 age-matched controls, we measured IgG and neutralizing antibodies specific for the receptor-binding domain of SARS-CoV-2 at baseline, 3 weeks and 2 months after the first dose of BNT162b2.

Results: IgG antibodies increased from baseline to 3 weeks and from 3 weeks to 2 months in both groups, but the concentrations of IgG antibodies were lower in PWH than that in controls at 3 weeks and 2 months (p = 0.025 and <0.001), respectively. The IgG titres in PWH with a humoral response at 2 months were 77.9% (95% confidence interval [62.5%-97.0%], age- and sex-adjusted p = 0.027) of controls.

Conclusions: Reduced IgG antibody response to vaccination with BNT162b2 was found in PWH, and thus increased awareness of breakthrough infections in PWH is needed.
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http://dx.doi.org/10.1111/joim.13419DOI Listing
November 2021

The Accuracy of Hemoglobin A1c and Fructosamine Evaluated by Long-Term Continuous Glucose Monitoring in Patients with Type 2 Diabetes Undergoing Hemodialysis.

Blood Purif 2021 Sep 28:1-9. Epub 2021 Sep 28.

Department of Nephrology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

Introduction: The accuracy of hemoglobin A1c (HbA1c) as a glycemic marker in patients with type 2 diabetes (T2D) receiving hemodialysis (HD) remains unknown. To assess accuracy, we compared HbA1c and fructosamine levels with interstitial glucose measured by continuous glucose monitoring (CGM) in patients with T2D receiving HD.

Methods: Thirty patients in the HD group and 36 patients in the control group (T2D and an estimated glomerular filtration rate >60 mL/min/1.73 m2) completed the study period of 17 weeks. CGM (Ipro2®, Medtronic) was performed 5 times for periods of up to 7 days (with 4-week intervals) during a 16-week period. HbA1c (mmol/mol), the estimated mean plasma glucose from HbA1c (eMPGA1c [mmol/L]) and fructosamine (μmol/L) was measured at week 17 and compared with mean sensor glucose levels from CGM.

Findings: In the HD group, mean sensor glucose was 1.4 mmol/L (95% confidence interval [CI]: 1.0-1.8) higher than the eMPGA1c, whereas the difference for controls was 0.1 mmol/L (95% CI: -0.1-[0.4]; p < 0.001). Adjusted for mean sensor glucose, HbA1c was lower in the HD group (-7.3 mmol/mol, 95% CI: -10.0-[-4.7]) than in the control group (p < 0.001), with no difference detected for fructosamine (p = 0.64).

Discussion: HbA1c evaluated by CGM underestimates plasma glucose levels in patients receiving HD. The underestimation represents a clinical challenge in optimizing glycemic control in the HD population. Fructosamine is unaffected by the factors affecting HbA1c and appears to be more accurate for glycemic monitoring. CGM or fructosamine could thus complement HbA1c in obtaining more accurate glycemic control in this patient group.
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http://dx.doi.org/10.1159/000519050DOI Listing
September 2021

Thyroid function in COVID-19 and the association with cytokine levels and mortality.

Endocr Connect 2021 Sep 28;10(10):1234-1242. Epub 2021 Sep 28.

Department of Growth and Reproduction, Copenhagen University Hospital, Copenhagen, Denmark.

The hypothalamic-pituitary-thyroid hormone axis might be affected in COVID-19, but existing studies have shown varying results. It has been hypothesized that hyperinflammation, as reflected by the secretion of cytokines, might induce thyroid dysfunction among patients with COVID-19. We explored thyroid hormone involvement in the acute phase of symptomatic COVID-19 and its possible associations with cytokine levels and mortality risk. This was a single-center study of 116 consecutive patients hospitalized for moderate-to-severe COVID-19 disease. Serum concentrations of thyroid-stimulating hormone (TSH), free thyroxine (T4), and 45 cytokines/chemokines were measured in all patients within 3 days of admission. Data were extracted retrospectively through a manual review of health records. At admission, 95 (81.9%) were euthyroid; while 21 (18.1%) had biochemically thyroid dysfunction including subclinical thyrotoxicosis (n = 11), overt thyrotoxicosis (n = 2), hypothyroidism (n = 1), non-thyroidal illness (n = 2), and normal TSH but high free T4 (n = 5). TSH levels were inversely correlated with IL-8 (rs = -0.248), IL-10 (rs = -0.253), IL-15 (rs = -0.213), IP-10 (rs = -0.334), and GM-CSF (rs = -0.254). Moreover, IL-8 levels, IP-10, and GM-CSF were significantly higher in patients with serum TSH < 0.4 mIU/L. Lastly, a two-fold increment of IL-8 and IL-10 was associated with significantly higher odds of having TSH < 0.4 mIU/L (odds ratio 1.86 (1.11-3.10) and 1.78 (1.03-3.06)). Serum TSH was not associated with 30- or 90-day mortality. In conclusion, this study suggests that fluctuations of TSH levels in patients with COVID-19 may be influenced by circulating IL-8, IL-10, IL-15, IP-10, and GM-CSF as previously described in autoimmune thyroid diseases.
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http://dx.doi.org/10.1530/EC-21-0301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494417PMC
September 2021

Comparison of 16 Serological SARS-CoV-2 Immunoassays in 16 Clinical Laboratories.

J Clin Microbiol 2021 04 20;59(5). Epub 2021 Apr 20.

Department of Clinical Immunology, Odense University Hospital, Odense, Denmark.

Serological assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to support clinical diagnosis and epidemiological investigations. Recently, assays for large-scale detection of total antibodies (Ab), immunoglobulin G (IgG), and IgM against SARS-CoV-2 antigens have been developed, but there are limited data on the diagnostic accuracy of these assays. This study was a Danish national collaboration and evaluated 15 commercial and one in-house anti-SARS-CoV-2 assays in 16 laboratories. Sensitivity was evaluated using 150 samples from individuals with asymptomatic, mild, or moderate COVID-19, nonhospitalized or hospitalized, confirmed by nucleic acid amplification tests (NAAT); samples were collected 13 to 73 days either from symptom onset or from positive NAAT (patients without symptoms). Specificity and cross-reactivity were evaluated in samples collected prior to the SARS-CoV-2 epidemic from >586 blood donors and patients with autoimmune diseases, cytomegalovirus or Epstein-Barr virus infections, and acute viral infections. A specificity of ≥99% was achieved by all total-Ab and IgG assays except one, DiaSorin Liaison XL IgG (97.2%). Sensitivities in descending order were Wantai ELISA total Ab (96.7%), CUH-NOVO in-house ELISA total Ab (96.0%), Ortho Vitros total Ab (95.3%), YHLO iFlash IgG (94.0%), Ortho Vitros IgG (93.3%), Siemens Atellica total Ab (93.2%), Roche Elecsys total Ab (92.7%), Abbott Architect IgG (90.0%), Abbott Alinity IgG (median 88.0%), DiaSorin Liaison XL IgG (median 84.6%), Siemens Vista total Ab (81.0%), Euroimmun/ELISA IgG (78.0%), and Snibe Maglumi IgG (median 78.0%). However, confidence intervals overlapped for several assays. The IgM results were variable, with the Wantai IgM ELISA showing the highest sensitivity (82.7%) and specificity (99%). The rate of seropositivity increased with time from symptom onset and symptom severity.
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http://dx.doi.org/10.1128/JCM.02596-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091860PMC
April 2021

Quantification of biotin in plasma samples by column switching liquid chromatography - tandem mass spectrometry.

Scand J Clin Lab Invest 2021 Apr 19;81(2):127-136. Epub 2021 Jan 19.

Department of Clinical Pharmacology, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.

Biotin (or Vitamin B7) is a vitamin where deficiency can be caused by inadequate intake. Biotin deficiency is rare, as most people get enough biotin from diet, since many foods contain biotin. In addition to biotin from food, intestinal bacteria can synthesize biotin, which can then be absorbed by the body. Supplementation with biotin has been advocated, mainly due to proposed beneficial effects on skin, nail and hair growth. There is no evidence that high biotin intakes are toxic, but a high intake may interfere with diagnostic assays that use biotin-streptavidin technology. These tests are commonly used to measure plasma concentrations of a wide range of hormones. Erroneous results may lead to misdiagnosis of various endocrine disorders. Supplementation with high-dose biotin has been used experimental for the treatment of diseases (e.g. multiple sclerosis) and high doses are used to obtain effect on nail and hair growth. On this background a demand for tests to determine if there is a risk of obtaining false test results when using biotin-streptavidin based tests have appeared. In this paper we present a method based on column switching liquid chromatography tandem mass spectrometry for the quantification of biotin in plasma and serum and explore the effects of biotin on an immunoassay based on biotin strept(avidin) chemistry.
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http://dx.doi.org/10.1080/00365513.2020.1871504DOI Listing
April 2021

Chromogranin A in cardiovascular endocrinology.

Acta Physiol (Oxf) 2021 04 31;231(4):e13615. Epub 2021 Jan 31.

Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

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http://dx.doi.org/10.1111/apha.13615DOI Listing
April 2021

A Potential Role for Endogenous Glucagon in Preventing Post-Bariatric Hypoglycemia.

Front Endocrinol (Lausanne) 2020 30;11:608248. Epub 2020 Nov 30.

Endocrine, Cardiovascular & Metabolic Research, Unit for Multidisciplinary Research in Biomedicine (UMIB), University of Porto, Porto, Portugal.

Obesity and obesity-related diseases are major public health concerns that have been exponentially growing in the last decades. Bariatric surgery is an effective long-term treatment to achieve weight loss and obesity comorbidity remission. Post-bariatric hypoglycemia (PBH) is a late complication of bariatric surgery most commonly reported after Roux-en-Y gastric bypass (RYGB). PBH is the end result of postprandial hyperinsulinemia but additional endocrine mechanisms involved are still under debate. Our aim was to characterize entero-pancreatic hormone dynamics associated with postprandial hypoglycemia after RYGB. Individuals previously submitted to RYGB (=23) in a single tertiary hospital presenting PBH symptoms (, =14) and asymptomatic weight-matched controls (, =9) were enrolled. Participants underwent a mixed-meal tolerance test (MMTT) to assess glucose, total amino acids (total AA), insulin, C-peptide, glucagon, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and neurotensin (NT). We found that hypoglycemia during the MMTT was equally frequent in  and  groups (=1.000). Re-grouped according to glucose nadir during the MMTT ( =11 vs  =12; nadir <3.05 mmol/l vs ≥3.05 mmol/l), subjects presented no differences in anthropometric (BMI: =0.527) or metabolic features (HbA: =0.358), yet distinct meal-elicited hormone dynamics were identified. Postprandial glucose excursion and peak glucose levels were similar (>0.05), despite distinct late glycemic outcomes (t=60 min and t=90 min: <0.01), with overall greater glycemic variability in group (minimum-to-maximum glucose ratio: <0.001).  group meal-triggered hormone profile was characterized by lower early glucagon (t=15 min: <0.01) and higher insulin (t=30 min: <0.05, t=45 min: <0.001), C-peptide (t=30 min: <0.01, t=45 min: <0.001, t=60 min: <0.05), and GLP-1 (t=45 min: <0.05) levels. Hyperinsulinemia was an independent risk factor for hypoglycemia (<0.05). After adjusting for hyperinsulinemia, early glucagon correlated with glycemic nadir (<0.01), and prevented postprandial hypoglycemia (<0.05). A higher insulin to glucagon balance in was observed (<0.05). No differences were observed in total AA, GIP or NT excursions (>0.05). In sum, after RYGB, postprandial hyperinsulinemia is key in triggering PBH, but a parallel and earlier rise in endogenous glucagon might sustain the inter-individual variability in glycemic outcome beyond the effect of hyperinsulinism, advocating a potential pivotal role for glucagon in preventing hyperinsulinemic hypoglycemia.
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http://dx.doi.org/10.3389/fendo.2020.608248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793799PMC
May 2021

Spectrophotometry of cerebrospinal fluid for xanthochromia is a sensitive and specific test for subarachnoid bleeding but adds little to computed tomography.

Scand J Clin Lab Invest 2020 Dec 13;80(8):681-686. Epub 2020 Nov 13.

Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Subarachnoid hemorrhage (SAH) is a serious neurological event associated with high morbidity and mortality. Computed tomography of the cerebrum (CTC) is the diagnostic method of choice, but in case of negative CTC but strong suspicion of SAH, lumbar puncture with spectrophotometric analysis of cerebrospinal fluid (CSF) for xanthochromia is performed. We wanted to examine the diagnostic properties of CSF spectrophotometry for xanthochromia testing. We performed a retrospective study of the diagnostic properties of CSF analysis for xanthochromia using spectrophotometry in the diagnosis of SAH. A total of 489 CSF samples were analyzed for xanthochromia, according to international guidelines, from 2009 until 2014 and for 411 of these the patient files were retrieved and examined for final clinical diagnosis and result of CTC. One patient with SAH did not have a positive spectrophotometry report and another patient with SAH had an equivocal report. In four patients did initial CTC not correctly identify SAH. For patients with a negative CTC within six hours of symptom onset spectrophotometry for xanthochromia in the CSF had a diagnostic sensitivity of 100% and a diagnostic specificity of 98.5%. The positive predictive value was 16.7% and the negative predictive value 100%. We conclude that spectrophotometry of CSF for xanthochromia is a sensitive and specific test for diagnosing SAH. However, it seems that an initial CTC identifies almost all patients with SAH. This suggests that in our and similar diagnostic settings, lumbar puncture and testing for xanthochromia might only be relevant in very few cases, if not obsolete.
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http://dx.doi.org/10.1080/00365513.2020.1846208DOI Listing
December 2020

Limited Diagnostic Utility of Chromogranin A Measurements in Workup of Neuroendocrine Tumors.

Diagnostics (Basel) 2020 Oct 29;10(11). Epub 2020 Oct 29.

ENETS Neuroendocrine Tumor Centre of Excellence, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark.

Background: Plasma chromogranin A (CgA) is related to tumor burden and recommended in the follow-up of patients diagnosed with neuroendocrine tumors (NETs). The use of CgA in the workup of a suspected NET is more questionable.

Objective: To assess the positive predictive value (PPV) of CgA plasma concentrations above the upper reference limit (URL) in patients with suspected NET.

Method: Patients referred to the NET Centre, Rigshospitalet, Copenhagen from 2015 to 2019 with clinically suspected NET were included if a CgA measurement was performed prior to referral. The utility of CgA was assessed by comparing pre-referral CgA concentrations to the outcome of a thorough workup. In 47 selected cases with continuously unexplained elevated CgA concentrations, a processing-independent analysis (PIA) for CgA was performed.

Results: A total of 197 patients were included. NET was ultimately diagnosed in 25 patients. CgA plasma concentrations were above the URL (elevated) in 19/25 patients diagnosed with NET. In total, 167/197 had elevated CgA concentrations at referral. The positive predictive value (PPV) of elevated CgA concentration was 11% (19/167). Proton pump inhibitor (PPI) treatment was identified as the possible cause of CgA elevation in 55/148 patients with falsely elevated CgA. CgA concentration was normal in 28/47 patients when using PIA.

Conclusion: Our data do not support using measurement of CgA for screening when NET is suspected since the PPV was rather low. PPI treatment is a common cause of increased CgA concentrations and should always be discontinued before CgA measurement. PIA of CgA could be a way of excluding NET when suspicion is based primarily on elevated CgA.
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http://dx.doi.org/10.3390/diagnostics10110881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693015PMC
October 2020

Comment on: Adrenal insufficiency in prednisolone-treated patients with polymyalgia rheumatica or giant cell arteritis-prevalence and clinical approach: reply.

Rheumatology (Oxford) 2020 10;59(10):e78

Center for Rheumatology and Spine Diseases, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Frederiksberg.

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http://dx.doi.org/10.1093/rheumatology/keaa239DOI Listing
October 2020

True Chromogranin A concentrations in plasma from patients with small intestinal neuroendocrine tumours.

Scand J Gastroenterol 2020 May 30;55(5):565-573. Epub 2020 Apr 30.

Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

: The incidence of enteropancreatic neuroendocrine tumours (NET) is increasing. Chromogranin A (CgA) in plasma is a marker in patients suspected of NET tumours. CgA, however, is a precursor protein subjected to cellular processing that challenges quantitation and hence the use of CgA in diagnostics.: CgA concentrations in plasma sampled from 130 well-characterized patients with small intestinal NETs and from 30 healthy subjects were measured with eight commercial CgA kits, an in-house radioimmunoassay (RIA) and a processing-independent assay (PIA). For the evaluation of diagnostic accuracy, we performed regression analyses and plotted receiver-operating characteristic curves (ROC). The specificity was further assessed by size chromatography.: Five commercial assays (Thermo-Fisher, DRG Diagnostics, Eurodiagnostica (RIA and ELISA), and Phoenix), displayed a diagnostic accuracy with area under the curve (AUC) values >0.90, whereas three immunoassays (Yanaihara, CisBio RIA, and CisBio ELISA) discriminated poorly between disease stages (AUC: 0.60-0.78). Compared with the in-house assays, however, even the most accurate commercial immunoassay still missed patients with metastatic disease. Chromatography showed non-uniform patterns of large and small CgA fragments in plasma.: Available commercial immunoassays measure CgA in plasma with gross variability. Three commercial CgA immunoassays discriminate so poorly between health and disease that they should not be used. The highest diagnostic accuracy was obtained with processing-independent measurement of total CgA concentrations in plasma.
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http://dx.doi.org/10.1080/00365521.2020.1759141DOI Listing
May 2020

Gastric Residual to Predict Necrotizing Enterocolitis in Preterm Piglets As Models for Infants.

JPEN J Parenter Enteral Nutr 2021 01 26;45(1):87-93. Epub 2020 Feb 26.

Department of Neonatology, Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark.

Background: Necrotizing enterocolitis (NEC) is a serious intestinal inflammatory disease in preterm infants. High volume of gastric residual (GR) after oral feedings is often used as a predictor of NEC, but evidence is limited. Using NEC-sensitive preterm piglets as models, we hypothesized that GR mass and related plasma biomarkers predict early onset of NEC.

Methods: In total, 258 newborn preterm piglets were fed bovine milk-based formulas for 5 days. At euthanasia, the stomach, small intestine, and colon were evaluated for NEC lesions. Mass, acidity, gastrin, and bile acid levels were determined for GR content, together with gastrin, glucagon-like peptide 2 (GLP-2), and gastric inhibitory polypeptide (GIP) levels in plasma.

Results: In total, 48% of piglets had NEC lesions in the small intestine and/or colon. These piglets had higher GR mass (+32%, P < 0.001) and lower gastric bile acid concentrations (-22%, P < 0.05) than piglets without NEC lesions. The positive and negative predictive values for these markers were 34%-61%. Gastric acidity, gastrin, GLP-2, and GIP levels were similar for piglets with and without NEC lesions.

Conclusion: Elevated GR mass correlates positively with NEC lesions but may be a poor predictor of NEC, even when combined with other biomarkers. More knowledge about gastric emptying and gut transit in preterm neonates is required to understand how GR volume and composition relate to morbidities, such as NEC, in preterm neonates.
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http://dx.doi.org/10.1002/jpen.1814DOI Listing
January 2021

Adrenal insufficiency in prednisolone-treated patients with polymyalgia rheumatica or giant cell arteritis-prevalence and clinical approach.

Rheumatology (Oxford) 2020 10;59(10):2764-2773

Center for Rheumatology and Spine Diseases, Copenhagen University Hospital Bispebjerg and Frederiksberg, Frederiksberg, Denmark.

Objectives: Glucocorticoid treatment is fundamental in polymyalgia rheumatica (PMR) and giant cell arteritis (GCA), but carries a risk of glucocorticoid-induced adrenal insufficiency. Adrenal insufficiency can cause reluctance to stop glucocorticoid treatment after disease remission as symptoms can resemble PMR/GCA flare. We aimed to determine the prevalence of adrenal insufficiency in prednisolone-treated patients with PMR/GCA.

Methods: We included 47 patients with PMR (n = 37), GCA (n = 1) or both (n = 9), treated with prednisolone for ≥5.4 months, current dose 2.5-10 mg/day. Adrenal function was evaluated using a corticotropin (Synacthen®) stimulation test following 48 h prednisolone pause. Two years' clinical follow-up data are provided.

Results: Seven patients (15%) had adrenal insufficiency, 4 (11%) of the 37 patients with PMR alone, and 3 (30%) of the 10 patients with GCA. Corticotropin-stimulated P-cortisol was significantly associated with current prednisolone dose, mean daily dose the last 3 and 6 months before testing, and basal P-cortisol, but not with total dose or treatment duration. Adrenal insufficiency occurred with all current prednisolone doses (2.5-10 mg/day). Five (71%) of the glucocorticoid-insufficient patients could discontinue prednisolone treatment; two of them recovered glucocorticoid function, whereas three still needed hydrocortisone replacement 2 years later. Two patients experienced in total four acute hospital admissions with symptoms of adrenal crises.

Conclusion: Glucocorticoid-induced adrenal insufficiency occurred in 15% of patients with PMR/GCA. Mean prednisolone dose the last 3 months and basal P-cortisol were the best and simplest predictors of adrenal function. Most of the glucocorticoid-insufficient patients could discontinue prednisolone with appropriate treatment for adrenal insufficiency.
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http://dx.doi.org/10.1093/rheumatology/keaa011DOI Listing
October 2020

Thyroid Peroxidase Antibodies and Prospective Live Birth Rate: A Cohort Study of Women with Recurrent Pregnancy Loss.

Thyroid 2019 10 24;29(10):1465-1474. Epub 2019 Sep 24.

Recurrent Pregnancy Loss Unit, Fertility Clinic 4071, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

Thyroid autoimmunity has been associated with pregnancy loss. Suggested mechanisms include thyroid function aberrations or an underlying breach of immunotolerance. We hypothesized that thyroid autoimmunity is a marker of the latter in women with recurrent pregnancy loss. This study investigated thyroid peroxidase antibody (TPOAb) status as a predictor of live birth in women with unexplained recurrent pregnancy loss. Cohort study of 825 consecutive women with recurrent pregnancy loss followed at the tertiary referral center for Recurrent Pregnancy Loss, Copenhagen University Hospital (Rigshospitalet), from 2011 to 2017. Recurrent pregnancy loss was defined as ≥3 consecutive losses, and as unexplained by absence of antiphospholipid syndrome, parental chromosome abnormality, or uterus malformation. Upon first visit, all women were screened for thyrotropin (TSH) and TPOAbs (TPOAb positivity: ≥60 kIU/L). Adjusted logistic regression analyses included as covariates the following: maternal age, TSH, previous number of losses, body mass index, smoking, pregnancy achieved by assisted reproductive technology, and thyroxine replacement (T4) treatment. We included 825 women with a total of 3246 previous losses, of whom 139 (16.8%) were TPOAb positive. TPOAb positivity was not associated with the previous number of losses ( = 0.41). Women with unexplained recurrent pregnancy loss had a live birth rate in the first pregnancy after referral of 62.8% (285 of 454). TPOAb positivity was found in 78 of 454 (17.2%) women and was associated with a reduced live birth rate (51.3% vs. 65.2%,  = 0.02, adjusted odds ratio [aOR] 0.2 [0.1-0.6]  = 0.001). Treatment with T4 increased live birth rate significantly (aOR 3.7 [1.4-9.8],  = 0.007), and TPOAb-positive women receiving T4 had a live birth rate similar to that of TPOAb-negative women not receiving T4 ( = 0.70). Only 30% of TPOAb-positive women and 39% of women treated with T4 during pregnancy had known thyroid disease at referral. In a large cohort of women with unexplained recurrent pregnancy loss, TPOAb positivity was predictive of a reduced live birth rate. However, T4 treatment improved odds of live birth. The study supports screening for TPOAbs as a risk factor in women with unexplained recurrent pregnancy loss. The beneficial effect of T4 treatment in this high-risk group needs confirmation by randomized controlled trials. Close collaboration between fertility experts and endocrinologists is paramount.
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http://dx.doi.org/10.1089/thy.2019.0077DOI Listing
October 2019

Biliopancreatic diversion with duodenal switch (BPD-DS) and single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) result in distinct post-prandial hormone profiles.

Int J Obes (Lond) 2019 12 11;43(12):2518-2527. Epub 2018 Dec 11.

Unit for Multidisciplinary Research in Biomedicine (UMIB), Endocrine, Cardiovascular and Metabolic Research, University of Porto, Porto, Portugal.

Background/objective: Biliopancreatic diversion with duodenal switch (BPD-DS) is the most effective bariatric intervention to treat morbid obesity and related disorders. Single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) is a new bariatric procedure devised with the purpose of simplifying the complexity of the BPD-DS technique while maintaining its efficacy. However, whether BPD-DS and SADI-S result in similar fasting and post-prandial hormone profiles has not yet been studied. Therefore, the purpose of this study was to assess and compare the hormone response to a standardized mixed meal in subjects operated with BPD-DS or SADI-S.

Subjects/methods: Subjects submitted to BPD-DS (n = 9) or SADI-S (n = 9) 1.5 years earlier on average, with no past nor current diabetes diagnosis underwent a liquid mixed-meal tolerance test (MMTT) to assess the baseline and post-prandial profile of glucose, enteropancreatic hormones and total bile acids.

Results: Fasting glucose, enteropancreatic hormones and total bile acids levels after BPD-DS and SADI-S were similar. After the MMTT, the response of subjects who underwent SADI-S was characterized by higher glucose (t = 30 min: p < 0.05; iAUC: 156.1 ± 46.2 vs. 103.4 ± 35.8 mmol/L × min, p = 0.02), GLP-1 (t = 30 min: p < 0.05; iAUC: 5388 ± 3010 vs. 2959.0 ± 2146 pmol/L × min, p = 0.02), glucagon (t = 30 min: p < 0.05; iAUC: 678.7 ± 295.2 vs. 376.9 ± 215.7 pmol/L × min, p = 0.02), insulin (t = 30 and 45 min: p < 0.05); and C-peptide levels (t = 30 and 45 min: p < 0.05), when compared to BPD-DS.

Conclusions: The post-prandial hormone secretion profile after SADI-S is characterized by increased GLP-1, glucagon and insulin secretion, when compared to BPD-DS, which suggests the existence of different endocrine driven mechanisms leading to weight loss and metabolic improvement after the two procedures.
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http://dx.doi.org/10.1038/s41366-018-0282-zDOI Listing
December 2019

Hypoxia-induced vagal withdrawal is independent of the hypoxic ventilatory response in men.

J Appl Physiol (1985) 2019 01 29;126(1):124-131. Epub 2018 Nov 29.

The Centre for Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen , Copenhagen , Denmark.

Hypoxia increases heart rate (HR) in humans by sympathetic activation and vagal withdrawal. However, in anaesthetized dogs hypoxia increases vagal activity and reduces HR if pulmonary ventilation does not increase and we evaluated whether that observation applies to awake humans. Ten healthy males were exposed to 15 min of normoxia and hypoxia (10.5% O), while respiratory rate and tidal volume were volitionally controlled at values identified during spontaneous breathing in hypoxia. End-tidal CO tension was clamped at 40 mmHg by CO supplementation. β-Adrenergic blockade by intravenous propranolol isolated vagal regulation of HR. During spontaneous breathing, hypoxia increased ventilation by 3.2 ± 2.1 l/min ( P = 0.0033) and HR by 8.9 ± 5.5 beats/min ( P < 0.001). During controlled breathing, respiratory rate (16.3 ± 3.2 vs. 16.4 ± 3.3 breaths/min) and tidal volume (1.05 ± 0.27 vs. 1.06 ± 0.24 l) were similar for normoxia and hypoxia, whereas the HR increase in hypoxia persisted without (8.6 ± 10.2 beats/min) and with (6.6 ± 5.6 beats/min) propranolol. Neither controlled breathing ( P = 0.80), propranolol ( P = 0.64), nor their combination ( P = 0.89) affected the HR increase in hypoxia. Arterial pressure was unaffected ( P = 0.48) by hypoxia across conditions. The hypoxia-induced increase in HR during controlled breathing and β-adrenergic blockade indicates that hypoxia reduces vagal activity in humans even when ventilation does not increase. Vagal withdrawal in hypoxia seems to be governed by the arterial chemoreflex rather than a pulmonary inflation reflex in humans. NEW & NOTEWORTHY Hypoxia accelerates the heart rate of humans by increasing sympathetic activity and reducing vagal activity. Animal studies have indicated that hypoxia-induced vagal withdrawal is governed by a pulmonary inflation reflex that is activated by the increased pulmonary ventilation in hypoxia. The present findings, however, indicate that humans experience vagal withdrawal in hypoxia even if ventilation does not increase, indicating that vagal withdrawal is governed by the arterial chemoreflex rather than a pulmonary inflation reflex.
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http://dx.doi.org/10.1152/japplphysiol.00701.2018DOI Listing
January 2019

Pediatric reference intervals for general clinical chemistry components - merging of studies from Denmark and Sweden.

Scand J Clin Lab Invest 2018 Sep 28;78(5):365-372. Epub 2018 May 28.

e Fürst Medical Laboratory , Oslo , Norway.

Background: Reference intervals are crucial tools aiding clinicians when making medical decisions. However, for children such values often are lacking or incomplete. The present study combines data from separate pediatric reference interval studies of Denmark and Sweden in order to increase sample size and to include also pre-school children who were lacking in the Danish study.

Methods: Results from two separate studies including 1988 healthy children and adolescents aged 6 months to 18 years of age were merged and recalculated. Eighteen general clinical chemistry components were measured on Abbott and Roche platforms. To facilitate commutability, the NFKK Reference Serum X was used.

Results: Age- and gender-specific pediatric reference intervals were defined by calculating 2.5 and 97.5 percentiles.

Conclusion: The data generated are primarily applicable to a Nordic population, but could be used by any laboratory if validated for the local patient population.
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http://dx.doi.org/10.1080/00365513.2018.1474493DOI Listing
September 2018

Gut hormone release after gastric bypass depends on the length of the biliopancreatic limb.

Int J Obes (Lond) 2019 05 24;43(5):1009-1018. Epub 2018 May 24.

Clinical and Experimental Endocrinology, Department of Anatomy, Unit for Multidisciplinary Research in Biomedicine, Abel Salazar Institute of Biomedical Sciences, University of Porto, Porto, Portugal.

Background/objectives: Changes in gut hormone secretion are important for the anti-diabetic effects of bariatric surgery. Roux-en-Y gastric bypass (RYGB) with extended biliopancreatic limb (BPL) length may improve the metabolic outcomes when compared to the classical procedure. The purpose of this study was to compare the gut hormone responses to a liquid mixed meal after RYGB with one of two different BPL lengths.

Subjects/methods: Non-diabetic weight-stable individuals previously submitted to classical RYGB (n = 9; BPL length: 87.8 ± 20.5 cm) or long BPL RYGB (n = 11; BPL length: 200 cm) underwent a liquid mixed-meal tolerance test (MMTT). Blood was sampled at baseline and 15, 30, 45, 60, 90 and 120 min later for measurement of plasma glucose, enteropancreatic hormones and total bile acids (TBA).

Results: Plasma glucose excursion curves were similar in the two groups. The long BPL RYGB group displayed significantly higher fasting and post-prandial GLP-1 (t = 0 min, p = 0.01 and t = 45 min, p < 0.05; tAUC: 11,205 ± 3399 vs 7889 ± 1686 pmol/L × min, p = 0.02) and neurotensin (t = 0 min, p = 0.02; t = 45 min, p < 0.05 and t = 60 min, p < 0.01; tAUC: 18,392 ± 7066 vs 11,437 ± 3658 pmol/L × min, p = 0.02) levels, while responses of GIP (t = 15 min, p < 0.01), insulin and C-peptide (t = 30 min, p < 0.001) were lower as compared to classical RYGB. There were no differences in glucagon, PP, PYY and TBA between the groups.

Conclusions: RYGB with a longer BPL results in a distinctive post-prandial hormone profile with augmented GLP-1 and neurotensin responses that could be beneficial for the metabolic outcomes of the surgery.
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http://dx.doi.org/10.1038/s41366-018-0117-yDOI Listing
May 2019

Investigation of anti-Müllerian hormone concentrations in relation to natural conception rate and time to pregnancy.

Reprod Biomed Online 2018 May 9;36(5):568-575. Epub 2018 Feb 9.

The Fertility Clinic, Copenhagen University Hospital, Rigshospitalet, 2100, Copenhagen, Denmark.

The objectives of this study were to investigate whether anti-Müllerian hormone (AMH) concentrations can predict pregnancy rates and time to pregnancy (TTP) in women attempting to conceive naturally/having an unplanned conception, and whether there is a lower AMH threshold compatible with natural conception. This prospective cohort study included 260 women aged 25-42 years in two subcohorts: (A) healthcare workers at Rigshospitalet (2008-2010), and (B) women consulting the Fertility Assessment and Counselling Clinic (2011-2014), Rigshospitalet, Denmark. Pregnancy rates and TTP at 2-year follow-up were stratified into AMH groups: low: < 9.5 pmol/l, intermediate: 9.5-33 pmol/l, high: > 33 pmol/l. Pregnancy rates increased with increasing AMH: 60.1% (low) versus 70.0% (intermediate) versus 78.3% (high) (P = 0.03). The highest pregnancy rate (84.1%) was seen in regular cycling women with high AMH. TTP was reduced in women with high AMH compared with intermediate or low AMH (stepwise trend test P = 0.01). Natural conceptions were observed with AMH concentrations down to 1.2 pmol/l. In conclusion, high AMH, especially in ovulatory women, was associated with higher pregnancy rates. Nonetheless, TTP reflected a large variation in fecundity within similar AMH concentrations and natural conceptions occurred with AMH down to 1.2 pmol/l.
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http://dx.doi.org/10.1016/j.rbmo.2018.01.013DOI Listing
May 2018

Corrigendum to "Challenges in Interpretation of Thyroid Function Tests in Pregnant Women with Autoimmune Thyroid Disease".

J Thyroid Res 2017 25;2017:4324130. Epub 2017 Oct 25.

Department of Growth and Reproduction, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.

[This corrects the article DOI: 10.4061/2011/598712.].
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http://dx.doi.org/10.1155/2017/4324130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5676469PMC
October 2017

Adrenal insufficiency is seen in more than one-third of patients during ongoing low-dose prednisolone treatment for rheumatoid arthritis.

Eur J Endocrinol 2017 Oct;177(4):287-295

Department of Medical Endocrinology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

Objective: Patients receiving long-term glucocorticoid treatment are at risk of developing adrenal insufficiency during treatment. We investigated the prevalence of prednisolone-induced adrenal insufficiency in the particular clinical situation where patients receive ongoing low-dose (5 mg/day) prednisolone treatment, a dose by itself too low to cover glucocorticoid needs during stress.

Design And Methods: Cross-sectional study in 42 patients with rheumatoid arthritis (29 women, aged 36-86 years) treated with 5 mg prednisolone/day, who had received prednisolone for ≥6 months (median: 66, range: 6-444 months). Adrenal function was evaluated by a 250 μg Synacthen test performed after mean 48.7 h prednisolone pause. Local assay-specific cut-off for normal adrenal function was P-cortisol ≥420 nmol/L 30 min after Synacthen injection.

Results: Overall, 20 of the 42 patients (48%, 95% CI: 33-62%) had an insufficient adrenal response to the Synacthen test. Including only patients who had not received concomitant treatment with any other glucocorticoid formulas within the last 3 months, 13 of 33 patients (39%, 95% CI: 25-56%) had an insufficient response. Adrenocorticotrophic hormone (ACTH) concentrations were generally low and anti-adrenal antibodies were negative indicating secondary adrenal insufficiency as the most likely diagnosis. There was no correlation between duration of treatment and 30 min P-cortisol ( = 0.62). Adrenal function did not depend on sex or seropositivity of rheumatoid arthritis.

Conclusion: We demonstrate a high prevalence of adrenal insufficiency during ongoing low-dose prednisolone treatment. The results urge to increase focus on the condition to ensure identification and correct management of insufficient patients during stress and withdrawal. Strategies for adrenal function evaluation during ongoing low-dose glucocorticoid treatment need to be established.
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http://dx.doi.org/10.1530/EJE-17-0251DOI Listing
October 2017

Increase in thyroglobulin antibody and thyroid peroxidase antibody levels, but not preterm birth-rate, in pregnant Danish women upon iodine fortification.

Eur J Endocrinol 2017 May;176(5):603-612

Departments of Medical EndocrinologySection 2132.

Objective: The presence of thyroid antibodies in pregnancy has been associated with preterm birth. In the non-pregnant population, the implementation of the Danish iodine fortification program has increased the prevalence of thyroid antibodies. This study investigated the prevalence of thyroid peroxidase antibodies (TPOAbs) and thyroglobulin antibodies (TgAbs) in pregnant Danish women before, during and after implementation of the iodine fortification program and association with preterm birth.

Design: Comparative cohort study of 1368 pregnancies from three cohorts gathered before (1996-1998), during (2000-2003) and after (2008-2009) the iodine fortification program.

Methods: In cohort 1 ( = 297), TPOAbs were measured (DYNOtest (BRAHMS)). In cohorts 2 ( = 148) and 3 ( = 923), both TPOAbs and TgAbs were measured (Kryptor immunofluorescent assay (BRAHMS)). The prevalence and effect of antibody positivity were explored using three cut-offs: TPOAbs and/or TgAbs >100 kU/L, TPOAbs and/or TgAbs >60 kU/L and TPOAbs >30 and/or TgAbs >20 kU/L. National preterm birth data were extracted from the National Birth Registry.

Results: In the three cohorts, TPOAb levels >60 kU/L were found in 5.4, 8.1 and 12.0% ((2,  = 1367) = 11.7,  = 0.003) respectively, and TPOAbs and/or TgAbs >60 kU/L in 8.1 and 16.2% in cohorts 2 and 3 respectively ((2,  = 1070) = 6.5,  = 0.01). TgAb levels (>20 kU/L) had increased plenty-fold from cohort 2 to 3 ((1,  = 1071) = 136.5,  < 0.001). Preterm birth occurred in 4.1% of all pregnancies with no effect from antibody positivity (TPOAbs and/or TgAbs >60 kU/L, (1,  = 1039) = 0.0,  = 0.98, aOR = 1.1, 95% CI (0.4-2.7)). The national preterm birth-rate showed no increase over the same period.

Conclusions: Thyroid antibody positivity in Danish pregnant women has more than doubled upon the implementation of the iodine fortification program without an increase in preterm birth-rate.
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http://dx.doi.org/10.1530/EJE-16-0987DOI Listing
May 2017

Acute effects of glucagon-like peptide-1, GLP-1, and exenatide on mesenteric blood flow, cardiovascular parameters, and biomarkers in healthy volunteers.

Physiol Rep 2017 Feb;5(4)

Department of Biomedical Sciences & NNF Center for Basic Metabolic Research, The Panum Institute, University of Copenhagen, Copenhagen, Denmark

Glucagon-like peptide-1 (GLP-1, GLP-1) and its sister peptide glucagon-like peptide 2 (GLP-2) influence numerous intestinal functions and GLP-2 greatly increases intestinal blood flow. We hypothesized that GLP-1 also stimulates intestinal blood flow and that this would impact on the overall digestive and cardiovascular effects of the hormone. To investigate the influence of GLP-1 receptor agonism on mesenteric and renal blood flow and cardiovascular parameters, we carried out a double-blinded randomized clinical trial. A total of eight healthy volunteers received high physiological subcutaneous injections of GLP-1, GLP-1 (bioactive metabolite), exenatide (stable GLP-1 agonist), or saline on four separate days. Blood flow in mesenteric, celiac, and renal arteries was measured by Doppler ultrasound. Blood pressure, heart rate, cardiac output, and stroke volume were measured continuously using an integrated system. Plasma was analyzed for glucose, GLP-1 (intact and total), exenatide and Pancreatic polypeptide (PP), and serum for insulin and C-peptide. Neither GLP-1, GLP-1, exenatide nor saline elicited any changes in blood flow parameters in the mesenteric or renal arteries. GLP-1 significantly increased heart rate (two-way ANOVA, injection [ = 0.0162], time [ = 0.0038], and injection × time [ = 0.082]; Tukey post hoc GLP-1 vs. saline and GLP-1 [ < 0.011]), and tended to increase cardiac output and decrease stroke volume compared to GLP-1 and saline. Blood pressures were not affected. As expected, glucose levels fell and insulin secretion increased after infusion of both GLP-1 and exenatide.
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http://dx.doi.org/10.14814/phy2.13102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5328764PMC
February 2017

Hypoglycemia-Associated EEG Changes Following Antecedent Hypoglycemia in Type 1 Diabetes Mellitus.

Diabetes Technol Ther 2017 02;19(2):85-90

1 Faculty of Health, University of Southern Denmark , Odense, Denmark .

Background: Recurrent hypoglycemia has been shown to blunt hypoglycemia symptom scores and counterregulatory hormonal responses during subsequent hypoglycemia. We therefore studied whether hypoglycemia-associated electroencephalogram (EEG) changes are affected by an antecedent episode of hypoglycemia.

Methods: Twenty-four patients with type 1 diabetes mellitus (10 with normal hypoglycemia awareness, 14 with hypoglycemia unawareness) were studied on 2 consecutive days by hyperinsulinemic glucose clamp at hypoglycemia (2.0-2.5 mmol/L) during a 1-h period. EEG was recorded, cognitive function assessed, and hypoglycemia symptom scores and counterregulatory hormonal responses were obtained.

Results: Twenty-one patients completed the study. Hypoglycemia-associated EEG changes were identified on both days with no differences in power or frequency distribution in the theta, alpha, or the combined theta-alpha band during hypoglycemia on the 2 days. Similar degree of cognitive dysfunction was also present during hypoglycemia on both days. When comparing the aware and unaware group, there were no differences in the hypoglycemia-associated EEG changes. There were very subtle differences in cognitive function between the two groups on day 2. The symptom response was higher in the aware group on both days, while only subtle differences were seen in the counterregulatory hormonal response.

Conclusion: Antecedent hypoglycemia does not affect hypoglycemia-associated EEG changes in patients with type 1 diabetes mellitus.
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http://dx.doi.org/10.1089/dia.2016.0331DOI Listing
February 2017

Glucagon-like Peptide 1 Receptor Signaling in Acinar Cells Causes Growth-Dependent Release of Pancreatic Enzymes.

Cell Rep 2016 12;17(11):2845-2856

Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; NNF Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark. Electronic address:

Incretin-based therapies are widely used for type 2 diabetes and now also for obesity, but they are associated with elevated plasma levels of pancreatic enzymes and perhaps a modestly increased risk of acute pancreatitis. However, little is known about the effects of the incretin hormone glucagon-like peptide 1 (GLP-1) on the exocrine pancreas. Here, we identify GLP-1 receptors on pancreatic acini and analyze the impact of receptor activation in humans, rodents, isolated acini, and cell lines from the exocrine pancreas. GLP-1 did not directly stimulate amylase or lipase release. However, we saw that GLP-1 induces phosphorylation of the epidermal growth factor receptor and activation of Foxo1, resulting in cell growth with concomitant enzyme release. Our work uncovers GLP-1-induced signaling pathways in the exocrine pancreas and suggests that increases in amylase and lipase levels in subjects treated with GLP-1 receptor agonists reflect adaptive growth rather than early-stage pancreatitis.
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http://dx.doi.org/10.1016/j.celrep.2016.11.051DOI Listing
December 2016

Chromogranin A as biomarker in diabetes.

Biomark Med 2016 Nov 9;10(11):1181-1189. Epub 2016 Sep 9.

Department of Clinical Biochemistry, Copenhagen University Hospital, Rigshospitalet, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark.

Chromogranin A (CgA) is an established plasma marker of neuroendocrine tumors and has been suggested to also have a role as biomarker in other diseases. Whether CgA has any role as biomarker in diabetes is, however, unresolved, but its widespread distribution in the secretory granules in endocrine tissues including β cells and α cells in pancreas, and the metabolic effects of its peptide fragments suggest that CgA may play a pathophysiological role in diabetes, and thus also be a potential diabetes biomarker. In this review, we summarize the available information on CgA and some of its functional post-translational cleavage products in diabetes, followed by a discussion of its potential as a plasma marker in diabetes and the methodological concerns involved.
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http://dx.doi.org/10.2217/bmm-2016-0091DOI Listing
November 2016

Rapid gut growth but persistent delay in digestive function in the postnatal period of preterm pigs.

Am J Physiol Gastrointest Liver Physiol 2016 04 28;310(8):G550-60. Epub 2016 Jan 28.

Comparative Pediatrics and Nutrition, University of Copenhagen, Copenhagen, Denmark; Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital, Denmark.

Preterm infants often tolerate full enteral nutrition a few weeks after birth but it is not known how this is related to gut maturation. Using pigs as models, we hypothesized that intestinal structure and digestive function are similar in preterm and term individuals at 3-4 wk after birth and that early enteral nutrition promotes maturation. Preterm or term cesarean-delivered pigs were fed total parenteral nutrition, or partial enteral nutrition [Enteral (Ent), 16-64 ml·kg(-1)·day(-1) of bovine colostrum] for 5 days, followed by full enteral milk feeding until day 26 The intestine was collected for histological and biochemical analyses at days 0, 5, and 26 (n = 8-12 in each of 10 treatment groups). Intestinal weight (relative to body weight) was reduced in preterm pigs at 0-5 days but ENT feeding stimulated the mucosal volume and peptidase activities. Relative to term pigs, mucosal volume remained reduced in preterm pigs until 26 days although plasma glucagon-like peptide 2 (GLP-2) and glucose-dependent insulin-trophic peptide (GIP) levels were increased. Preterm pigs also showed reduced hexose absorptive capacity and brush-border enzyme (sucrase, maltase) activities at 26 days, relative to term pigs. Intestinal structure shows a remarkable growth adaptation in the first week after preterm birth, especially with enteral nutrition, whereas some digestive functions remain immature until at least 3-4 wk. It is important to identify feeding regimens that stimulate intestinal maturation in the postnatal period of preterm infants because some intestinal functions may show long-term developmental delay.
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http://dx.doi.org/10.1152/ajpgi.00221.2015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4836131PMC
April 2016

Somatostatin-Immunoreactive Pancreaticoduodenal Neuroendocrine Neoplasms: Twenty-Three Cases Evaluated according to the WHO 2010 Classification.

Neuroendocrinology 2016 28;103(5):567-77. Epub 2015 Oct 28.

Background/objective: Neuroendocrine neoplasms of the pancreas and duodenum with predominant or exclusive immunoreactivity for somatostatin (pdSOMs) are rare, and knowledge about tumour biology, treatment, survival and prognostic factors is limited. This study aims to describe clinical, pathological and biochemical features as well as treatment and prognosis of pdSOMs.

Design: Twenty-three patients with pdSOM (9 duodenal, 12 pancreatic and 2 unknown primary tumours) were identified from our prospective neuroendocrine tumour database, and data according to the study aims were recorded.

Results: Among the 9 patients with duodenal SOM, the male/female ratio was 4/5. All males and 1 female had neurofibromatosis type 1. Seven patients had stage 1A/B and 2 had stage 2B disease. The Ki-67 index was 1-5% (median 2%). Plasma somatostatin was elevated in the patients with 2B disease. Of the 14 patients with pancreatic SOM or an unknown primary tumour, the male/female ratio was 2/12. One male had multiple endocrine neoplasia type 1. Five had stage 1A/2B and 9 had stage 4. The Ki-67 index was 1-40% (median 7%). Plasma somatostatin was elevated in 7 patients. Patients reported symptoms related to the somatostatinoma syndrome, but none fulfilled the criteria for a full syndrome. Primary tumour in the pancreas, metastatic disease at diagnosis and higher tumour grade were all associated with significantly poorer survival.

Conclusion: None of the patients with pdSOM presented with the full somatostatinoma syndrome. Prognostic factors are localisation of the primary tumour, dissemination and tumour grade. A Ki-67 index of 5% may discriminate the course of the disease.
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http://dx.doi.org/10.1159/000441605DOI Listing
May 2017

Peptide YY3-36 and glucagon-like peptide-1 in functional dyspepsia. Secretion and role in symptom generation.

Scand J Gastroenterol 2016 26;51(4):400-9. Epub 2015 Oct 26.

a Center for Digestive Diseases, Karolinska University Hospital, Karolinska Institute , Stockholm , Sweden ;

Objective: The role of peptide YY3-36 (PYY3-36), glucagon-like peptide-1 (GLP-1), and glucose homoeostasis in symptom development in functional dyspepsia (FD) is unclear. The aim was to investigate postprandial changes in plasma PYY3-36, GLP-1, glucose and insulin, and the relationship between PYY3-36, GLP-1, dyspeptic symptoms, and satiety measurements.

Materials And Methods: Thirty-six patients with functional dyspepsia and 18 healthy controls consumed a liquid meal at two occasions. Firstly, a fixed amount of 250 mL (300 kcal) was consumed and gastric emptying was assessed using the paracetamol method. Secondly, participants drank 75 mL (90 kcal) per five min until maximal satiety. PYY3-36, GLP-1, glucose, and insulin concentrations were assessed. Satiety measures and dyspeptic symptoms were registered using visual analogue scales.

Results: Gastric emptying, glucose, PYY3-36, and GLP-1 concentrations were similar in patients and controls. Patients with epigastric pain syndrome had higher postprandial insulin levels. Patients reported more satiety, nausea, and pain. Area under the curve (AUC) for GLP-1 correlated positively to nausea in patients and negatively to nausea in controls during a single meal. AUC for PYY3-36 correlated similarly to sensation of fullness in the two groups; however, the correlation was negative for the single meal and positive for the satiety test.

Conclusions: In epigastric pain syndrome, postprandial insulin secretion seems to be increased. Neither GLP-1 nor PYY3-36 secretion is altered in functional dyspepsia, but postprandial GLP-1 secretion seems to correlate with nausea and PYY3-36 to the sensation of fullness, and therefore, these hormones might be involved in symptom generation.
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http://dx.doi.org/10.3109/00365521.2015.1101780DOI Listing
November 2016
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