Autoimmune hypercalcemia due to autoantibodies against the calcium-sensing receptor

Context Autoimmune hypocalciuric hypercalcemia (AHH) is an acquired disorder caused by the presence of blocking autoantibodies against the calcium-sensing receptor (CaSR). Few cases of this condition have been described to date in the literature. Objective The objectives of this study were to describe two patients in whom the presence of AHH was suspected and to assess the patients for the presence of CaSR antibodies. Methods CaSR antibodies were detected and characterised by immunoprecipitation assays, CaSR peptide ELISAs, and functional assays based on the calcium-stimulated accumulation of inositol-1-phosphate in a mammalian cell line expressing the CaSR. Results Both patients presented with an acquired form of hypocalciuric hypercalcemia. Mutational analyses of CASR, GNA11 and AP2S1 for familial hypocalciuric hypercalcemia, were negative. According to the presence of Hashimoto’s disease in one patient and latent autoimmune diabetes of adulthood and thyroid autoimmunity in the other, AHH was suspected. Immunoprecipitation assays detected CaSR antibodies in both patients. Analysis of the antibody binding sites revealed two main epitopes at amino acids 41-69 and 114-126. Preincubation with purified CaSR antibodies against epitope 114-126 resulted in a significant decrease in inositol-1-phophate accumulation upon calcium-stimulation of mammalian cells expressing the CaSR, suggesting that the antibodies had receptor-blocking activity. Conclusions AHH is to be suspected in patients with an acquired biochemical pattern of PTH-dependant hypocalciuric hypercalcemia, especially in those with other concomitant autoimmune diseases. Diagnosis by means of detecting CaSR antibodies may help to better characterise this probably under-reported condition

Which growth standards should be used to identify large- and small-for-gestational age infants of mothers with type 1 diabetes? A pre-specified analysis of the CONCEPTT trial.

BACKGROUND: Offspring of women with type 1 diabetes are at increased risk of fetal growth patterns which are associated with perinatal morbidity. Our aim was to compare rates of large- and small-for-gestational age (LGA; SGA) defined according to different criteria, using data from the Continuous Glucose Monitoring in Type 1 Diabetes Pregnancy Trial (CONCEPTT). METHODS: This was a pre-specified analysis of CONCEPTT involving 225 pregnant women and liveborn infants from 31 international centres ( ClinicalTrials.gov NCT01788527; registered 11/2/2013). Infants were weighed immediately at birth and GROW, INTERGROWTH and WHO centiles were calculated. Relative risk ratios, sensitivity and specificity were used to assess the different growth standards with respect to perinatal outcomes, including neonatal hypoglycaemia, hyperbilirubinaemia, respiratory distress, neonatal intensive care unit (NICU) admission and a composite neonatal outcome. RESULTS: Accelerated fetal growth was common, with mean birthweight percentiles of 82.1, 85.7 and 63.9 and LGA rates of 62, 67 and 30% using GROW, INTERGROWTH and WHO standards respectively. Corresponding rates of SGA were 2.2, 1.3 and 8.9% respectively. LGA defined according to GROW centiles showed stronger associations with preterm delivery, neonatal hypoglycaemia, hyperbilirubinaemia and NICU admission. Infants born > 97.7th centile were at highest risk of complications. SGA defined according to INTERGROWTH centiles showed slightly stronger associations with perinatal outcomes. CONCLUSIONS: GROW and INTERGROWTH standards performed similarly and identified similar numbers of neonates with LGA and SGA. GROW-defined LGA and INTERGROWTH-defined SGA had slightly stronger associations with neonatal complications. WHO standards underestimated size in preterm infants and are less applicable for use in type 1 diabetes. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov . number NCT01788527 . Trial registered 11/2/2013

The unexplored role of sedentary time and physical activity in glucose and lipid metabolism-related placental mRNAs in pregnant women who are obese: the DALI lifestyle randomised controlled trial

Objective: We aimed to explore: (i) the association of sedentary time (ST) and physical activity (PA) during pregnancy with the placental expression of genes related to glucose and lipid metabolism in pregnant women who are obese; (ii) maternal metabolic factors mediating changes in these placental transcripts; and (iii) cord blood markers related to the mRNAs mediating neonatal adiposity. Design: Multicentre randomised controlled trial. Setting: Hospitals in nine European countries. Population: A cohort of 112 pregnant women with placental tissue. Methods: Both ST and moderate-to-vigorous PA (MVPA) levels were measured objectively using accelerometry at three time periods during pregnancy. Main outcome measures: Placental mRNAs (FATP2, FATP3, FABP4, GLUT1 and PPAR-γ) were measured with NanoString technology. Maternal and fetal metabolic markers and neonatal adiposity were assessed. Results: Longer periods of ST, especially in early to middle pregnancy, was associated with lower placental FATP2 and FATP3 expression (P \u3c 0.05), whereas MVPA at baseline was inversely associated with GLUT1 mRNA (P = 0.02). Although placental FATP2 and FATP3 expression were regulated by the insulin–glucose axis (P \u3c 0.05), no maternal metabolic marker mediated the association of ST/MVPA with placental mRNAs (P \u3e 0.05). Additionally, placental FATP2 expression was inversely associated with cord blood triglycerides and free fatty acids (FFAs; P \u3c 0.01). No cord blood marker mediated neonatal adiposity except for cord blood leptin, which mediated the effects of PPAR-γ on neonatal sum of skinfolds (P \u3c 0.05). Conclusions: In early to middle pregnancy, ST is associated with the expression of placental genes linked to lipid transport. PA is hardly related to transporter mRNAs. Strategies aimed at reducing sedentary behaviour during pregnancy could modulate placental gene expression, which may help to prevent unfavourable fetal and maternal pregnancy outcomes. Tweetable abstract: Reducing sedentary behaviour in pregnancy might modulate placental expression of genes related to lipid metabolism in women who are obese

Beliefs, barriers and preferences of European overweight women to adopt a healthier lifestyle in pregnancy to minimize risk of developing gestational diabetes mellitus: an explorative study

Introduction: Overweight and obese women are at high risk of developing gestational diabetes mellitus (GDM). Lifestyle programs might help curb the GDM risk. We explored beliefs, perceived barriers and preferences regarding lifestyle changes among overweight European pregnant women to help inform the development of future high quality lifestyle interventions. Methods: An explorative mixed methods, two-staged study was conducted to gather information from pregnant European women (BMI≥25kg/m2). In three European countries (Belgium, Netherlands, United Kingdom) interviews were conducted, followed by questionnaires in six other European countries (Austria, Denmark, Ireland, Italy, Poland, Spain). Content analysis, descriptive and chi square statistics were applied (p<0.05). Results: Women preferred to obtain detailed information about their personal risk. The health of their baby was major motivating factor. Perceived barriers for physical activity included pregnancy-specific issues such as tiredness and experiencing physical complaints. Insufficient time was a barrier more frequently reported by women with children. Abstaining from snacking was identified as a challenge for the majority of women, especially for those without children. Women preferred to obtain support from their partner, as well as health professionals and valued flexible lifestyle programs. Conclusions: Healthcare professionals need to inform overweight pregnant women about their personal risk, discuss lifestyle modification and assist in weight management. Lifestyle programs should be tailored to the individual, taking into account barriers experienced by overweight first-time mothers and multipara women

The importance of maternal insulin resistance throughout pregnancy on neonatal adiposity

Background: Although previous studies evaluated the association of maternal health parameters with neonatal adiposity, little is known regarding the complexity of the relationships among different maternal health parameters throughout pregnancy and its impact on neonatal adiposity. Objectives: To evaluate the direct and indirect associations between maternal insulin resistance during pregnancy, in women with obesity, and neonatal adiposity. In addition, associations between maternal fasting glucose, triglycerides (TG), non-esterified fatty acids (NEFA), and neonatal adiposity were also assessed. Methods: This is a longitudinal, secondary analysis of the DALI study, an international project conducted in nine European countries with pregnant women with obesity. Maternal insulin resistance (HOMA-IR), fasting glucose, TG, and NEFA were measured three times during pregnancy (<20, 24-28, and 35-37 weeks of gestation). Offspring neonatal adiposity was estimated by the sum of four skinfolds. Structural equation modelling was conducted to evaluate the direct and indirect relationships among the variables of interest. Results: Data on 657 mother-infant pairs (50.7% boys) were analysed. Neonatal boys exhibited lower mean sum of skinfolds compared to girls (20.3 mm, 95% CI 19.7, 21.0 vs 21.5 mm, 95% CI 20.8, 22.2). In boys, maternal HOMA-IR at <20 weeks was directly associated with neonatal adiposity (β = 0.35 mm, 95% CI 0.01, 0.70). In girls, maternal HOMA-IR at 24-28 weeks was only indirectly associated with neonatal adiposity, which implies that this association was mediated via maternal HOMA-IR, glucose, triglycerides, and NEFA during pregnancy (β = 0.26 mm, 95% CI 0.08, 0.44). Conclusions: The timing of the role of maternal insulin resistance on neonatal adiposity depends on fetal sex. Although the association was time-dependent, maternal insulin resistance was associated with neonatal adiposity in both sexes

Usual dietary treatment of gestational diabetes mellitus assessed after control diet in randomized controlled trials : subanalysis of a systematic review and meta-analysis

Peer reviewe

The Weak Relationship between Vitamin D Compounds and Glucose Homeostasis Measures in Pregnant Women with Obesity : An Exploratory Sub-Analysis of the DALI Study

Altres ajuts: Netherlands Organization for Health Research and Development (ZonMw, 200310013); Polish Ministry of Science (2203/7, PR/2011/2); Odense University Free Research Fund; NIHR Clinical Research Network: Eastern; In Spain (CAIBER 1527-B-226); Spanish Diabetes Society (SED) XI Grant for clinical research projects in diabetes.Studies on the relationship between vitamin D (VitD) and glucose homeostasis usually consider either total VitD or 25OHD3 but not 25OHD2 and epimers. We aimed to evaluate the cross-sectional association of VitD compounds with glucose homeostasis measurements in pregnant women with overweight/obesity participating in the Vitamin D And Lifestyle Intervention for Gestational Diabetes Mellitus Prevention study. Methods: The analysis included 912 women. Inclusion criteria: <20 weeks gestation, body mass index ≥29 kg/m and information on exposure and outcome variables at baseline. Measurements: A 75 g OGTT at <20, 24-28 and 35-37 weeks gestation (except if previous diabetes diagnosis). Exposure variables: 25OHD2, 25OHD3 and C3-epimer. Outcome variables: fasting and post-challenge insulin sensitivity and secretion indices, corresponding disposition indices (DI), plasma glucose at fasting and 1 and 2 h, hyperglycemia in pregnancy (HiP). Statistics: Multivariate regression analyses with adjustment. Results: Baseline VitD sufficiency was 66.3%. Overall, VitD compounds did not show strong associations with any glucose homeostasis measures. 25OHD3 showed direct significant associations with: FPG at <20 and 24-28 weeks (standardized β coefficient (β) 0.124, p = 0.030 and 0.111, p = 0.026 respectively), 2 h plasma glucose at 24-28 weeks (β 0.120, p = 0.018), and insulin sensitivity (1/HOMA-IR, β 0.127, p = 0.027) at 35-37 weeks; it showed an inverse association with fasting DI (QUCKI*HOMA-β) at <20 and 24-28 weeks (β −0.124, p = 0.045 and β −0.148, p = 0.004 respectively). 25OHD2 showed direct associations with post-challenge insulin sensitivity (Matsuda, β 0.149, p = 0.048) at 24-28 weeks) and post-challenge DI (Matsuda*Stumvoll phase 1) at 24-28 and 35-37 weeks (β 0.168, p = 0.030, β 0.239, p = 0.006). No significant association with C3-epimer was observed at any time period. Conclusions: In these women with average baseline VitD in sufficiency range, VitD compounds did not show clear beneficial associations with glucose homeostasis measures

Traumapotilaan golden hour Kainuun ensihoidossa : Tutkimus traumapotilaan golden hour:n toteutumisesta sekä siihen vaikuttavista tekijöistä Kainuun ensihoidossa

Tutkimuksen tarkoituksena oli kuvailla Kainuun ensihoidon laatua traumapotilaiden hoidossa. Opinnäytetyömme on tehty yhteistyössä Kainuun sosiaali- ja terveydenhuollon kuntayhtymän ensihoidon kanssa. Tutkimuksen tavoitteena oli hyödyntää tutkimusta Kainuun ensihoidossa traumapotilaiden hoidon kehittämisessä. Tutkimuksemme on toteutettu kvantitatiivisena ja retrospektiivisena tutkimuksena. Aineiston keräämiseen käytimme valmista tiedonkeruupohjaa, johon keräsimme 391 ensihoitotehtävän tiedot. Analysoimme tutkimuksen tulokset Excel- ja SPSS-ohjelmilla. Tutkimuksen perusteella 50 % (N= 196) traumapotilaista pääsi kultaisen tunnin aikana lopulliseen hoitopaikkaan. Keskimäärin ensihoitajilla kului kohteessa 21 minuuttia, joka on yli suositellun 10 minuutin. Tutkimuksen mukaan 15 %:lla (N= 58) ensihoitotehtävistä kuljetus päästiin aloittamaan 10 minuutin sisällä. Tutkimuksessa kävi ilmi, että mitä enemmän kohteessa tehtiin hoitotoimenpiteitä, sitä pidempi kohteessa oloaika oli. Tutkimuksessa kävi ilmi, että ensihoitotehtävien kokonaisajasta suurin osa kului matkalla potilaan luokse ja potilaan kuljettamiseen hoitolaitokseen. Tämä selittyy Kainuun alueen pitkillä välimatkoilla. Ensihoitotehtävien kokonaisaika kasvoi huomattavasti, mikäli potilas jatkokuljetettiin Kainuun keskussairaalasta yliopistolliseen sairaalaan Ouluun. Ensihoitotehtävillä, joissa potilas jatkokuljetettiin, aikaa kului merkittävästi keskussairaalassa potilaan tilan stabilointiin ennen jat-kokuljetuksen aloittamista. Tutkimme myös vaikuttaako ensihoitotehtävien kokonaisaikaan eri viranomaisjohtajuudet. Tutkimuksen perusteella voidaan todeta, että poliisijohtoisilla ensihoitotehtävillä kohteessa oloaika oli keskimäärin kaikista lyhyin. Opinnäytetyötämme voidaan hyödyntää ensihoidon laadun kehittämiseksi Kainuun ensihoidossa sekä henkilöstön ammattitaidon ylläpitämiseksi. Tutkimustuloksia voidaan käyttää simulaatiokoulutuksen suunnittelun tukena, jolloin tunnistetaan mahdolliset kehittämishaasteet ensihoitajien toiminnassa. Traumapotilaiden lopullinen hoito tapahtuu aina sairaalassa, jossa on mahdollista saada mm. leikkaushoitoa. Jotta traumapotilas saa parasta mahdollista hoitoa, tulee ensihoidossa pyrkiä mahdollisimman nopeaan kuljetukseen, jolla pyritään turvaamaan traumapotilaan nopea sairaalahoitoon pääsy.Purpose of this study was to describe the quality of emergency care in Kainuu in trauma patients care. Our thesis is made in co-operation with emergency care centre of Kainuu. Objective of the study was to exploit research in developing of care for trauma patients in emergency care of Kainuu. Our study is implemented as a quantitative and retrospective research. For collecting the material, we used ready data collection sheet which we gathered the information of 391 alarms. We analyzed the result of the research by using Excel- and SPSS-programs. Based on the study 50% (N= 196) of trauma patients were transported in the final sequel care facility during the golden hour. Paramedics spent approximately 21 minutes on scene which is over than the recommended 10 minutes. According to the study in 15% (N= 58) of the alarms transportation was achieved to start within 10 minutes. The study showed that the on-scene time was the longer the more procedures were accomplished in the destination. The study also showed that most of the time on the alarms were spent by travelling to the patient and transporting the patient to care facility. This is explained by the long distances of the area of Kainuu. The total time of alarms was highly increased if the patient was sequel transported from central Hospital of Kainuu to University Hospital in Oulu. In alarms which the patient was sequel transported, significant amount of time was spent in central Hospital stabilizing the patient before continuing the transport. We also investigated if authority leaderships affect to the total time spent on alarms. The study lightened out that in those alarms which was lead by police, the on-scene time was averagely shortest. Our thesis can be utilized in developing the quality of emergency care in Kainuu and maintaining the professionality of personnel. Results of the study can be used as a support of simulation education which allows to identify the possible developing challenges in the action of paramedics. The final care of trauma patients always occurs at hospital where multiple procedures are availa-ble. To guarantee that the patient receives best care, must emergency care always strive to quick transportation which secures that patients gets quickly the care they need