Endocarditis protésica precoz por un germen atípico, absceso perivalvular mitral: rocking motion

80 year-old patient with an incidental finding of thrombotic mitral valve disease. Prosthetic mitral endocarditis probably as a complication of the previous finding (B. hanselae). This cause is unique due to the unusual clinical presentation and the cause of the infection. The new multimodality imaging techniques were a key factor to establish a correct diagnosis.Paciente de 80 años de edad con afectación trombótica sobre válvula mitral prótesica diagnósticada de forma incidental, que posteriormente desarrolló una endocarditis precoz (B. Hanselae) sobre la misma zona. El germen causante de la infección es atípico y cursó como una endocarditis con cultivo negativo. Las técnicas de imagen fueron clave para poder establecer un diagnóstica y tratamiento adecuados

Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT): a multicentre international randomised controlled trial.

BACKGROUND: Pregnant women with type 1 diabetes are a high-risk population who are recommended to strive for optimal glucose control, but neonatal outcomes attributed to maternal hyperglycaemia remain suboptimal. Our aim was to examine the effectiveness of continuous glucose monitoring (CGM) on maternal glucose control and obstetric and neonatal health outcomes. METHODS: In this multicentre, open-label, randomised controlled trial, we recruited women aged 18-40 years with type 1 diabetes for a minimum of 12 months who were receiving intensive insulin therapy. Participants were pregnant (≤13 weeks and 6 days' gestation) or planning pregnancy from 31 hospitals in Canada, England, Scotland, Spain, Italy, Ireland, and the USA. We ran two trials in parallel for pregnant participants and for participants planning pregnancy. In both trials, participants were randomly assigned to either CGM in addition to capillary glucose monitoring or capillary glucose monitoring alone. Randomisation was stratified by insulin delivery (pump or injections) and baseline glycated haemoglobin (HbA1c). The primary outcome was change in HbA1c from randomisation to 34 weeks' gestation in pregnant women and to 24 weeks or conception in women planning pregnancy, and was assessed in all randomised participants with baseline assessments. Secondary outcomes included obstetric and neonatal health outcomes, assessed with all available data without imputation. This trial is registered with ClinicalTrials.gov, number NCT01788527. FINDINGS: Between March 25, 2013, and March 22, 2016, we randomly assigned 325 women (215 pregnant, 110 planning pregnancy) to capillary glucose monitoring with CGM (108 pregnant and 53 planning pregnancy) or without (107 pregnant and 57 planning pregnancy). We found a small difference in HbA1c in pregnant women using CGM (mean difference -0·19%; 95% CI -0·34 to -0·03; p=0·0207). Pregnant CGM users spent more time in target (68% vs 61%; p=0·0034) and less time hyperglycaemic (27% vs 32%; p=0·0279) than did pregnant control participants, with comparable severe hypoglycaemia episodes (18 CGM and 21 control) and time spent hypoglycaemic (3% vs 4%; p=0·10). Neonatal health outcomes were significantly improved, with lower incidence of large for gestational age (odds ratio 0·51, 95% CI 0·28 to 0·90; p=0·0210), fewer neonatal intensive care admissions lasting more than 24 h (0·48; 0·26 to 0·86; p=0·0157), fewer incidences of neonatal hypoglycaemia (0·45; 0·22 to 0·89; p=0·0250), and 1-day shorter length of hospital stay (p=0·0091). We found no apparent benefit of CGM in women planning pregnancy. Adverse events occurred in 51 (48%) of CGM participants and 43 (40%) of control participants in the pregnancy trial, and in 12 (27%) of CGM participants and 21 (37%) of control participants in the planning pregnancy trial. Serious adverse events occurred in 13 (6%) participants in the pregnancy trial (eight [7%] CGM, five [5%] control) and in three (3%) participants in the planning pregnancy trial (two [4%] CGM and one [2%] control). The most common adverse events were skin reactions occurring in 49 (48%) of 103 CGM participants and eight (8%) of 104 control participants during pregnancy and in 23 (44%) of 52 CGM participants and five (9%) of 57 control participants in the planning pregnancy trial. The most common serious adverse events were gastrointestinal (nausea and vomiting in four participants during pregnancy and three participants planning pregnancy). INTERPRETATION: Use of CGM during pregnancy in patients with type 1 diabetes is associated with improved neonatal outcomes, which are likely to be attributed to reduced exposure to maternal hyperglycaemia. CGM should be offered to all pregnant women with type 1 diabetes using intensive insulin therapy. This study is the first to indicate potential for improvements in non-glycaemic health outcomes from CGM use. FUNDING: Juvenile Diabetes Research Foundation, Canadian Clinical Trials Network, and National Institute for Health Research

Monitorización continua de la glucosa en la gestación : estudio y tratamiento de las alteraciones del metabolismo hidrocarbonado

CONCEPTT (CONtinuous GluCosE Monitoring in Pregnant Women with Type 1 Diabetes in Trial) i DALI (Vitamin D And Lifestyle Intervention for Gestational Diabetes Mellitus Prevention) són assajos clínics internacionals multicèntrics que van utilitzar el monitoratge continu de la glucosa (MCG) en gestants, en el primer, com a part del tractament. L'objectiu principal d'aquesta tesi ha estat comparar la capacitat dels indicadors glucomètrics obtinguts de la MCG i dels biomarcadors de laboratori per predir resultats perinatals en gestants amb diabetes mellitus tipus 1 (DM1) participants a l'estudi CONCEPTT. Els objectius secundaris han sigut en primer lloc, determinar la freqüència de compliment dels objectius de MCG i de hemoblobina glicada (HbA1c) i avaluar les associacions entre el compliment dels objectius de MCG i d'HbA1c amb els resultats perinatals, també a les participants de l'estudi CONCEPTT. El següent objectiu secundari, a les participants del subestudi de MCG de l'assaig DALI, l'objectiu ha sigut comparar els indicadors glucomètrics obtinguts de la MCG en gestants amb risc de diabetes gestacional segons el grup d'intervenció d'estil de vida al qual van ser aleatoritzades. Per l'objectiu principal, es varen incloure 157 participants de l'estudi CONCEPTT i l'HbA1c, i el TIR es van associar significativament amb els resultats perinatals. La HbA1c pot predir RNGEG en el primer trimestre i part preterme, RNGEG, hipoglucèmia neonatal i ingrés a UCIN a les 24 i 34 setmanes. TIR pot predir tots els resultats perinatals analitzats a les 24 setmanes i alguns d'ells a les 12 i 34 setmanes. Alguns marcadors alternatius de laboratori van tenir resultats prometedors, però en general la seva capacitat predictiva no era clarament superior a la de l'HbA1c. Per l'objectiu secundari de compliments dels objectius de control de glucosa, es van incloure 221 participants de l'estudi CONCEPTT. Els objectius de TIR/TAR/TBR van ser aconseguits per 7.7/14.5/30.3% de les dones gestants en el primer trimestre, per 10.2/14.2/52.8% en el segon trimestre i per 35.5/37.2/52.9% en el tercer trimestre. L'assoliment dels objectius de MCG va ser baix, però va augmentar durant l'embaràs i amb l'ús de la MCG-tr. En les anàlisis ajustades, aconseguir l'objectiu de TBR es va associar amb un major risc de preeclàmpsia i hipoglucèmia neonatal. L'assoliment de l'objectiu d'HbA1c segons l'ADA va ser baix i no es va modificar durant l'embaràs (23.5/27.9/23.8% en primer, segon i tercer trimestres) però va augmentar amb l'ús de la MCG-tr. En les análisis ajustades, l'assoliment de l'objectiu d'HbA1c es va associar amb un menor risc de part preterme, RNGEG i hipoglucèmia neonatal. En el subestudi de MCG de l'assaig DALI, en el qual es van incloure 61 gestants, no es van trovar diferències significatives en les 11 variables glucomètriques analitzades en els quatre grups d'intervenció. En conclusió, en l'estudi CONCEPTT, l'HbA1c i el TIR van ser indicadors consistentment predictius dels resultats gestacionals analitzats. La taxa de compliment dels objectius de MCG i d'HbA1c fóu baixa, va augmentar al llarg de la gestació i tant per MCG com per HbA1c va ser més alta en el grup de MCG-tr a les 34 setmanes. En les análisis ajustades, l'assoliment de l'objectiu d'HbA1c segons l'ADA es va associar amb millors resultats perinatals, mentre que el compliment de l'objectiu de l'TBR ho va fer amb un major risc perinatal, el que justifica estudis addicionals. En l'estudi DALI la intervenció en l'estil de vida no va modificar els resultats de MCG a les 35-37 setmanes de gestació.CONCEPTT (CONtinuous GluCosE Monitoring in Pregnant Women with Type 1 Diabetes in Trial) y DALI (Vitamin D And Lifestyle Intervention for Gestational Diabetes Mellitus Prevention) son ensayos clínicos aleatorizados, internacionales y multicéntricos que utilizaron la monitorización continua de la glucosa (MCG) en mujeres gestantes, en el primero como parte del tratamiento. El objetivo principal de esta tesis doctoral ha sido comparar la capacidad de los indicadores glucométricos obtenidos de la MCG y de los biomarcadores de laboratorio para predecir resultados perinatales en mujeres gestantes con diabetes mellitus tipo 1 (DM1) participantes en el estudio CONCEPTT. Los objetivos secundarios, han sido en primer lugar, determinar la frecuencia de cumplimiento de los objetivos de MCG y de hemoglobina glicada (HbA1c) y evaluar las asociaciones entre el cumplimiento de dichos objetivos y los resultados perinatales, también en las participantes del estudio CONCEPTT. El siguiente objetivo secundario, en las participantes del subestudio de MCG del ensayo DALI, fue comparar los indicadores glucométricos obtenidos de la MCG en mujeres gestantes con riesgo de diabetes mellitus gestacional según el grupo de intervención de estilo de vida al que fueron aleatorizadas. Para el objetivo principal, se incluyeron 157 participantes del estudio CONCEPTT y HbA1c y TIR se asociaron significativamente con los resultados perinatales. La HbA1c puede predecir RNGEG en el primer trimestre y parto pretérmino, RNGEG, hipoglucemia neonatal e ingreso en UCIN a las 24 y 34 semanas. TIR puede predecir todos los resultados perinatales analizados a las 24 semanas y algunos de ellos a las 12 y a las 34 semanas. TAR tiene un rendimiento similar. Algunos marcadores de laboratorio alternativos tuvieron resultados significativos, pero en general su capacidad predictiva no era claramente superior a la de la HbA1c. Para el objetivo secundario de cumplimiento de objetivos de control de glucosa, se incluyeron 221 participantes del estudio CONCEPTT. Los objetivos de TIR/TAR/TBR fueron alcanzados por 7.7/14.5/30.3% de las mujeres gestantes en el primer trimestre, por 10.2/14.2/52.8% en el segundo trimestre y por 35.5/37.2/52.9% en el tercer trimestre. El logro de los objetivos de MCG fue bajo, pero aumentó durante el embarazo y con el uso de la MCG-tr. En los análisis ajustados, lograr el objetivo del TBR se asoció con un mayor riesgo de preeclampsia e hipoglucemia neonatal. El logro del objetivo de HbA1c según la ADA fue bajo y no se modificó durante el embarazo (23.5/27.9/23.8% en primer, segundo y tercer trimestres) pero aumentó con el uso de la MCG-tr. En los análisis ajustados, el logro del objetivo de HbA1c se asoció con un menor riesgo de parto pretérmino, RNGEG e hipoglucemia neonatal. En el subestudio de MCG del ensayo DALI, en el que se incluyeron 61 mujeres gestantes, no se encontraron diferencias significativas en las 11 variables glucométricas analizadas entre los 4 grupos de intervención. En conclusión, en el estudio CONCEPTT, la HbA1c y el TIR fueron indicadores consistentemente predictivos de los resultados perinatales analizados. La tasa de cumplimiento de los objetivos de MCG y de HbA1c fue baja, aumentó a lo largo de la gestación y tanto para MCG como HbA1c fue mayor en el grupo de MCG-tr a las 34 semanas de gestación. En los análisis ajustados, el logro del objetivo de HbA1c según la ADA se asoció con mejores resultados perinatales, mientras que el cumplimiento del objetivo del TBR lo hizo con un mayor riesgo perinatal, lo que justifica estudios adicionales. En el estudio DALI la intervención en el estilo de vida no modificó los resultados de MCG a las 35-37 semanas de gestación.CONCEPTT (CONtinuous GluCosE Monitoring in Pregnant Women with Type 1 Diabetes in Trial) and DALI (Vitamin D And Lifestyle Intervention for Gestational Diabetes Mellitus Prevention) are international multicenter randomized controlled trials that used continuous glucose monitoring (CGM) in pregnant women, as part of the treatment in the first case. The main aim of this thesis has been to assess the ability of CGM metrics and laboratory biomarkers to predict perinatal outcomes in pregnant women with type 1 diabetes mellitus (T1D) that participate in the CONCEPTT trial. Secondary objectives were, first, to determine the frequency of meeting CGM and glycated hemoglobin (HbA1c) targets and to assess the associations between meeting CGM and HbA1c targets with perinatal outcomes, again in CONCEPTT trial participants. The next secondary objective, in participants of the CGM substudy of the DALI trial, was to compare CGM metrics in pregnant women at risk of gestational diabetes mellitus according to the randomization group. For the main outcome, 157 participants of the CONCEPTT trial were included and HbA1c, and TIR were significantly associated with perinatal outcomes. HbA1c can predict LGA in the first trimester and preterm delivery, LGA, neonatal hypoglycemia, and NICU admission at 24 and 34 weeks. TIR can predict all perinatal outcomes analyzed at 24 weeks and some of them at 12 and 34 weeks. Some alternative laboratory biomarkers showed promise, but overall, they had lower predictive ability than HbA1c. In the secondary aim of achievement of glucose targets, 221 participants of the CONCEPTT study were included. TIR/TAR/TBR targets were achieved by 7.7/14.5/30.3% of pregnant women in the first trimester, by 10.2/14.2/52.8% in the second trimester and by 35.5/37.2/52.9% in the third trimester. CGM target attainment was low but increased during pregnancy and with the RT-CGM use. In the adjusted analyzes, achieving TBR target was associated with a higher risk of pre-eclampsia and neonatal hypoglycemia. ADA HbA1c target attainment was low and unchanged during pregnancy (23.5/27.9/23.8% in the first, second and third trimesters) but increased with rt-CGM use. In adjusted analyses, HbA1c target attainment was associated with a lower risk of preterm birth, LGA, and neonatal hypoglycemia. In the DALI trial CGM substudy, 61 pregnant women were included, and no significant differences were found in the 11 glucometric variables analyzed across the four intervention groups. In conclusion, in the CONCEPTT study, HbA1c and TIR were consistent predictive markers of analyzed pregnancy outcomes. The rate of CGM and HbA1c target attainment was low, increased throughout gestation and for both CGM and HbA1c was more likely to be achieved by rt-CGM users, at 34 weeks' gestation. In the adjusted analyses, ADA HbA1c target achievement was associated with better perinatal outcomes, while TBR target achievement was associated with increased risk, warranting further studies. In the DALI study, lifestyle intervention did not modify CGM results at 35-37 weeks' gestation

Continuous Glucose Monitoring Time-in-Range and HbA1c Targets in Pregnant Women with Type 1 Diabetes.

The CONCEPTT trial compared real-time Continuous Glucose Monitoring (RT-CGM) to capillary glucose monitoring in pregnant women with type 1 diabetes. We analyzed CGM and glycated hemoglobin (HbA1c) measures in first (n = 221), second (n = 197), and third (n = 172) trimesters, aiming to examine target glucose attainment and associations with pregnancy outcomes. CGM targets were Time-in-range (TIR) > 70%, Time-above-range (TAR) <25%, and Time-below-range (TBR) < 4%, and HbA1c targets < 6.5% (National Institute for Health and Care Excellence [NICE]) and HbA1c < 6.0% in second and third trimesters (American Diabetes Association [ADA]). TIR/TAR/TBR targets were achieved by 7.7/14.5/30.3% participants in first, 10.2/14.2/52.8% in second, and 35.5/37.2/52.9% in third trimesters. CGM target attainment was low but increased during pregnancy and with RT-CGM use. In the adjusted analyses, achieving TBR target was associated with a higher risk of pre-eclampsia and neonatal hypoglycemia. ADA HbA1c target attainment was low and unchanged during pregnancy (23.5/27.9/23.8%) but increased with RT-CGM use. In the adjusted analyses, HbA1c target attainment was associated with a lower risk of preterm birth, large-for-gestational age and neonatal hypoglycemia. We conclude that CONCEPTT trial participants had a low rate of CGM and of HbA1c target attainment. Attainment of CGM and NICE HbA1c targets increased throughout gestation and all targets (both NICE/ADA HbA1c and CGM) were more likely to be achieved by RT-CGM users, at 34 weeks' gestation. ADA HbA1c target achievement was independently associated with better perinatal outcomes, while the independent association of TBR target achievement with increased risk warrants further study. ClinicalTrials.gov Registration Identifier NCT01788527.The trial was funded by Juvenile Diabetes Research Foundation (JDRF) grants #17‐2011‐533, and grants under the JDRF Canadian Clinical Trial Network, a public‐private partnership including JDRF and FedDev Ontario and supported by JDRF #80‐2010‐585. Medtronic supplied the CGM sensors and CGM systems at reduced cost. The sub-analysis was funded by the EFSD/Sanofi European Pilot Research Grants for Innovative Measurement of Diabetes Outcomes, 2017. H.R.M. conducts independent research supported by the National Institute for Health Research (Career Development Fellowship, CDF-2013-06-035), and is supported by Tommy’s charity. C.L.M. is supported by the Diabetes UK Harry Keen Intermediate Clinical Fellowship (DUK-HKF 17/0005712) and the EFSD-Novo Nordisk Foundation Future Leader’s Award (NNF19SA058974)

Novel Biochemical Markers of Glycemia to Predict Pregnancy Outcomes in Women With Type 1 Diabetes.

OBJECTIVE: The optimal method of monitoring glycemia in pregnant women with type 1 diabetes remains controversial. This study aimed to assess the predictive performance of HbA1c, continuous glucose monitoring (CGM) metrics, and alternative biochemical markers of glycemia to predict obstetric and neonatal outcomes. RESEARCH DESIGN AND METHODS: One hundred fifty-seven women from the Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial (CONCEPTT) were included in this prespecified secondary analysis. HbA1c, CGM data, and alternative biochemical markers (glycated CD59, 1,5-anhydroglucitol, fructosamine, glycated albumin) were compared at ∼12, 24, and 34 weeks' gestation using logistic regression and receiver operating characteristic (ROC) curves to predict pregnancy complications (preeclampsia, preterm delivery, large for gestational age, neonatal hypoglycemia, admission to neonatal intensive care unit). RESULTS: HbA1c, CGM metrics, and alternative laboratory markers were all significantly associated with obstetric and neonatal outcomes at 24 weeks' gestation. More outcomes were associated with CGM metrics during the first trimester and with laboratory markers (area under the ROC curve generally 140 mg/dL [>7.8 mmol/L]) were the most consistently predictive CGM metrics. HbA1c was also a consistent predictor of suboptimal pregnancy outcomes. Some alternative laboratory markers showed promise, but overall, they had lower predictive ability than HbA1c. CONCLUSIONS: HbA1c is still an important biomarker for obstetric and neonatal outcomes in type 1 diabetes pregnancy. Alternative biochemical markers of glycemia and other CGM metrics did not substantially increase the prediction of pregnancy outcomes compared with widely available HbA1c and increasingly available CGM metrics (TIR and TAR)