Pulse pressure and cardiovascular autonomic neuropathy according to duration of type 1 diabetes.

peer reviewedBACKGROUND: To evaluate changes in pulse pressure (PP) and markers of cardiovascular autonomic neuropathy (CAN) according to duration of type 1 diabetes mellitus (T1DM). METHODS: This cross-sectional controlled study evaluated 159 diabetic patients during a 3-min posture test (standing-squatting-standing) with continuous measurement of systolic (SBP), diastolic (DBP) and mean (MBP) blood pressure by a Finapres device. Arterial stiffness was indirectly assessed by PP and the slope of PP as a function of MBP calculated during the whole 3-min test. CAN was assessed by the expiration/inspiration pulse interval ratio (E/I R-R ratio) during deep breathing and by three indices measured during the squatting test. Patients were divided into four groups according to diabetes duration ( 30 years from group 1 to group 4, respectively) and compared with age-matched non-diabetic subjects. RESULTS: PP progressively increased (p < 0.0001) and PP/MBP decreased (p < 0.0005) according to T1DM duration, whereas these parameters remained almost unchanged in age-matched control subjects. E/I ratio (p < 0.0001) and baroreflex gain (p < 0.0005) progressively decreased with T1DM duration. The parasympathetic index (squatting test vagal ratio-SqTv) significantly increased (p < 0.0001), whereas the sympathetic index (squatting test sympathetic ratio-SqTs) only tended to decrease (p = 0.12) according to diabetes duration. No such changes in CAN indices were observed in the non-diabetic population. CONCLUSIONS: PP increased according to T1DM duration in an age range where PP remained almost stable in controls, in agreement with accelerated arterial stiffening due to chronic hyperglycaemia. The baroreflex gain decreased and other indices of CAN also deteriorated with diabetes duration, more so indices reflecting parasympathetic rather than sympathetic dysfunction

La microalbuminurie du patient diabétique de type 1 n'est pas associée à une augmentation de la pression artérielle moyenne ou pulsée, mais à une hypertension relative en position accroupie

Peer reviewe

Effets de la durée du diabète de type 1 sur la pression artérielle pulsée : résultats d’une étude transversale comparative à un groupe contrôle non diabétique.

peer reviewe

Arterial pulse pressure in relation to the duration of type 1 diabetes: a cross-sectional controlled study

Diabetes mellitus and arterial pulse pressure (PP) are two independent cardiovascular risk factors. This cross-sectional study investigated the influence of diabetes duration on PP in type 1 diabetic patients without any cardiovascular disease. PP was measured continuously during 3 minutes (active orthostatic test: 1 min standing--1 min squatting--1 min standing) using a fingertip plethysmograph (Finapres) in 159 type 1 diabetic patients aged 20-60 yrs. They were divided into 4 groups according to diabetes duration: (1) G1 : 30 yrs (n=18). In order to separate the effects of age from the effects of diabetes duration, diabetic patients were compared to age- and sex-matched non diabetic controls. PP (expressed in mmHg; mean +/- SD) was higher in men than in women in both diabetic (58 +/- 15 vs. 50 +/- 14; p = 0.001) and non diabetic subjects (55 +/- 14 vs. 47 +/- 12; p = 0.001). Overall PP was higher in diabetic than in non diabetic individuals (54 +/- 15 vs. 50 +/- 13; p = 0.025). PP progressively increased according to diabetes duration: 47 +/- 16 vs. 51 +/- 13 vs. 59 +/- 14 vs. 62 +/- 12, from G1 to G4 respectively; p or =8% (55 +/- 16), with (57 +/- 17) or without (54 +/- 14) microalbuminuria, treated (56 +/- 14) or not (54 +/- 15) by inhibitors of the renin-angiotensin system. In conclusion, PP progressively increased with the duration of type 1 diabetes, independently of age. Such increase was more marked in squatting than in standing position. The role of such PP rise in the increased cardiovascular risk of patients with type 1 diabetes, although suspected in the recent EURODIAB Prospective Complications Study, deserves further investigation

Clinical Chorioamnionitis and Neurodevelopment at 5 Years of Age in Children Born Preterm: The EPIPAGE-2 Cohort Study.

OBJECTIVE To assess the association between clinical chorioamnionitis and neurodevelopmental disorders at 5 years of age in children born preterm. STUDY DESIGN EPIPAGE 2 is a national, population-based cohort study of children born before 35 weeks of gestation in France in 2011. We included infants born alive between 24+0 and 34+6 weeks following preterm labor (PTL) or preterm premature rupture of membranes (PPROM). Clinical chorioamnionitis was defined as maternal fever before labor (>37.8°C) with at least two of the following criteria: maternal tachycardia, hyperleukocytosis, uterine contractions, purulent amniotic fluid, or fetal tachycardia. The primary outcome was a composite including cerebral palsy, coordination disorders, cognitive disorders, sensory disorders, or behavioral disorders. We also analyzed each of these disorders separately as secondary outcomes. We performed a multivariable analysis using logistic regression models. We accounted for the non-independence of twins and missing data by generalized estimating equation models and multiple imputations, respectively. RESULTS Among 2927 children alive at 5 years of age, 124 (3%) were born in a context of clinical chorioamnionitis. Overall, 8.2% and 9.6% of children exposed and unexposed respectively to clinical chorioamnionitis had moderate-to-severe neurodevelopmental disorders. After multiple imputations and multivariable analysis, clinical chorioamnionitis was not associated with the occurrence of moderate-to-severe neurodevelopmental disorders (adjusted odds ratio = 0.9, 95%CI: 0.5-1.8). CONCLUSION We did not find any association between clinical chorioamnionitis and neurodevelopmental disorders at 5 years of age in children born before 35 weeks of gestation after PTL or PPROM

Hepatocyte and keratinocyte growth factors and their receptors in human lung emphysema

BACKGROUND: Hepatocyte and keratinocyte growth factors are key growth factors in the process of alveolar repair. We hypothesized that excessive alveolar destruction observed in lung emphysema involves impaired expression of hepatocyte and keratinocyte growth factors or their respective receptors, c-met and keratinocyte growth factor receptor. The aim of our study was to compare the expression of hepatocyte and keratinocyte growth factors and their receptors in lung samples from 3 groups of patients: emphysema; smokers without emphysema and non-smokers without emphysema. METHODS: Hepatocyte and keratinocyte growth factor proteins were analysed by immunoassay and western blot; mRNA expression was measured by real time quantitative polymerase chain reaction. RESULTS: Hepatocyte and keratinocyte growth factors, c-met and keratinocyte growth factor receptor mRNA levels were similar in emphysema and non-emphysema patients. Hepatocyte growth factor mRNA correlated negatively with FEV1 and the FEV1/FVC ratio both in emphysema patients and in smokers with or without emphysema. Hepatocyte and keratinocyte growth factor protein concentrations were similar in all patients' groups. CONCLUSION: The expression of hepatocyte and keratinocyte growth factors and their receptors is preserved in patients with lung emphysema as compared to patients without emphysema. Hepatocyte growth factor mRNA correlates with the severity of airflow obstruction in smokers

Special Care and School Difficulties in 8-Year-Old Very Preterm Children: The Epipage Cohort Study

OBJECTIVES: To investigate school difficulties, special care and behavioral problems in 8 year-old very preterm (VPT) children. PATIENT AND METHODS: Longitudinal population-based cohort in nine regions of France of VPT children and a reference group born at 39-40 weeks of gestation (WG). The main outcome measures were information about school, special care and behavioral problems using Strengths and Difficulties Questionnaire from a questionnaire to parents. RESULTS: Among the 1439 VPT children, 5% (75/1439) were in a specialised school or class, 18% (259/1439) had repeated a grade in a mainstream class and 77% (1105/1439) were in the appropriate grade-level in mainstream class; these figures were 1% (3/327) , 5% (16/327) and 94% (308/327) , respectively, for the reference group. Also, 15% (221/1435) of VPT children in a mainstream class received support at school versus 5% (16/326) of reference group. More VPT children between the ages of five and eight years received special care (55% (794/1436)) than children born at term (38% (124/325)); more VPT children (21% (292/1387)) had behavioral difficulties than the reference group (11% (35/319)). School difficulties, support at school, special care and behavioral difficulties in VPT children without neuromotor or sensory deficits varied with gestational age, socioeconomic status, and cognitive score at the age of five. CONCLUSIONS: Most 8-year-old VPT children are in mainstream schools. However, they have a high risk of difficulty in school, with more than half requiring additional support at school and/or special care. Referral to special services has increased between the ages of 5 and 8 years, but remained insufficient for those with borderline cognitive scores

Hepatic Stem-like Phenotype and Interplay of Wnt/β-Catenin and Myc Signaling in Aggressive Childhood Liver Cancer

SummaryHepatoblastoma, the most common pediatric liver cancer, is tightly linked to excessive Wnt/β-catenin signaling. Here, we used microarray analysis to identify two tumor subclasses resembling distinct phases of liver development and a discriminating 16-gene signature. β-catenin activated different transcriptional programs in the two tumor types, with distinctive expression of hepatic stem/progenitor markers in immature tumors. This highly proliferating subclass was typified by gains of chromosomes 8q and 2p and upregulated Myc signaling. Myc-induced hepatoblastoma-like tumors in mice strikingly resembled the human immature subtype, and Myc downregulation in hepatoblastoma cells impaired tumorigenesis in vivo. Remarkably, the 16-gene signature discriminated invasive and metastatic hepatoblastomas and predicted prognosis with high accuracy