7 research outputs found
Polymorphisms of the glucose transporter (GLUT1) gene are associated with diabetic nephropathy
Polymorphisms of the glucose transporter (GLUT1) gene are associated with diabetic nephropathy.BackgroundDiabetic nephropathy (DN) is a major cause of morbidity and mortality in patients with type 1 diabetes mellitus. Recent studies suggest that genetic factors, including polymorphisms in the flanking region of the aldose reductase gene (5â˛ALR2), play an important role in the pathogenesis of nephropathy. Glucose transporter (GLUT1) activity has been implicated in renal hypertrophy and extracellular matrix formation in mesangial cells. The aim was to investigate the frequency of a polymorphism within the GLUT1 gene in 186 Caucasoid patients with type 1 diabetes and 104 normal controls.MethodsAmplimers flanking the Xba-I polymorphic site in the second intron were employed to amplify DNA from subjects. The amplified DNA was restricted with endonuclease Xba-I, separated by gel electrophoresis, and visualized. In the absence of an Xba-I site, a fragment of 1.1 kilobase was seen, whereas fragments of 0.9 and 0.2 were generated if the Xba-I site was present.ResultsThere was a highly significant increase in the frequency of the 1.1 allele in those patients with nephropathy (N = 70) compared with those with no proteinuria or retinopathy after 20 years of diabetes (uncomplicated N = 44, 61.4 vs. 40.9%, respectively, P < 0.001). The 1.1/1.1 genotype was also significantly increased in the nephropathy group compared with the uncomplicated group of patients (37.1 vs. 13.6%, respectively, P < 0.01). The frequency of the 1.1/1.1 genotype was similar in 30 patients with retinopathy but not nephropathy when compared with the uncomplicated group of patients (13.6 vs. 16.7%). Furthermore, only 8 out of 49 patients with DN had the Z+2 5â˛ALR2 DN âprotectiveâ allele and the 0.9 GLUT1 allele in contrast to 21 out of 39 uncomplicated patients (P < 0.0002).ConclusionThese results suggest that the GLUT1 gene together with the aldose reductase gene are associated with susceptibility to DN in patients with type 1 diabetes
High glucose-induced DNA-binding activities of nuclear factor of activated T cells 5 and carbohydrate response element binding protein to the myo-inositol oxygenase gene are inhibited by sorbinil in peripheral blood mononuclear cells from patients with type 1 diabetes mellitus and nephropathy
High glucose induction of DNA-binding activity of the transcription factor NFÎşB in patients with diabetic nephropathy
Protective effect of statin therapy on connective tissue growth factor induction by diabetes in vivo
Pregnancy and neonatal outcomes of COVID -19: coreporting of common outcomes from PAN-COVID and AAP-SONPM registries
Objective
Few large cohort studies have reported data on maternal, fetal, perinatal and neonatal outcomes associated with severe acute respiratory syndrome coronavirus 2 (SARSâCoVâ2) infection in pregnancy. We report the outcome of infected pregnancies from a collaboration formed early during the pandemic between the investigators of two registries, the UK and Global Pregnancy and Neonatal outcomes in COVIDâ19 (PANâCOVID) study and the American Academy of Pediatrics (AAP) Section on NeonatalâPerinatal Medicine (SONPM) National Perinatal COVIDâ19 Registry.
Methods
This was an analysis of data from the PANâCOVID registry (1 January to 25 July 2020), which includes pregnancies with suspected or confirmed maternal SARSâCoVâ2 infection at any stage in pregnancy, and the AAPâSONPM National Perinatal COVIDâ19 registry (4 April to 8 August 2020), which includes pregnancies with positive maternal testing for SARSâCoVâ2 from 14âdays before delivery to 3âdays after delivery. The registries collected data on maternal, fetal, perinatal and neonatal outcomes. The PANâCOVID results are presented overall for pregnancies with suspected or confirmed SARSâCoVâ2 infection and separately in those with confirmed infection.
Results
We report on 4005 pregnant women with suspected or confirmed SARSâCoVâ2 infection (1606 from PANâCOVID and 2399 from AAPâSONPM). For obstetric outcomes, in PANâCOVID overall and in those with confirmed infection in PANâCOVID and AAPâSONPM, respectively, maternal death occurred in 0.5%, 0.5% and 0.2% of cases, early neonatal death in 0.2%, 0.3% and 0.3% of cases and stillbirth in 0.5%, 0.6% and 0.4% of cases. Delivery was preterm (<â37âweeks' gestation) in 12.0% of all women in PANâCOVID, in 16.1% of those women with confirmed infection in PANâCOVID and in 15.7% of women in AAPâSONPM. Extreme preterm delivery (<â27âweeks' gestation) occurred in 0.5% of cases in PANâCOVID and 0.3% in AAPâSONPM. Neonatal SARSâCoVâ2 infection was reported in 0.9% of all deliveries in PANâCOVID overall, in 2.0% in those with confirmed infection in PANâCOVID and in 1.8% in AAPâSONPM; the proportions of neonates tested were 9.5%, 20.7% and 87.2%, respectively. The rates of a smallâforâgestationalâage (SGA) neonate were 8.2% in PANâCOVID overall, 9.7% in those with confirmed infection and 9.6% in AAPâSONPM. Mean gestationalâageâadjusted birthâweight Zâscores were â0.03 in PANâCOVID and â0.18 in AAPâSONPM.
Conclusions
The findings from the UK and USA registries of pregnancies with SARSâCoVâ2 infection were remarkably concordant. Preterm delivery affected a higher proportion of women than expected based on historical and contemporaneous national data. The proportions of pregnancies affected by stillbirth, a SGA infant or early neonatal death were comparable to those in historical and contemporaneous UK and USA data. Although maternal death was uncommon, the rate was higher than expected based on UK and USA population data, which is likely explained by underascertainment of women affected by milder or asymptomatic infection in pregnancy in the PANâCOVID study, although not in the AAPâSONPM study. The data presented support strong guidance for enhanced precautions to prevent SARSâCoVâ2 infection in pregnancy, particularly in the context of increased risks of preterm delivery and maternal mortality, and for priority vaccination of pregnant women and women planning pregnancy. Copyright Š 2021 ISUOG. Published by John Wiley & Sons Ltd