Maternal fuel metabolism is known to exert long range effects on the later development of children of diabetic mothers. Recently cardiovascular disease in adult life has been linked retrospectively ...with foetal malnutrition. The aim of this study was to identify whether markers for fuel-related cardiovascular programming exist for the offspring of diabetic pregnancy.
Sixty-one children aged 5 to 11 years, of mothers with Type I (insulin-dependent) diabetes mellitus were compared with 57 randomly selected control children of non-diabetic mothers similar in age, sex and social class. Fasting blood was taken for plasma glucose, insulin, lipids, IGF-1, plasminogen activating inhibitor 1 (PAI-1) and the adhesion molecules ICAM-1, VCAM-1 and E-Selectin.
Fasting glucose and insulin were similar in the two groups. Differences existed between the offspring of diabetic and non-diabetic pregnancies (mean +/- SD) for total cholesterol (4.45+/-0.56 vs 4.18+/-0.66, p=0.03 ), LDL cholesterol (2.73+/-0.49 vs 2.39+/-0.54, p=0.001), Cholesterol-to-HDL ratio (3.41+/-0.76 vs 3.09+/-0.73, p=0.03), IGF-1 (22.5+/-7.3 vs 19.3+/-8, p=0.04), PAI-1 (20.1+/-6.2 vs 14.9+/-7.3, p=0.000), VCAM-1 (1852+/-444 vs 1509+/-385, p=0.000) and E-Selectin (geometric mean; 83.1 vs 63.9, p=0.001).
These results indicate that important differences in cardiovascular risk factors exist between glucose-tolerant children of Type I diabetic and non-diabetic mothers, even in childhood. These data suggest that offspring of diabetic mothers might be at an increased risk for the development of vascular disease in later life.
Background. Transcriptionally silent human immunodeficiency virus type 1 (HIV-1) DNA persists in resting memory CD4 + T cells despite antiretroviral therapy. In a primary cell model, the ...antialcoholism drug disulfiram has been shown to induce HIV-1 transcription in latently infected resting memory CD4 + T cells at concentrations achieved in vivo. Methods. We conducted a single-arm pilot study to evaluate whether 500 mg of disulfiram administered daily for 14 days to HIV-1–infected individuals on stable suppressive antiretroviral therapy would result in reversal of HIV-1 latency with a concomitant transient increase in residual viremia or depletion of the latent reservoir in resting memory CD4 + T cells. Results. Disulfiram was safe and well tolerated. There was a high level of subject-to-subject variability in plasma disulfiram levels. The latent reservoir did not change significantly (1.16-fold change; 95% confidence interval CI, .70- to 1.92-fold; P = .56). During disulfiram administration, residual viremia did not change significantly compared to baseline (1.53-fold; 95% CI, .88- to 2.69-fold; P = .13), although residual viremia was estimated to increase by 1.88-fold compared to baseline during the postdosing period (95% CI, 1.03- to 3.43-fold; P = .04). In a post hoc analysis, a rapid and transient increase in viremia was noted in a subset of individuals (n = 6) with immediate post-dose sampling (HIV-1 RNA increase, 2.96-fold; 95% CI, 1.29- to 6.81-fold; P = .01). Conclusions. Administration of disulfiram to patients on antiretroviral therapy does not reduce the size of the latent reservoir. A possible dose-related effect on residual viremia supports future studies assessing the impact of higher doses on HIV-1 production. Disulfiram affects relevant signaling pathways and can be safely administered, supporting future studies of this drug.
OBJECTIVE: This study was undertaken to compare preprandial and postprandial capillary glucose monitoring in pregnant women with type 1 diabetes.
STUDY DESIGN: Sixty-one women with type 1 diabetes ...were randomly assigned at 16 weeks' gestation to preprandial or postprandial blood glucose monitoring using memory-based glucose reflectance meters throughout pregnancy. Serial measurements of hemoglobin A1c and fructosamine were obtained throughout pregnancy. Insulin, glucose, and insulin-like growth factor-I (IGF-I) were measured in cord blood at delivery. Neonatal anthropometric measures were performed within 72 hours of delivery
RESULTS: Maternal age, parity, age of onset of diabetes, number of prior miscarriages, smoking status, social class, weight gain in pregnancy, and compliance with therapy were similar in the two groups. The postprandial monitoring group had a significantly reduced incidence of preeclampsia (3% vs 21%,
P<.048), a greater success in achieving glycemic control targets (55% vs 30%,
P<.001) and a smaller neonatal triceps skinfold thickness (4.5±0.9 vs 5.1±1.3,
P
=
.05).
CONCLUSION: Postprandial capillary blood glucose monitoring in type 1 diabetic pregnancy may significantly reduce the incidence of preeclampsia and neonatal triceps skinfold thickness compared with preprandial monitoring.
Genetic variation is a well‐known indicator of population fitness yet is not typically included in monitoring programs for sensitive species. Additionally, most programs monitor populations at one ...scale, which can lead to potential mismatches with ecological processes critical to species' conservation. Recently developed methods generating hierarchically nested population units (i.e., clusters of varying scales) for greater sage‐grouse (Centrocercus urophasianus) have identified population trend declines across spatiotemporal scales to help managers target areas for conservation. The same clusters used as a proxy for spatial scale can alert managers to local units (i.e., neighborhood‐scale) with low genetic diversity, further facilitating identification of management targets. We developed a genetic warning system utilizing previously developed hierarchical population units to identify management‐relevant areas with low genetic diversity within the greater sage‐grouse range. Within this warning system we characterized conservation concern thresholds based on values of genetic diversity and developed a statistical model for microsatellite data to robustly estimate these values for hierarchically nested populations. We found that 41 of 224 neighborhood‐scale clusters had low genetic diversity, 23 of which were coupled with documented local population trend decline. We also found evidence of cross‐scale low genetic diversity in the small and isolated Washington population, unlikely to be reversed through typical local management actions alone. The combination of low genetic diversity and a declining population suggests relatively high conservation concern. Our findings could further facilitate conservation action prioritization in combination with population trend assessments and (or) local information, and act as a base‐line of genetic diversity for future comparison. Importantly, the approach we used is broadly applicable across taxa.
We intended to identify the prognostic factors and the results of interventions on patients with liver metastatic midgut carcinoids. Five institutions that are part of United Kingdom and Ireland ...neuroendocrine tumour (NET) group took part in this study. Patients were included if they had histology proven NET of midgut origin and liver metastases at the time of the study. Clinical and biochemical data were collected retrospectively from hospital charts, pathology reports, radiology reports and biochemistry records for each patient. Three hundred and sixty patients were included in the study. The median survival from date of diagnosis was 7.69 years (confidence interval (CI) 6.40–8.99) and 5.95 years (CI 5.02–6.88) from date of diagnosis of liver metastases. On univariate analysis, increasing age at diagnosis, increasing urinary hydroxyindole acetic acid levels, increasing plasma chromogranin A levels, high Ki67, high tumour volume and treatment with chemotherapy were identified as factors associated with a significantly poorer outcome. Resection of liver metastases, resection of small bowel primary, treatment with somatostatin analogue therapy and treatment with peptide receptor therapy were associated with improved prognosis. Multivariate analysis revealed that age at diagnosis (P=0.014), Ki67 level (P=0.039) and resection of primary (P=0.015) were independent predictors of survival. This is the largest study to our knowledge looking specifically at the prognosis and clinical course of patients with liver metastatic midgut NETs. For the first time, we have shown that Ki67 and resection of primary are independent predictors of survival for this group of patients.
Objective The physiological importance of the C3 epimers of vitamin D (3-epi-25OHD2/3) is uncertain and there have been limited studies determining the levels of these epimers in human populations. ...The aims of the current study were (1) to determine 3-epi-25OHD2/3 levels throughout non-diabetic and T1DM pregnancy, (2) to examine the relationships between 25OHD and 3-epi-25OHD, (3) to assess the impact of maternal BMI on 3-epi-25OHD and examine associations with markers of glycaemic control. Methodology An observational study of 52 pregnant controls without diabetes and 65 pregnant women with T1DM in a university teaching hospital. 25OHD and 3-epi-25OHD were measured by liquid chromatography tandem mass spectrometry. Results 3-Epi-25OHD was found in 90.2% of control (median 0.9 nmol/L; range 0.1–5.9 nmol/L), and in 94.5% of T1DM, women (median 1.4 nmol/L; range 0.1–10.5 nmol/L). In both control and T1DM groups, maternal and cord 3-epi-25OHD correlated significantly with 25OHD. Seasonal variation in maternal 3-epi-25OHD levels was evident in both groups; Summer levels were significantly higher than all other seasons in the control group ( p < 0.001) and significantly higher than Spring ( p = 0.003) and Winter ( p < 0.001) in the T1DM group. In T1DM women HbA1c was significantly negatively correlated with 3-epi-25OHD at trimesters 1 and 2 ( p = 0.049; p = 0.001) and with cord 3-epi-25OHD ( p = 0.012). Maternal BMI >30 kg/m2 had a significant negative impact on 3-epi-25OHD. Conclusion Maternal 3-epi-25OHD exhibits seasonal variation and, in common with cord 3-epi-25OHD, correlates with 25OHD throughout both non-diabetic and T1D pregnancy. In T1DM women 3-epi-25OHD is associated with a key marker of glycaemic control.
PDF
