The main objective of this study was to investigate the effect of maternal obesity on offspring’s glucose metabolism during the perinatal period. Maternal obesity was established by feeding C57BL/6 mice with a high-fat (HF) diet before or during pregnancy. Our results showed that prolonged prepregnant HF feeding but not HF feeding during pregnancy significantly reduced fetal and neonatal blood glucose concentrations. Remarkably, elevated blood insulin concentrations and increased activation of insulin signaling were observed in fetuses and neonates from prepregnant HF-fed dams. In addition, significantly larger β-cell areas were observed in pancreases of fetuses and neonates from prepregnant HF-fed dams. Although there was no significant change in placental cross-sectional area or GLUT 1 expression, prepregnant HF feeding significantly enhanced the expression of genes that control placental fatty acid supply. Interestingly, reducing fatty acid supply to the placenta and fetus by placental-specific knockout of adipose triglyceride lipase not only reduced fetal β-cell area and blood insulin concentration but also attenuated prepregnant HF feeding–induced reduction in offspring blood glucose concentrations during the perinatal period. Together, these results indicate that placental and fetal fatty acid supply plays an important role in fetal β-cell development, insulin secretion, and glucose metabolism. Prolonged prepregnant maternal HF feeding resembles pregravid maternal obesity in mice, which reduces fetal and neonatal blood glucose concentrations by enhancing fetal β-cell development and insulin secretion.
Patients receiving iodixanol had significantly lower moderate-to-severe or severe discomfort than patients receiving iopamidol, with heat being the major contributor. Iodixanol use trended towards better image quality but the difference was not statistically significant. No significant differences in incidences of overall or contrast-related AEs or delayed skin reactions were seen between the two groups. These data support that CM osmolality may be a key determinant of patient discomfort.
We read the article by Reed et al. (1) from the July 2009 issue of JACC: Cardiovascular Interventions with great interest, and we applaud the authors for their thoughtful analysis. We are pleased to see that the results, although not reaching statistical significance, favored iodixanol. However, there are several points to consider when interpreting the data. We would welcome any response from the authors.First, the meta-analysis excluded publications favoring isosmolar iodixanol that were available during the scope of the published data capture. These publications include Hardiek et al. (2) (iodixanol vs. iopamidol), Nie et al. (3) (iodixanol vs. iopromide), and the Hernandez et al. (4) European Society of Cardiology abstract (iodixanol vs. ioversol).Second, the studies included in the analysis varied regarding important parameters (e.g., patient demographic data, definition of contrast-induced acute kidney injury [CI-AKI]). One important variation is in the post-dose serum creatinine (SCr) protocol employed in terms of numbers of measurements and their timing. For example, 4 of the included studies collected only a single SCr measurement with sample timing over a wide period of time. Assuming that each patient's renal response to contrast media varies, these studies might not have obtained a true CI-AKI rate. These studies are: the CARE (Cardiac Angiography in Renally Impaired Patients) study (iopamidol vs. iodixanol; SCr measured sometime between 45 and 120 h) (5); the PREDICT (A randomized double-blind comparison of contrast-induced nephropathy after low-or isoosmolar contrast agent exposure) study (iopamidol vs. iodixanol; SCr measured sometime between 48 and 72 h) (6); the ACTIVE (Investigators in the Abdominal Computed Tomography: Iomeron 400 versus Visipaque 320 Enhancement) study (iomeprol vs. iodixanol; SCr measure sometime between 48 and 72 h) (7); and the IMPACT (Contrast-induced nephropathy in patients with chronic kidney disease undergoing computed tomography: a double-blind comparison of iodixanol and iopamidol) study (iopamidol vs. iodixanol; SCr measure sometime between 42 and 78 h) (8).To date, there are no CI-AKI studies statistically favoring a low-osmolar contrast agent that obtained a true CI-AKI rate through multiple fixed (timing standardized for all patients in the study) SCr collections.Third, the IMPACT study (8) should be excluded from the meta-analysis. The IMPACT study was a combination of 2 separate studies, VIRPACT (Visipaque 320 and Isovue 370 in Patients Undergoing Computed Tomographic Angiography of the Liver) and INVICTA (Isovue 370 and Visipaque 320 in Patients Undergoing Computed Tomographic Angiography of the Lower Extremities). Neither study examined contrast-induced nephropathy (CIN) as the primary end point, contrary to the impression given by the article by Barrett et al. (8). The primary objective of INVICTA was to examine the image quality in patients undergoing peripheral vascular imaging with either iopamidol-370 or iodixanol-320. The primary objective of VIRPACT was...
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