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Objective: To determine if temporal glucose profiles differed between 1) women who were randomized to real-time continuous glucose monitoring (RT-CGM) or self-monitored blood glucose (SMBG), 2) women who used insulin pumps or multiple daily insulin injections (MDIs), and 3) women whose infants were born large for gestational age (LGA) or not, by assessing CGM data obtained from the Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial (CONCEPTT).Research Design and Methods: Standard summary metrics and functional data analysis (FDA) were applied to CGM data from the CONCEPTT trial (RT-CGM, n = 100; SMBG, n = 100) taken at baseline and at 24- and 34-weeks' gestation. Multivariable regression analysis determined if temporal differences in 24-h glucose profiles occurred between comparators in each of the three groups.Results: FDA revealed that women using RT-CGM had significantly lower glucose (0.4-0.8 mmol/L [7-14 mg/dL]) for 7 h/day (0800 h to 1200 h and 1600 h to 1900 h) compared with those with SMBG. Women using pumps had significantly higher glucose (0.4-0.9 mmol/L [7-16 mg/dL]) for 12 h/day (0300 h to 0600 h, 1300 h to 1800 h, and 2030 h to 0030 h) at 24 weeks with no difference at 34 weeks compared with MDI. Women who had an LGA infant ran a significantly higher glucose by 0.4-0.7 mmol/L (7-13 mg/dL) for 4.5 h/day at baseline, by 0.4-0.9 mmol/L (7-16 mg/dL) for 16 h/day at 24 weeks, and by 0.4-0.7 mmol/L (7-13 mg/dL) for 14 h/day at 34 weeks.Conclusions: FDA of temporal glucose profiles gives important information about differences in glucose control and its timing, which are undetectable by standard summary metrics. Women using RT-CGM were able to achieve better daytime glucose control, reducing fetal exposure to maternal glucose. [ABSTRACT FROM AUTHOR]

Oncolytic viruses (OVs) target and destroy cancer cells while sparing their normal counterparts. These viruses have been evaluated in numerous studies at both pre-clinical and clinical levels and the recent Food and Drug Administration (FDA) approval of an oncolytic herpesvirus-based treatment raises optimism that OVs will become a therapeutic option for cancer patients. However, to improve clinical outcome, there is a need to increase OV efficacy. In addition to killing cancer cells directly through lysis, OVs can stimulate the induction of anti-tumour immune responses. The host immune system thus represents a "double-edged sword" for oncolytic virotherapy: on the one hand, a robust anti-viral response will limit OV replication and spread; on the other hand, the immune-mediated component of OV therapy may be its most important anti-cancer mechanism. Although the relative contribution of direct viral oncolysis and indirect, immune-mediated oncosuppression to overall OV efficacy is unclear, it is likely that an initial period of vigorous OV multiplication and lytic activity will most optimally set the stage for subsequent adaptive anti-tumour immunity. In this review, we consider the use of histone deacetylase (HDAC) inhibitors as a means of boosting virus replication and lessening the negative impact of innate immunity on the direct oncolytic effect. We also discuss an alternative approach, aimed at potentiating OV-elicited anti-tumour immunity through the blockade of immune checkpoints. We conclude by proposing a two-phase combinatorial strategy in which initial OV replication and spread is maximised through transient HDAC inhibition, with anti-tumour immune responses subsequently enhanced by immune checkpoint blockade. [ABSTRACT FROM AUTHOR]

Metformin is the first-line treatment for many people with type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM) to maintain glycaemic control. Recent evidence suggests metformin can cross the placenta during pregnancy, thereby exposing the fetus to high concentrations of metformin and potentially restricting placental and fetal growth. Offspring exposed to metformin during gestation are at increased risk of being born small for gestational age (SGA) and show signs of 'catch up' growth and obesity during childhood which increases their risk of future cardiometabolic diseases. The mechanisms by which metformin impacts on the fetal growth and long-term health of the offspring remain to be established. Metformin is associated with maternal vitamin B12 deficiency and antifolate like activity. Vitamin B12 and folate balance is vital for one carbon metabolism, which is essential for DNA methylation and purine/pyrimidine synthesis of nucleic acids. Folate:vitamin B12 imbalance induced by metformin may lead to genomic instability and aberrant gene expression, thus promoting fetal programming. Mitochondrial aerobic respiration may also be affected, thereby inhibiting placental and fetal growth, and suppressing mammalian target of rapamycin (mTOR) activity for cellular nutrient transport. Vitamin supplementation, before or during metformin treatment in pregnancy, could be a promising strategy to improve maternal vitamin B12 and folate levels and reduce the incidence of SGA births and childhood obesity. Heterogeneous diagnostic and screening criteria for GDM and the transient nature of nutrient biomarkers have led to inconsistencies in clinical study designs to investigate the effects of metformin on folate:vitamin B12 balance and child development. As rates of diabetes in pregnancy continue to escalate, more women are likely to be prescribed metformin; thus, it is of paramount importance to improve our understanding of metformin's transgenerational effects to develop prophylactic strategies for the prevention of adverse fetal outcomes. [ABSTRACT FROM AUTHOR]

This study examines nutritional intakes in Gestational diabetes mellitus piloting the myfood24 tool, to explore frequency of meals/snacks, and daily distribution of calories and carbohydrates in relation to glycaemic control. A total of 200 women aged 20–43 years were recruited into this prospective observational study between February 2015 and February 2016. Diet was assessed using myfood24, a novel online 24-h dietary recall tool. Out of 200 women 102 completed both ≥1 dietary recalls and all blood glucose measurements. Blood glucose was self-measured as part of usual care. Differences between groups meeting and exceeding glucose targets in relation to frequency of meal/snack consumption and nutrients were assessed using chi-squared and Mann–Whitney tests. Women achieving a fasting glucose target <5.3 mmol/L, compared to those exceeding it, consumed three meals (92% vs. 78%: p = 0.04) and three snacks (10% vs. 4%: p = 0.06) per day, compared with two or less; and in relation to evening snacks, consumed a higher percentage of daily energy (6% vs. 5%: p = 0.03) and carbohydrates (8% vs. 6%: p = 0.01). Achieving glycaemic control throughout the day was positively associated with snacking (p = 0.008). Achieving glucose targets was associated with having more snacks across the day, and may be associated with frequency and distribution of meals and nutrients. A larger study is required to confirm this. [ABSTRACT FROM AUTHOR]

Background: Continuous glucose monitoring (CGM) provides far greater detail about fetal exposure to maternal glucose across the 24 hour day, but recommended summary statistics give no dynamic information about the glucose profile across 24 hours. Aim: To examine whether differences in temporal glucose control occur in women with type 1 diabetes who develop large for gestational age infants (LGA). Research Design and Methods: CGM data was available from 200 pregnant women (100 CGM intervention; 100 controls) in the CONCEPTT study, at baseline, 24 and 34 weeks gestation. All women were being treated to tight glycemic targets (mean HbA1c 6.4% at 34 weeks gestation). Functional data analysis (FDA) was applied to determine differences in temporal glucose profiles. LGA was defined as birth weight ≥90th percentile adjusted for infant sex, gestational age, maternal BMI, ethnicity and parity. Results: 122/200 women had a LGA infant (61%). FDA revealed that those women who gave birth to a LGA infant ran a significantly higher glucose (by 9-14mg/dL; 0.5-0.8 mmol/l) for 16.5 hours of the day compared to those women who did not have a LGA infant (see fig). Conclusion: Women who go on to have LGA infants have significantly higher fetal exposure to glucose across the 24 hour day, despite being treated to tight glucose targets. Disclosure: E.M. Scott: Advisory Panel; Self; Abbott. Speaker's Bureau; Self; Abbott, Eli Lilly and Company. H.R. Murphy: Advisory Panel; Self; Medtronic MiniMed, Inc. D. Feig: Advisory Panel; Self; Medtronic. Speaker's Bureau; Self; Medtronic. G. Law: None. Funding: JDRF; Canadian Clinical Trials Network; National Institute for Health Research [ABSTRACT FROM AUTHOR]

Background: The CONCEPTT randomized trial of CGM in pregnant women with type 1 diabetes showed significant improvement in pregnancy outcomes, but no difference in mean CGM glucose between those allocated to CGM vs. capillary glucose monitoring. Whilst summary statistics are recommended for the reporting of CGM data, they do not give dynamic information about the glucose profile across 24 hours. Aim: To determine, using novel functional data analysis (FDA), if differences in the temporal glucose profile occurred in women randomized to CGM. Methods: CGM data was available from 200 pregnant women (100 CGM intervention; 100 control) in the CONCEPTT study, at baseline, 24 and 34 weeks gestation. FDA was applied to the glucose data to generate functional glucose curves and multivariable statistical analysis applied. Results: Despite having the same mean CGM glucose as those on capillary glucose monitoring alone 121 vs. 126 mg/dL; 6.7 vs. 7.0 mmol/l p=0.14, FDA revealed that pregnant CGM users were in fact running a significantly lower glucose (by 9-14mg/dL; 0.5-0.8 mmol/l) for a total of 8 hours a day (08.30-12.30 and 15.00-19.00). Conclusion: Analysis of temporal glucose profiles gives key information about glucose control, missed by commonly reported CGM metrics. The women allocated to CGM ran a significantly lower glucose for 33% of the day. Disclosure: E.M. Scott: Advisory Panel; Self; Abbott. Speaker's Bureau; Self; Abbott, Eli Lilly and Company. H.R. Murphy: Advisory Panel; Self; Medtronic MiniMed, Inc. D. Feig: Advisory Panel; Self; Medtronic. Speaker's Bureau; Self; Medtronic. G. Law: None. Funding: JDRF; Canadian Clinical Trials Network; National Institute for Health Research [ABSTRACT FROM AUTHOR]

myfood24 is an online 24 hr dietary recall tool developed for nutritional epidemiological research. Its clinical application has been unexplored. This mixed methods study explores the feasibility and usability of myfood24 as a food record in a clinical population, women with gestational diabetes (GDM). Women were asked to complete five myfood24 food records, followed by a user questionnaire (including the System Usability Scale (SUS), a measure of usability), and were invited to participate in a semi-structured interview. Of the 199 participants, the mean age was 33 years, mean booking body mass index (BMI) 29.7 kg/m2, 36% primiparous, 57% White, 33% Asian. Of these, 121 (61%) completed myfood24 at least once and 73 (37%) completed the user questionnaire; 15 were interviewed. The SUS was found to be good (mean 70.9, 95% CI 67.1, 74.6). Interviews identified areas for improvement, including optimisation for mobile devices, and as a clinical management tool. This study demonstrates that myfood24 can be used as an online food record in a clinical population, and has the potential to support self-management in women with GDM. However, results should be interpreted cautiously given the responders' demographic characteristics. Further research to explore the barriers and facilitators of uptake in people from ethnic minority and lower socioeconomic backgrounds is recommended. [ABSTRACT FROM AUTHOR]

Background: In patients with type 1 diabetes who are not pregnant, closed-loop (automated) insulin delivery can provide better glycemic control than sensor-augmented pump therapy, but data are lacking on the efficacy, safety, and feasibility of closed-loop therapy during pregnancy.Methods: We performed an open-label, randomized, crossover study comparing overnight closed-loop therapy with sensor-augmented pump therapy, followed by a continuation phase in which the closed-loop system was used day and night. Sixteen pregnant women with type 1 diabetes completed 4 weeks of closed-loop pump therapy (intervention) and sensor-augmented pump therapy (control) in random order. During the continuation phase, 14 of the participants used the closed-loop system day and night until delivery. The primary outcome was the percentage of time that overnight glucose levels were within the target range (63 to 140 mg per deciliter [3.5 to 7.8 mmol per liter]).Results: The percentage of time that overnight glucose levels were in the target range was higher during closed-loop therapy than during control therapy (74.7% vs. 59.5%; absolute difference, 15.2 percentage points; 95% confidence interval, 6.1 to 24.2; P=0.002). The overnight mean glucose level was lower during closed-loop therapy than during control therapy (119 vs. 133 mg per deciliter [6.6 vs. 7.4 mmol per liter], P=0.009). There were no significant differences between closed-loop and control therapy in the percentage of time in which glucose levels were below the target range (1.3% and 1.9%, respectively; P=0.28), in insulin doses, or in adverse-event rates. During the continuation phase (up to 14.6 additional weeks, including antenatal hospitalizations, labor, and delivery), glucose levels were in the target range 68.7% of the time; the mean glucose level was 126 mg per deciliter (7.0 mmol per liter). No episodes of severe hypoglycemia requiring third-party assistance occurred during either phase.Conclusions: Overnight closed-loop therapy resulted in better glucose control than sensor-augmented pump therapy in pregnant women with type 1 diabetes. Women receiving day-and-night closed-loop therapy maintained glycemic control during a high proportion of the time in a period that encompassed antenatal hospital admission, labor, and delivery. (Funded by the National Institute for Health Research and others; Current Controlled Trials number, ISRCTN71510001.). [ABSTRACT FROM AUTHOR]