SummaryBackgroundPregnant women with type 1 diabetes are a high-risk population who are recommended to strive for optimal glucose control, but neonatal outcomes attributed to maternal hyperglycaemia remain suboptimal. Our aim was to examine the effectiveness of continuous glucose monitoring (CGM) on maternal glucose control and obstetric and neonatal health outcomes.MethodsIn this multicentre, open-label, randomised controlled trial, we recruited women aged 18–40 years with type 1 diabetes for a minimum of 12 months who were receiving intensive insulin therapy. Participants were pregnant (≤13 weeks and 6 days' gestation) or planning pregnancy from 31 hospitals in Canada, England, Scotland, Spain, Italy, Ireland, and the USA. We ran two trials in parallel for pregnant participants and for participants planning pregnancy. In both trials, participants were randomly assigned to either CGM in addition to capillary glucose monitoring or capillary glucose monitoring alone. Randomisation was stratified by insulin delivery (pump or injections) and baseline glycated haemoglobin (HbA1c). The primary outcome was change in HbA1c from randomisation to 34 weeks' gestation in pregnant women and to 24 weeks or conception in women planning pregnancy, and was assessed in all randomised participants with baseline assessments. Secondary outcomes included obstetric and neonatal health outcomes, assessed with all available data without imputation. This trial is registered with ClinicalTrials.gov, number NCT01788527.FindingsBetween March 25, 2013, and March 22, 2016, we randomly assigned 325 women (215 pregnant, 110 planning pregnancy) to capillary glucose monitoring with CGM (108 pregnant and 53 planning pregnancy) or without (107 pregnant and 57 planning pregnancy). We found a small difference in HbA1c in pregnant women using CGM (mean difference −0·19%; 95% CI −0·34 to −0·03; p=0·0207). Pregnant CGM users spent more time in target (68% vs 61%; p=0·0034) and less time hyperglycaemic (27% vs 32%; p=0·0279) than did pregnant control participants, with comparable severe hypoglycaemia episodes (18 CGM and 21 control) and time spent hypoglycaemic (3% vs 4%; p=0·10). Neonatal health outcomes were significantly improved, with lower incidence of large for gestational age (odds ratio 0·51, 95% CI 0·28 to 0·90; p=0·0210), fewer neonatal intensive care admissions lasting more than 24 h (0·48; 0·26 to 0·86; p=0·0157), fewer incidences of neonatal hypoglycaemia (0·45; 0·22 to 0·89; p=0·0250), and 1-day shorter length of hospital stay (p=0·0091). We found no apparent benefit of CGM in women planning pregnancy. Adverse events occurred in 51 (48%) of CGM participants and 43 (40%) of control participants in the pregnancy trial, and in 12 (27%) of CGM participants and 21 (37%) of control participants in the planning pregnancy trial. Serious adverse events occurred in 13 (6%) participants in the pregnancy trial (eight [7%] CGM, five [5%] control) and in three (3%) participants in the planning pregnancy trial (two [4%] CGM and one [2%] control). The most...

Angiogenesis restores blood flow to healing tissues, a process that is inhibited by high doses of glucocorticoids. However, the role of endogenous glucocorticoids and the potential for antiglucocorticoid therapy to enhance angiogenesis is unknown. Using in vitro and in vivo models of angiogenesis in mice, we examined effects of (i) endogenous glucocorticoids, (ii) blocking endogenous glucocorticoid action with the glucocorticoid receptor antagonist RU38486, and (iii) abolishing local regeneration of glucocorticoids by the enzyme 11␤-hydroxysteroid dehydrogenase type 1 (11␤HSD1). Glucocorticoids, administered at physiological concentrations, inhibited angiogenesis in an in vitro aortic ring model and in vivo in polyurethane sponges implanted s.c. RU38486-enhanced angiogenesis in s.c. sponges, in healing surgical wounds, and in the myocardium of mice 7 days after myocardial infarction induced by coronary artery ligation. 11␤HSD1 knockout mice showed enhanced angiogenesis in vitro and in vivo within sponges, wounds, and infarcted myocardium. Endogenous glucocorticoids, including those generated locally by 11␤HSD1, exert tonic inhibition of angiogenesis. Inhibition of 11␤HSD1 in liver and adipose has been advocated to reduce cardiovascular risk in the metabolic syndrome: these data suggest that 11␤HSD1 inhibition offers a previously uncharacterized therapeutic approach to improve healing of ischemic or injured tissue. myocardial infarction ͉ wound healing

Aims/hypothesis Minimal evidence supports the efficacy of flash monitoring in lowering HbA 1c . We sought to assess the impact of introducing flash monitoring in our centre. Methods We undertook a prospective observational study to assess change in HbA 1c in 900 individuals with type 1 diabetes following flash monitoring (comparator group of 518 with no flash monitoring). Secondary outcomes included changes in hypoglycaemia, quality of life, flash monitoring data and hospital admissions. Results Those with baseline HbA 1c ≥58 mmol/mol (7.5%) achieved a median −7 mmol/mol (interquartile range [IQR] −13 to −1) (0.6% [−1.2 to −0.1]%) change in HbA 1c ( p < 0.001). The percentage achieving HbA 1c <58 mmol/mol rose from 34.2% to 50.9% ( p < 0.001). Median follow-up was 245 days (IQR 182 to 330). Individuals not using flash monitoring experienced no change in HbA 1c across a similar timescale ( p = 0.508). Higher HbA 1c ( p < 0.001), younger age at diagnosis ( p = 0.003) and lower social deprivation ( p = 0.024) were independently associated with an HbA 1c fall of ≥5 mmol/mol (0.5%). More symptomatic (OR 1.9, p < 0.001) and asymptomatic (OR 1.4, p < 0.001) hypoglycaemia was reported after flash monitoring. Following flash monitoring, regimen-related and emotional components of the diabetes distress scale improved although the proportion with elevated anxiety (OR 1.2, p = 0.028) and depression (OR 2.0, p < 0.001) scores increased. Blood glucose test strip use fell from 3.8 to 0.6 per day ( p < 0.001). Diabetic ketoacidosis admissions fell significantly following flash monitoring ( p = 0.043). Conclusions/interpretation Flash monitoring is associated with significant improvements in HbA 1c and fewer diabetic ketoacidosis admissions. Higher rates of hypoglycaemia may relate to greater recognition of hitherto unrecognised events. Impact upon quality of life parameters was mixed but overall treatment satisfaction was overwhelmingly positive. Electronic supplementary material The online version of this article (10.1007/s00125-019-4894-1) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

The Freestyle Libre flash glucose monitoring (FGM; Abbott Diabetes Care, Witney, UK) system was introduced in the United Kingdom in 2013. Although similar to conventional continuous glucose monitoring (CGM) systems, a few significant differences exist. FGM sensors are factory calibrated and therefore do not require calibration with blood glucose testing over their 14-day lifespan. FGM is also considerably cheaper than conventional CGM 1 but lacks alarm features and connectivity with continuous subcutaneous insulin infusion (CSII) devices, such as low-glucose suspend.2 The accuracy and usability of FGM have been validated in patients with both type 1 and type 2 diabetes. 3 We sought to prospectively assess the impact of introducing FGM to patients attending our type 1 diabetes clinic in a university teaching hospital, over a 16-week period. In particular, we assessed the impact on HbA1c, hypoglycemia (recorded and self-reported) and quality of life measures (Diabetes Distress Scale). The only inclusion criteria were a diagnosis of type 1 diabetes and a willingness to upload FGM data at least monthly. Data were analyzed as intention-to-treat.Of the 25 participants, 13 were men, and the mean age was 39.8 ± 2.0 years. Mean duration of diabetes was 19 ± 2 years. A total of 8 patients were treated with CSII, and 17 used multiple daily injections. Immediately prior to commencement of FGM, the mean HbA1c of participants was 8.0 ± 0.14%, which did not differ from the mean of the previous 4 clinic recorded HbA1c values (8.0 ± 0.2%, P = .833). Mean HbA1c fell from 8.0 ± 0.14% to 7.5 ± 0.14% (-0.48%, P = .001) following 16 weeks of FGM. The number of people with an HbA1c of 7.5% or below more than doubled after FGM use (Figure 1). The mean reduction in HbA1c was greater in those with a baseline HbA1c > 7.5%: -0.59 ± 0.15% compared to −0.2 ± 0.11% in those with HbA1c <7.5% at baseline (P = .005). Female participants had greater mean reduction in HbA1c (-0.74 ± 0.19%) compared to men (-0.23 ± 0.15%, P = .049) despite no significant difference in baseline HbA1c (8.2 ± 0.25% vs 7.8 ± 0.14%, P = .174). Of participants, 24% (6/25) achieved an HbA1c reduction of greater than 1.0%.Episodes of hypoglycemia (glucose <72 mg/dl), as determined from FGM glucose data, reduced from 17 in the first 2 weeks of use to 12 (IQR 8.5-16) in the final 2 weeks (P = .019). Significant reductions were observed in the Diabetes Distress Scale mean score (P = .006), as well as emotional burden (P = .035) and regimen-related distress subscores (P = .005). FGM use was associated with a significant increase in delivering bolus insulin 15-20 minutes in advance of meals (compared to immediately before or after meals), from 16% to 44% (P = .026).In summary, these results support the wider use of FGM to improve outcomes in people with type 1 diabetes. Benefits are realized across a number of important domains including improved HbA1c, hypoglycemia, and quality of life. Figure 1. FGM increases the proportion of patients achieving good glycemic control. Data ...