Aims. Polycystic ovarian syndrome (PCOS) is a common endocrine disorder characterised by ovarian morphological, systemic biochemical, and menstrual changes. Women with PCOS are at significantly increased risk of raised fasting glucose, impaired glucose tolerance, and diabetes. Recognition of these complications and early intervention are key to good health outcomes. We sought to identify DNA methylation patterns that may predict future diabetes onset in this high-risk PCOS population. Patients and Methods. Peripheral blood samples from women with PCOS and women with PCOS who later developed diabetes, were analysed by Illumina HumanMethylation450 BeadChip-arrays. Bisulphite-Pyrosequencing™ was used to validate and confirm array methylation data. Results. Array analyses identified 273 differentially methylated CpG loci (≥0.2 β-value change) at initial diagnosis of PCOS, between women who did or did not later develop diabetes. 19 of these sites demonstrated differential methylation in the same direction in ≥five sample pairs. Methylation in three of the candidates (cg11897887, cg02819655, and cg25542007) showed the best concordance with corresponding array β-values, and, most clearly differentiated ‘cases’ from ‘controls’. Conclusions. We have identified novel methylation biomarkers that could predict future onset of diabetes in this high-risk population. Use of methylation analyses to identify women who are likely to develop diabetes at diagnosis of PCOS may facilitate timely lifestyle interventions to reduce future morbidity.

Introduction: Women with gestational diabetes (GDM) are at greatly increased risk of type 2 diabetes (T2DM). The UK guidance recommends screening for T2DM at around 6 weeks post-partum and annually thereafter. We evaluated conformity to this guidance in two separate time periods. Methods: The proportion of tests performed within guidance was assessed using longitudinal plasma glucose and glycated haemoglobin data in two cohorts (1999-2007, n=251; 2015-2016, n=260) from hospital records on women previously diagnosed with GDM. Results: In the 1999-2007 and 2015-2016 cohorts, 59.8% and 35.0% of women had the recommended post-partum testing, respectively (p<0.001); just 13.5% and 14.2%, respectively, underwent the first annual test on time. During long-term follow-up of the 1999-2007 cohort (median follow-up: 12.3 years), the proportion of women tested in any given year averaged 34.2% over a 17-year period; there was a progressive decline in the proportion of women receiving a yearly test with time since delivery (p=0.002). Over the follow-up period, 85 women from the 1999-2007 cohort developed blood test results in the diabetic range with a median time to presumed DM diagnosis of 5.2 years (range 0.11-15.95 years). Kaplan-Meier analysis showed that 18.8% of women had blood test results in the diabetes range by 5 years and 37.8% by 10 years post-partum. Conclusions: Despite high profile guidelines and a clear clinical rationale to screen women with a past diagnosis of GDM, many women did not receive adequate screening for T2DM, both in the short- and long-term. This suggests alternative approaches are needed to ensure effective follow-up of this high-risk group. To have an impact, interventions need to be tailored to a young, generally healthy group in which traditional approaches to follow-up may not be best suited.

The Short Synacthen Test is the way that we most often determine whether people's adrenal glands are working. We here have shown that an extra blood sample taken at 60 minutes post Synacthen vs a 30 minute sample alone, may make the test more effective at excluding those people who do not need to go on hydrocortisone supplementation or need further evaluation.

Our findings illustrate the widespread collateral impact of implementing measures to mitigate the impact of COVID-19 in people with, or being investigated for diabetes mellitus (DM). Ironically, failure to focus of the wider implications for people with DM and other groups with long-term conditions, may place them at increased risk of poor outcomes from SARS-CoV-2 infection itself, irrespective of the implications for their longer-term health prospects.