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...

We previously reported a syndrome of severe hyperinsulinemia and early-onset hypertension in three patients with dominant-negative mutations in the nuclear hormone receptor peroxisome proliferator-activated receptor (PPAR)-␥. We now report the results of further detailed pathophysiological evaluation of these subjects, the identification of affected prepubertal children within one of the original families, and the effects of thiazolidinedione therapy in two subjects. These studies 1) definitively demonstrate the presence of severe peripheral and hepatic insulin resistance in the affected subjects; 2) describe a stereotyped pattern of partial lipodystrophy associated with all the features of the metabolic syndrome and nonalcoholic steatohepatitis; 3) document abnormalities in the in vivo function of remaining adipose tissue, including the inability of subcutaneous abdominal adipose tissue to trap and store free fatty acids postprandially and the presence of very low circulating levels of adiponectin; 4) document the presence of severe hyperinsulinemia in prepubertal carriers of the proline-467-leucine (P467L) PPAR-␥ mutation; 5) provide the first direct evidence of cellular resistance to PPAR-␥ agonists in mononuclear cells derived from the patients; and 6) report on the metabolic response to thiazolidinedione therapy in two affected subjects. Although the condition is rare, the study of humans with dominant-negative mutations in PPAR-␥ can provide important insight into the roles of this nuclear receptor in human metabolism. Diabetes 52:910 -917, 2003

The DALI Lifestyle Study Context: Lifestyle approaches for preventing gestational diabetes mellitus (GDM) have produced mixed results. Objective: The aim of this study was to compare the effectiveness of three lifestyle interventions (Healthy eating (HE), Physical activity (PA) and both HE and PA (HE+PA)) with usual care (UC) in reducing GDM risk. Design: Multicentre Randomised Controlled Trial 2012-2014: The Dali Lifestyle Study Setting: Antenatal clinics across 11 centres in 9 European countries Patients: Consecutive pregnant women <20 weeks gestation with a BMI≥29 kg/m 2 and without GDM by IADPSG criteria (n=436).Intervention: Women were randomized, stratified by site, to Control, HE, PA or HE+PA. Women received 5 face-to-face and up to 4 telephone coaching sessions, based on the principles of motivational interviewing. Gestational weight gain (GWG) <5kg was targeted. Coaches received standardized training and an intervention toolkit tailored to their culture/language. Main outcome measures: GWG at 35-37 weeks, fasting glucose and insulin sensitivity (HOMA-IR) at 24-28 weeks. Results: We randomized 108 women to HE&PA, 113 to HE, 110 to PA and 105 to UC. In the HE+PA group, but not HE or PA alone, women achieved substantially less GWG than controls by 35-37 weeks . Despite this reduction there were no improvements in fasting or post-load glucose or,insulin concentrations or HOMA-IR. Birthweight, large and small for gestational age rates were similar. Copyright 2016 DOI: 10.1210/jc.2016 Conclusions: The combined HE+PA intervention was able to limit GWG but did not reduce fasting glycaemia. Lifestyle change alone is unlikely to prevent GDM among women with a BMI≥29 kg/m 2 .PRECIS: We studied pregnant women in a large European multi-centre RCT of physical activity and/or healthy eating and found no effect on GDM risk in spite of significant gestational weight gain limitation INTRODUCTIONGestational diabetes mellitus (GDM), high pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) are independently associated with an increased risk of adverse perinatal outcomes, including macrosomia, operative delivery and shoulder dystocia (1). In GDM, such complications have a continuous relationship with maternal glucose concentrations during the oral glucose tolerance test (OGTT) (2). With the increasing prevalence of obesity in pregnancy and GDM (3), it has become increasingly important to develop evidence based clinical interventions that prevent the development of GDM and minimise excess GWG. The development of type 2 diabetes through intensive lifestyle interventions can be reduced by 58% over 4 years in non-pregnant women who have previously had GDM (4). However, whether GDM can be prevented through antenatal lifestyle interventions, even with limitation in excess GWG, is disputed (5). RCTs have provided variable evidence that lifestyle interventions 'work' (6); likely because of different intervention protocols and study populations. Furthermore, at the moment, no studies are available that assessed, ...

Background Gestational diabetes mellitus is a potentially serious condition that affects many pregnancies and its prevalence is increasing. Evidence suggests early detection and treatment improves outcomes, but this is hampered by continued disagreement and inconsistency regarding many aspects of its diagnosis.

GDM prevalence is higher when using newer IADPSG, compared with WHO, criteria, and these women and their offspring experience significant adverse pregnancy outcomes. Higher rates of GDM pose a challenge to healthcare systems, but improved screening provides an opportunity to attempt to reduce the associated morbidity for mother and child.