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Background Non-alcoholic fatty liver disease (NAFLD), identified by the Fatty Liver Index (FLI), is associated with increased mortality and cardiovascular (CV) outcomes. Whether this also applies to type 1 diabetes (T1D) has not been yet reported. Methods We prospectively observed 774 subjects with type 1 diabetes (males 52%, 30.3 ± 11.1 years old, diabetes duration (DD) 18.5 ± 11.6 years, HbA1c 7.8 ± 1.2%) to assess the associations between FLI (based on BMI, waist circumference, gamma-glutamyl transferase and triglycerides) and all-cause death and first CV events. Results Over a median 11-year follow-up, 57 subjects died (7.4%) and 49 CV events (6.7%) occurred among 736 individuals with retrievable incidence data. At baseline, FLI was < 30 in 515 subjects (66.5%), 30–59 in 169 (21.8%), and ≥ 60 in 90 (11.6%). Mortality increased steeply with FLI: 3.9, 10.1, 22.2% (p < 0.0001). In unadjusted Cox analysis, compared to FLI < 30, risk of death increased in FLI 30–59 (HR 2.85, 95% CI 1.49–5.45, p = 0.002) and FLI ≥ 60 (6.07, 3.27–11.29, p < 0.0001). Adjusting for Steno Type 1 Risk Engine (ST1-RE; based on age, sex, DD, systolic BP, LDL cholesterol, HbA1c, albuminuria, eGFR, smoking and exercise), HR was 1.52 (0.78–2.97) for FLI 30–59 and 3.04 (1.59–5.82, p = 0.001) for FLI ≥ 60. Inclusion of prior CV events slightly modified HRs. FLI impact was confirmed upon adjustment for EURODIAB Risk Engine (EURO-RE; based on age, HbA1c, waist-to-hip ratio, albuminuria and HDL cholesterol): FLI 30–59: HR 1.24, 0.62–2.48; FLI ≥ 60: 2.54, 1.30–4.95, p = 0.007), even after inclusion of prior CVD. CV events incidence increased with FLI: 3.5, 10.5, 17.2% (p < 0.0001). In unadjusted Cox, HR was 3.24 (1.65–6.34, p = 0.001) for FLI 30–59 and 5.41 (2.70–10.83, p < 0.0001) for FLI ≥ 60. After adjustment for ST1-RE or EURO-RE, FLI ≥ 60 remained statistically associated with risk of incident CV events, with trivial modification with prior CVD inclusion. Conclusions This observational prospective study shows that FLI is associated with higher all-cause mortality and increased risk of incident CV events in type 1 diabetes.

We evaluated possible mediators underlying lifestyle intervention effects on neonatal adiposity, assessed with sum of skinfolds and cord blood leptin. This is a secondary analysis of the DALI study, a randomised controlled trial in nine European countries. Pregnant women with a pre-pregnancy body mass index of ≥29 kg/m2 were randomly assigned to counselling for healthy eating (HE), physical activity (PA), HE&PA combined, or to usual care. We considered five maternal metabolic factors at 24–28 and 35–37 weeks of gestation, and four cord blood factors as possible mediators of the effect of combined HE&PA counselling on neonatal adiposity. From all potential mediators, the intervention only affected cord blood non-esterified fatty acids (NEFA), which was higher in the HE&PA group compared to UC (0.068 (mmol/L), 95% CI: 0.004 to 0.133). Cord blood NEFA did not mediate the HE&PA intervention effects on neonatal sum of skinfolds or cord blood leptin, based on an indirect effect on skinfolds of 0.018 (mm), 95% CI: −0.217 to 0.253 and an indirect effect on leptin of −0.143 (μg/l), 95% CI: −0.560 to 0.273. The Dali study observed reductions in neonatal adiposity in pregnant women with obesity, but we were not able to identify the underlying metabolic pathway.

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Background The purpose of this study was to examine the association between mental health status (i.e. depressed mood and pregnancy-related worries) and objectively measured physical activity levels in obese pregnant women from seven European countries. Methods Baseline data from the vitamin D and lifestyle intervention for the prevention of gestational diabetes mellitus (DALI) study were used. Time spent in moderate-to-vigorous physical activity (MVPA) and sedentary behaviour was measured with accelerometers. Depressed mood was measured with the WHO well-being index (WHO-5) and pregnancy-related worries with the Cambridge Worry Scale (CWS). In addition, socio-demographic characteristics, lifestyle factors, and perceptions and attitude regarding weight management and physical activity were measured. Linear regression analyses were performed to assess the association of mental health status with MVPA and sedentary behaviour. Results A total of 98 obese pregnant women from Austria, Belgium, Ireland, Italy, Poland, Spain and the Netherlands were included. Women had a mean age of 31.6 ± 5.8 years, a pre-pregnancy BMI of 34.1 ± 4.3 kg/m 2 , and were on average 15.4 ± 2.8 weeks pregnant. WHO-5 scores indicative of depressed mood (<50) were reported by 27.1 % of the women and most frequently endorsed pregnancy-related worries pertained to own and the baby’s health. Women with good well-being spent 85 % more time in MVPA compared to women with a depressed mood ( P  = 0.03). No differences in MVPA levels were found for women with no, some, or many pregnancy worries. Depressed mood and pregnancy-related worries were not associated with sedentary behaviour. Conclusions These findings suggest that in pregnant women who are obese, a depressed mood, but not pregnancy-related worries, may be associated with less physical activity. The combined risk of poor mental health and low physical activity levels makes women vulnerable for pregnancy complications. Whether a depressed mood may be a barrier for improving physical activity warrants further study.

We studied pregnant women in a large European multicenter randomized controlled trial of physical activity and/or healthy eating and found no effect on gestational diabetes mellitus risk, despite the significant gestational weight gain limitation.AbstractContext:Lifestyle approaches for preventing gestational diabetes mellitus (GDM) have produced mixed results.Objective:The aim of the present study was to compare the effectiveness of 3 lifestyle interventions [healthy eating (HE), physical activity (PA), and both HE and PA (HE+PA)] with usual care (UC) in reducing GDM risk.Design:The present study was a multicenter randomized controlled trial conducted from 2012 to 2014 [the DALI (vitamin D and lifestyle intervention for GDM prevention) lifestyle study].Setting:The study occurred at antenatal clinics across 11 centers in 9 European countries.Patients:Consecutive pregnant women at <20 weeks of gestation with a body mass index (BMI) of ≥29 kg/m2 and without GDM using the International Association of Diabetes and Pregnancy Study Group criteria (n = 436). For the intervention, women were randomized, stratified by site, to UC, HE, PA, or HE+PA. The women received 5 face-to-face and ≤4 telephone coaching sessions using the principles of motivational interviewing. A gestational weight gain (GWG) <5 kg was targeted. The coaches received standardized training and an intervention toolkit tailored to their culture and language.Main Outcome Measures:The endpoints were the GWG at 35 to 37 weeks and the fasting glucose and insulin sensitivity [homeostasis model assessment insulin resistance (HOMA-IR)] at 24 to 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 did the controls (UC) by 35 to 37 weeks (−2.02; 95% confidence interval, −3.58 to −0.46 kg). Despite this reduction, no improvements were seen in fasting or postload glucose levels, insulin concentrations, or HOMA-IR. The birthweights and large and small for gestational age rates were similar.Conclusions:The combined HE+PA intervention was able to limit GWG but did not reduce fasting glycemia. Thus, lifestyle changes alone are unlikely to prevent GDM among women with a BMI of ≥29 kg/m2.

Aims/hypothesis Accurate prevalence estimates for gestational diabetes mellitus (GDM) among pregnant women in Europe are lacking owing to the use of a multitude of diagnostic criteria and screening strategies in both high-risk women and the general pregnant population. Our aims were to report important risk factors for GDM development and calculate the prevalence of GDM in a cohort of women with BMI ≥29 kg/m 2 across 11 centres in Europe using the International Association of the Diabetes and Pregnancy Study Groups (IADPSG)/WHO 2013 diagnostic criteria. Methods Pregnant women ( n  = 1023, 86.3% European ethnicity) with a BMI ≥29.0 kg/m 2 enrolled into the Vitamin D and Lifestyle Intervention for GDM Prevention (DALI) pilot, lifestyle and vitamin D studies of this pan-European multicentre trial, attended for an OGTT during pregnancy. Demographic, anthropometric and metabolic data were collected at enrolment and throughout pregnancy. GDM was diagnosed using IADPSG/WHO 2013 criteria. GDM treatment followed local policies. Results The number of women recruited per country ranged from 80 to 217, and the dropout rate was 7.1%. Overall, 39% of women developed GDM during pregnancy, with no significant differences in prevalence across countries. The prevalence of GDM was high (24%; 242/1023) in early pregnancy. Despite interventions used in the DALI study, a further 14% (94/672) had developed GDM when tested at mid gestation (24–28 weeks) and 13% (59/476) of the remaining cohort at late gestation (35–37 weeks). Demographics and lifestyle factors were similar at baseline between women with GDM and those who maintained normal glucose tolerance. Previous GDM (16.5% vs 7.9%, p  = 0.002), congenital malformations (6.4% vs 3.3%, p  = 0.045) and a baby with macrosomia (31.4% vs 17.9%, p  = 0.001) were reported more frequently in those who developed GDM. Significant anthropometric and metabolic differences were already present in early pregnancy between women who developed GDM and those who did not. Conclusions/interpretation The prevalence of GDM diagnosed by the IADPSG/WHO 2013 GDM criteria in European pregnant women with a BMI ≥29.0 kg/m 2 is substantial, and poses a significant health burden to these pregnancies and to the future health of the mother and her offspring. Uniform criteria for GDM diagnosis, supported by robust evidence for the benefits of treatment, are urgently needed to guide modern GDM screening and treatment strategies.

Aims/hypothesisOffspring of obese women are at increased risk of features of the metabolic syndrome, including obesity and diabetes. Lifestyle intervention in pregnancy might reduce adverse effects of maternal obesity on neonatal adiposity.MethodsIn the Vitamin D And Lifestyle Intervention for Gestational Diabetes Mellitus (GDM) Prevention (DALI) lifestyle trial, 436 women with a BMI ≥29 kg/m2 were randomly assigned to counselling on healthy eating (HE), physical activity (PA) or HE&PA, or to usual care (UC). In secondary analyses of the lifestyle trial, intervention effects on neonatal outcomes (head, abdominal, arm and leg circumferences and skinfold thicknesses, estimated fat mass, fat percentage, fat-free mass and cord blood leptin) were assessed using multilevel regression analyses. Mediation of intervention effects by lifestyle and gestational weight gain was assessed.ResultsOutcomes were available from 334 neonates. A reduction in sum of skinfolds (−1.8 mm; 95% CI −3.5, −0.2; p = 0.03), fat mass (−63 g; 95% CI −124, −2; p = 0.04), fat percentage (−1.2%; 95% CI −2.4%, −0.04%; p = 0.04) and leptin (−3.80 μg/l; 95% CI −7.15, −0.45; p = 0.03) was found in the HE&PA group, and reduced leptin in female neonates in the PA group (−5.79 μg/l; 95% CI −11.43, −0.14; p = 0.05) compared with UC. Reduced sedentary time, but not gestational weight gain, mediated intervention effects on leptin in both the HE&PA and PA groups.Conclusions/interpretationThe HE&PA intervention resulted in reduced adiposity in neonates. Reduced sedentary time seemed to drive the intervention effect on cord blood leptin. Implications for future adiposity and diabetes risk of the offspring need to be elucidated.Trial registrationISRCTN70595832.

For women with previous gestational diabetes (GDM), international guidelines recommend 75 g oral glucose tolerance test (OGTT) at 4–12 weeks after delivery to assess glucose tolerance, considering their increased risk of type 2 diabetes. We evaluated prevalence of postpartum impaired glucose regulation (IGR) and identified associated risk factors. We retrospectively collected data from 749 women with previous GDM (IADPSG criteria) who underwent postpartum OGTT for type 2 diabetes screening between 2011 and 2019. IGR was identified according to ADA criteria. Prevalence of IGR was 12.7%, lower in women with pre-pregnancy normal weight, higher in women with family history of type 2 diabetes and in those treated with insulin during pregnancy. Prevalence of IGR raised with increasing number of altered glucose values at OGTT performed during pregnancy for GDM screening. HbA1c and triglycerides measured during the third trimester of pregnancy were higher in women with postpartum IGR. At postpartum screening, women with IGR had higher BMI, waist, blood pressure. At multivariate logistic regression analysis, family history of diabetes (OR 2.21; 95% CI: 1.33–3.69; p < 0.01) and presence of all three glucose values exceeding threshold at OGTT during pregnancy (OR 2.89; 95% CI: 1.42–5.86; p < 0.01) were independently associated with IGR. In women with GDM, persistence of IGR in the immediate postpartum period is associated with family history of diabetes and the presence of all three glucose values exceeding diagnostic threshold for GDM at OGTT in pregnancy, suggesting that these women should undergo specific diabetes monitoring and prevention programs. •Family history of diabetes is a risk factor for deterioration of glucose tolerance in postpartum•FPG ≥5.1 mmol/l at OGTT during pregnancy increases the risk of glucose abnormalities in postpartum•Having all glucose values above threshold for GDM at OGTT in pregnancy is risk factor for postpartum glucose abnormalities

Freestyle Libre (FSL) system is a new method to detect glucose enabling a new paradigm in glucose monitoring and self-management. The sensor, reading the interstitial fluid glucose concentration, provides a numerical data of glucose level and a trend arrow that add context to static measurement of glucose level. Therefore, patients could easily follow the progression of their glucose levels over the time, allowing early detection and timely treatment of deviations from targeted glucose level range, thus preventing extreme fluctuations. In order to take full advantage of the system both the caregiver and the person with diabetes must appreciate the need of careful interpretation of the data generated by the FSL. To this purpose we have generated recommendations that are based on methods suggested for CGM, our clinical experience and discussion with experienced patients using FSL, to provide a pragmatic approach to use FSL trend arrow data for managing diabetes in adults.