Recent findings suggest an association between obesity, loss of gut barrier function and changes in microbiota profiles. Our primary objective was to examine the effect of caloric restriction and subsequent weight reduction on gut permeability in obese women. The impact on inflammatory markers and fecal microbiota was also investigated. The 4-week very-low calorie diet (VLCD, 800 kcal/day) induced a mean weight loss of 6.9 ± 1.9 kg accompanied by a reduction in HOMA-IR (Homeostasis model assessment-insulin resistance), fasting plasma glucose and insulin, plasma leptin, and leptin gene expression in subcutaneous adipose tissue. Plasma high-molecular weight adiponectin (HMW adiponectin) was significantly increased after VLCD. Plasma levels of high-sensitivity C-reactive protein (hsCRP) and lipopolysaccharide-binding protein (LBP) were significantly decreased after 28 days of VLCD. Using three different methods, gut paracellular permeability was decreased after VLCD. These changes in clinical parameters were not associated with major consistent changes in dominant bacterial communities in feces. In summary, a 4-week caloric restriction resulted in significant weight loss, improved gut barrier integrity and reduced systemic inflammation in obese women.

Excessive gestational weight gain (GWG) may be a risk factor for gestational diabetes mellitus (GDM). We aimed to study the association between excessive GWG (defined according to Institute of Medicine recommendations) prior to GDM screening, and GDM. We systematically searched four electronic databases from 1990 until September 2014 for observational studies published in English or German that reported an association between excessive GWG and GDM as the outcome. Random effects meta-analyses were performed to provide a pooled estimate of the OR comparing the risk of GDM in women with and without excessive GWG. A total of eight studies involving 13,748 participants were included. The pooled analysis of unadjusted OR yielded a summary OR of 1.40 (95% CI 1.21, 1.61; p < 0.001) with low between-study heterogeneity (I ² = 16.7%). A sensitivity analysis based on four studies reporting adjusted effect estimates revealed similar results (OR 1.42; 95% CI 1.20, 1.68; p < 0.001; I ² = 0%). No evidence was found that the effect of GWG on GDM differs depending on maternal pre-pregnancy BMI category. A funnel plot did not indicate substantial publication bias. Avoiding excessive weight gain in pregnancy prior to the GDM screening test may be a potential strategy to reduce GDM risk. www.​crd.​york.​ac.​uk/​PROSPERO CRD42014008802

—Plasminogen activator inhibitor (PAI)-1 is the main inhibitor of the fibrinolytic system and was recently shown to be produced by adipose cells. Obesity is associated with an increased production and release of PAI-1 protein. The aim of this study was to investigate the role of angiotensin (Ang) II and its degradation products for PAI-1 release from human adipose cells. For this purpose, we used the model of in vitro differentiated human adipocytes in primary culture. Exposure of human adipocytes to Ang II resulted in a dose- and time-dependent stimulation of PAI-1 release into the culture medium. The maximum effect of Ang II was found at a concentration of 10 ⁻⁵ mol/L for 48 hours, increasing PAI-1 release by 276±53% compared with control cultures ( P <0.05). This stimulation was preceded by an increase in specific PAI-1 mRNA copies by 65±12% ( P <0.05), with a maximum after 6 hours. Incubation of adipocytes with 10 ⁻⁵ mol/L Ang III and Ang IV, respectively, also resulted in a stimulation of PAI-1 release into the medium by 195±60% ( P <0.05) and 142±24% ( P <0.05), respectively, compared with control cultures. Addition of the angiotensin-receptor subtype 1 (AT ₁ ) blocker candesartan abolished the stimulatory action of Ang II and its metabolites, indicating that this effect is mediated by AT ₁ . Addition of the AT ₁ blocker alone to unstimulated cultures reduced PAI-1 release by 41%±25% ( P <0.05), suggesting that endogenous Ang II synthesis contributes to PAI-1 secretion from adipose tissue in an autocrine/paracrine manner. In conclusion, Ang II and its metabolites promote PAI-1 production and release by human fat cells and may contribute to the impairment of the fibrinolytic system typical for obesity. AT ₁ receptor blockade reduces basal and abolishes Ang II–stimulated PAI-1 release from human adipocytes.

Lifestyle intervention (LI) can prevent type 2 diabetes, but response to LI varies depending on risk subphenotypes. We tested whether individuals with prediabetes with low risk (LR) benefit from conventional LI and individuals with high risk (HR) benefit from an intensification of LI in a multicenter randomized controlled intervention over 12 months with 2 years’ follow-up. A total of 1,105 individuals with prediabetes based on American Diabetes Association glucose criteria were stratified into an HR or LR phenotype based on previously described thresholds of insulin secretion, insulin sensitivity, and liver fat content. LR individuals were randomly assigned to conventional LI according to the Diabetes Prevention Program (DPP) protocol or control (1:1) and HR individuals to conventional or intensified LI with doubling of required exercise (1:1). A total of 908 (82%) participants completed the study. In HR individuals, the difference between conventional and intensified LI in postchallenge glucose change was −0.29 mmol/L [95% CI −0.54; −0.04], P = 0.025. Liver fat (−1.34 percentage points [95% CI −2.17; −0.50], P = 0.002) and cardiovascular risk (−1.82 percentage points [95% CI −3.13; −0.50], P = 0.007) underwent larger reductions with intensified than with conventional LI. During a follow-up of 3 years, intensified compared with conventional LI had a higher probability of normalizing glucose tolerance (P = 0.008). In conclusion, it is possible in HR individuals with prediabetes to improve glycemic and cardiometabolic outcomes by intensification of LI. Individualized, risk phenotype–based LI may be beneficial for the prevention of diabetes.

Excessive gestational weight gain (GWG) leads to obstetric complications, maternal postpartum weight retention and an increased risk of offspring obesity. The GeliS study examines the effect of a lifestyle intervention during pregnancy on the proportion of women with excessive GWG and pregnancy and obstetric complications, as well as the long-term risk of maternal and infant obesity. The GeliS study is a cluster-randomised multicentre controlled trial including 2286 women with a pre-pregnancy BMI between 18.5 and 40.0 kg/m2 recruited from gynaecological and midwifery practices prior to the end of the 12th week of gestation in five Bavarian regions. In the intervention regions, four lifestyle counselling sessions covering a balanced healthy diet, regular physical activity and self-monitoring of weight gain were performed by trained healthcare providers alongside routine pre- and postnatal practice visits. In the control regions, leaflets with general recommendations for a healthy lifestyle during pregnancy were provided. The intervention did not result in a significant reduction of women showing excessive GWG (adjusted OR 0.95, 95% CI 0.66–1.38, p = 0.789), with 45.1% and 45.7% of women in the intervention and control groups, respectively, gaining weight above the Institute of Medicine recommendations. Gestational diabetes mellitus was diagnosed in 10.8% and 11.1% of women in the intervention and control groups, respectively (p = 0.622). Mean birth weight and length were slightly lower in the intervention group (3313 ± 536 g vs. 3363 ± 498 g, p = 0.020; 51.1 ± 2.7 cm vs. 51.6 ± 2.5 cm, p = 0.001). In the setting of routine prenatal care, lifestyle advice given by trained healthcare providers was not successful in limiting GWG and pregnancy complications. Nevertheless, the potential long-term effects of the intervention remain to be assessed. NCT01958307 , ClinicalTrials.gov, retrospectively registered October 9, 2013.