Short-term variability of proton density fat fraction in pancreas and liver assessed by multiecho chemical-shift encoding-based MRI at 3 T.

Background: Quantification of pancreatic fat (PF) and intrahepatic lipids (IHL) is of increasing interest in subjects at risk for metabolic diseases. There is limited data available on short- and medium-term variability of PF/IHL and on their dependence on nutritional status. Purpose: To assess short-term intraday variations of PF/IHL after a high-fat meal as well as medium-term changes after 5 days of high-caloric diet. Study Type: Prospective cohort study. Subjects: A total of 12 subjects (six males) for intraday variations study, 15 male subjects for medium-term high-caloric diet study and 11 age- and body mass index (BMI)-matched controls. Field Strength/Sequence: A 3 T; chemical-shift encoded multiecho gradient echo sequence. Assessment: For the intraday study, subjects were scanned after overnight fasting and after a high fat meal on the same day. For the medium-term study, 26 subjects were scanned after overnight fasting with 15/11 rescanned after 5 days of high-calorie diet/isocaloric diet. Proton density fat fraction (PDFF) maps were generated inline on the scanner. Regions of interest were manually drawn in head, body, and tail of pancreas and in the liver by a medical physicist and a doctoral student (26/4 years of experience). PF was calculated as the average of the head, body, and tail measurements. Statistical Tests: Repeated measurements ANOVA for assessing changes in PF/IHL, linear correlation analyses for assessing relationships of PF/IHL with BMI. Significance level P < 0.05 for all. Results: Nonsignificant changes in PF (2.6 ± 1.0 vs. 2.7 ± 0.9% after high-fat meal, 1.4 ± 0.8 vs. 1.5 ± 0.6% [high-caloric diet] and 1.5 ± 0.8 vs. 1.8 ± 1.0% [isocaloric control group]), nonsignificant changes in IHL after high-fat meal (2.6 ± 1.3 vs. 2.5 ± 0.9%) and in the control group (1.1 ± 0.6 vs. 1.2 ± 1.1%), significantly increased IHL after high-caloric diet (1.7 ± 2.2% vs. 2.7 ± 3.6%). Nonsignificant changes in PF (2.6 ± 1.0 vs. 2.7 ± 0.9% after high-fat meal, 1.4 ± 0.8 vs. 1.5 ± 0.6% [high-caloric diet] and 1.5 ± 0.8 vs. 1.8 ± 1.0% [isocaloric control group]), nonsignificant changes in IHL after high-fat meal (2.6 ± 1.3 vs. 2.5 ± 0.9%) and in the control group (1.1 ± 0.6 vs. 1.2 ± 1.1%), significantly increased IHL after 5-days of high-caloric diet (1.7 ± 2.2% vs. 2.7 ± 3.6%). Data Conclusion: Time of day and nutritional status have no significant influence on PF/IHL and are therefore not likely to be major confounders in epidemiologic or clinical studies. Evidence Level: 2. Technical Efficacy: Stage 1

Lower hepatic fat is associated with improved insulin secretion in a high-risk prediabetes subphenotype during lifestyle intervention.

The objective of this work was to investigate whether impaired insulin secretion can be restored by lifestyle intervention in specific subphenotypes of prediabetes. One thousand forty-five participants from the Prediabetes Lifestyle Intervention Study (PLIS) were assigned to 6 recently established prediabetes clusters. Insulin secretion was assessed by a C-peptide-based index derived from oral glucose tolerance tests and modeled from three time-points during a 1-yr intervention. We also analyzed the change of glycemia, insulin sensitivity and liver fat. All pre-diabetes high-risk clusters (cluster 3, 5 and 6) had improved glycemic traits during lifestyle intervention, whereas insulin secretion only increased in clusters 3 and 5 (p<0.001); however, high liver fat in cluster 5 was associated with a failure to improve insulin secretion (pinteraction<0.001). Thus, interventions to reduce liver fat have the potential to improve insulin secretion in a defined subgroup of prediabetes. Prediabetes is a heterogenous condition comprising subphenotypes with different risks of diabetes and its complications (1). From its two key features, insulin resistance and impaired insulin secretion, insulin resistance can be clearly improved by lifestyle intervention (LI); however, it is not known, if LI can improve insulin secretion in specific subphenotypes of reduced insulin secretion (2). Recently, we described 6 clusters of prediabetic metabolism (1). Two of these clusters (cluster 3 and 5) have high risk of progression to diabetes. Another group (cluster 6) has an intermediate risk of diabetes as these persons are capable of compensating insulin resistance via hyperinsulinemia over years. In this study, we retrospectively stratified participants of a large multi-center study into these novel clusters of prediabetic metabolism (1) and investigated whether LI improved their insulin secretion and other glycemic traits

Systematic review and meta‐analysis: the incidence and prevalence of paediatric coeliac disease across Europe

International audienceBackground Coeliac disease is one of the most prevalent immune-mediated gastrointestinal disorders in children.Aim To review the incidence and prevalence of paediatric coeliac disease, and their trends, regionally across Europe, overall and according to age at diagnosis.Methods Systematic review and meta-analysis from January 1, 1950 to December 31, 2019, based on PubMed, CINAHL and the Cochrane Library, searches of grey literature and websites and hand searching of reference lists. A total of 127 eligible studies were included.Results The prevalence of previously undiagnosed coeliac disease from screening surveys (histology based) ranged from 0.10% to 3.03% (median = 0.70%), with a significantly increasing annual trend (P = 0.029). Prevalence since 2000 was significantly higher in northern Europe (1.60%) than in eastern (0.98%), southern (0.69%) and western (0.60%) Europe. Large increases in the incidence of diagnosed coeliac disease across Europe have reached 50 per 100 000 person-years in Scandinavia, Finland and Spain. The median age at diagnosis increased from 1.9 years before 1990 to 7.6 since 2000. Larger increases in incidence were found in older age groups than in infants and ages Paediatric coeliac disease incidence and prevalence have risen across Europe and appear highest in Scandinavia, Finland and Spain. The most recent evidence shows large increases in incidence in most regions, but stabilisation in some (notably Sweden and Finland). Sharp increases in the age at diagnosis may reflect increases in milder and asymptomatic cases diagnosed since reliable serology testing became widely used, through endomysial antibodies after 1990 and tissue transglutaminase antibodies around 2000

Mechanisms of weight loss-induced remission in people with prediabetes: a post-hoc analysis of the randomised, controlled, multicentre Prediabetes Lifestyle Intervention Study (PLIS)

BACKGROUND Remission of type 2 diabetes can occur as a result of weight loss and is characterised by liver fat and pancreas fat reduction and recovered insulin secretion. In this analysis, we aimed to investigate the mechanisms of weight loss- induced remission in people with prediabetes. METHODS In this prespecified post-hoc analysis, weight loss-induced resolution of prediabetes in the randomised, controlled, multicentre Prediabetes Lifestyle Intervention Study (PLIS) was assessed, and the results were validated against participants from the Diabetes Prevention Program (DPP) study. For PLIS, between March 1, 2012, and Aug 31, 2016, participants were recruited from eight clinical study centres (including seven university hospitals) in Germany and randomly assigned to receive either a control intervention, a standard lifestyle intervention (ie, DPP-based intervention), or an intensified lifestyle intervention for 12 months. For DPP, participants were recruited from 23 clinical study centres in the USA between July 31, 1996, and May 18, 1999, and randomly assigned to receive either a standard lifestyle intervention, metformin, or placebo. In both PLIS and DPP, only participants who were randomly assigned to receive lifestyle intervention or placebo and who lost at least 5% of their bodyweight were included in this analysis. Responders were defined as people who returned to normal fasting plasma glucose (FPG; <5·6 mmol/L), normal glucose tolerance (<7·8 mmol/L), and HbA$_{1c}$ less than 39 mmol/mol after 12 months of lifestyle intervention or placebo or control intervention. Non-responders were defined as people who had FPG, 2 h glucose, or HbA$_{1c}$ more than these thresholds. The main outcomes for this analysis were insulin sensitivity, insulin secretion, visceral adipose tissue (VAT), and intrahepatic lipid content (IHL) and were evaluated via linear mixed models. FINDINGS Of 1160 participants recruited to PLIS, 298 (25·7%) had weight loss of 5% or more of their bodyweight at baseline. 128 (43%) of 298 participants were responders and 170 (57%) were non-responders. Responders were younger than non-responders (mean age 55·6 years [SD 9·9] vs 60·4 years [8·6]; p<0·0001). The DPP validation cohort included 683 participants who lost at least 5% of their bodyweight at baseline. Of these, 132 (19%) were responders and 551 (81%) were non-responders. In PLIS, BMI reduction was similar between responders and non-responders (responders mean at baseline 32·4 kg/m$^{2}$ [SD 5·6] to mean at 12 months 29·0 kg/m$^{2}$ [4·9] vs non-responders 32·1 kg/m$^{2}$ [5·9] to 29·2 kg/m$^{2}$ [5·4]; p=0·86). However, whole-body insulin sensitivity increased more in responders than in non-responders (mean at baseline 291 mL/[min × m$^{2}$], SD 60 to mean at 12 months 378 mL/[min × m$^{2}$], 56 vs 278 mL/[min × m$^{2}$], 62, to 323 mL/[min × m$^{2}$], 66; p<0·0001), whereas insulin secretion did not differ within groups over time or between groups (responders mean at baseline 175 pmol/mmol [SD 64] to mean at 12 months 163·7 pmol/mmol [60·6] vs non-responders 158·0 pmol/mmol [55·6] to 154·1 pmol/mmol [56·2]; p=0·46). IHL decreased in both groups, without a difference between groups (responders mean at baseline 10·1% [SD 8·7] to mean at 12 months 3·5% [3·9] vs non-responders 10·3% [8·1] to 4·2% [4·2]; p=0·34); however, VAT decreased more in responders than in non-responders (mean at baseline 6·2 L [SD 2·9] to mean at 12 months 4·1 L [2·3] vs 5·7 L [2·3] to 4·5 L [2·2]; p=0·0003). Responders had a 73% lower risk of developing type 2 diabetes than non-responders in the 2 years after the intervention ended. INTERPRETATION By contrast to remission of type 2 diabetes, resolution of prediabetes was characterised by an improvement in insulin sensitivity and reduced VAT. Because return to normal glucose regulation (NGR) prevents development of type 2 diabetes, we propose the concept of remission of prediabetes in analogy to type 2 diabetes. We suggest that remission of prediabetes should be the primary therapeutic aim in individuals with prediabetes. FUNDING German Federal Ministry for Education and Research via the German Center for Diabetes Research; the Ministry of Science, Research and the Arts Baden-Württemberg; the Helmholtz Association and Helmholtz Munich; the Cluster of Excellence Controlling Microbes to Fight Infections; and the German Research Foundation