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Aims/hypothesis: Lifestyle modification and weight loss are cornerstones of type 2 diabetes management. However, carbohydrate restriction may have weight-independent beneficial effects on glycaemic control. This has been difficult to demonstrate because low-carbohydrate diets readily decrease body weight. We hypothesised that carbohydrate restriction enhances the beneficial metabolic effects of weight loss in type 2 diabetes. Methods: This open-label, parallel RCT included adults with type 2 diabetes, HbA1c 48–97 mmol/mol (6.5–11%), BMI >25 kg/m2, eGFR >30 ml min−1 [1.73 m]−2 and glucose-lowering therapy restricted to metformin or dipeptidyl peptidase-4 inhibitors. Participants were randomised by a third party and assigned to 6 weeks of energy restriction (all foods were provided) aiming at ~6% weight loss with either a carbohydrate-reduced high-protein diet (CRHP, percentage of total energy intake [E%]: CH30/P30/F40) or a conventional diabetes diet (CD, E%: CH50/P17/F33). Fasting blood samples, continuous glucose monitoring and magnetic resonance spectroscopy were used to assess glycaemic control, lipid metabolism and intrahepatic fat. Change in HbA1c was the primary outcome; changes in circulating and intrahepatic triacylglycerol were secondary outcomes. Data were collected at Copenhagen University Hospital (Bispebjerg and Herlev). Results: Seventy-two adults (CD 36, CRHP 36, all white, 38 male sex) with type 2 diabetes (mean duration 8 years, mean HbA1c 57 mmol/mol [7.4%]) and mean BMI of 33 kg/m2 were enrolled, of which 67 (CD 33, CRHP 34) completed the study. Body weight decreased by 5.8 kg (5.9%) in both groups after 6 weeks. Compared with the CD diet, the CRHP diet further reduced HbA1c (mean [95% CI] −1.9 [−3.5, −0.3] mmol/mol [−0.18 (−0.32, −0.03)%], p = 0.018) and diurnal mean glucose (mean [95% CI] −0.8 [−1.2, −0.4] mmol/l, p < 0.001), stabilised glucose excursions by reducing glucose CV (mean [95% CI] −4.1 [−5.9, −2.2]%, p < 0.001), and augmented the reductions in fasting triacylglycerol concentration (by mean [95% CI] −18 [−29, −6]%, p < 0.01) and liver fat content (by mean [95% CI] −26 [−45, 0]%, p = 0.051). However, pancreatic fat content was decreased to a lesser extent by the CRHP than the CD diet (mean [95% CI] 33 [7, 65]%, p = 0.010). Fasting glucose, insulin, HOMA2-IR and cholesterol concentrations (total, LDL and HDL) were reduced significantly and similarly by both diets. Conclusions/interpretation: Moderate carbohydrate restriction for 6 weeks modestly improved glycaemic control, and decreased circulating and intrahepatic triacylglycerol levels beyond the effects of weight loss itself compared with a CD diet in individuals with type 2 diabetes. Concurrent differences in protein and fat intakes, and the quality of dietary macronutrients, may have contributed to these results and should be explored in future studies. Trial registration: ClinicalTrials.gov NCT03814694. Funding: The study was funded by Arla Foods amba, The Danish Dairy Research Foundation, and Copenhagen University Hospital Bispebjerg Frederiksberg. Graphical abstract: [Figure not available: see fulltext.].

AIMS: To evaluate the effect of curcumin treatment on hepatic fat content in obese individuals.MATERIALS AND METHODS: In a double-blind, parallel-group trial, 37 obese, non-diabetic individuals were randomised to placebo or curcumin treatment for six weeks. Curcumin was dosed as lecithin-formulated tablet; 200 mg twice daily. Primary endpoint was hepatic fat content as assessed by magnetic resonance spectroscopy (MRS). Other endpoints included anthropometric measurements, hepatic biomarkers including FibroScan® measurements, metabolic parameters, inflammation markers, appetite measures and ad libitum food intake.RESULTS: Baseline characteristics (mean ± SD): age 46 ±14 years; hepatic fat content 12.2 ± 8.8 percent points; body mass index 38.8 ±6.1 kg/m 2 ; waist circumference 125.8 ± 12.3 cm. After six weeks treatment with curcumin, hepatic fat content was changed by -0.86 percent points (95% CI -3.65;1.94) compared to 0.71 percent points (95% CI -2.08;3.51) with placebo, thus resulting in a non-significant estimated treatment difference of -1.57 percent points (95% CI -5.36; 2.22, P = 0.412). Compared to placebo, curcumin treatment caused small reductions in fasting plasma glucose (estimated treatment difference (ETD) -0.24 mmol/L (95% CI -0.45; -0.03)), triglycerides (ETD (percentage change) -20.22% (95% CI -33.21; -6.03)), and gamma glutamyltransferase (ETD (percentage change) -15.70 (95% CI -23.32; -7.32)), but except for gamma glutamyltransferase, none of these differences remained statistically significant after adjusting for multiple testing. Treatment was well tolerated. CONCLUSIONS: Compared to placebo, curcumin treatment for six weeks had no significant effect on MRS-assessed hepatic fat content in obese individuals with primarily mild steatosis. Curcumin was well tolerated. This article is protected by copyright. All rights reserved.

Purpose: We previously reported beneficial glucoregulatory effects of a fully provided carbohydrate-reduced, high-protein (CRHP) diet in patients with type 2 diabetes mellitus (T2DM) in a crossover 2 × 6-week trial, in which patients maintained their body weight. Here, we investigated physiological changes during an additional 6-month period on a self-selected and self-prepared CRHP diet. Methods: Twenty-eight patients with T2DM were instructed to consume a CRHP diet (30% of energy from carbohydrate and 30% from protein) for 24 weeks, after an initial 2 × 6-week trial when all food was prepared and provided to them. Patients received dietary advice every 2 weeks. At weeks 0, 6, 12 and 36, they underwent a 3-h intravenous glucose tolerance test, a 4-h mixed meal test, and a 48-h continuous glucose monitoring. Liver, muscle, pancreas, and visceral fat contents were measured by magnetic resonance imaging. Results: During the 24-week self-selected diet period (weeks 12–36), body weight, visceral fat, liver fat, and glycated haemoglobin were maintained at the same levels achieved at the end of the fully provided diet period, and were still lower than at baseline (P < 0.05). Postprandial insulinaemia and insulin secretion were significantly greater (P < 0.05). At week 36, fasting insulin and C-peptide levels increased (P < 0.01) and daily glycaemia decreased further (P < 0.05) when compared with the end of the fully provided diet period. Conclusion: Substituting dietary carbohydrate for protein and fat has metabolic benefits in patients with T2DM. These beneficial effects are maintained or augmented over the next 6 months when patients self-select and self-prepare this diet in a dietitian-supported setting. Trial registration: ClinicalTrials.gov NCT02764021.

Type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) often co-occur. Defining causal pathways underlying this relationship may help optimize the prevention and treatment of both diseases. Thus, we assessed the strength and magnitude of the putative causal pathways linking dysglycemia and fatty liver, using a combination of causal inference methods.Measures of glycemia, insulin dynamics, magnetic resonance imaging (MRI)-derived abdominal and liver fat content, serological biomarkers, lifestyle, and anthropometry were obtained in participants from the IMI DIRECT cohorts (n=795 with new onset T2D and 2234 individuals free from diabetes). UK Biobank (n=3641) was used for modelling and replication purposes. Bayesian networks were employed to infer causal pathways, with causal validation using two-sample Mendelian randomization.Bayesian networks fitted to IMI DIRECT data identified higher basal insulin secretion rate (BasalISR) and MRI-derived excess visceral fat (VAT) accumulation as the features of dysmetabolism most likely to cause liver fat accumulation; the unconditional probability of fatty liver (>5%) increased significantly when conditioning on high levels of BasalISR and VAT (by 23%, 32% respectively; 40% for both). Analyses in UK Biobank yielded comparable results. MR confirmed most causal pathways predicted by the Bayesian networks.Here, BasalISR had the highest causal effect on fatty liver predisposition, providing mechanistic evidence underpinning the established association of NAFLD and T2D. BasalISR may represent a pragmatic biomarker for NAFLD prediction in clinical practice.

AIMS/HYPOTHESIS: Dietary recommendations for treating type 2 diabetes are unclear but a trend towards recommending a diet reduced in carbohydrate content is acknowledged. We compared a carbohydrate-reduced high-protein (CRHP) diet with an iso-energetic conventional diabetes (CD) diet to elucidate the effects on glycaemic control and selected cardiovascular risk markers during 6 weeks of full food provision of each diet.METHODS: The primary outcome of the study was change in HbA1c. Secondary outcomes reported in the present paper include glycaemic variables, ectopic fat content and 24 h blood pressure. Eligibility criteria were: men and women with type 2 diabetes, HbA1c 48-97 mmol/mol (6.5-11%), age >18 years, haemoglobin >6/>7 mmol/l (women/men) and eGFR >30 ml min-1 (1.73 m)-2. Participants were randomised by drawing blinded ballots to 6 + 6 weeks of an iso-energetic CRHP vs CD diet in an open label, crossover design aiming at body weight stability. The CRHP/CD diets contained carbohydrate 30/50 energy per cent (E%), protein 30/17E% and fat 40/33E%, respectively. Participants underwent a meal test at the end of each diet period and glycaemic variables, lipid profiles, 24 h blood pressure and ectopic fat including liver and pancreatic fat content were assessed at baseline and at the end of each diet period. Data were collected at Copenhagen University Hospital, Bispebjerg and Copenhagen University Hospital, Herlev.RESULTS: Twenty-eight participants completed the study. Fourteen participants carried out 6 weeks of the CRHP intervention followed by 6 weeks of the CD intervention, and 14 participants received the dietary interventions in the reverse order. Compared with a CD diet, a CRHP diet reduced the primary outcome of HbA1c (mean ± SEM: -6.2 ± 0.8 mmol/mol (-0.6 ± 0.1%) vs -0.75 ± 1.0 mmol/mol (-0.1 ± 0.1%); p CONCLUSIONS/INTERPRETATION: A moderate macronutrient shift by substituting carbohydrates with protein and fat for 6 weeks reduced HbA1c and hepatic fat content in weight stable individuals with type 2 diabetes.TRIAL REGISTRATION: ClinicalTrials.gov NCT02764021.FUNDING: The study was funded by grants from Arla Food for Health; the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen; the Department of Clinical Medicine, Aarhus University; the Department of Nutrition, Exercise and Sports, University of Copenhagen; and Copenhagen University Hospital, Bispebjerg.

Aim To investigate whether the mineralocorticoid receptor antagonist eplerenone has beneficial effects on liver fat and metabolism in patients with type 2 diabetes (T2D), the mineralocorticoid receptor antagonist in type 2 diabetes (MIRAD) trial. Material and methods In this 26-week, double-blind, randomized, placebo-controlled trial, we enrolled 140 patients with T2D and high risk of cardiovascular disease. Patients were randomized 1:1 to either eplerenone with a target dose of 200 mg/day for patients with estimated glomerular filtration rate (eGFR) of 60 mL/min per 1.73 m2 or more and 100 mg/day for patients with eGFR between 41 and 59 mL/min per 1.73 m2 or placebo. The primary outcome measure was change in liver fat by proton magnetic resonance spectroscopy at week 26 from baseline; secondary outcomes were changes in metabolism, and safety by incident hyperkalaemia. Results No changes in liver fat in the eplerenone group 0.91% (95% CI -0.57 to 2.39) or the placebo group -1.01% (-2.23 to 0.21) were found. The estimated absolute treatment difference was 1.92% (-3.81 to 0.01; P = 0.049). There was no beneficial impact on supporting secondary outcome variables of metabolism as fat mass distribution, lipid metabolism or insulin resistance. Despite a high dosage of eplerenone 164 versus 175 mg in patients treated with placebo (P = 0.228), the number of patients with incident hyperkalaemia (≥5.5 mmol/L) was low, with six in the eplerenone versus two in the placebo group (P = 0.276). Conclusion The addition of high doses of eplerenone to background antidiabetic and antihypertensive therapy does not show beneficial effects on liver fat and metabolism in patients with T2D.

Prepregnancy overweight and excessive gestational weight gain (GWG) increase the risk of complications and offspring obesity.We aimed to investigate the effect of a high-protein low-glycemic index (HPLGI) diet on GWG, birth weight, and risk of gestational complications in pregnant women with obesity.A total of 279 women with prepregnancy overweight or obesity (BMI: 28-45 kg/m2), between 18 and 45 y old, and in their late first trimester with singleton pregnancies, were randomly assigned to 1 of 2 ad libitum diets: a high-protein low-glycemic index diet (HPLGI: 25%-28% of energy from protein and glycemic index ≤ 55) and a moderate-protein moderate-glycemic index diet (MPMGI: 15%-18% of energy from protein and glycemic index ∼60). Diets were consumed from gestational week 15 and throughout pregnancy. Participants received dietary guidance by a clinical dietician 9 times to facilitate adherence.Out of 141 and 138 women randomly assigned to the HPLGI and MPMGI diets, 105 and 104 completed the intervention, respectively (75%). In the available case analyses, GWG was 6.8 ± 1.3 kg among women assigned the HPLGI diet and this was significantly lower, by -1.7 kg (95% CI: -2.8, -0.5 kg; P = 0.004), than the GWG of 8.5 ± 1.3 kg among women assigned the MPMGI diet. There were no significant differences between diets on major neonatal outcomes (birth weight and other anthropometric measures). The incidence of composite pregnancy complications was lower for the HPLGI than for the MPMGI diet (35.4% compared with 53.7%, respectively; P = 0.009), including cesarean delivery (15.4% compared with 28.8%, respectively; P = 0.03). There were no reported maternal, fetal, or neonatal deaths. Incidence of miscarriages (1%-2%) did not differ between groups.A moderate increase in dietary protein in conjunction with a reduction in glycemic index during the last 2 trimesters of pregnancy reduced GWG and limited complications and cesarean deliveries among women with overweight or obesity.

Objective: Elevated triglyceride-rich lipoproteins (TRL), excess small dense LDL particles (LDL5) and decreased HDL2/HDL3 ratio promote atherogenesis in type 2 diabetes (T2D). Carbohydrate restriction reduced intrahepatic triglyceride (IHTG) content beyond the positive effect of weight loss in a group of T2D patients, the present study sought to determine whether parallel improvements in lipoprotein density profiles occurred in these same patients. Research Design and Methods: Seventy-two adult T2D patients with a mean BMI of 33 kg/m2 were assigned to 6 weeks of fully-provided hypocaloric dietary treatment aimed at ~6% weight loss, either with a carbohydrate-reduced high-protein (CRHP, C30E%/P30E%/F40E%) diet or a conventional diabetes (CD, C50E%/P17E%/F33E%) diet. Density profiles of lipoproteins were determined by ultracentrifugation of fluorescently labelled plasma. Magnetic resonance spectroscopy was used to assess IHTG. Results: Body weight decreased by 5.8 kg (~6%) in both groups. Compared with the CD diet, the CRHP diet reduced TRL (mean [95% CI]) by -16 [-30;1]% (p=0.07) and LDL5 by -13 [-22;-3]% (p=0.01), and increased HDL2/HDL3 by 11 [1;22]% (p=0.04). The CRHP diet also decreased IHTG more than the CD diet (-26 [-45;0]%, p=0.05), and changes in IHTG including both groups correlated significantly with changes in TRL and LDL5 (Spearman’s ρ 0.39 and 0.38, p Conclusions: Carbohydrate restriction adds to the positive effect of weight loss in T2D patients by inducing greater improvements in atherogenic lipid profile, maybe facilitated by a reduction in intrahepatic fat. Disclosure M. N. Thomsen: None. S. Madsbad: Advisory Panel; Self; AstraZeneca; Boehringer Ingelheim; Eli Lilly; Merck Sharp & Dohme; Novo Nordisk; Sanofi, Research Support; Self; Novo Nordisk, Boehringer Ingelheim, Speaker’s Bureau; Self; AstraZeneca; Boehringer Ingelheim; Merck Sharp & Dohme; Novo Nordisk; Sanofi. F. Magkos: None. H. S. Thomsen: None. R. Walzem: None. S. B. Haugaard: None. T. Krarup: None. M. J. Skytte: None. A. Samkani: None. A. Astrup: Consultant; Self; Groupe Éthique et Santé, France, Employee; Self; Novo Nordisk Foundation, Other Relationship; Self; Flaxslim ApS, Denmark, Gelesis, Personalized Weight Management Research Consortium ApS (Gluco-Diet. dk). J. Frystyk: None. E. Chabanova: None. B. Hartmann: None. J. J. Holst: Consultant; Self; Novo Nordisk, Other Relationship; Self; Antag Therapeutics, Bainan Biotech, MSD Corporation, Novo Nordisk, Other Relationship; Spouse/Partner; Antag Therapeutics, Bainan Biotech, Synklino ApS. T. M. Larsen: None. Funding Arla Foods; Danish Dairy Research Foundation

We previously reported beneficial glucoregulatory effects of a fully provided carbohydrate-reduced, high-protein (CRHP) diet in patients with type 2 diabetes mellitus (T2DM) in a crossover 2 × 6-week trial, in which patients maintained their body weight. Here, we investigated physiological changes during an additional 6-month period on a self-selected and self-prepared CRHP diet.Twenty-eight patients with T2DM were instructed to consume a CRHP diet (30% of energy from carbohydrate and 30% from protein) for 24 weeks, after an initial 2 × 6-week trial when all food was prepared and provided to them. Patients received dietary advice every 2 weeks. At weeks 0, 6, 12 and 36, they underwent a 3-h intravenous glucose tolerance test, a 4-h mixed meal test, and a 48-h continuous glucose monitoring. Liver, muscle, pancreas, and visceral fat contents were measured by magnetic resonance imaging.During the 24-week self-selected diet period (weeks 12-36), body weight, visceral fat, liver fat, and glycated haemoglobin were maintained at the same levels achieved at the end of the fully provided diet period, and were still lower than at baseline (P 0.05). Postprandial insulinaemia and insulin secretion were significantly greater (P 0.05). At week 36, fasting insulin and C-peptide levels increased (P 0.01) and daily glycaemia decreased further (P 0.05) when compared with the end of the fully provided diet period.Substituting dietary carbohydrate for protein and fat has metabolic benefits in patients with T2DM. These beneficial effects are maintained or augmented over the next 6 months when patients self-select and self-prepare this diet in a dietitian-supported setting.ClinicalTrials.gov NCT02764021.

Background: We hypothesized that dietary carbohydrate reduction will add to the effect of a diet-induced 6% body-weight loss on glycemic control and hepatic fat content in patients with type 2 diabetes (T2D). Methods: Forty-four persons of mean HbA1c 56.4 mmol/mol and 9 years of T2D were randomized 1:1 for 6-weeks full food provision, a hypo-caloric carbohydrate-reduced high-protein (CRHP) or a conventional diabetes (CD) diet (carbohydrate 30E%/50E%, protein 30E%/17E% and fat 40E%/33E%). Body-weight loss was aimed at 6% and reinforced bi-weekly by adjustment of hypo-caloric diets. Hepatic fat content was estimated by Magnetic Resonance (MR) spectroscopy and analyzed by a MR research technician, blinded to the protocol. Results: Six weeks of a hypo-caloric CRHP diet compared with a CD diet improved HbA1c (mean±SD) by further 2 mmol/mol (-8.7±4.6 mmol/mol vs. -6.7±3.9 mmol/mol, p=0.04) with comparable weight losses, 5.5±1.7 kg (5.6 %) and 5.6±2.2 kg (5.9 %) of body-weight, respectively. Hepatic fat content (median (IQR) was reduced significantly while consuming the CRHP diet (5.2% (1.3-6.9)) and CD diet (2.6% (1.6-6.5)), but with no difference between diets (p=0.40). Conclusion: Reducing carbohydrate and increasing protein and fat adds clinical relevance to the positive effects of body-weight loss on glucose control in T2D patients. Disclosure M.N. Thomsen: None. M.J. Skytte: None. A. Samkani: None. M.H. Carl: None. P. Weber: None. A. Astrup: Advisory Panel; Self; Gelesis, Novo Nordisk A/S, Saniona, Weight Watchers International, Inc. Research Support; Self; Arla Food for Health, Gelesis, Novo Nordisk A/S. Speaker’s Bureau; Self; Arla Food for Health. Stock/Shareholder; Self; Gelesis. T.M. Larsen: Advisory Panel; Self; Advisor for Sense diet programme. J. Frystyk: None. J.J. Holst: Advisory Panel; Self; AstraZeneca, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Zealand Pharma A/S. Other Relationship; Spouse/Partner; Antag Therapeutics. B. Hartmann: None. H. Thomsen: None. E. Chabanova: None. S. Madsbad: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis. Research Support; Self; Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. S.B. Haugaard: None. T. Krarup: None.

AIMS To test the in vivo activity of Cytochrome P450 (CYP) 2E1 in obese children vs. nonobese children, aged 11-18 years. Secondly, whether the activity of CYP2E1 in these patients is associated with NALFD, diabetes or hyperlipidaemia. METHODS Seventy children were divided into groups by body mass index (BMI) standard deviation score (SDS). All children received 250 mg oral chlorzoxazone (CLZ) as probe for CYP2E1 activity. Thirteen blood samples and 20-h urine samples were collected per participant. RESULTS Obese children had an increased oral clearance and distribution of CLZ, indicating increased CYP2E1 activity, similar to obese adults. The mean AUC0-∞ value of CLZ was decreased by 46% in obese children compared to nonobese children. The F was was increased twofold in obese children compared to nonobese children, P

Women with polycystic ovary syndrome (PCOS) were treated with the GLP-1 receptor agonist liraglutide to investigate the effect on liver fat content, visceral adipose tissue (VAT), and the prevalence of nonalcoholic fatty liver disease (NAFLD). In a double-blind, placebo-controlled, randomized clinical trial 72 women with PCOS and BMI >25 kg/m(2) and/or insulin resistance were treated with liraglutide or placebo 1.8 mg/day (2:1) for 26 weeks. Liver fat content was assessed by (1) HMR spectroscopy, VAT by MRI, body composition by DXA, and glucose metabolism by oral glucose tolerance test. Compared with placebo, liraglutide treatment reduced body weight by 5.2 kg (5.6%), liver fat content by 44%, VAT by 18%, and the prevalence of NAFLD with two-thirds (all p

Rationale and Objectives The purpose of the present study was to obtain a cutoff value of liver fat content for the diagnosis of hepatic steatosis by comparing magnetic resonance (MR) spectroscopy results in children and adolescents with normal and excess weight. Materials and Methods The study included 420 children and adolescents (91 normal-weight, 99 overweight, and 230 obese) 8–18 years of age. Proton magnetic resonance spectroscopy was performed with a 3T MR system using point resolved spectroscopy sequence with series echo times. Results The mean absolute mass concentration of liver fat was obtained: 0.5 ± 0.04% in normal-weight boys; 0.5 ± 0.03% in normal-weight girls; 0.9 ± 0.16% in boys with overweight; 1.1 ± 0.24% in girls with overweight; 1.7 ± 0.24% in boys with obesity; and 1.4 ± 0.21% in girls with obesity. The cutoff value of absolute mass concentration of liver fat for hepatic steatosis was found to be 1.5%. Based on this cutoff value, hepatic steatosis was diagnosed in 16% of boys with overweight, 11% of girls with overweight, 32% of boys with obesity, and 27% of girls with obesity. Conclusions Proton magnetic resonance spectroscopy was successfully applied to obtain the cutoff value of absolute mass concentration of liver fat for the diagnosis of hepatic steatosis in children and adolescents. Children and adolescents with obesity have higher risk of hepatic steatosis than their peers with overweight.

BackgroundNon-alcoholic fatty liver disease (NAFLD) is highly prevalent and causes serious health complications in type 2 diabetes (T2D) and beyond. Early diagnosis of NAFLD is important, as this can help prevent irreversible damage to the liver and ultimately hepatocellular carcinomas.Methods and FindingsUtilizing the baseline data from the IMI DIRECT participants (n=1514) we sought to expand etiological understanding and develop a diagnostic tool for NAFLD using machine learning. Multi-omic (genetic, transcriptomic, proteomic, and metabolomic) and clinical (liver enzymes and other serological biomarkers, anthropometry, and measures of beta-cell function, insulin sensitivity, and lifestyle) data comprised the key input variables. The models were trained on MRI image-derived liver fat content (ConclusionsWe have developed clinically useful liver fat prediction models (see:www.predictliverfat.org) and identified biological features that appear to affect liver fat accumulation.

Background Elevated plasma concentrations of liver enzymes are routinely used as markers of liver injury in adults and children. Currently, the age- and sex-specific effects of adiposity on pediatric liver enzyme concentrations are unclear. Methods We included participants from 2 cohorts of Danish children and adolescents: 1858 from a population-based cohort and 2155 with overweight or obesity, aged from 6 to 18 years. Age- and sex-specific percentile curves were calculated for fasting plasma concentrations of alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), gamma-glutamyltransferase (GGT), bilirubin, and alkaline phosphatase (ALP) in both cohorts. Hepatic fat content was assessed by proton magnetic resonance spectroscopy in 458 participants. Results Concentrations of ALT, AST, LDH, and ALP decreased with age in both girls and boys, while GGT and bilirubin were comparable across age groups in girls and increased slightly with age in boys. Children and adolescents with overweight or obesity exhibited higher concentrations of ALT in all age groups. Concentrations of ALT, and to a lesser degree GGT, increased with age in boys with overweight or obesity. Optimal ALT cut-points for diagnosing hepatic steatosis (liver fat content > 5%) was 24.5 U/L for girls (sensitivity: 55.6%, specificity: 84.0%), and 34.5 U/L for boys (sensitivity: 83.7%, specificity: 68.2%). Conclusions Pediatric normal values of liver enzymes vary with both age and sex. Overweight and obesity is associated with elevated biochemical markers of liver damage. These findings emphasize the need for prevention and treatment of overweight and obesity in children and adolescents. (J Clin Endocrinol Metab XX: 0-0, 2019)

OBJECTIVE Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in patients with type 2 diabetes. A growing body of evidence points at a beneficial effect of MR antagonists (MRAs) on adipocyte function via the inhibition of adipocyte differentiation, downregulation of rho-kinase activity, pro-inflammatory proteins and increase of adiponectin expression in visceral fat. Therefore, intervention with MRAs may improve dysfunctional adipose tissue metabolism and reverse NAFLD. The primary hypothesis of the MIRAD trial was that treatment with high dose of the selective MRA eplerenone as an add-on to standard therapy, would improve liver fat content, lipid and glucose metabolism in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS In this investigator-initiated, double-blinded clinical trial, 140 patients with type 2 diabetes and high cardiovascular disease risk were randomized 1:1 to eplerenone 100 - 200 mg or placebo for 26 weeks. The primary outcome was change in liver fat assessed by proton magnetic resonance spectroscopy. Secondary outcomes were changes in fat distribution assessed by DXA scan, measures of lipid and glucose metabolism by 4 point OGTT with measurements of glucose and insulin, and safety as evaluated by incident hyperkalaemia and increase in serum creatinine. RESULTS The mean ± SD age was 63.4 ± 9 years, BMI 30.7 ± 4.2 kg/m2, HbA1c 7.6 ± 3.5% (59.6 ± 14.5 mmol/mol) and duration of diabetes was 11.7 ± 7.2 years. At baseline, more than 80% of the patients were on ACE-inhibitor or ARB. The prevalence of NAFLD, defined as liver fat content ≥5.6%, was 48%. Liver fat content did not change after 26 weeks of treatment with eplerenone (1.1% [0.68; 1.66], P = 0.776) or with a placebo (-0.8% [-1.4; 0.5], P = 0.500), while a minor difference between groups was observed (P=0.026). Furthermore, there was no beneficial impact on supporting secondary outcome measures of lipid and glucose metabolism as abdominal fat distribution, lipids, circulating free fatty acids, plasma adiponectin or IR. Despite a high dosage of eplerenone (164 vs 175 mg) in patients treated with placebo (P = 0.228), the incidence of hyperkalaemia during the 26 weeks was low (p-potassium ≥5.5 mmol/L; 10 vs 2) for eplerenone vs placebo (P = 0.038). Only four patients had an increase ≥ 30% in s-creatinine during titration, with no difference between groups. At baseline, no differences between groups in liver fibrosis score NFS was observed, while at week 26, the NFS score decreased in the eplerenone group compared to placebo (P = 0.021). CONCLUSIONS We report no metabolic beneficial effect from eplerenone on liver fat or parameters of glucose and lipid metabolism in patients with type 2 diabetes, although a potential beneficial effect on liver fibrosis was found.

Background Due to improved ultrasound scanners, new three-dimensional (3D) modalities, and novel Anti-Müllerian hormone (AMH)-assays, the ultrasound criteria for polycystic ovarian morphology are under debate and the appropriate thresholds are often requested. Purpose To quantify the differences in estimates of ovarian volume and antral follicle count (AFC) from two-dimensional (2D) and 3D transvaginal ultrasound (TVUS) and magnetic resonance imaging (MRI). Material and Methods A cross-sectional study on 66 overweight women with polycystic ovary syndrome (PCOS) according to Rotterdam criteria. Ovarian volume and AFC were estimated from MRI, 2D TVUS, and 3D TVUS, and serum AMH levels were assessed. Bland–Altman statistics were used for comparison. Results Participants had a median age of 29 years (age range, 19–44 years) with a mean BMI of 32.7 kg/m2 (SD 4.5). Ovarian volume from 2D TVUS was 1.48 mL (95% confidence interval [CI], 0.94–2.03; P Conclusion In an overweight PCOS population, 2D TVUS underestimated ovarian volume and AFC as compared with 3D TVUS and MRI. Serum AMH correlated best with AFC from 3D TVUS, followed by MRI and 2D TVUS. The advantage of 3D TVUS might be of minor clinical importance when diagnosing PCOS, but useful when the actual AFC are of interest, e.g. in fertility counseling and research.

Background The metabolic syndrome (MetS) is a complication to overweight and obesity, which can be observed already in childhood. Ectopic lipid accumulation in muscle and liver has been shown to associate with the development of insulin resistance and dyslipidemia. Thus, the interaction between Mets and ectopic fat may offer clinical relevance. Objectives To investigate the prevalence of MetS, or components hereof, and ectopic fat accumulation in liver and skeletal muscle tissue in children, as well as interactions between these. Methods Two-hundred-and-sixteen children and adolescents (95 boys) with overweight/obesity were investigated, as well as 47 controls (22 boys) with normal weight. The assessments included anthropometry, fasting blood biochemistry, and blood pressure measurements. Liver and muscle lipid contents were assessed by proton magnetic resonance spectroscopy. Results We observed an odds ratio in girls with overweight/obesity of 12.2 (95% CI: [3.8; 49.0]) for exhibiting MetS when hepatic steatosis was present, whereas no association was observed in boys with overweight/obesity (odds ratio 0.7 [0.2; 2.7]). The odds ratio of exhibiting MetS in the presence of muscular steatosis was 3.5 [1.4; 9.5] in girls with overweight/obesity and 1.0 [0.2; 5.6] in boys with overweight/obesity. Similar results were seen for girls with overweight/obesity exhibiting concurrent hepatic and muscular steatoses. Conclusion Hepatic and muscular steatoses were associated with MetS among girls, but not among boys with overweight/obesity. Trial registration ClinicalTrials.gov registration number: NCT00928473, the Danish Childhood Obesity Biobank. Registered June 25, 2009.

Dietary recommendations for treating type 2 diabetes are unclear but a trend towards recommending a diet reduced in carbohydrate content is acknowledged. We compared a carbohydrate-reduced high-protein (CRHP) diet with an iso-energetic conventional diabetes (CD) diet to elucidate the effects on glycaemic control and selected cardiovascular risk markers during 6 weeks of full food provision of each diet.The primary outcome of the study was change in HbATwenty-eight participants completed the study. Fourteen participants carried out 6 weeks of the CRHP intervention followed by 6 weeks of the CD intervention, and 14 participants received the dietary interventions in the reverse order. Compared with a CD diet, a CRHP diet reduced the primary outcome of HbAA moderate macronutrient shift by substituting carbohydrates with protein and fat for 6 weeks reduced HbAClinicalTrials.gov NCT02764021.The study was funded by grants from Arla Food for Health; the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen; the Department of Clinical Medicine, Aarhus University; the Department of Nutrition, Exercise and Sports, University of Copenhagen; and Copenhagen University Hospital, Bispebjerg.

Aim Natriuretic peptides (NPs) have emerged as important regulators of lipid metabolism. Reduced levels of NPs are reported in obesity and in patients with type 2 diabetes (T2D). This NP deficiency may affect their ectopic fat distribution and lead to high risk of non-alcoholic fatty liver disease (NAFLD). Methods In this cross-sectional study, the association between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and liver fat content was quantified using 1H-magnetic resonance spectroscopy in 120 patients with T2D. Results NAFLD (defined as liver fat content ≥ 5.6%) was found in 57 (48%) of the T2D patients, who also had significantly lower NT-proBNP (P = 0.002) levels compared with patients without NAFLD, but did not differ as regards the presence of cardiovascular disease (CVD) or in kidney function. After adjusting for potential confounders (age, gender, HbA1c, BMI, HOMA2-IR, CVD, eGFR), the odds ratio for the presence of NAFLD was increased by 2.9 (P = 0.048) for NT-proBNP levels Conclusion Reduced plasma NT-proBNP levels are independently associated with high liver fat content in patients with T2D. The present study suggests that NP deficiency may play a role in the development of NAFLD in T2D.

BackgroundPolycystic ovary syndrome (PCOS) is associated with frequent overweight and abdominal obesity. Quantifying visceral adipose tissue (VAT) in PCOS patients can be a tool to assess metabolic risk and monitor effects of treatment. The latest dual-energy X-ray absorptiometry (DXA) technology can measure VAT and subcutaneous adipose tissue (SAT) in a clinical setting.PurposeTo compare DXA-measurements of VAT and SAT with the gold standard MRI in women with PCOS.Material and MethodsA cross-sectional study of 67 overweight women with PCOS was performed. Measurements of VAT and SAT were performed by DXA in a 5-cm thick transverse slice at the L4/L5 level and by MRI in a 1-cm thick transverse slice at the L3 level.ResultsMean (SD) DXA-VAT was 81 (34) cm3, DXA-SAT was 498 (118) cm3, MRI-VAT was 117 (48) cm3, and MRI-SAT was 408 (122) cm3. MRI and DXA measures of VAT (r = 0.82, P ConclusionDXA and MRI measurements of VAT and SAT correlated closely despite different size of region of interest, and DXA-VAT was superior to waist circumference and BMI in estimating MRI-VAT. DXA showed high reproducibility making it is suitable for repeated measurements in the same individual over time.

To evaluate the diagnostic performance of preoperative multiparametric MRI with extracapsular extension (ECE) risk-scoring in the assessment of prostate cancer tumour stage (T-stage) and prediction of ECE at final pathology. Eighty-seven patients with clinically localised prostate cancer scheduled for radical prostatectomy were prospectively enrolled. Multiparametric MRI was performed prior to prostatectomy, and evaluated according to the ESUR MR prostate guidelines by two different readers. An MRI clinical T-stage (cTMRI), an ECE risk score, and suspicion of ECE based on tumour characteristics and personal opinion were assigned. Histopathological prostatectomy results were standard reference. Histopathology and cTMRI showed a spearman rho correlation of 0.658 (p

Purpose To evaluate the correlation between apparent diffusion coefficient measurements (ADCtumor and ADCratio) and the Gleason score from radical prostatectomy specimens. Materials and Methods Seventy-one patients with clinically localized prostate cancer scheduled for radical prostatectomy were prospectively enrolled. Multiparametric magnetic resonance imaging (MRI) was performed prior to prostatectomy and mean ADC values from both cancerous (ADCtumor) and benign (ADCbenign) tissue were measured to calculate the ADCratio (ADCtumor divided by ADCbenign). The ADC measurements were correlated with the Gleason score from the prostatectomy specimens. Results The association between ADC measurements and Gleason score showed a significant negative correlation (P

We aimed to compare the effect of aerobic interval training (AIT) versus a low energy diet (LED) on physical fitness, body composition, cardiovascular risk factors and symptoms in overweight individuals with coronary artery disease (CAD).Seventy non-diabetic participants with CAD, a BMI28 kg/m(2) and aged 45 to 75 years were randomised to 12 weeks' AIT at 90% peak heart rate three times a week or LED (800-1000 kcal/day) for 8-10 weeks followed by 2-4 weeks' weight maintenance diet.Twenty-six (74%) AIT and 29 (83%) LED participants completed intervention per protocol. VO2peak (mL/kg fat free mass(0.67)/min) increased by 10.4% (p = 0.002) following AIT, whereas no change was observed after LED (-3.0%, p = 0.095). The LED group lost 10.6% body weight and 26.6% body fat mass (p 0.001) compared to 1.6% (p = 0.002) and 5.5% (p 0.001) following AIT. Waist circumference and visceral abdominal fat were reduced by both interventions but were most pronounced following LED (between-group, p 0.001). Total cholesterol, non-HDL-C and triglycerides decreased significantly in both groups whereas HDL-C and blood pressure were unchanged. Six participants had their antihypertensive treatment reduced following LED (between-group, p = 0.032). Canadian Cardiovascular Society (CCS), New York Heart Association (NYHA) and anxiety scores were improved, while depressive symptoms remained unchanged. Intention-to-treat analyses including 65 participants (93%) were similar to per protocol analysis.Both interventions were feasible and effective in achieving the desired effects. LED was superior in improving body composition and blood pressure, whereas effects on lipids and symptoms were similar in the two groups. Thus, both AIT and LED improve the cardiovascular risk profile in overweight individuals with contemporarily treated CAD.

In recent years, proton magnetic resonance spectroscopy (MRS) has emerged as a non-invasive technique for measurement of fat content in the liver. The technique is often applied for overweight and obese patients. However, excessively obese patients cannot be examined in most conventional magnetic resonance systems due to limited space. The purpose of this study was to examine the ability of open 1T system to monitor liver fat with proton MRS and to compare hepatic fat fractions (HFFs) obtained using an open 1T system with assessment with 3T proton MRS.The study included 23 children and adolescents up to 20 years of age with a body mass index above the 97th percentile according to age and gender. Proton MRS for each patient was performed in both 1T and 3T using point resolved spectroscopy sequence in a single volume positioned in the right liver lobe.Average T2 relaxation times obtained for an open 1T system (55 ± 7 ms for water and 85 ± 11 ms for fat) were higher than average T2 relaxation times obtained for a 3T system (31 ± 4 ms for water and 66 ± 10 ms for fat). HFFs measured using an open 1T system showed strong correlation with HFFs measured using a 3T system (r = 0.99, P0.0001).Proton MRS measurements of HFF with an open 1T system are feasible. Open 1T system may reliably replace 3T magnetic resonance system for the assessment of liver fat.

Objective The objective was to investigate T 2 relaxation values and to optimize hepatic fat quantification using proton MR spectroscopy ( 1 H MRS) at 3 T in overweight and obese children and adolescents. Subjects The study included 123 consecutive children and adolescents with a body mass index above the 97th percentile according to age and sex. 1 H MR spectroscopy was performed at 3.0 T using point resolved spectroscopy sequence with series TE. T 2 relaxation values and hepatic fat content corrected for the T 2 relaxation effects were calculated. Results T 2 values for water ranged from 22 ms to 42 ms (mean value 28 ms) and T 2 values for fat ranged from 36 ms to 99 ms (mean value 64 ms). Poor correlation was observed: (1) between T 2 relaxation times of fat and T 2 relaxation times of water (correlation coefficient r = 0.038, P = 0.79); (2) between T 2 relaxation times of fat and fat content ( r = 0.057, P = 0.69); (3) between T 2 relaxation times of water and fat content ( r = 0.160, P = 0.26). Correlation between fat peak content and the T 2 corrected fat content decreased with increasing echo time TE: r = 0.97 for TE = 45, r = 0.93 for TE = 75, r = 0.89 for TE = 105, P Conclusion 1 H MRS at 3 T is an effective technique for measuring hepatic fat content in overweight and obese children and adolescents. It is necessary to measure T 2 relaxation values and to correct the spectra for the T 2 relaxation effects in order to obtain an accurate estimate of the hepatic fat content.

What is already known about this subject • Investigations of non-alcoholic fatty liver disease (NAFLD) by non-invasive imaging procedures have limited evidence. • Thirty percent of obese children are estimated to have NAFLD and implications for future morbidity are uncertain. What this study adds • Many obese children and youths exhibit a high liver fat content as examined by magnetic resonance spectroscopy. • Associations between liver fat content, anthropometry, abdominal adipose tissue distribution and liver enzymes are illustrated. Summary The study aims to investigate the degree of hepatic steatosis and associations with the amount of abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), anthropometric data and biochemical measures of liver enzymes in children and youths included in obesity treatment. The study included 164 patients, aged 6–20 years, with a body mass index (BMI) above the 90th percentile for sex and age. Liver fat content was measured by magnetic resonance spectroscopy (MRS). SAT and VAT were measured by magnetic resonance imaging. Hepatic steatosis was defined as liver fat content >5% (steatosis-5%) and 9% (steatosis-9%), respectively. Data on waist circumference (WC) and blood samples were available in 124 patients. Steatosis-5% and steatosis-9% were identified in 45% and 27% of the patients, respectively. These patients had increased SAT, VAT, BMI standard deviation score, WC/height ratio, alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) levels. GGT, ALT and VAT were found to be independent risk factors of hepatic steatosis. In this study, a substantial proportion of obese children and youths have hepatic steatosis. Therefore, it is important to examine these subjects for the degree of fat in their liver. Future studies focusing on hepatic steatosis should consider the use of MRS in addition to blood samples.

Purpose To investigate diagnostic accuracy of detection of prostate cancer by magnetic resonance: to evaluate the performance of T2WI, DCEMRI and CSI and to correlate the results with biopsy and radical prostatectomy histopathological data. Materials and methods 43 patients, scheduled for radical prostatectomy, underwent prostate MR examination. Prostate cancer was identified by transrectal ultrasonographically (TRUS) guided sextant biopsy. MR examination was performed at 1.5T with an endorectal MR coil. Cancer localisation was performed on sextant-basis – for comparison between TRUS biopsy, MR techniques and histopathological findings on prostatectomy specimens. Results Prostate cancer was identified in all 43 patients by combination of the three MR techniques. The detection of prostate cancer on sextant-basis showed sensitivity and specificity: 50% and 91% for TRUS, 72% and 55% for T2WI, 49% and 69% for DCEMRI, and 46% and 78% for CSI. Conclusion T2WI, DCEMRI and CSI in combination can identify prostate cancer. Further development of MR technologies for these MR methods is necessary to improve the detection of the prostate cancer.

Purpose The purpose of the study was to evaluate unenhanced Magnetic Resonance Imaging (MRI) for the diagnosis of appendicitis or another surgery-requiring condition in an adult population scheduled for emergency appendectomy based on a clinical diagnosis of suspected acute appendicitis. Materials and methods The prospective study included 48 consecutive patients (29 female, 19 male, 18–70 years old, mean age = 37.1 years). MRI examination was designed to be comfortable and fast; no contrast was administered. The sequences were performed during quiet respiration. The MRI findings were reviewed by two radiologists and one surgeon independent of each other and compared with surgical and pathological records. Results According to the surgical and histopathological findings 30 of 48 patients (63%) had acute appendicitis. Of the remaining 18 patients, 4 patients had no reasons for the clinical symptoms and 14 patients had other pathology. For the three reviewers the performance of MRI in the diagnosis of acute appendicitis showed the following sensitivity, specificity and accuracy ranges: 83–93%, 50–83% and 77–83%. Moderate (κ = 0.51) and fair (κ = 0.31) interobserver agreements in the MR diagnosis of acute appendicitis were found between the reviewers. Sensitivity, specificity and accuracy values for overall performance of MRI in detecting pelvic abnormalities were 100%, 75% (3 of 4 healthy patients were identified by MRI) and 98%, respectively. Conclusion Unenhanced fast MRI is feasible as an additional fast screening before the appendectomy. It may prevent unnecessary surgeries. The fast MRI examination can be adequately performed on an MRI unit of broad range of field strengths.

This paper discusses the development and clinical applications of positive manganese based MR contrast agents, including both intravenous (i.v.) and oral formulations. The i.v. formulation is a manganese-dipyridoxyl diphos- phate chelate which is commercially available; whereas the oral formulation is a mixture of MnCl2, alanine and Vitamin D3, which is currently under clinical trials. The compositions, preclinical studies and pharmacokinetics of both form- ulations are discussed. The main reported clinical difference between the two formulations is that i.v. administration ex- poses all the organs, whereas oral ingestion exposes only the enterohepatic circulation. Manganese based MR contrast agents are particularly suitable for detection of focal liver lesions due to their uptake by the mitochondria rich hepatocytes, and biliary delineation due to their biliary excretion; it can provide useful information in diffuse liver lesions. Further, the i.v. formulation can be used for focal pancreatic lesions.

Background Colorectal cancer will present itself as a bowel obstruction in 16–23% of all cases. However, not all obstructing tumors are malignant and the differentiation between a benign and a malignant tumor can be difficult. The purpose of our study was to determine whether fast dynamic gadolinium-enhanced MR imaging combined with MR colonography could be used to differentiate a benign from a malignant obstructing colon tumor. Methods Patients with benign colon tumor stenosis, based on diverticulitis, were asked to participate in the study. The same number of patients with verified colorectal cancer was included. Both groups had to be scheduled for surgery to be included. Two blinded observers analyzed the tumors on MR by placing a region of interest in the tumor and a series of parameters were evaluated, e.g. wash-in, wash-out and time-to-peak. Results 14 patients were included. The wash-in and wash-out rates were significantly different between the benign and malignant tumors, and a clear distinction between benign and malignant disease was therefore possible by looking only at the MR data. Furthermore, MR colography evaluating the rest of the colon past the stenosis was possible with all patients. Conclusion The results showed the feasibility of using fast dynamic gadolinium-enhanced MR imaging to differentiate between benign and malignant colonic tumors. With a high intra-class correlation and significant differences found on independent segments of the tumor, the method appears to be reproducible. Furthermore, the potential is big in performing a full preoperative colon evaluation even in patients with obstructing cancer. Trial number: NCT00114829 .

Rationale and Objectives It is well known that synchronous cancers (incidence, 2%–11%) and polyps (incidence, 12%–58%) occur in patients with colorectal cancer. Magnetic resonance colonography (MRC) seems like the obvious choice as a diagnostic tool in preoperative evaluation, because it is noninvasive, and most of the colon can be evaluated. Furthermore, it has higher patient acceptance, and no sedation or radiation is used. The purpose of this study was to determine the feasibility of performing MRC preoperatively in an everyday clinical situation in a group of patients who were not offered a full conventional colonoscopy or in whom full conventional colonoscopy was not possible. Materials and Methods In a 13-month period, 47 patients diagnosed with rectal or sigmoid colon cancer scheduled for operation were included in the study. MRC was performed with bowel purgation either the night before surgery or as ambulatory MRC the week before surgery. Results Full MRC was performed in 98% of the patients. In four patients, 12 synchronous lesions (one cancer, two plaques of carcinosis, and nine adenomas) were found. One flat adenoma and five small polyps were missed by MRC and perioperative palpation but found on postoperative colonoscopy. The findings resulted in altered operative strategies in three patients. Conclusion This study shows the feasibility and potential gain of preoperative MRC in patients with sigmoid colon cancer or rectal cancer.

Rationale and Objectives Both magnetic resonance (MR) and computed tomographic (CT) colonography are useful for colon examination. With sensitivities close to those for conventional colonoscopy (CC) for polyps, colonography has been proposed as an alternative to diagnostic CC. MR colonography (MRC) with fecal tagging may be a method of gaining further patient acceptance and widespread use, but the method has to be optimized. The aim of our study was to evaluate the quality of a new contrast agent mixture and to validate a new method for evaluating the tagging efficiency of contrast agents. Materials and Methods Twenty patients referred to CC underwent dark lumen MRC prior to the colonoscopy. Two groups of patients received two different oral contrast agents (barium sulfate and barium sulfate/ferumoxsil) as a laxative-free fecal tagging prior to the MRC. After MRC, the contrast agent was rated qualitatively (with the standard method using contrast-to-wall ratio) and subjectively (using a visual analog scale [VAS]) by three different blinded observers. Results Evaluated both qualitatively and subjectively, the tagging efficiency of barium sulfate/ferumoxsil was significantly better (P 10 mm. Conclusion MRC with fecal tagging using barium sulfate/ferumoxsil as contrast agent will give better overall assessment of the colon wall compared to barium sulfate alone. Furthermore, the VAS method of evaluating fecal tagging efficiency correlated with the standard method of calculating the contrast-to-wall ratio.

Background Ectopic fat deposition in liver and skeletal muscle tissue is related to cardiovascular disease risk and is a common metabolic complication in obese children. We evaluated the hypotheses of ectopic fat in these organs could be diminished following 1 year of multidisciplinary care specialized in childhood obesity, and whether this reduction would associate with changes in other markers of metabolic function. Methods This observational longitudinal study evaluated 40 overweight children and adolescents enrolled in a multidisciplinary treatment protocol at the Children’s Obesity Clinic, Holbæk, Denmark. The participants were assessed by anthropometry, fasting blood samples (HbA1c, glucose, insulin, lipids, and biochemical variables of liver function), and liver and muscle fat content assessed by magnetic resonance spectroscopy at enrollment and following an average of 12.2 months of care. Univariate linear regression models adjusted for age, sex, treatment duration, baseline degree of obesity, and pubertal developmental stage were used for investigating possible associations. Results The standard deviation score (SDS) of baseline median body mass index (BMI) was 2.80 (range: 1.49–3.85) and the median age was 14 years (10–17). At the end of the observational period, the 40 children and adolescents (21 girls) significantly decreased their BMI SDS, liver fat, muscle fat, and visceral adipose tissue volume. The prevalence of hepatic steatosis changed from 28 to 20 % (p = 0.26) and the prevalence of muscular steatosis decreased from 75 to 45 % (p = 0.007). Changes in liver and muscle fat were independent of changes in BMI SDS, baseline degree of obesity, duration of treatment, age, sex, and pubertal developmental stage. Conclusions A 1-year multidisciplinary intervention program in the setting of a childhood obesity outpatient clinic confers a biologically important reduction in liver and muscle fat; metabolic improvements that are independent of the magnitude of concurrent weight loss. Trial registration ClinicalTrials.gov registration number: NCT00928473, the Danish Childhood Obesity Biobank. Registered June 25, 2009. Electronic supplementary material The online version of this article (doi:10.1186/s12887-015-0513-6) contains supplementary material, which is available to authorized users.

Contains fulltext : 51338.pdf (Publisher’s version ) (Closed access) RATIONALE AND OBJECTIVES: The purpose of the study was a preliminary evaluation of a new oral, manganese-based, liver-specific contrast medium (CMC-001; CMC Contrast AB, Malmoe, Sweden) for magnetic resonance imaging (MRI) in patients with liver metastases. MATERIALS AND METHODS: The study included 10 consecutive patients with known liver metastases. Patients underwent abdominal MRI as a supplement to routine diagnostics. Patients fasted for at least 10 hours before ingesting CMC-001 (1.6 g manganese chloride tetrahydrate, 1 g alanine, and 1,600 IU vitamin D3 were dissolved in water). MRI took place before and 2 hours after drinking CMC-001. The 1.5-T MRI protocol included two-dimensional T1w sequences to visualize metastases. T2w and diffusion weighted imaging (DWI) sequences were used to identify cysts and blood vessels correspondingly. RESULTS: The intake of CMC-001 caused an increase in the signal intensity of the "healthy" liver tissue, making the internal structure of the liver significantly better visualized. Compared with our routine examinations, MRI showed more metastases in four patients and allowed determining a more precise outline of metastases. CONCLUSION: CMC-001 improves imaging of liver metastases in comparison with computed tomography and with MRI without CMC-001.

Rationale and objectives The purpose of this study was to evaluate our preliminary experience with routine contrast-enhanced magnetic resonance angiography (CE-MRA) of the lower limb arteries in patients with end-stage renal failure. Materials and methods A retrospective analysis was performed on clinical, physiological, and imaging data for 104 patients with end-stage renal failure. Patients were considered to be in end-stage renal failure if they were on renal replacement therapy (peritoneal or hemodialysis) or were being evaluated as part of a pretransplant workup. CE-MRA was carried out on a 1.5-T scanner using a single-injection, three-station moving table technique. Results Eleven percent of asymptomatic patients with normal ankle/brachial pressure indexes (ABPI) were found to have severe arterial disease on CE-MRA, and in 30% of asymptomatic patients with abnormal ABPI, CE-MRA showed mild or no disease. Moreover two of three symptomatic patients with normal ABPI were shown to have severe disease. Two patients on peritoneal dialysis had to be switched to hemodialysis. No other adverse events were revealed. Conclusion CE-MRA is a useful adjunct to clinical and physiological examination for the evaluation of the lower limb arteries in a group of patients who have a higher-than-average incidence of peripheral vascular disease, yet have previously been severely restricted from traditional angiography because of contrast-medium-induced nephrotoxicity.

Rationale and objectives To study the magnetic resonance imaging signal intensity of the liver and gall bladder before and after ingestion of a new oral manganese containing contrast medium at three different field strengths. Materials and methods Twelve healthy male volunteers (mean age, 24.9 years; range, 20–39 years) underwent abdominal magnetic resonance imaging (T2W COR, T1W COR, T1W TRA) at 0.23T, 0.6T, and 1.5 T before and after the contrast administration. The duration of fasting was identical before the two studies. Volunteers were randomized into two equal groups (n = 6) to ingest either half or full strength CMC-001 providing either 0.8 or 1.6.g MnCl2 plus absorption promoters. The CMC-001 dose was dissolved in 400 mL water and ingested 2 1 2 hours before imaging. The resulting images were evaluated with regard to visualization of the liver and the gall bladder by three radiologists. The signal intensity of the liver was also measured. Blood and urine samples were collected before and after ingestion of CMC-001. Results The intake of CMC-001 caused a significant increase in the signal intensity of the liver at all three field strengths and at both dosages (up to 90%) on the T1W images. The internal structure of the liver was significantly better delineated. The bile in gall bladder was bright after ingestion of the low dose, but dark after the full dose. On the T2W images, CMC-001 lowered the signal intensity of liver with up to 30%. CMC-001 had a slight metallic taste, but of no importance according to the volunteers. No systematic adverse reactions caused by the contrast medium were registered. No changes in the blood levels of various routine parameters were measured. Conclusion It is possible to increase the signal intensity of the liver significantly by oral intake of essential nutritional elements including manganese. The imaging window is more than 2 hours.

To evaluate the correlation between apparent diffusion coefficient measurements (ADCtumor and ADCratio ) and the Gleason score from radical prostatectomy specimens.Seventy-one patients with clinically localized prostate cancer scheduled for radical prostatectomy were prospectively enrolled. Multiparametric magnetic resonance imaging (MRI) was performed prior to prostatectomy and mean ADC values from both cancerous (ADCtumor ) and benign (ADCbenign ) tissue were measured to calculate the ADCratio (ADCtumor divided by ADCbenign ). The ADC measurements were correlated with the Gleason score from the prostatectomy specimens.The association between ADC measurements and Gleason score showed a significant negative correlation (P0.001) with Spearman's rho for ADCtumor (-0.421) and ADCratio (-0.649). There was a statistically significant difference between ADC measurements and the Gleason score for all tumors (P = 0.001). Receiver operating characteristic curve analysis showed an overall area under the curve (AUC) of 0.73 (ADCtumor ) to 0.80 (ADCratio ) in discriminating Gleason score 6 from Gleason score ≥7 tumors. The AUC changed to 0.72 (ADCtumor ) and 0.90 (ADCratio ) when discriminating Gleason score ≤7(3+4) from Gleason score ≥7(4+3).ADC measurements showed a significant correlation with tumor Gleason score at final pathology. The ADCratio demonstrated the best correlation compared to the ADCtumor value and radically improved accuracy in discriminating Gleason score ≤7(3+4) from Gleason score ≥7(4+3) tumors.