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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.

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.

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

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

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 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.

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.

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.

Background : Proton MR Spectroscopy ( 1 H MRS) can be used to measure hepatic fat fractions (HFF) in liver cells for assessment of non-alcoholic fatty liver disease (NAFLD). The measurement is typically performed in a single volume. For correct diagnosis it is important to know variability of HFF within liver. The purpose of this study was to investigate regional differences in HFF in a large group of overweight and obese children and adolescents using 1H MRS at 3T. Methods: The study included 175 consecutive children and adolescents from 7 to 18 years old with a body mass index above the 97th percentile according to age and gender. 1 H MRS was performed at 3.0T using a point resolved spectroscopy sequence in two 11mmx11mmx11mm volumes positioned in different parts of the right liver lobe. Results: Up to 12% difference in HFF between the two volumes was observed: the regional differences in HFF are below 1% for patients with HFF under 3%; patients with HFF between 3% and 20% have regional differences in HFF up to 5%; patients with HFF over 20% have regional differences in HFF up to 12%. Conclusions: 1H MRS diagnosis and severity assessment of NAFLD in overweight and obese children and adolescents should take up to 12% regional differences in hepatic fat fractions into account.

Background: Intake of industrially produced trans fatty acids (TFAs) is, according to observational studies, associated with an increased risk of cardiovascular disease, but the causal mechanisms have not been fully elucidated. Besides inducing dyslipidemia, TFA intake is suspected to promote abdominal and liver fat deposition. Objective: We examined the effect of a high intake of TFA as part of an isocaloric diet on whole-body, abdominal and hepatic fat deposition, and blood lipids in postmenopausal women. Methods: In a 16-week double-blind parallel intervention study, 52 healthy overweight postmenopausal women were randomized to receive either partially hydrogenated soybean oil providing 15.7 g day−1 of TFA or a control oil with mainly oleic and palmitic acid. Before and after the intervention, body composition was assessed by dual-energy X-ray absorptiometry, abdominal fat by magnetic resonance (MR) imaging, and liver fat by 1H MR spectroscopy. Results: Compared with the control fat, TFA intake decreased plasma high-density lipoprotein (HDL)-cholesterol by 10%, increased low-density lipoprotein (LDL)-cholesterol by 18% and resulted in an increased LDL/HDL-cholesterol ratio (baseline adjusted mean (95% CI) difference between diet groups 0.41 (0.22; 0.60); P

Background: The consumption of sucrose-sweetened soft drinks (SSSDs) has been associated with obesity, the metabolic syndrome, and cardiovascular disorders in observational and short-term intervention studies. Too few long-term intervention studies in humans have examined the effects of soft drinks. Objective: We compared the effects of SSSDs with those of isocaloric milk and a noncaloric soft drink on changes in total fat mass and ectopic fat deposition (in liver and muscle tissue). Design: Overweight subjects (n = 47) were randomly assigned to 4 different test drinks (1 L/d for 6 mo): SSSD (regular cola), isocaloric semiskim milk, aspartame-sweetened diet cola, and water. The amount of intrahepatic fat and intramyocellular fat was measured with 1 H-magnetic resonance spectroscopy. Other endpoints were fat mass, fat distribution (dual-energy X-ray absorptiometry and magnetic resonance imaging), and metabolic risk factors. Results: The relative changes between baseline and the end of 6-mo intervention were significantly higher in the regular cola group than in the 3 other groups for liver fat (132‐143%, sex-adjusted mean;P , 0.01), skeletal muscle fat (117‐221%; P , 0.05), visceral fat (24‐31%; P , 0.05), blood triglycerides (32%; P , 0.01), and total cholesterol (11%; P , 0.01). Total fat mass was not significantly different between the 4 beverage groups. Milk and diet cola reduced systolic blood pressure by 10‐15% compared with regular cola (P , 0.05). Otherwise, diet cola had effects similar to those of water. Conclusion: Daily intake of SSSDs for 6 mo increases ectopic fat accumulation and lipids compared with milk, diet cola, and water. Thus, daily intake of SSSDs is likely to enhance the risk of cardiovascular and metabolic diseases. This trial is registered at clinicaltrials.gov as NCT00777647. Am J Clin Nutr doi: 10.3945/ajcn. 111.022533.

The degree of fat deposition in muscle and its implications for obesity-related complications in youth are not well understood. One hundred and fifty-nine patients (mean age: 13.3 years; range: 6-20) with a body mass index (BMI) >90th percentile for age and sex were included. Muscle fat content (MFC) was measured in the psoas muscle by proton magnetic resonance spectroscopy. The patients were assigned to two groups: MFC

Contains fulltext : 53230.pdf (Publisher’s version ) (Closed access) Recently, a new oral liver-specific manganese-based MR agent (CMC-001) has been introduced. This contrast medium is delivered to the liver in high concentrations in the portal vein and very low doses in the hepatic artery, as only small amounts of manganese enter the general circulation. It is taken up by the hepatocytes and excreted in the bile. Our initial experience with the new MR contrast medium in a variety of patients is reported. A total of 20 patients (11 males and 9 females) were studied with MR imaging 2 h after oral ingestion of the contrast agent. Sixteen patients were referred for evaluation of focal liver lesion(s), whereas in the remaining four patients, evaluation of the biliary tract was requested. In the 17 patients without biliary obstruction, there was an increased signal intensity of the liver parenchyma, whereas in the three patients with biliary obstruction, the uptake was delayed. There was excellent visualization of the biliary system on the T1-weighted images in the 16 patients without biliary obstruction referred for evaluation of a focal liver lesion. In seven patients, the uptake was patchy. In patients with focal liver lesions or biliary tract diseases, it is possible to increase the signal intensity of the liver parenchyma after the oral intake of CMC-001. In patients without biliary tract obstruction, the biliary system is easily visualized. Oral manganese seems to be useful in hepatobiliary MRI. Further research is strongly warranted.

Purpose To evaluate application of MRI and magnetic resonance spectroscopy (MRS) to monitor bone marrow cellularity during pretransplant priming with chemotherapy and hematopoietic growth factor (HGF) administration. Materials and Methods A total of 10 lymphoma and myeloma patients, in remission following induction therapy and considered eligible for high-dose therapy and autologous stem cell transplantation, were included in the study. MR investigation was scheduled four times: at study entry, and one, two, and four weeks following priming. Priming with cyclophosphamide and recombinant human granulocyte colony-stimulating factor (rhG-CSF) started the day after study entry. MR parameters studied in a region of interest were as follows: bone marrow intensity on short-time inversion-recovery (STIR) turbo spin-echo (TSE; thus STIRTSE) and on T1-weighted TSE (T1TSE) images, T2 value for fat component, T2 value for water component, water/fat ratio (W/F), T1 value for fat component, and T1 value for water component. Results The results did not support the hypothesis that hematopoietic expansion quantitated and monitored by MR correlates to the level of mobilized progenitor cells. Conclusion The results indicate that release of stem cells is a more complex phenomenon than hematopoietic expansion and reduction of fat tissue in bone marrow. J. Magn. Reson. Imaging 2006. © 2006 Wiley-Liss, Inc.

The study population included 12 healthy male volunteers (mean age: 24.9 years range: 20 39). All underwent abdominal MR imaging (T2W COR, T1W COR, T1W TRA) in both a Panorama 0.23T-V MR unit, a Panorama 0.6T-V MR unit and an Infinion 1.5 T-H MR unit (all Philip Medical Systems, Best, the Netherlands) after randomization. The total examination time in the three units was 2 hours, so 40 min after start of the first examination they switched to another MR-unit and 40 min later the volunteers started their examination in the remaining unit. They had fasted for at least 121⁄2 hours and they had not been allowed to drink fluids for 81⁄2 hours before they underwent the baseline MRI. Seven days after the baseline MRI, the volunteers were randomized (6 in each group) to ingest either half strength CMC-001 (0.8 g manganese chloride (MnCl2)) or full strength (1.6 g manganese chloride (MnCl2)) dissolved in 400 ml water. At time of drinking CMC-001 they had fasted for at least 10 hours and they had not been allowed to drink for 6 hours. 21⁄2 hours after drinking CMC-001 the same imaging procedure as 7 days earlier took place. Thus 41⁄2 hours after drinking all volunteers had been examined at all three field strengths. The resulting images were evaluated with regard to signal intensity in the liver, the bile as well as bowel content by three independent radiologists using a 4 point scoring system (much better/higher, better/higher, unchanged, worse/less).

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.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.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.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.

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.Twelve healthy male volunteers (mean age, 24.9 years; range, 20-39 years) underwent abdominal magnetic resonance imaging (T(2)W COR, T(1)W COR, T(1)W TRA) at 0.23 T, 0.6 T, 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 MnCl(2) plus absorption promoters. The CMC-001 dose was dissolved in 400 mL water and ingested 2.5 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.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 T(1)W 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 T(2)W 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.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.

Prostate cancer is one of the most common malignancies leading to cancer-related mortality in elderly men. Despite recent improvements in detection and treatment, more accurate disease characteriza...

Background Coronary artery disease (CAD) is accountable for more than 7 million deaths each year according to the World Health Organization (WHO). In a European population 80% of patients diagnosed with CAD are overweight and 31% are obese. Physical inactivity and overweight are major risk factors in CAD, thus central strategies in secondary prevention are increased physical activity and weight loss. Methods/Design In a randomized controlled trial 70 participants with stable CAD, age 45–75, body mass index 28–40 kg/m2 and no diabetes are randomized (1:1) to 12 weeks of intensive exercise or weight loss both succeeded by a 40-week follow-up. The exercise protocol consist of supervised aerobic interval training (AIT) at 85-90% of VO2peak 3 times weekly for 12 weeks followed by supervised AIT twice weekly for 40 weeks. In the weight loss arm dieticians instruct the participants in a low energy diet (800–1000 kcal/day) for 12 weeks, followed by 40 weeks of weight maintenance combined with supervised AIT twice weekly. The primary endpoint of the study is change in coronary flow reserve after the first 12 weeks’ intervention. Secondary endpoints include cardiovascular, metabolic, inflammatory and anthropometric measures. Discussion The study will compare the short and long-term effects of a protocol consisting of AIT alone or a rapid weight loss followed by AIT. Additionally, it will provide new insight in mechanisms behind the benefits of exercise and weight loss. We wish to contribute to the creation of effective secondary prevention and sustainable rehabilitation strategies in the large population of overweight and obese patients diagnosed with CAD. © 2013 Pedersen et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Background Coronary artery disease (CAD) has a negative impact on exercise capacity. The aim of this study was to determine how coronary microvascular function, glucose metabolism and body composition contribute to exercise capacity in overweight patients with CAD and without diabetes. Methods Sixty-five non-diabetic, overweight patients with stable CAD, BMI 28–40 kg/m2 and left ventricular ejection fraction (LVEF) above 35 % were recruited. A 3-hour oral glucose tolerance test was used to evaluate glucose metabolism. Peak aerobic exercise capacity (VO2peak) was assessed by a cardiopulmonary exercise test. Body composition was determined by whole body dual-energy X-ray absorptiometry scan and magnetic resonance imaging. Coronary flow reserve (CFR) assessed by transthoracic Doppler echocardiography was used as a measure of microvascular function. Results Median BMI was 31.3 and 72 % had impaired glucose tolerance or impaired fasting glucose. VO2peak adjusted for fat free mass was correlated with CFR (r = 0.41, p = 0.0007), LVEF (r = 0.33, p = 0.008) and left ventricular end-diastolic volume (EDV) (r = 0.32, p = 0.01) while it was only weakly linked to measures of glucose metabolism and body composition. CFR, EDV and LVEF remained independent predictors of VO2peak in multivariable regression analysis. Conclusion The study established CFR, EDV and LVEF as independent predictors of VO2peak in overweight CAD patients with no or only mild functional symptoms and a LVEF > 35 %. Glucose metabolism and body composition had minor impact on VO2peak. The findings suggest that central hemodynamic factors are important in limiting exercise capacity in overweight non-diabetic CAD patients.