Low N-terminal pro-brain natriuretic peptide levels are associated with non-alcoholic fatty liver disease in patients with type 2 diabetes.

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 < 45 ng/L. In a multivariable linear regression model, the relationship with NT-proBNP was further analyzed as a continuous variable, and was independently and inversely associated with increasing liver fat content after full adjustment (P = 0.031). 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.

Higher chlorzoxazone clearance in obese children compared with nonobese peers.

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 < 0.0001. Diabetic biomarkers were significantly increased in obese children, while fasting blood glucose and Hba1c levels were nonsignificant between groups. Liver fat content was not associated with CLZ Cl. CONCLUSION: Oral clearance of CLZ was increased two-fold in obese children vs. nonobese children aged 11-18 years. This indicates an increased CYP2E1 activity of clinical importance, and dose adjustment should be considered for CLZ.

1H-MRS measured ectopic fat in liver and muscle is associated with the metabolic syndrome in Danish girls but not in boys with overweight and obesity.

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% confidence interval: [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.

Liver fat content investigated by magnetic resonance spectroscopy in obese children and youths included in multidisciplinary treatment.

UNLABELLED: 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.

Effect of trans fatty acid intake on abdominal and liver fat deposition and blood lipids: a randomized trial in overweight postmenopausal women.

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 (1)H 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<0.001). TFA tended to increase the body fat (0.46 (-0.20; 1.17) kg; P=0.16) and waist circumference (1.1 (-0.1; 2.4) cm; P=0.08) more than the control fat, whereas neither abdominal nor liver fat deposition was affected by TFA. CONCLUSION: The adverse effect of dietary TFA on cardiovascular disease risk involves induction of dyslipidemia, and perhaps body fat, whereas weight gain-independent accumulation of ectopic fat could not be identified as a contributory factor during short-term intake.

Differentiation between benign and malignant colon tumors using fast dynamic gadolinium-enhanced MR colonography; a feasibility study.

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.

Patient acceptance of MR colonography with improved fecal tagging versus conventional colonoscopy.

OBJECTIVE: Conventional colonoscopy (CC) is the gold standard for colonic examinations. However, patient acceptance is not high. Patient acceptance is influenced by several factors, notably anticipation and experience. This has led to the assumption that patient acceptance would be higher in non-invasive examinations such as MR/CT colonography (MRC/CTC) and perhaps even higher without bowel preparation. The purpose of this study was to evaluate patient acceptance of MRC with fecal tagging versus CC. MATERIALS AND METHODS: In a 14-month period, all patients first-time referred to our department for CC were asked to participate in the study. Two days prior to MRC, patients ingested an oral contrast mixture (barium/ferumoxsil) together with four meals each day. Standard bowel purgation was performed before CC. Before and after MRC and CC a number of questions were addressed. RESULTS: Sixty-four (34 men, 30 women) patients referred for CC participated in the study. 27% had some discomfort ingesting the contrast mixture, and 49% had some discomfort with the bowel purgation. As a future colonic examination preference, 71% preferred MRC, 13% preferred CC and 15% had no preference. If MRC was to be performed with bowel purgation, 75% would prefer MRC, 12% would prefer CC and 12% had no preference. CONCLUSION: This study shows that there is a potential gain in patient acceptance by using MRC for colonic examination, since MRC is considered less painful and less unpleasant than CC. In addition, the results indicate that patients in this study prefer fecal tagging instead of bowel purgation.

Magnetic resonance imaging with liver-specific contrast agent in primary amyloidosis and intrahepatic cholestasis.

Magnetic resonance imaging (MRI) findings in hepatic amyloidosis are not well defined. Here, we report on a patient with renal failure caused by primary amyloidosis (AL type) who developed jaundice. Ultrasound and computed tomography were normal except for some ascites. MRI with oral manganese-containing contrast agent revealed several focal areas without contrast uptake in the hepatocytes and no bile secretion after 8 hours. No extrahepatic bile obstructions were found. Liver biopsy showed severe intraportal, vascular, and parenchymal amyloidosis causing severe cholestasis and atrophy of hepatocytes.

Implementation of MR colonography.

BACKGROUND: MR colonography (MRC) is a promising method of examining the colon, but is limited to a few specialist centres. The purpose of this article was to describe the implementation of MRC with fecal tagging. MATERIALS AND METHODS: Patients referred for conventional colonoscopy (CC) were offered MRC with fecal tagging before CC. Two days before MRC patients ingested an oral contrast agent. Before and after MRC and CC a number of questions were addressed. MR images were rated by a blinded investigator. RESULTS: In 6 months, 30 consecutive patients were included. The median time in the MR suite was 44 min, 23 min for the MRC examination and 9 min for the evaluation. The median time for CC was 32 min. Sixty-six percent of the patients preferred MRC as the future method of examination, 10% preferred CC, 21% had no preferences. Of the oral contrast agents, barium sulphate with ferumoxsil was significantly better than barium sulphate alone. CONCLUSION: The majority of the patients found MRC less unpleasant than CC and a majority would prefer MRC over CC as a future colon examination. MRC also appears to be less time consuming to the patients and medical personnel than CC with post-procedural monitoring.

Magnetic resonance investigation of bone marrow following priming and stem cell mobilization.

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.

Combined MR examination of prostate: is it reliable?

A combination of magnetic resonance (MR) methods (T2-weighted MRI, proton MR spectroscopy, and dynamic contrast enhancement) gives the highest sensitivity and specificity for identification of prostate cancer by MRI. The prostate MR findings of a patient with a congenital cystic disease of seminal vesicle are presented. To our knowledge, this is the only case described in the literature. The MR examination resulted in a false-positive indication of prostate cancer.

Effect of new manganese contrast agent on tissue intensities in human volunteers: comparison of 0.23, 0.6 and 1.5 T MRI, a part of a phase I trial.

To evaluate the effect of a new oral manganese contrast agent (CMC-001) on magnetic resonance imaging (MRI) intensities at different magnetic field strengths. Twelve healthy volunteers underwent abdominal MRI 1 week before and within 2.5-4.5 h after CMC-001 (MnCl(2) and absorption promoters dissolved in water) intake at three different MR scanners of 0.23, 0.6 and 1.5 T. Image contrast and intensity enhancement of liver and pancreas were analysed relatively to muscle and fat intensities. Manganese blood levels were followed for 24 h. Whole-blood manganese concentration levels stayed within the normal range. The liver intensities on T2w images decreased about 10% for the 1/2 contrast dose and about 20% for the full contrast dose independent of the field strength. The liver intensities on T1w images increased more than 30% for 1/2 contrast dose and over 40% for full contrast dose. The maximum T1 enhancement was achieved at the highest field. Pancreas intensities were not affected. Contrast between liver, muscle and fat intensities increased with magnetic field, as well as standard errors of the volunteer-averaged intensities. Oral intake of CMC-001 influences liver intensities and does not affect pancreas intensities at different magnetic field strengths.