Reduced intrahepatic fat content is associated with increased whole-body lipid oxidation in patients with type 1 diabetes

Aims/hypothesis Insulin resistance may be associated with ectopic fat accumulation potentially determined by reduced lipid oxidation. In patients with type 1 diabetes peripheral insulin resistance is associated with higher intramyocellular lipid content. We assessed whether these patients are also characterised by intrahepatic fat accumulation and abnormal fat oxidation. Methods Nineteen patients with type 1 diabetes (6 women, 13 men, age 35±7 years, BMI 23±3 kg/m², HbA₁c 8.7±1.4%) and 19 healthy matched individuals were studied by (1) euglycaemic–hyperinsulinaemic clamp combined with [6,6−²H₂]glucose infusion to assess whole–body glucose metabolism; (2) indirect calorimetry to assess glucose and lipid oxidation; and (3) localised ¹H−magnetic resonance spectroscopy of the liver to assess intrahepatic fat content. Results Patients with type 1 diabetes showed a reduced insulin−stimulated metabolic clearance rate of glucose (4.3±1.3 ml kg⁻¹ min⁻¹) in comparison with normal subjects (6.0±1.6 ml kg⁻¹ min⁻¹; p<0.001). Endogenous glucose production was higher in diabetic patients (p=0.001) and its suppression was impaired during insulin administration (66±30 vs 92±8%; p=0.047) in comparison with normal subjects. Plasma glucagon concentrations were not different between groups. The estimated hepatic insulin concentration was lower in diabetic patients than in normal subjects (p<0.05), as was the intrahepatic fat content (1.5±0.7% and 2.2±1.0% respectively; p<0.03), the latter in association with a reduced respiratory quotient (0.74±0.05 vs 0.84±0.06; p=0.01) and increased fasting lipid oxidation (1.5±0.5 vs 0.8±0.4 mg kg⁻¹ min⁻¹; p<0.01). Conclusions/interpretation In patients with type 1 diabetes, insulin resistance was not associated with increased intrahepatic fat accumulation. In fact, diabetic patients had reduced intrahepatic fat content, which was associated with increased fasting lipid oxidation. The unbalanced hepatic glucagon and insulin concentrations affecting patients with type 1 diabetes may be involved in this abnormality of intrahepatic lipid metabolism.     

Non-invasive assessment of hepatic lipid subspecies matched with non-alcoholic fatty liver disease phenotype

Background and aimsNonalcoholic fatty liver disease (NAFLD) is characterized by excessive hepatic fat accumulation. Increased hepatic saturated fats and decreased hepatic polyunsaturated fats may be particularly lipotoxic, contributing to metabolic dysfunction. We compared hepatic lipid subspecies in adults with and without NAFLD, and examined links with hallmark metabolic and clinical characteristics of NAFLD.Methods and resultsNineteen adults with NAFLD (total hepatic fat:18.8 ± 0.1%) were compared to sixteen adults without NAFLD (total hepatic fat: 2.1 ± 0.01%). ¹H-MRS was used to assess hepatic lipid subspecies. Methyl, allylic, methylene, and diallylic proton peaks were measured. Saturation, unsaturation, and polyunsaturation indices were calculated. Whole-body phenotyping in a subset of participants included insulin sensitivity (40 mU/m² hyperinsulinemic-euglycemic clamps), CT-measured abdominal adipose tissue depots, exercise capacity, and serum lipid profiles. Participants with NAFLD exhibited more saturated and less unsaturated hepatic fat, accompanied by increased insulin resistance, total and visceral adiposity, triglycerides, and reduced exercise capacity compared to controls (all P < 0.05). All proton lipid peaks were related to insulin resistance and hypertriglyceridemia (P < 0.05).ConclusionParticipants with NAFLD preferentially stored excess hepatic lipids as saturated fat, at the expense of unsaturated fat, compared to controls. This hepatic lipid profile was accompanied by an unhealthy metabolic phenotype.     

Noninvasive imaging of hepatic dysfunction: A state-of-the-art review

Hepatic dysfunction represents a wide spectrum of pathological changes, which can be frequently found in hepatitis, cholestasis, metabolic diseases, and focal liver lesions. As hepatic dysfunction is often clinically silent until advanced stages, there remains an unmet need to identify affected patients at early stages to enable individualized intervention which can improve prognosis. Passive liver function tests include biochemical parameters and clinical grading systems (e.g., the Child-Pugh score and Model for End-Stage Liver Disease score). Despite widely used and readily available, these approaches provide indirect and limited information regarding hepatic function. Dynamic quantitative tests of liver function are based on clearance capacity tests such as the indocyanine green (ICG) clearance test. However, controversial results have been reported for the ICG clearance test in relation with clinical outcome and the accuracy is easily affected by various factors. Imaging techniques, including ultrasound, computed tomography, and magnetic resonance imaging, allow morphological and functional assessment of the entire hepatobiliary system, hence demonstrating great potential in evaluating hepatic dysfunction noninvasively. In this article, we provide a state-of-the-art summary of noninvasive imaging modalities for hepatic dysfunction assessment along the pathophysiological track, with special emphasis on the imaging modality comparison and selection for each clinical scenario.     

Liver fat content determined by magnetic resonance imaging and spectroscopy

Hepatic steatosis as the most prevalent liver disorder can either be related to alcoholic liver disease (ALD) or non-alcoholic fatty liver disease (NAFLD). In both conditions, hepatocytes excessively accumulate fatcontaining vacuoles within their cytoplasm, which is the key histological feature. In contrast to ALD, NAFLD is commonly associated with metabolic syndrome, obesity and insulin resistance. To determine increased liver fat content, liver biopsy is currently considered the gold standard. Besides the...     

糖耐量正常人股部脂肪分布及含量与胰岛素敏感性的关系

目的建立应用MRI测量股部脂肪分布和含量的方法,初步探讨中国人群中股部脂肪分布和含量与胰岛素抵抗的关系。方法选取30例上海地区糖耐量正常者,其中正常体重组和超重/肥胖组各15例。利用高胰岛素正葡萄糖钳夹试验评价其胰岛素敏感性并用MRI测定股部脂肪分布和含量。结果与正常体重组比较,超重/肥胖组股部皮下脂肪[(176．7±21．6)cm~2 vs(115．0±12．8)cm~2,P＜0．05],筋膜下脂肪[(75．4±4．4)cm~2 vs(57．5±4．7)cm~2,P＜0．01],肌间隙脂肪[(28．3±3．2)cm~2 vs (14．5±1．1)cm~2,P＜0．01]明显增多,且胰岛素敏感性(稳态期葡萄糖利用率)显著降低[(4．54±0．43) cm~2vs(7．88±0．75)cm~2,P＜0．01]。在股部脂肪分布中,股部筋膜下脂肪与胰岛素敏感性的相关性最强。多元逐步回归分析进一步证实股部筋膜下脂肪增加是引起胰岛素抵抗的独立因素。结论股部脂肪分布与含量与胰岛素敏感性相关,其中股部筋膜下脂肪对胰岛素敏感性影响最显著。     

Effect of nutritional counselling on hepatic, muscle and adipose tissue fat content and distribution in non-alcoholic fatty liver disease

INTRODUCTIONThe incidence of non-alcoholic fatty liver disease (NAFLD) has increased rapidly over the last few years and is now one of the commonest causes of abnormal liver function test (LFT) results in patients presenting to hepatology clinics in both …     

2型糖尿病患者脂联素和体脂含量及分布与胰岛素敏感性的相关研究

目的　分析脂联素 (ADIPO)与机体脂肪含量、分布及组织胰岛素敏感性 (IS)的关系。　方法　符合 1999年WHO糖尿病诊断标准的 2型糖尿病 (T2DM )患者 4 0例 ,男 16例 ,女 2 4例 ,平均年龄 (5 5± 7)岁 ,体质指数 (BMI) (2 5 0± 2 5 )kg/m2 ,病程 (3± 4 )年。测定常规临床检查项目和血糖、血浆胰岛素水平。按HOMA模型计算胰岛素抵抗 (IR)指数。其中 2 0例患者应用正常血糖高胰岛素钳夹试验测定组织葡萄糖代谢率 (M)。同时测定ADIPO、肿瘤坏死因子α(TNFα)和游离脂肪酸(FFA)水平。应用双能X线测定机体的全身脂肪含量、全身瘦肉组织含量 ,并计算全身脂肪含量百分比。其中 17例患者同时应用核磁共振测定脂肪分布 ,以电子计算机计算腹内脂肪面积 (VFA)、腹部皮下脂肪面积 (SFA) ,并计算VFA/SFA比值。　结果　 (1)肥胖或体脂含量增加的T2DM患者其血浆ADIPO显著降低 ;(2 )腰围或腹内脂肪增加的T2DM患者其血浆ADIPO显著降低 ;(3)T2DM患者ADIPO水平与M值显著正相关 ,与TNFα、FFA呈显著负相关。　结论　T2DM患者体脂含量和分布影响血浆ADIPO水平 ,ADIPO与IS呈显著正相关。     

MRI-determined fat content of human liver,pancreas and kidney

AIM:To assess and correlate the lipid content of various organs in obese subjects and in persons with a normal body weight.METHODS:Magnetic resonance spectroscopy and a previously validated gradient echo magnetic resonance imaging method with Dixon‘s two point technique were used in this study to quantify fat in liver,pancreas as well as kidney.RESULTS:In 36 volunteers with body mass index(BMI) ranging from 20.0 to 42.9 kg/m2,the median fat content of liver,pancreas and kidney was 2.3%(interquartile range:0...     

Assessment of abdominal adipose tissue and organ fat content by magnetic resonance imaging

As the prevalence of obesity continues to rise, rapid and accurate tools for assessing abdominal body and organ fat quantity and distribution are critically needed to assist researchers investigating therapeutic and preventive measures against obesity and its comorbidities. Magnetic resonance imaging (MRI) is the most promising modality to address such need. It is non‐invasive, utilizes no ionizing radiation, provides unmatched 3‐D visualization, is repeatable, and is applicable to subject cohorts of all ages. This article is aimed to provide the reader with an overview of current and state‐of‐the‐art techniques in MRI and associated image analysis methods for fat quantification. The principles underlying traditional approaches such as T₁‐weighted imaging and magnetic resonance spectroscopy as well as more modern chemical‐shift imaging techniques are discussed and compared. The benefits of contiguous 3‐D acquisitions over 2‐D multislice approaches are highlighted. Typical post‐processing procedures for extracting adipose tissue depot volumes and percent organ fat content from abdominal MRI data sets are explained. Furthermore, the advantages and disadvantages of each MRI approach with respect to imaging parameters, spatial resolution, subject motion, scan time and appropriate fat quantitative endpoints are also provided. Practical considerations in implementing these methods are also presented.     

26例肝窦阻塞综合征临床及影像分析

目的了解肝窦阻塞综合征患者的临床特点及影像特征。方法回顾性分析2010年11月至2019年2月在解放军总医院第五医学中心住院诊治的26例肝窦阻塞综合征患者的临床资料,归纳总结其主诉、临床表现、实验室检查、影像学特征及病因。结果26例肝窦阻塞综合征患者以腹胀、乏力、纳差、腹水为主要症状,1例为肝移植术后患者,1例为肾移植术后患者,均有明确的化学治疗史,1例患者病因不明,23例患者有明确的中草药服用史,其中21例服用土三七。ALT升高17例,AST升高20例,糖类抗原CA125升高23例。CT及MR影像学显示,脾脏增大11例,腹水24例,肝脏密度及信号不均21例,增强扫描强化不均匀23例,肝静脉变细或显示不清11例。结论肝窦阻塞综合征的病因以服用土三七为主,临床表现为腹胀、乏力、纳差,可有肝功能异常及CA125升高,影像学表现以肝脾肿大、腹水、肝脏密度及信号不均,增强扫描强化不均及肝静脉变细或显示不清为主。     

肝脏脂肪含量与胰岛素抵抗及胰岛β细胞功能的关系

目的 观察肝脏脂肪含量(LFC)与胰岛素抵抗及胰岛β细胞功能的关系.方法 109例受试者分为糖调节受损组(IGR,31例)、新诊断2型糖尿病组(NT2DM,31例)和正常对照组(NC,47例),采用质子磁共振波谱分析(1H MRS)定量测定LFC;口服75 g葡萄糖耐量和胰岛素、C肽释放试验评估胰岛素抵抗及B细胞功能,分析LFC与胰岛素抵抗及B细胞功能的关系.结果 (1)LFC在NC、IGR、NT2DM组中分别为3.83%(2.35%～7.59%)、12.82%(8.10%～21.37%)、21.99%(11.89%～34.43%),随着糖代谢异常程度增加依次增高(P<0.01);(2)根据LFC四分位数分组,由低至高分为Quartile 1(LFC<4.04%)、Quartile 2(4.04%≤LFC<9.77%)、Quartile 3(9.77%≤LFC<20.78%)、Quartile 4(LFC≥20.78%)组,稳态模型评估的胰岛素抵抗指数(HOMA-IR)随着LFC增加从Quartile 2开始依次升高(P<0.01);(3)胰岛素30 min增量(△I30)、△I30/血糖30 win增量(△G30)与C肽30 min增量(△CP30)在Quartile 2时均呈现增高趋势,从Quartile 3开始呈逐步下降趋势;△CP30和△I30/△G30在Quartile 4明显降低(P<0.05或P<0.01).△CP30/△G30从Quartile 3开始降低(P<0.05).C肽曲线下面积与血糖曲线下面积的比值(CPAUC/GAUC)从Quartile 3开始降低(P<0.05).与之相应血糖增高,在Quartile 3达到空腹血糖受损和糖耐量受损水平(P<0.01);(4)LFC与HOMA-IR(rs=0.618,P<0.01)呈正相关;与△CP30(rs=-0.282)、△CP30/△G30(rs:-0.404)、CPAUC/GAUC(rs=-0.308)呈负相关(均P<0.01);(5)多元回归分析显示LFC是HOMA-IR独立影响因子(P<0.01).结论 本研究发现LFC增加至4%时.开始出现胰岛素抵抗,β细胞早相分泌代偿增高;当增加至10%时,早相和整体β细胞分泌功能恶化伴血糖升高.     

肝性脊髓病并大脑苍白球磁共振成像异常信号1例

患者,男,46岁,因患乙型肝炎16年,反复腹胀8年,加重1 d入院。既往入院已确诊为乙型肝炎后肝硬化失代偿期,脾功能亢进。此次住院期间反复发生肝性脑病,并于住院4月后逐渐出现双下肢乏力僵硬、自觉腓肠肌疼痛、行走障碍,行走时呈剪刀样步态,每于肝性脑病发作后,其双下肢僵硬程度略有加重。查体:面部毛细血管扩张,皮肤巩膜轻度黄染,肝掌( ),胸背部可见蜘蛛痣,双侧胸腔积液征,腹膨隆,腹壁浅表     

Multimodality magnetic resonance imaging in hepatic encephalopathy: An update

Hepatic encephalopathy (HE) is a neuropsychiatric complication of cirrhosis or acute liver failure. Currently, HE is regarded as a continuous cognitive impairment ranging from the mildest stage, minimal HE to overt HE. Hyperammonaemia and neuroinflammation are two main underlying factors which contribute to the neurological alterations in HE. Both structural and functional impairments are found in the white mater and grey mater involved in HE. Although the investigations into HE pathophysiological mechanism are enormous, the exact pathophysiological causes underlying HE remain controversial. Multimodality magnetic resonance imaging (MRI) plays an important role in helping to understand the pathological process of HE. This paper reviews the up-to-date multimodality MRI methods and predominant findings in HE patients with a highlight of the increasingly important role of blood oxygen level dependent functional MRI.     

肝脏局灶性结节增生CT、MRI征象和病理特点的综合分析

目的探讨肝脏局灶性结节增生（FNH）的CT、MRI征象和病理特点。方法回顾性分析经手术切除病理证实为FNH病例15例,其中7例术前行多层螺旋CT平扫及多期增强扫描,另8例行MR平扫及多期增强扫描。结果15例病灶多呈类圆形、椭圆形,少数呈分叶状;病灶直径3．0～8．0cm;病灶的边界在平扫时显示模糊,增强后显示清楚;CT平扫病灶多呈稍低或等密度,中心部分瘢痕结构呈更低密度,增强后动脉期病灶实质部分多明显均匀强化,瘢痕结构未见强化,门静脉期和延迟期实质部分强化程度下降呈稍低或等密度,瘢痕结构延迟强化,其中4例瘢痕结构可见;MRI平扫病灶呈稍长或等T1WI及T2WI信号,瘢痕结构于T2WI上呈特征性高信号,增强后三期信号变化特点类似CT三期增强特点,其中5例瘢痕结构可见;9例增强后病灶内或周围可见增粗、扭曲的动脉,在T2WI上表现为血管流空。结论熟悉FNH多种影像征象,可提高FNH术前诊断率。CT和MRI能够反映FNH病理特点及血供血管情况,可为临床选择手术方案提供重要参考。     

Current and future applications of magnetic resonance imaging and spectroscopy of the brain in hepatic encephalopathy

Hepatic encephalopathy (HE) is a common neuro-psychiatric abnormality, which complicates the course of patients with liver disease and results from hepatocellular failure and/or portosystemic shunting. The manifestations of HE are widely variable and involve a spectrum from mild subciinical disturbance to deep coma. Research interest has focused on the role of circulating gut-derived toxins, particularly ammonia, the development of brain swelling and changes in cerebral neurotransmitter systems that lead to global CNS depression and disordered function. Until recently the direct investigation of cerebral function has been difficult in man. However, new magnetic resonance imaging (MRI) techniques provide a non-invasive means of assessment of changes in brain volume (coregistered MRI) and impaired brain function (fMRI), while proton magnetic resonance spectroscopy (1H MRS) detects changes in brain biochemistry, including direct measurement of cerebral osmolytes, such as myoinositol, glutamate and glutamine which govern processes intrinsic to cellular homeostasis, including the accumulation of intracellular water. The concentrations of these intracellular osmolytes alter with hyperammonaemia. MRS-detected metabolite abnormalities correlate with the severity of neuropsychiatric impairment and since MR spectra return towards normal after treatment, the technique may be of use in objective patient monitoring and in assessing the effectiveness of various treatment regimens.     

Accuracy of multi-echo Dixon sequence in quantification of hepatic steatosis in Chinese children and adolescents

BACKGROUND Nonalcoholic fatty liver disease(NAFLD) is currently the outstanding cause of chronic liver disease in children and adolescents, especially in overweight and obese groups. Liver biopsy is the reference standard to diagnose NAFLD but invasive, thus it is not the best choice in clinical diagnosis and follow-up.Magnetic resonance(MR) is widely used in clinical trials to noninvasively quantify liver fat content in adults and children in foreign countries. While currently, it is rarely used in Chinese children and adolescents. We postulated that quantifying hepatic steatosis by MR could be extended to children and adolescents in China.AIM To investigate the accuracy of MR imaging(MRI) in quantifying liver fat with MR spectroscopy(MRS) as a reference. A secondary goal was to assess the prevalence of NAFLD in overweight and obese Chinese children and adolescents.METHODSThere were 86 children and adolescents enrolled in this study, including 65 overweight and obese children and 21 healthy children. The participants underwent MRI and MRS. MRI and MRS were performed using multi-echo Dixon and HISTO sequences, respectively, to calculate hepatic proton density fat fraction(PDFF). Hepatic steatosis was diagnosed using MRS-PDFF > 5% as the threshold. Spearman's analysis was used to evaluate the correlation between MRI and MRS. The agreement between these two methods was assessed by BlandAltman analysis.RESULTS The MRI-PDFF in the MRS region of interest and the entire liver was 9.9% ±10.3% with a range of 0.3%-39.9%, and 10.6% ± 9.4% with a range of 1.9%-38.9%,respectively. The MRS-PDFF was 9.1% ± 10.0%, with a range of 0.5%-37.8%. The incidence of hepatic steatosis detected by MRS-PDFF was 46.5%(40/86) of all participants, all of whom belonged to the overweight and obese group.Spearman's analysis indicated an excellent correlation between multi-echo Dixon and MRS(r > 0.9, P < 0.01). Bland-Altman analysis also demonstrated a good agreement between these two methods.CONCLUSION Multi-echo Dixon shows an excellent correlation and agreement with MRS in quantifying liver fat content and could be a potential tool to detect hepatic steatosis in Chinese children and adolescents.     

Structured medium and long chain triglycerides show short-term increases in fat oxidation, but no changes in adiposity in men

BackgroundMedium chain triglycerides (MCT) have been suggested as modulators of human energy expenditure (EE) and thus may influence total and regional body fat distribution.ObjectiveTo investigate in overweight men the effects of structured medium and long chain triglycerides on EE, substrate oxidation and body adiposity, compared to extra virgin olive oil (OO).MethodsIn a 6 week single-blind crossover study, 23 overweight men were randomly assigned to consume a standard high-fat diet of which 75% total fat was provided as either structured medium and long chain triglycerides referred to as structured oil (StO), or OO. EE and body composition were measured using indirect calorimetry and magnetic resonance imaging, respectively, at weeks 1 and 6 of each phase.ResultsBody weight decreased (p < 0.01) from baseline to end-point during consumption of both the StO (−1.46 ± 0.4 kg) and OO (−1.17 ± 0.4 kg); however, no significant treatment differences were observed. There were no changes in body composition among treatment groups. No differences between diets for EE measurements were reported. Fat oxidation rates did not differ between oils, but were reduced (p < 0.05) in the StO group between baseline (0.0020 ± 0.0003 g/kg fat free mass per min) in comparison to after week 6 (0.0013 ± 0.0001 g/kg fat free mass per min). No differences in carbohydrate oxidation rate were noted across diets or time.ConclusionThe present structured medium and long chain triglyceride oil increases short-term fat oxidation but fails to modulate body weight or adiposity through a change in EE.     

Non-invasive detection of vulnerable coronary plaque

Critical coronary stenosis have been shown to contribute to only a minority of acute coronary syndromes and sudden cardiac death.Autopsy studies have identified a subgroup of high-risk patients with disrupted vulnerable plaque and modest stenosis.Consequently,a clinical need exists to develop methods to identify these plaques prospectively before disruption and clinical expression of disease.Recent advances in invasive and non-invasive imaging techniques have shown the potential to identify these high-risk plaques.Non-invasive imaging with magnetic resonance imaging,computed tomography and positron emission tomography holds the potential to differentiate between low-and highrisk plaques.There have been significant technological advances in non-invasive imaging modalities,and the aim is to achieve a diagnostic sensitivity for these technologies similar to that of the invasive modalities.Molecular imaging with the use of novel targeted nanoparticles may help in detecting high-risk plaques that will ultimately cause acute myocardial infarction.Moreover,nanoparticle-based imaging may even provide non-invasive treatments for these plaques.However,at present none of these imaging modalities are able to detect vulnerable plaque nor have they been shown to definitively predict outcome.Further trials are needed to provide more information regarding the natural history of high-risk but non-flow-limiting plaque to establish patient specific targeted therapy and to refine plaque stabilizing strategies in the future.     

Pediatric nonalcoholic fatty liver disease: A clinical and laboratory challenge

The true prevalence of pediatric nonalcoholic fatty liver disease (NAFLD) is unknown. Challenges in determining the population prevalence of NAFLD include the type of test (and the reference intervals used to define normal and abnormal), the type of population (general population, hospital series), the demographic characteristics of the population sampled, and the nature of the study design. The natural history of pediatric NAFLD remains uncertain. The issue of when to perform a liver biopsy in children with suspected NAFLD remains controversial. Children with NAFLD but normal alanine aminotransferase are rarely investigated. However, evidence of alterations in glucose metabolism parameters should prompt a better understanding of the natural history of pediatric NAFLD not only in terms of the progression of liver disease but also regarding its potential relationship with other health outcomes such as type 2 diabetes mellitus and cardiovascular disease. This evidence could make liver biopsy mandatory in the majority of cases at risk of progressive and severe hepatic and extrahepatic disease. This conclusion, however, raises the question of the feasibility of liver biopsy assessment in an extremely large at risk population, and of the cost/effectiveness of this policy. There is a considerable, continuous interest in reliable, noninvasive alternatives that will allow the prognosis of pediatric NAFLD to be followed in large community or population-based studies.