Nonalcoholic fatty liver disease and diabetes

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease in the world and represents a clinical-histopathologic entity where the steatosis component may vary in degree and may or may not have fibrotic progression. The key concept of NAFLD pathogenesis is excessive triglyceride hepatic accumulation because of an imbalance between free fatty acid influx and efflux. Strong epidemiological, biochemical, and therapeutic evidence supports the premise that the primary pathophysiological derangement in most patients with NAFLD is insulin resistance; thus the association between diabetes and NAFLD is widely recognized in the literature. Since NAFLD is the hepatic manifestation of a metabolic disease, it is also associated with a higher cardio-vascular risk. Conventional B-mode ultrasound is widely adopted as a first-line imaging modality for hepatic steatosis, although magnetic resonance imaging represents the gold standard noninvasive modality for quantifying the amount of fat in these patients. Treatment of NAFLD patients depends on the disease severity, ranging from a more benign condition of nonalcoholic fatty liver to nonalcoholic steatohepatitis. Abstinence from alcohol, a Mediterranean diet, and modification of risk factors are recommended for patients suffering from NAFLD to avoid major cardiovascular events, as per all diabetic patients. In addition, weight loss induced by bariatric surgery seems to also be effective in improving liver features, together with the benefits for diabetes control or resolution, dyslipidemia, and hypertension. Finally, liver transplantation represents the ultimate treatment for severe nonalcoholic fatty liver disease and is growing rapidly as a main indication in Western countries. This review offers a comprehensive multidisciplinary approach to NAFLD, highlighting its connection with diabetes.     

钙调素在肝脏疾病中的作用

钙调素(Regucalcin)是一种多功能蛋白,参与维持细胞内钙稳态,调节多种酶活性,抑制氧化应激以及调控细胞增殖凋亡.钙调素在肝脏中含量较高.在多种肝脏疾病中,钙调素基因及其蛋白表达水平发生改变.这些改变在肝脏疾病的发生发展中起到重要作用.本文就钙调素在肝脏疾病中的作用进行综述.     

Patients with clinically metabolically healthy obesity are not necessarily healthy subclinically: further support for bariatric surgery in patients without metabolic disease?

Background

Nonalcoholic fatty liver disease (NAFLD) increases the risk of liver cirrhosis and hepatocellular carcinoma and is also strongly correlated with extrahepatic diseases, including cardiovascular disease and type 2 diabetes. This risk of NAFLD among obese individuals who are otherwise metabolically healthy is not well characterized.

Skeletal muscle loss is associated with diabetes in middle-aged and older Chinese men without non-alcoholic fatty liver disease

BACKGROUNDSkeletal muscle, a key insulin target organ, has been reported to be associated with diabetes mellitus (DM). Compared to non-diabetic patients, diabetic patients have decreased muscle mass and a higher prevalence of sarcopenia, and patients with sarcopenia may be at increased risk of developing diabetes. In individuals with nonalcoholic fatty liver disease (NAFLD), sarcopenia is associated with the severity of fibrosis and steatosis. Previous studies have demonstrated that NAFLD is strongly associated with DM and sarcopenia.AIMTo determine the relationship between skeletal muscle mass and DM in Chinese middle-aged and elderly men, and whether the association is affected by NAFLD. METHODSSkeletal muscle mass was calculated as appendicular skeletal muscle mass (ASM) in kg/body weight × 100%. Liver fat content (LFC) was measured using a quantitative ultrasound method. RESULTSAs the ASM decreased, fasting blood glucose (FBG), 2-h postprandial blood glucose (2hBG), and LFC increased in both genders, as did the prevalence of DM and NAFLD. Spearman analysis showed that the ASM was negatively correlated with the FBG, 2hBG, and LFC. Stepwise logistic regression analysis showed that after adjustments, the ASM quartile was negatively associated with the presence of DM in males, but not in females. Subgroup analysis showed that the ASM quartiles remained negatively correlated with the presence of DM in the non-NAFLD population (including males and females), but no correlation was found between ASM quartiles and the presence of DM in the NAFLD population. When stratified by LFC quartiles, ASM was negatively correlated with the presence of DM in the first and second LFC quartiles in males.CONCLUSIONSkeletal muscle mass loss was shown to be associated with the presence of DM in males, but not in females; NAFLD weakens this association. The results suggested that the stratified management of diabetes mellitus should be considered according to skeletal muscle mass and NAFLD.     

Gastrointestinal complications of diabetes mellitus

Diabetes mellitus affects virtually every organ system in the body and the degree of organ involvement depends on the duration and severity of the disease, and other co-morbidities. Gastrointestinal (GI) involvement can present with esophageal dysmotility, gastro-esophageal reflux disease (GERD), gastroparesis, enteropathy, non alcoholic fatty liver disease (NAFLD) and glycogenic hepatopathy. Severity of GERD is inversely related to glycemic control and management is with prokinetics and proton pump inhibitors. Diabetic gastroparesis manifests as early satiety, bloating, vomiting, abdominal pain and erratic glycemic control. Gastric emptying scintigraphy is considered the gold standard test for diagnosis. Management includes dietary modifications, maintaining euglycemia, prokinetics, endoscopic and surgical treatments. Diabetic enteropathy is also common and management involves glycemic control and symptomatic measures. NAFLD is considered a hepatic manifestation of metabolic syndrome and treatment is mainly lifestyle measures, with diabetes and dyslipidemia management when coexistent. Glycogenic hepatopathy is a manifestation of poorly controlled type 1 diabetes and is managed by prompt insulin treatment. Though GI complications of diabetes are relatively common, awareness about its manifestations and treatment options are low among physicians. Optimal management of GI complications is important for appropriate metabolic control of diabetes and improvement in quality of life of the patient. This review is an update on the GI complications of diabetes, their pathophysiology, diagnostic evaluation and management.     

Fatty liver disease in diabetes mellitus

Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in type 2 diabetes mellitus (T2DM), likely reflecting the frequent occurrence of obesity and insulin resistance in T2DM. NAFLD also can occur in type 1 DM (T1DM), but must be distinguished from the more common glycogen hepatopathy as a cause of hepatomegaly and liver function abnormalities in T1DM. Weight reduction achieved by diet and exercise is effective in preventing and treating NAFLD in obese diabetic subjects. Bariatric surgery also has been shown to reverse NAFLD in T2DM, and recently approved weight loss medications should be evaluated for their impact on the development and progression of NAFLD. There is limited evidence suggesting that specific drugs used for blood glucose control in T2DM [thiazolidinediones (TZDs), glucagon-like peptide-1 (GLP-1) analogs, and dipeptidyl peptidase-4 (DPP-4) inhibitors] and also statins may have a role in preventing or treating NAFLD in patients with diabetes.     

线粒体自噬在肝相关疾病中的作用

细胞自噬是细胞依赖溶酶体的分解代谢过程,能降解受损蛋白、衰老或损伤的细胞器等细胞结构,来维持细胞内稳态。众所周知,线粒体调节异常是许多疾病的发病机制。本文主要探讨线粒体自噬在肝相关疾病如非酒精性脂肪肝病、肝癌和肝缺血再灌注损伤中的作用。     

Use of noninvasive scores for advanced liver fibrosis can guide the need for hepatic biopsy during bariatric procedures

BackgroundPatients with obesity are at increased risk for nonalcoholic fatty liver disease (NAFLD). The effectiveness of noninvasive screening tests for ruling out advanced fibrosis (stage 3–4) is unknown.ObjectivesTo determine the prevalence of advanced fibrosis in patients undergoing routine liver biopsy during bariatric surgery and assess the effectiveness of existing noninvasive risk calculators.SettingAcademic medical center in the United States.MethodsRoutine liver biopsies were obtained during first-time bariatric surgery (January 2001–December 2017). Patient demographic characteristics, co-morbidities, and preoperative laboratory values were compiled. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) were compared between 3 noninvasive risk calculators for advanced fibrosis: the fibrosis-4 index, NAFLD fibrosis score, and aminotransferase-to-platelet ratio index (APRI).ResultsAmong 2465 patients, the prevalence of advanced fibrosis (stage 3–4) was 3.4%. The mean age was 45.5 years, and the mean body mass index was 46.8. The sensitivity of noninvasive risk calculators ranged from 85% (NAFLD fibrosis score) to 24% (APRI). The NAFLD fibrosis score performed best in screening out advanced fibrosis, with an NPV of 99%. The PPV ranged from 9% to 65%. In this study cohort, the use of the NALFD fibrosis score correctly ruled out advanced fibrosis in 893 (36%) patients, with 13 false negatives.ConclusionsThe prevalence of advanced fibrosis in individuals undergoing routine first-time bariatric procedures is 3.4%. Use of the NALFD fibrosis score can rule out advanced fibrosis in one-third of this population, and guide surgical decision-making.     

Nonalcoholic steatohepatitis and insulin resistance in children

Various pathological conditions can cause fatty liver in children. Nonalcoholic steatohepatitis (NASH) in children has been known since 1983. However, NASH diagnosed in childhood does not have a favorable outcome. The pathological characteristics of NASH are significantly different between children and adults. Nonalcoholic fatty liver disease (NAFLD)/NASH is accompanied by insulin resistance, which plays a pivotal role in its pathophysiology in both children and adults. In NASH, a “two-hit” model involving triglyceride accumulation (first hit) and liver damage (second hit) has been accepted. Insulin resistance was found to correlate with changes in fat levels; however, it did not correlate with fibrosis or NAFLD activity score in children. Therefore, insulin resistance may be important in the first hit. Because there is obvious familial clustering in NASH, genetic predisposition as well as environmental factors including diet might be the second hit of NAFLD/NASH.     

非酒精性脂肪性肝炎的诊断和治疗进展

非酒精性脂肪肝疾病(nonalcoholic fatty liver disease,NAFLD)以肝细胞中脂肪过多积累为标志,包括非酒精性脂肪肝(nonalcoholic fatty liver,NAFL)和非酒精性脂肪性肝炎(nonalcohol-ic steatohepatitis,NASH),其中NASH可能会...     

Hypoglycemia in diabetes: An update on pathophysiology,treatment, and prevention

Hypoglycemia is a common complication in patients with diabetes, mainly in those treated with insulin, sulfonylurea, or glinide. Impairments in counterregulatory responses and hypoglycemia unawareness constitute the main risk factors for severe hypoglycemia. Episodes of hypoglycemia are associated with physical and psychological morbidity. The fear of hypoglycemia constitutes a barrier that impairs the patient’s ability to reach good glycemic control. To prevent hypoglycemia, much effort must be invested in patient education regarding risk factors, warning signs, and treatment of hypoglycemia at an early stage, together with setting personalized goals for glycemic control. In this review, we present a comprehensive update on the treatment and prevention of hypoglycemia in type 1 and type 2 diabetic patients.     

胰十二指肠切除术后新发非酒精性脂肪性肝病的相关因素分析

目的探讨胰十二指肠切除术(PD)后患者新发非酒精性脂肪性肝病(NAFLD)的相关因素。方法回顾性收集2018年6月至2020年12月南京大学医学院附属鼓楼医院肝胆胰中心连续收治的130例接受PD的患者资料。男性74例, 女性56例, 年龄[M(IQR)]为62(16)岁(范围:22～84岁)。其中29例患者术后发生NAFLD, 设为NAFLD组;101例患者未发生NAFLD, 设为非NAFLD组。观察指标:(1)两组患者术前一般情况、术中与术后相关指标;(2)PD术后新发NAFLD的相关因素。分类资料的比较采用χ2检验或Fisher确切概率法, 定量资料的比较采用独立样本t检验或Mann-WhitneyU检验, 多因素分析采用逐步向前法的Logistic回归模型。结果 130例患者均成功完成PD, 术后6个月内NAFLD的发生率为22.3%(29/130)。单因素分析结果显示, 体重指数、糖尿病、术前甘油三酯水平、胰腺癌是发生NAFLD的相关因素(t=-2.655、χ2=4.563、U=-2.192、χ2=7.044, P值均<0.05)。多因素分析结果显示, 性别、体重指数、是...     

Effect of body mass index on nonalcoholic fatty liver disease in patients undergoing minimally invasive bariatric surgery

The risk factors for nonalcoholic fatty liver disease in patients undergoing bariatric surgery are under study. We wanted to determine the correlation between nonalcoholic fatty liver disease and patient factors such as obesity and liver function tests. A retrospective analysis was performed on 177 nonalcoholic morbidly obese patients who underwent laparoscopic Roux-en-Y gastric bypass with liver biopsy, to identify risk factors for nonalcoholic fatty liver disease. The histologic grade of liver disease was compared with preoperative body mass index, age, and liver function tests. Simple steatosis and steatohepatitis were present in 90% and 42% of patients, respectively. Elevated transaminaselevels were an independent risk for liver disease. Body mass index and liver disease were not correlated with univariate analysis. Regression analysis performed on age, body mass index, and liver disease demonstrated that the risk for liver disease increased with body mass index in the younger (<35 years old) age group and decreased with body mass index in the older (<45 years old) age group. There was a high incidence of steatosis and steatohepatitis in these nonalcoholic bariatric patients, and elevated transaminase level was indicative of disease. Body mass index was a positive risk factor for liver disease in younger patients but a negative risk factor in the older patients. Presented at the Forty-Fifth Meeting of The Society for Surgery of the Alimentary Tract, New Orleans, Louisiana, May 15–19, 2004 (poster presentation).     

The metabolic and liver-related outcomes of bariatric surgery in adult patients with insulin-treated type 2 diabetes and nonalcoholic fatty liver disease at high risk of liver fibrosis

BackgroundNonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease, with a prevalence estimated to between 20% and 30% of the general population and approximately 70% of stage 2 obese people with type 2 diabetes (T2D) with normal liver enzymes.ObjectivesTo investigate the metabolic and liver-related outcomes of bariatric surgery among patients with insulin-treated T2D and NAFLD who are at high risk of liver fibrosis.SettingMore than 600 locations within the United Kingdom.MethodsThe study comprises a retrospective cohort comparison of patients with NAFLD and a fibrosis 4 (Fib-4) score > 1.45 who received a bariatric intervention versus comparable patients who received no bariatric intervention. Metabolic outcomes (glycated hemoglobin [HbA1C] level, weight, body mass index [BMI], and Fib-4 score) and composite liver-related outcomes (cirrhosis, portal hypertension, liver failure, and hepatoma) were compared between groups over a period of 5 years. The outcomes were adjusted for baseline and time-varying covariates.ResultsThe study sample included 4108 patients, 45 of whom underwent bariatric surgery. The mean age at baseline was 62.4 ± 12.4 years; 43.8% of patients were female; the mean weight was 89.5 ± 20.8 kg; the mean BMI was 31.7 ± 7.6 kg/m²; and the mean HbA1C level was 68.4 ± 16.7 mmol/mol. In addition, the median Fib-4 score was 2.3 (interquartile range, 1.7–4.2). During the 5 years during which follow-up outcomes were recorded, the weight and BMI reductions were significantly lowered compared with baseline in the bariatric surgery group. Similarly, the HbA1C levels were lower in the bariatric surgery group, with statistically significant differences observed in the first and second postintervention years (bariatric surgery versus non–bariatric surgery patient levels at 1 year, 63.1 mmol/mol versus 68.1 mmol/mol, respectively [P = .042], and at 2 years, 62.7 mmol/mol versus 68.1 mmol/mol, respectively [P = .028]). No significant difference was observed between groups in the proportion of patients with liver fibrosis or the likelihood of developing composite liver disease during the follow-up period (bariatric surgery group, 8.9%; non–bariatric surgery group, 4.7%; X² = 1.75; P = .18).ConclusionBariatric surgery amongst patients with insulin-treated T2D with NAFLD who were at high risk of liver fibrosis was associated with significant improvements in metabolic outcomes. No significant adverse effects were observed with regards to liver-related outcomes.     

Bariatric Therapy with Intragastric Balloon Improves Liver Dysfunction and Insulin Resistance in Obese Patients

Background

Obesity is often associated with fatty liver (FL). In most cases, bright liver at ultrasound (US) and increased alanine aminotransferase (ALT) and gamma-glutamyltranspeptidase (GGT) levels are considered the hallmarks of nonalcoholic fatty liver disease (NAFLD). Insulin resistance (IR) is the main link between obesity and NAFLD. The use of the Bioenterics® intragastric balloon (BIB) is a safe procedure either for inducing a sustained weight loss with diet support or for preparing those patients who are candidates for bariatric surgery. The aim of the study was to investigate whether the weight loss induced by intragastric balloon might improve IR and liver enzymes. The presence or absence of FL at US and the influence of a body mass index (BMI) decrease ≥10% after BIB (ΔBMI?≥?10%) were also considered.

Methods

One hundred and three consecutive obese (BMI?>?30 kg/m²) patients (38 males/65 females; mean age 41.3, range 20–63 years) underwent BIB insertion under endoscopic control. The BIB was removed 6 months later. US, clinical, and routine laboratory investigations were performed before and after BIB. IR was calculated by the homeostasis model assessment (HOMA-IR?>?2.5). Exclusion criteria were hepatitis B virus positive, hepatitis C virus positive, alcohol consumption >30 g/day, history of hepato-steatogenic drugs, and type 1 diabetes.

Results

Ninety-three patients were eligible for the study. The BMI significantly decreased in all investigated patients, and it was ≥10% in 59% of the patients. FL was seen at US in 70%, impaired fasting blood glucose was present in 13%, ALT exceeded the normal limit in 30.1%, GGT exceeded the normal limit in 15%, and HOMA-IR was >2.5 in 85%. Median HOMA-IR decreased significantly in FL (4.71 vs 3.10; p?p?p?p?p?p?p?p?

Conclusions

Weight loss induced by intragrastric balloon reduces IR. The ALT and GGT decrease suggests an improvement in hepatic damage. The benefit depends on the decrease of BMI higher than 10%.

     

Role of micronutrients in staging of nonalcoholic fatty liver disease:A retrospective cross-sectional study

BACKGROUND Nonalcoholic fatty liver disease(NAFLD) presents high incidence throughout the world and has been progressively increasing in prevalence. This disease has a heterogeneous natural history, including simple steatosis, nonalcoholic steatohepatitis(NASH), and cirrhosis. The factors that determine its evolution to more severe forms of the disease are still poorly understood, and micronutrients with antioxidant potential may be involved in the pathophysiology of the disease.AIM To evaluate the relationship between serum levels of micronutrients and the severity of NAFLD.METHODS A retrospective, observational and cross-sectional study was conducted. This study included all patients undergoing bariatric surgery who experienced liver biopsy during the procedure, and had serum levels of micronutrients(vitamin D,vitamin B12, zinc, iron, and magnesium), which was assessed in a preoperative evaluation conducted at a reference center in southern Brazil.RESULTS A total of 614 patients were analyzed, of which 93% had steatosis, 70.7% had NASH, and 49.3% had some degree of fibrosis. Serum levels of vitamin D were negatively correlated with the severity of steatosis and NASH, and serum levels of vitamin B12 were positively correlated with the severity of steatosis and fibrosis. The other micronutrients showed no association with NAFLD staging.CONCLUSION Serum levels of vitamin D are inversely related to the severity of steatosis and NASH, and serum levels of vitamin B12 are higher in more advanced stages of simple steatosis and liver fibrosis. Serum levels of zinc, iron, and magnesium were not associated with NAFLD severity.     

Non-alcoholic fatty liver disease in diabetes: When to refer to the hepatologist?

Non-alcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases worldwide. A strong relationship exists between NAFLD and diabetes mellitus. There is growing evidence of a mechanistically complex and strong association between the two diseases. Current data also shows that one disease actually leads to worsening of the other and vice versa. Understanding of the various pathophysiological mechanisms involved, natural history and spectrum of these two diseases is essential not only for early diagnosis and management but also for prevention of severe disease forms. Despite the tremendous progress made in recent times in acquiring knowledge about these highly prevalent diseases, the guidelines and recommendations for screening and management of diabetics with NAFLD remain ambiguous. An interdisciplinary approach is required to not only raise awareness of the prevalence of NAFLD in diabetics but also for better patient management. This can help attenuate the development of significant complications, such as cirrhosis, decompensation and hepatocellular carcinoma in these patients, thereby halting NAFLD in its tracks. This review focuses on the pivotal role of primary care physicians and endocrinologists in identification of NAFLD in diabetics in early stages and the role of proactive screening for prompt referral to hepatologist.