- Endotext: Nonalcoholic Fatty Liver Disease: The Overlooked Complication of Type 2 Diabetes [BOOK]
- BOOKMDText.com, Inc.: South Dartmouth (MA)
- Nonalcoholic fatty liver disease (NAFLD) is a common complication of obesity and type 2 diabetes mellitus (T2DM). Most times it is an unrecognized comorbidity to the primary care provider and endocri…
Nonalcoholic fatty liver disease (NAFLD) is a common complication of obesity and type 2 diabetes mellitus (T2DM). Most times it is an unrecognized comorbidity to the primary care provider and endocrinologist. Today it is the most common chronic liver disease in developed countries. It is characterized by insulin resistance and hepatic triglyceride accumulation in the absence of co-existing etiologies, such as excessive alcohol consumption, viral hepatitis, medications or other etiologies for hepatic steatosis. Its more severe form of the disease with steatohepatitis (NASH) is associated with hepatocyte injury (necrosis and inflammation) and frequently with fibrosis. Although it appears to be an indolent condition, with few symptoms and often normal plasma aminotransferases, NASH is a leading cause of end-stage liver disease and hepatocellular carcinoma (HCC), and significantly increases the risk of developing cardiovascular disease (CVD) and T2DM. The pathogenesis of NASH remains poorly understood, and likely to be multifactorial, but insulin-resistant adipose tissue plays an important role. The natural history of NAFLD is incompletely understood, but risk factors for disease progression include weight gain, obesity and T2DM, as well as the severity of fibrosis stage at diagnosis. Diagnostic algorithms are evolving but we offer an approach that integrates for the non-hepatologist plasma biomarkers, imaging, and the role of liver biopsy for the management of these complex patients. At the present time, early screening -with biomarker panels or a liver ultrasound, ideally with transient elastography- is reserved for high-risk patients (i.e., obese patients with T2DM or elevated plasma AST/ALT levels or evidence of steatosis at a random liver exam) until more accurate non-invasive methods are available. A liver biopsy should be considered on a case-by-case basis, to identify those at risk of NASH-cirrhosis, working in close collaboration with a hepatologist. Treatment should include a comprehensive approach with lifestyle modification and therapeutic agents tested in RCTs, such as vitamin E (in patients without diabetes) or pioglitazone for patients with or without diabetes. Pioglitazone, given its low-cost as a generic medication, long-standing track record of efficacy in NASH, and cardiometabolic benefits, is likely to be for NASH what metformin has become for the management of T2DM. However, proper patient selection and close monitoring is needed. In addition, a number of new pharmacological agents are being studied in phase II/III trials and future management will involve the use of combination therapy, as for other chronic metabolic conditions. In summary, endocrinologists need to be aware of the severe metabolic and liver-specific complications of NASH and establish early-on a long-term management plan. Screening will likely take place in the same way as for diabetic retinopathy or nephropathy. A better understanding of its natural history and pathogenesis of NASH, combined with improved diagnostic and treatment options, will likely place endocrinologists at the forefront of the management efforts to prevent end-stage liver disease in patients with NASH. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.
- Assessment of mouse liver [1-13C]pyruvate metabolism by dynamic hyperpolarized MRS. [Journal Article]
- JEJ Endocrinol 2019 Jul 01
- Hyperpolarized [1-13C]pyruvate magnetic resonance (MR) spectroscopy has the unique ability to detect real-time metabolic changes in vivo owing to its high sensitivity compared with thermal MR and hig…
Hyperpolarized [1-13C]pyruvate magnetic resonance (MR) spectroscopy has the unique ability to detect real-time metabolic changes in vivo owing to its high sensitivity compared with thermal MR and high specificity compared with other metabolic imaging methods. The aim of this study was to explore the potential of hyperpolarized MR spectroscopy for quantification of liver pyruvate metabolism during a hyperinsulinemic isoglycemic clamp in mice. Hyperpolarized [1-13C]pyruvate was used for in vivo MR spectroscopy of liver pyruvate metabolism in mice. Mice were divided into two groups: i) non-stimulated 5-hour fasted mice and ii) hyperinsulinemic isoglycemic clamped mice. During clamp conditions, insulin and donor blood were administered at a constant rate whereas glucose were infused to maintain isoglycemia. When steady state was reached, insulin-stimulated mice were rapidly infused with hyperpolarized [1-13C]pyruvate for real-time tracking of the dynamic distribution of metabolic derivatives from pyruvate, such as [1-13C]lactate, [1-13C]alanine, and [13C]bicarbonate. Isotopomer analysis of plasma glucose confirmed 13C-incorporation from [1-13C]pyruvate into glucose was increased in fasted mice compared with insulin-stimulated mice, demonstrating an increased gluconeogenesis in fasted mice. The AUC ratios for [1-13C]alanine/[1-13C]pyruvate (38.2%), [1-13C]lactate/[1-13C]pyruvate (41.8%), and [13C]bicarbonate/[1-13C]pyruvate (169%) all increased significantly during insulin stimulation. Hyperpolarized [1-13C]pyruvate can be used for in vivo MR spectroscopy of liver pyruvate metabolism during hyperinsulinemic isoglycemic clamp conditions. Under these conditions, insulin decreased gluconeogenesis and increased [1-13C]alanine, [1-13C]lactate, and [13C]bicarbonate after a [1-13C]pyruvate bolus. This application of in vivo spectroscopy has the potential to identify impairments in specific metabolic pathways in the liver associated with obesity, insulin resistance, and non-alcoholic fatty liver disease.
- Polygonum cuspidatum extract attenuates fructose-induced liver lipid accumulation through inhibiting Keap1 and activating Nrf2 antioxidant pathway. [Journal Article]
- PPhytomedicine 2019 Jun 10; 63:152986
- CONCLUSIONS: These results demonstrate that PCE reduces oxidative stress, and prevent lipid accumulation in the liver of fructose-fed rats possibly by targeting the Keap1/Nrf2 pathway. PCE may be a promising therapeutic strategy for fructose-associated liver lipid accumulation.
- Acute Kidney Injury after Cardiac Surgery: Risk Factors and Novel Biomarkers. [Review]
- BJBraz J Cardiovasc Surg 2019 Jun 01; 34(3):352-360
- Acute kidney injury (AKI) is a common and severe complication after cardiac surgery. Currently, a series of novel biomarkers have favored the assessment of AKI after cardiac surgery in addition to th…
Acute kidney injury (AKI) is a common and severe complication after cardiac surgery. Currently, a series of novel biomarkers have favored the assessment of AKI after cardiac surgery in addition to the conventional indicators. The biomartkers, such as urinary liver fatty acid binding protein (L-FABP), urinary neutrophil gelatinase-associated lipocalin (NGAL), serum L-FABP, heart-type FABP, kidney injury molecule 1 (KIM-1), and interleukin-18 were found to be significantly higher in patients who developed AKI after cardiac surgery than those who did not. Apart from urinary interleukin-18, the novel biomarkers have been recognized as reliable indicators for predicting the diagnosis, adverse outcome, and even mortality of AKI after cardiac surgery. The timing of the renal replacement therapy is a significant predictor relating to patients' prognoses. In patients with AKI after cardiac surgery, renal replacement therapy should be performed as early as possible in order to achieve promising outcomes. In children, AKI after cardiac surgery can be managed with peritoneal dialysis. AKI after cardiac surgery has received extensive attention as it may increase early mortality and impact long-term survival of patients as well. The purpose of this article was to analyze the changes of the pertinent biomarkers, to explore the related risk factors leading to the occurrence of AKI after cardiac surgery, and to provide a basis for the clinical prevention and reduction of AKI.
- Author response to Letter to the Editor: "Statins and non-alcoholic fatty liver disease". [Letter]
- LILiver Int 2019 Jul 16
- We thank Angelico and colleagues for their interest in our recent article in which we revealed that a substantial proportion of subjects with suspected non-alcoholic fatty liver disease (NAFLD) has i…
We thank Angelico and colleagues for their interest in our recent article in which we revealed that a substantial proportion of subjects with suspected non-alcoholic fatty liver disease (NAFLD) has increased cardiovascular risk and subjects with dyslipidemias such as high low-density lipoprotein (LDL) cholesterol could benefit from lipid-lowering treatment with statins. This article is protected by copyright. All rights reserved.
- Comparing point shear wave elastography (ElastPQ) and transient elastography for diagnosis of fibrosis stage in nonalcoholic fatty liver disease. [Journal Article]
- JGJ Gastroenterol Hepatol 2019 Jul 16
- CONCLUSIONS: TE was significantly better than pSWE for the diagnosis of fibrosis stage ≥F2 and ≥F3. Both TE and pSWE had excellent intra- and inter-observer variability when performed by healthcare personnel of different backgrounds.
- Postprandial Hypertriglyceridaemia Revisited in the Era of Non-Fasting Lipid Profile Testing: A 2019 Expert Panel Statement, Narrative Review [Review]
- CVCurr Vasc Pharmacol 2019 Jul 15
- Postprandial hypertriglyceridaemia, defined as an increase in plasma triglyceride-containing lipoproteins following a fat meal, is a potential risk predictor of atherosclerotic cardiovascular disease…
Postprandial hypertriglyceridaemia, defined as an increase in plasma triglyceride-containing lipoproteins following a fat meal, is a potential risk predictor of atherosclerotic cardiovascular disease and other chronic diseases. Several non-modifiable factors (genetics, age, sex and menopausal status) and lifestyle factors (diet, physical activity, smoking status, obesity, alcohol and medication use) may influence postprandial hypertriglyceridaemia. This narrative review considers the studies published over the last decade that evaluated postprandial hypertriglyceridaemia. Additionally, the genetic determinants of postprandial plasma triglyceride levels, the types of meals for studying postprandial triglyceride response, and underlying conditions (e.g. familial dyslipidaemias, diabetes mellitus, metabolic syndrome, non-alcoholic fatty liver and chronic kidney disease) that are associated with postprandial hypertriglyceridaemia are reviewed; therapeutic aspects are also considered.
- [Biomarkers of cardiac surgery-associated acute kidney injury: a narrative review]. [Journal Article]
- ZDZhejiang Da Xue Xue Bao Yi Xue Ban 2019 Apr 25; 48(2):224-229
- Cardiac surgery-related acute kidney injury (CSA-AKI) is a common and serious complication after cardiac surgery in adults. Currently, there is no specific examination method, and the diagnosis relyi…
Cardiac surgery-related acute kidney injury (CSA-AKI) is a common and serious complication after cardiac surgery in adults. Currently, there is no specific examination method, and the diagnosis relying on serum creatinine and urine volume changes is of hysteresis. Biomarkers with the potential to predict CSA-AKI have become the focus in recent years. Clinical studies have shown that neutrophil gelatinase related lipid transporters and cell cycle inhibitors are of high diagnostic value; liver fatty acid binding protein can be used to assist in the diagnosis of CSA-AKI; microRNAs help to assess the poor prognosis of patients; the combined application of biomarkers may be used to predict the occurrence of CSA-AKI. CSA-AKI biomarkers provide the possibility for early clinical diagnosis and timely intervention, and are expected to become a new breakthrough in the diagnosis and treatment of CSA-AKI.
- The roles of transmembrane 6 superfamily member 2 rs58542926 polymorphism in chronic liver disease: A meta-analysis of 24,147 subjects. [Journal Article]
- MGMol Genet Genomic Med 2019 Jul 15; :e824
- CONCLUSIONS: These results suggested that TM6SF2 rs58542926 could be used to identify individuals at higher susceptibility to chronic liver disease, especially for HCC, cirrhosis, ALD, and NAFLD.
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- Diabetes is Associated with Increased Risk of Hepatocellular Carcinoma in Cirrhosis Patients with Nonalcoholic Fatty Liver Disease. [Journal Article]
- HepHepatology 2019 Jul 15
- Diabetes increases the risk of liver disease progression and cirrhosis development in patients with non-alcoholic steatohepatitis (NASH). The association between diabetes and the risk of hepatocellul…
Diabetes increases the risk of liver disease progression and cirrhosis development in patients with non-alcoholic steatohepatitis (NASH). The association between diabetes and the risk of hepatocellular carcinoma (HCC) in NASH cirrhosis patients is not well quantified. All patients with the diagnosis of NASH cirrhosis seen at Mayo Clinic Rochester between January 2006 and December 2015 were identified. All adult liver transplant registrants with NASH between 2004 and 2017 were identified using the UNOS/OPTN registry for external validation. Cox proportional hazard analysis was performed to investigate the association between diabetes and HCC risk. Among 354 Mayo Clinic patients with NASH cirrhosis, 253 (71%) had diabetes and 145 (41%) were male. Mean age at cirrhosis evaluation was 62. During a median follow up of 47 months, 30 patients developed HCC. Diabetes was associated with an increased risk of developing HCC in univariate (hazard ratio [HR] = 3.6, 95% confidence interval [CI] =1.1-11.9, P=0.04) and multivariable analysis (HR = 4.2, 95% CI =1.2-14.2, P=0.02). In addition, age (per decade: HR = 1.8, 95% CI =1.2-2.6, P<0.01) and low serum albumin (HR = 2.1, 95% CI =1.5-2.9, P<0.01) were significantly associated with an increased risk of developing HCC in multivariable analysis. Other metabolic risk factors including BMI, hyperlipidemia and hypertension were not associated with HCC risk. Among UNOS NASH registrants (N=6,630), 58% had diabetes. Diabetes was associated with an increased risk of developing HCC in univariate (HR = 1.4, 95% CI =1.1-1.8, P<0.01) and multivariable (HR = 1.3, 95% CI =1.0-1.7, P=0.03) analysis. In conclusion, diabetes is associated with an increased risk of HCC in patients with NASH cirrhosis. This article is protected by copyright. All rights reserved.