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76 active trials for NAFLD

Postprandial VLDL-triglyceride Metabolism in Type 2 Diabetes Patients With and Without NAFLD

Non-alcoholic fatty liver disease (NAFLD) covers a spectrum from simple reversible hepatic steatosis to inflammation and fibrosis termed steatohepatitis (NASH). The mechanisms behind why some subjects progress from NAFLD to NASH are not clear and the responsible mechanism for storage of excess amounts of liver fat in patients with NAFLD are poorly understood. Patients with type 2 diabetes mellitus (T2D) and abdominally obese subjects very often have accumulation of liver fat (NAFLD). T2D is also associated with abnormal lipid metabolism (dyslipidemia), including free fatty acids (FFA), hypertriglyceridemia and excessive postprandial hyperlipidemia which increases the risk of ischemic cardiovascular disease (CVD) and heart failure. In healthy, insulin sensitive subjects the postprandial increase in triglycerides (TG) is primarily caused by meal derived chylomicrons, whereas endogenously produced TG (VLDL-TG) and decreased peripheral TG clearance only becomes quantitatively important in insulin resistant subjects .Thus, postprandial lipidemia in T2D results from both chylomicronemia as well as a reduction in both insulin mediated suppression of VLDL-TG secretion and lipoprotein lipase (LPL) mediated peripheral clearance. A recent study demonstrated that the ability of insulin to suppress hepatic VLDL-TG after a fat-enriched meal and the duration of the postprandial hyperlipidemia was similar in patients with T2D compared with age- and BMI matched individuals without T2D, indicating that the degree of insulin mediated VLDL-TG secretion and hyperlipidemia primarily depends on insulin sensitivity and not the presence of T2D diabetes per se. In these studies, the investigators want to examine the effect of a fat enriched mixed-meal on hepatic VLDL-TG handling and adipose storage capacity in patients with T2D with and without NAFLD. Investigators will address these questions using carboxyl-14C triolein labeled VLDL-TG, magnetic resonance (MR) spectroscopy of liver, muscle and fat biopsies in combination with state-of-the art muscle and adipose tissue enzyme kinetics, gene- and protein expression. The overarching goals are to define abnormalities and differences between patients with T2D with and without NAFLD in terms of hepatic lipid metabolism.

Aarhus NStart: September 2021
Nonalcoholic Fatty Liver Disease in HIV Database

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver conditions associated with fat accumulation that ranges from benign, non-progressive liver fat accumulation to severe liver injury, cirrhosis, and liver failure. The spectrum of NAFLD encompasses simple nonalcoholic steatosis (nonalcoholic fatty liver [NAFL]) and nonalcoholic steatohepatitis (NASH) in which there is evidence of hepatocellular injury and/or fibrosis. NAFLD is the most common liver disease in adults and the second leading cause for liver transplantation in the U.S. The natural history of NAFLD in the general population has been well described. The NASH Clinical Research Network (NASH CRN) was established by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) in 2002 to further the understanding of the diagnosis, mechanisms, progression and therapies of NASH. This effort has resulted in numerous seminal studies in the field. However, NASH CRN studies have systematically excluded persons living with HIV (PLWH) , as NAFLD in PLWH was thought to be different from that in the general population due to HIV infection, antiretroviral therapy (ART), concomitant medications and co-infections. This resulted in major knowledge gaps regarding NAFLD in the setting of HIV infection. Thus, the natural history of NAFLD in PLWH is largely unknown. The goal of this ancillary study of NAFLD and NASH in Adults with HIV (HIV NASH CRN), is to conduct a prospective, observational, multicenter study of biopsy-proven NAFLD in PLWH (HIV-associated NAFLD).

Richmond, VirginiaStart: October 2021
Prevalence and Predictors of Hepatic Steatosis in Persons Living With HIV

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver conditions associated with fat accumulation that ranges from benign, non-progressive liver fat accumulation to severe liver injury, cirrhosis, and liver failure. NAFLD is the most common liver disease in US adults and the second leading cause for liver transplantation in the US. The natural history of NAFLD in the general population has been well described, with those with non-alcoholic fatty liver (NAFL, or simple steatosis) destined to have rare incidence of hepatic events compared to those with non-alcoholic steatohepatitis (NASH), who are at high risk for future development of cirrhosis, liver cancer and liver failure. The NASH Clinical Research Network (NASH CRN) was established by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) in 2002, through the mechanism of RFA-DK-01-025, to further the understanding of diagnosis, mechanisms, progression and therapies of NASH. The NASH CRN effort has resulted in numerous seminal studies in the field. However, NASH CRN studies have systematically excluded persons living with HIV (PLWH), as NAFLD in these persons was thought to be different from that in the general population due to HIV, ART, concomitant medications, and co-infections. This has resulted in major knowledge gaps regarding NAFLD in the setting of HIV. This ancillary study of NAFLD and NASH in Adults with HIV (HIV NASH CRN), HNC 001 goal is to examine the prevalence of hepatic steatosis and NAFLD in a large, multicenter, and multiethnic cohort of PLWH (Steatosis in HIV Study)

Durham, North CarolinaStart: July 2021
Whey or Casein - Liver Fat Reduction and Metabolic Improvement by Fast vs. Slow Proteins

High-protein diets have been recently demonstrated to effectively reduce insulin resistance, derangements of the lipid profile and liver fat content in subjects with moderately and severely impaired glucose metabolism and non-alcoholic fatty liver disease (LeguAN, LEMBAS, DiNA-P, DiNA-D). The effects can be attributed to prolonged insulin secretion and improved second meal effect, higher energy expenditure by urea synthesis, suppression of glucagon or other mechanisms. Up to now, it is unclear, if proteins with slower or faster digestibility lead to differential results in these study designs. The proposed study will elucidate this question. The Investigators hypothesize, that slowly-digestible proteins induce a prolonged insulin plateau supporting the second-meal effect. The investigators also assume, that these dietary proteins lead to a markedly stronger short-term secretion of glucagon followed by desensitisation of this hormone release. Fast-digestible proteins, on the other hand, will presumably induce a smaller second-meal effect and do not inhibit a second rise of glucagon in a consecutive meal. The investigators intend to study the effects of a 3-weeks high-protein diet in subjects with NAFLD (40 subjects without T2DM, 40 subjects with T2DM) on insulin resistance (mixed-meal tolerance tests; MMTT), second meal effect (second, consecutive MMTT on the same day) and liver fat content (MR spectroscopy) as well body-fat distribution (MR tomography). The investigators expect different results for slow protein (casein) and fast protein (whey), thus comparing both protein species. The two major clinical visits before and after the intervention period will also include fasting blood sampling for later analysis, full anthropometric assessment and a set of behavioral tests, investigating postprandial decision making processes. All clinical assessments will be conducted in Charité (Lead: A.F.H. Pfeiffer). Psychobehavioral tests (Prof. Park), assessment of body fat distribution including liver fat (Dr. Machann) and measurements of amino acid levels throughout the meal tests (Prof. Rohn) are secondary work packages.

BerlinStart: September 2020
Determination of Insulin-stimulated Hepatic Glucose Uptake by PET-CT Measurements

In the absence of excessive alcohol consumption, increased levels of fat in the liver (>5%) are diagnosed as non-alcoholic fatty liver (NAFL). It has been shown that NAFL is strongly associated with impairments in metabolic health such as hepatic and whole-body insulin resistance. Insulin resistance is seen as the earliest hallmark in the development of type 2 diabetes. Insulin has two main effects on the liver: suppressing endogenous glucose production (EGP) and increasing glucose uptake. While the former has been extensively studied and is known to be impaired in NAFL, no studies have yet examined whether insulin-stimulated hepatic glucose uptake is affected by NAFL. Recent methodological developments allow us to visualize and quantify glucose uptake in any given tissue using dynamic Positron Emission Tomography (PET) with 18Fluorinated glucose tracer (FDG) during insulin stimulation. In the present study, we will in a first instance optimize the insulin-stimulated whole-body PET protocol and apply the dose as reported in the literature 4 megabequerels per kg of body weight (MBq/kg) (±8 mSv) in the first three subjects. It will then be evaluated whether the dose can be decreased in the remaining measurements. Another twelve individuals will then undergo the optimized dynamic PET protocol to assess insulin-stimulated hepatic glucose together with whole-body glucose uptake measures. Liver fat content and composition will be assessed by proton magnetic resonance spectroscopy (1H-MRS). Fasted De Novo Lipogenesis (DNL) will also be measured by deuterated water. Additionally, a two-step clamp will be performed to measure whole-body insulin sensitivity and insulin-stimulated suppression of EGP. The identification of the contributing factors to insulin resistance during the development of NAFL is crucial in order to develop more effective strategies for the prevention and treatment of metabolic disorders.

Start: August 2021