1,703 research outputs found
Insulinresistenz und Kinetik freier Fettsäuren bei Patienten mif Typ-2 Diabetes während 2-jähriger Behandlung mit Pioglitazon zusätzlich zu Sulfonyharnstoff oder Metformin
No full text[Mein lieber Freund].
No full textHandwritten and signed letter from author Max Roden regarding a review of one of his books.Author, 1881-1968.The original German-language inventory is available in the folderProcessed for digitizatio
Response to: Comment to “EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease”
No full textWe thank Jorge Fonseca et al. for their comments, which give us the opportunity to clarify the controversial issue of dietary approach to NAFLD, an issue that did not receive adequate attention in the Clinical Practice Guidelines (CPG) due to space constraints. They are concerned about the sentence suggesting ‘‘low-to-moderate fat and moderate-to-high carbohydrate intake” as a reasonable option for NAFLD cases. Indeed, no recommendation on nutrient composition of the diet was issued within the CPG, but a formal recommendation reads ‘‘Dietary recommendations should consider energy restriction and exclusion of NAFLD-promoting components (processed food, and food and beverages high in added fructose). The macronutrient composition should be adjusted according to the Mediterranean diet (B1)” [1]. This recommendation is based on a single experimental study [2] and a lot of indirect evidence, granting the B1 grade. On the contrary, the sentence in Table 5 is a mere suggestion derived from literature review, also considering the mandatory need for calorie restriction and weight loss
The complex link between NAFLD and type 2 diabetes mellitus - mechanisms and treatments
No full textNonalcoholic fatty liver disease (NAFLD) has reached epidemic proportions worldwide. NAFLD and type 2 diabetes mellitus (T2DM) are known to frequently coexist and act synergistically to increase the risk of adverse (hepatic and extra-hepatic) clinical outcomes. T2DM is also one of the strongest risk factors for the faster progression of NAFLD to nonalcoholic steatohepatitis, advanced fibrosis or cirrhosis. However, the link between NAFLD and T2DM is more complex than previously believed. Strong evidence indicates that NAFLD is associated with an approximate twofold higher risk of developing T2DM, irrespective of obesity and other common metabolic risk factors. This risk parallels the severity of NAFLD, such that patients with more advanced stages of liver fibrosis are at increased risk of incident T2DM. In addition, the improvement or resolution of NAFLD (on ultrasonography) is associated with a reduction of T2DM risk, adding weight to causality and suggesting that liver-focused treatments might reduce the risk of developing T2DM. This Review describes the evidence of an association and causal link between NAFLD and T2DM, discusses the putative pathophysiological mechanisms linking NAFLD to T2DM and summarizes the current pharmacological treatments for NAFLD or T2DM that might benefit or adversely affect the risk of T2DM or NAFLD progression.This Review describes the evidence of an association and causal link between nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM), discusses their pathophysiological mechanisms and summarizes the pharmacological treatments that might benefit or adversely affect the risk of T2DM or NAFLD progression
Is Nonalcoholic Fatty Liver Disease Not a Risk Factor for Cardiovascular Disease: Not Yet Time for a Change of Heart
No full textCardiovascular disease (CVD) is the leading cause of death among individuals with non-alcoholic fatty liver disease (NAFLD), and a growing body of evidence indicates that NAFLD is strongly associated with an increased risk of incident CVD events.(1) The independent contribution of NAFLD to CVD development, however, remains an area of debate. Recently, Alexander et al. performed a population-based, retrospective, case-control study using data from four large European electronic primary care databases (United Kingdom, Netherlands, Italy and Spain) to estimate the incidence of fatal and non-fatal acute myocardial infarction (AMI) and ischemic/unspecified stroke in patients with NAFLD compared to the general population after adjustment for traditional CVD risk factors.(2) Among nearly 17.7 million individuals, 120,795 adults had a recorded diagnosis of NAFLD or non-alcoholic steatohepatitis (NASH) without other known liver diseases, a diagnosis of excessive alcohol use, or prior AMI or stroke. Cases were matched with up to 100 controls by age, sex, practice site, and visit within six months of the case’s NAFLD/NASH diagnosis. Participants were followed until the occurrence of a primary outcome, end of the study period, or database exit, and the median follow-up time was 2.1-5.5 years (with a total of 205,046 recorded diagnoses of CVD events that occurred during follow-up). Cox proportional hazards models estimated the hazard ratios (HR) of AMI and stroke within each database and then pooled HR using a random effect meta-analysis
Nonalcoholic Fatty Liver Disease and Cardiovascular Disease
No full textWatch a video presentation of this article Answer questions and earn CME
Diabetes Mellitus, Energy Metabolism, and COVID-19
No full textObesity, diabetes mellitus (mostly type 2), and COVID-19 show mutual interactions because they are not only risk factors for both acute and chronic COVID-19 manifestations, but also because COVID-19 alters energy metabolism. Such metabolic alterations can lead to dysglycemia and long-lasting effects. Thus, the COVID-19 pandemic has the potential for a further rise of the diabetes pandemic. This review outlines how preexisting metabolic alterations spanning from excess visceral adipose tissue to hyperglycemia and overt diabetes may exacerbate COVID-19 severity. We also summarize the different effects of SARS-CoV-2 infection on the key organs and tissues orchestrating energy metabolism, including adipose tissue, liver, skeletal muscle, and pancreas. Last, we provide an integrative view of the metabolic derangements that occur during COVID-19. Altogether, this review allows for better understanding of the metabolic derangements occurring when a fire starts from a small flame, and thereby help reducing the impact of the COVID-19 pandemic.Graphical Abstrac
The role of mitochondria in statin-induced myopathy
No full textBackground: Statins inhibit hydroxymethylglutaryl-coenzyme A reductase, decrease plasma low-density lipoprotein cholesterol and reduce cardiovascular morbidity and mortality. They can also exert adverse effects, mostly affecting skeletal muscle, ranging from mild myalgia to rhabdomyolysis. Materials and methods: Based on a PubMed search until December 2014, this review summarizes studies on statin effects on muscle mitochondrial morphology and function in the context of myopathy. Results: Possible mechanisms of statin-induced myopathy include lower cholesterol synthesis and production of prenylated proteins, reduced dolichols and increased atrogin-1 expression. Statin-treated patients frequently feature decreased muscle coenzyme Q10 (CoQ10) contents, suggesting that statins might impair mitochondrial function. In cell cultures, statins diminish muscle oxygen consumption, promote mitochondrial permeability transient pore opening and generate apoptotic proteins. Animal models confirm the statin-induced decrease in muscle CoQ10, but reveal no changes in mitochondrial enzyme activities. Human studies yield contradictory results, with decreased CoQ10, elevated lipids, decreased enzyme activities in muscle and impaired maximal oxygen uptake in several but not all studies. Some patients are susceptible to statin-induced myopathy due to variations in genes encoding proteins involved in statin uptake and biotransformation such as the solute carrier organic anion transporter family member 1B1 (SLCO1B1) or cytochrome P450 (CYP2D6, CYP3A4, CYP3A5). Carriers for carnitine palmitoyltransferase II deficiency and McArdle disease also present with higher prevalence of statin-induced myopathy. Conclusions: Despite the widespread use of statins, the pathogenesis of statin-induced myopathy remains unclear, requiring prospective randomized controlled trials with intensive phenotyping also for identifying strategies for its risk assessment, prevention and treatment
Tissue Biopsies in Diabetes Research
No full textType 2 diabetes is characterized by insulin resistance in major metabolic tissues such as skeletal muscle, liver and fat cells, and failure of the pancreatic ß-cells to compensate for this abnormality (1,2). Skeletal muscle is the major site of glucose disposal in response to insulin, and insulin resistance of glucose disposal and glycogen synthesis in this tissue are hallmark features of type 2 diabetes in humans (2,3). During the past two decades, we have carried out more than 1200 needle biopsies of skeletal muscle to study the cellular mechanisms underlying insulin resistance in type 2 diabetes. Together with morphological studies, measurement of energy stores and metabolites, enzyme activity and phosphorylation, gene and protein expression in skeletal muscle biopsies have revealed a variety of cellular abnormalities in patients with type 2 diabetes and prediabetes. The possibility to establish human muscle cell cultures from muscle biopsies of diabetic subjects has further extended our possibilities to study cellular mechanisms of insulin resistance and potentially distinguish between primary and secondary defects (3). More recently, the application of global approaches such as proteomics and gene expression profiling on skeletal muscle biopsies have pointed to abnormalities in mitochondrial oxidative phosphorylation in type 2 diabetes. These novel insights will inevitably cause a renewed interest in studying skeletal muscle. This chapter reviews our experience to date and gives a thorough description of the technique of percutaneous needle biopsy of skeletal muscle and the establishment of human muscle cell cultures together with a discussion of advantages and limitations of the methods in diabetes researc
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