Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient with no history of alcohol abuse or other causes for secondary hepatic steatosis. The pathogenesis of NAFLD and nonalcoholic steatohepatitis (NASH) has not been fully elucidated. The "two-hit" hypothesis is probably a too simplified model to elaborate complex pathogenetic events occurring in patients with NASH. It should be better regarded as a multiple step process, with accumulation of liver fat being the first step, followed by the development of necroinflammation and fibrosis. Adipose tissue, which has emerged as an endocrine organ with a key role in energy homeostasis, is responsive to both central and peripheral metabolic signals and is itself capable of secreting a number of proteins. These adipocyte-specific or enriched proteins, termed adipokines, have been shown to have a variety of local, peripheral, and central effects. In the current review, we explore the role of adipocytokines and proinflammatory cytokines in the pathogenesis of NAFLD. We particularly focus on adiponectin, leptin and ghrelin, with a brief mention of resistin, visfatin and retinol-binding protein 4 among adipokines, and tumor necrosis factor-α, interleukin (IL)-6, IL-1, and briefly IL-18 among proinflammatory cytokines. We update their role in NAFLD, as elucidated in experimental models and clinical practice.

Evidence from randomized controlled trials (RCTs) suggests that viscous dietary fiber may offer beneficial effects on glycemic control and, thus, an improved cardiovascular disease risk profile. Our purpose was to conduct a systematic review and meta-analysis of RCTs to synthesize the therapeutic effect of viscous fiber supplementation on glycemic control in type 2 diabetes. RESEARCH DESIGN AND METHODS MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched through 15 June 2018. We included RCTs ‡3 weeks in duration that assessed the effects of viscous fiber on markers of glycemic control in type 2 diabetes. Two independent reviewers extracted data. Data were pooled using the generic inverse variance method and expressed as mean differences (MD) with 95% CIs. Heterogeneity was assessed (Cochran Q statistic) and quantified (I 2 statistic). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the overall certainty of the evidence. RESULTS We identified 28 eligible trial comparisons (n = 1,394). Viscous fiber at a median dose of ∼13.1 g/day significantly reduced HbA 1c (

Psyllium fiber effectively improves conventional and alternative lipids markers, potentially delaying the process of atherosclerosis-associated CVD risk in those with or without hypercholesterolemia. This trial is registered at www.clinicaltrials.gov as NCT03346733.

Background: For patients with type 2 diabetes (T2D), cardiovascular disease (CVD) is the single most common cause of mortality. In 2008 and 2012, the Federal Drug Administration (FDA) and the European Medicines Agency (EMA) respectively mandated cardiovascular outcomes trials (CVOTs) on all new anti-diabetic agents, as prospective trials statistically powered to rule out excess cardiovascular risk in patients with T2D. Unexpectedly, some of these CVOTs have demonstrated not only cardiovascular safety, but also cardioprotective effects, as was first shown for the SGLT2 inhibitor empagliflozin in EMPA-REG OUTCOME. Expert opinion: To debate newly available CVOT data and to put them into context, we convened as a group of medical experts from the Central and Eastern European Region. Here we describe our discussions, focusing on the conclusions we can draw from EMPA-REG OUTCOME and other SGLT2 inhibitor CVOTs, including when considered alongside real-world evidence. Conclusion: CVOTs investigating SGLT2 inhibitors have suggested benefits beyond glucose lowering that have been confirmed in real-world evidence studies.

Cardiovascular disease (CVD) is the most significant prognostic factor in individuals with type 2 diabetes (T2D). However, a significant number of individuals may develop CVD that does not present with the classic angina-related or heart failure symptoms. In these cases, CVD may seem to be ‘silent’ or ‘asymptomatic’, but may be more accurately characterised as unrecognised diabetic cardiac impairment. An initial step to raise awareness of unrecognised CVD in individuals with T2D would be to reach a consensus regarding the terminology used to describe this phenomenon. By standardising the terminologies, and agreeing on the implementation of an efficient screening program, it is anticipated that patients will receive an earlier diagnosis and appropriate and timely treatment. Given the availability of anti-diabetic medications that have been shown to concomitantly reduce CV risk and mortality, it is imperative to improve early identification and initiate treatment as soon as possible in order to enable as many patients with T2D as possible to benefit.

These findings indicate that higher levels of ALT, AST and ALK are additional markers of insulin resistance in type 1 diabetes and suggest that those subjects must be considered as potentially affected not only by a hepatic but also by a multisystemic disease through altered insulin sensitivity.

NCT02626325.

Nonalcoholic fatty liver disease (NAFLD) is associated with an increased prevalence of chronic kidney disease in patients with type 1 diabetes. The aim of this study was to explore the relationship between markers of NAFLD, namely concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALK), g-glutamyltransferase (GGT), bilirubin, and renal function in type 1 diabetic patients. This study included 313 normoalbuminuric type 1 diabetic patients with estimated glomerular filtration rate (eGFR) 460 mL/min/1.73 m 2 , without clinical evidence of cirrhosis or other causes of chronic liver disease and before any interventions with statins, angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers. ALT, GGT, and bilirubin levels were significantly higher in subjects in the highest quartile of serum creatinine compared to those in lowest quartile (21 vs. 20 U/L, 18 vs. 14 U/L, and 14 vs. 10 mmol/L, respectively, for all p50.05). ALK levels were significantly higher in subjects in the highest quartile of urinary albumin excretion rate compared to those in lowest quartile (71 vs. 69 U/L, p ¼ 0.03), as well as in hyperfiltrating subjects compared to those with normal or mildly impaired eGFR (81 vs. 68 and 64 U/L, p50.001). In a multiple logistic regression model adjusted for age, sex, duration of diabetes, HbA1c, and body mass index (BMI), only ALK levels were significantly associated with disturbances in serum creatinine and eGFR in our subjects (p 0.007), with odds ratios of 0.98-1.02. NAFLD associated markers, particularly ALK, are associated with renal function in normoalbuminuric type 1 diabetic patients.