Nonalcoholic fatty liver disease in lean subjects:Prognosis,outcomes and management

Nonalcoholic fatty liver disease(NAFLD)accounts for most cases of chronic liver disease worldwide,with an estimated global prevalence of approximately 25%and ranges from simple steatosis to nonalcoholic steatohepatitis and cirrhosis.NAFLD is strongly connected to metabolic syndrome,and for many years,fatty liver was considered to be an exclusive feature of obese patients.However,recent studies have highlighted the presence of NAFLD in non-obese subjects,with or without increased visceral fat or even in lean subjects without increased waist circumference.“Lean NAFLD”is a relatively new concept and there is significant scientific interest in understanding the differences in pathophysiology,prognosis and management compared with NAFLD in overweight/obese patients.In the present editorial,we discuss the clinical and metabolic profiles and outcomes of lean NAFLD compared with both obese NAFLD and lean healthy individuals from Asian and Western countries.Moreover,we shed light to the challenging topic of management of NAFLD in lean subjects since there are no specific guidelines for this population.Finally,we discuss open questions and issues to be addressed in the future in order to categorize NAFLD patients into lean and nonlean cohorts.

Metabolic and cardiovascular benefits with combination therapy of SGLT-2 inhibitors and GLP-1 receptor agonists in type 2 diabetes

Both GLP-1 receptor agonists(GLP-1RA)and SGLT-2 inhibitors(SGLT-2I)are newer classes of anti-diabetic agents that lower HbA1c moderately and decrease body weight and systolic blood pressure(SBP)modestly.Combination therapy with GLP-1RA plus SGLT-2I have shown a greater reduction in HbA1c,body weight,and SBP compared to either agent alone without any significant increase in hypoglycemia or other side effects.Since several agents from each class of these drugs have shown an improvement in cardiovascular(CV)and renal outcomes in their respective cardiovascular outcome trials(CVOT),combination therapy is theoretically expected to have additional CV and renal benefits.In this comprehensive opinion review,we found HbA1c lowering with GLP-1RA plus SGLT-2I to be less than additive compared to the sum of HbA1c lowering with either agent alone,although body weight lowering was nearly additive and the SBP lowering was more than additive.Our additional meta-analysis of CV outcomes with GLP1RA plus SGLT-2I combination therapy from the pooled data of five CVOT found a similar reduction in three-point major adverse cardiovascular events compared to GLP-1RA or SGLT-2I alone,against placebo.Interestingly,a greater benefit in reduction of heart failure hospitalization with GLP-1RA plus SGLT-2I combination therapy was noted in the pooled meta-analysis of two randomized controlled trials.Future adequately powered trials can confirm whether additional CV or renal benefit is truly exerted by GLP-1RA plus SGLT-2I combination therapy.

Developmental origins of health and disease: Impact of paternal nutrition and lifestyle

Most epidemiological and experimental studies have focused on maternal influences on offspring’s health.The impact of maternal undernutrition,overnutrition,hypoxia,and stress is linked to adverse offspring outcomes across a range of systems including cardiometabolic,respiratory,endocrine,and reproduction among others.During the past decade,it has become evident that paternal environmental factors are also linked to the development of diseases in offspring.In this article,we aim to outline the current understanding of the impact of male health and environmental exposure on offspring development,health,and disease and explore the mechanisms underlying the paternal programming of offspring health.The available evidence suggests that poor paternal pre-conceptional nutrition and lifestyle,and advanced age can increase the risk of negative outcomes in offspring,via both direct(genetic/epigenetic)and indirect(maternal uterine environment)effects.Beginning at preconception,and during utero and the early life after birth,cells acquire an epigenetic memory of the early exposure which can be influential across the entire lifespan and program a child’s health.Potentially not only mothers but also fathers should be advised that maintaining a healthy diet and lifestyle is important to improve offspring health as well as the parental health status.However,the evidence is mostly based on animal studies,and well-designed human studies are urgently needed to verify findings from animal data.