The Roles of Non-Pharmacologic and Emerging Pharmacologic Management of Non-alcoholic Fatty Liver Disease and Sarcopenia: A Narrative Review.

Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent causes of chronic liver disease worldwide which is often seen in patients with metabolic abnormalities such as those with obesity and insulin resistance. On the other hand, sarcopenia is a generalized and progressive skeletal muscle disorder characterized by low muscle strength, low muscle quality, low physical performance, or a combination of the three. Both disease entities share several underlying risk factors and pathophysiologic mechanisms. These include: (1) cardiometabolic overlaps such as insulin resistance, chronic systemic inflammation, decreased vitamin D levels, sex hormone modifications; (2) muscle-related factors such as those mitigated by myostatin signaling, and myokines (i.e., irisin); and (3) liver-dysfunction related factors such as those associated with growth hormone/insulin-like growth factor 1 Axis, hepatokines (i.e., selenoprotein P and leukocyte cell-derived chemotaxin-2), fibroblast growth factors 21 and 19 (FGF21 and FGF19), and hyperammonemia. This narrative review will examine the pathophysiologic overlaps that can explain the links between NAFLD and sarcopenia. Furthermore, this review will explore the emerging roles of nonpharmacologic (e.g., weight reduction, diet, alcohol, and smoking cessation, and physical activity) and pharmacologic management (e.g., roles of ß-hydroxy-ß-methylbutyrate, branched-chain amino acid supplements, and testosterone therapy) to improve care, intervention sustainability, and acceptability for patients with sarcopenia-associated NAFLD.

Interrelationship of Sarcopenia and Cardiovascular Diseases: A Review of Potential Mechanisms and Management.

Sarcopenia refers to an age-related reduction of lean body mass. It showed a reciprocal relationship with cardiovascular diseases. Thus, it is imperative to explore pathophysiological mechanisms explaining the relationship between sarcopenia and cardiovascular diseases, along with the clinical assessment, and associated management. In this review, we discuss how processes such as inflammation, oxidative stress, endothelial dysfunction, neural and hormonal modifications, as well as other metabolic disturbances influence sarcopenia as well as its association with cardiovascular diseases. Moreover, this review provides an overview of both non-pharmacological and pharmacological management for patients with sarcopenia and cardiovascular diseases, with a focus on the potential role of cardiovascular drugs to mitigate sarcopenia.

Protective Factors and the Pathogenesis of Complications in Diabetes.

Chronic complications of diabetes are due to myriad disorders of numerous metabolic pathways that are responsible for most of the morbidity and mortality associated with the disease. Traditionally, diabetes complications are divided into those of microvascular and macrovascular origin. We suggest revising this antiquated classification into diabetes complications of vascular, parenchymal, and hybrid (both vascular and parenchymal) tissue origin, since the profile of diabetes complications ranges from those involving only vascular tissues to those involving mostly parenchymal organs. A major paradigm shift has occurred in recent years regarding the pathogenesis of diabetes complications, in which the focus has shifted from studies on risks to those on the interplay between risk and protective factors. While risk factors are clearly important for the development of chronic complications in diabetes, recent studies have established that protective factors are equally significant in modulating the development and severity of diabetes complications. These protective responses may help explain the differential severity of complications, and even the lack of pathologies, in some tissues. Nevertheless, despite the growing number of studies on this field, comprehensive reviews on protective factors and their mechanisms of action are not available. This review thus focused on the clinical, biochemical, and molecular mechanisms that support the idea of endogenous protective factors, and their roles in the initiation and progression of chronic complications in diabetes. In addition, this review also aimed to identify the main needs of this field for future studies.

Cardiovascular Effects of Excess Growth Hormone: How Real is the Threat?

Patients with acromegaly carry a high risk of developing cardiovascular diseases (CVD). In fact, CVD is the leading cause of mortality among this group of patients. The most frequent cardiovascular complications are heart failure (HF), valvular disease, hypertension, arrhythmias, and coronary artery disease (CAD). The pathophysiology centers on the family of growth hormone (GH). These hormones are involved in normal cardiac development and function; however, excess of insulin-like growth factor-1 (IGF-1), the principally active hormone, can also cause negative effects on the cardiovascular system. HF in acromegaly usually presents with biventricular enlargement and diastolic dysfunction and is strongly associated with the duration of GH excess rather than the degree of hormone elevation. There is a high prevalence of valvular disease affecting aortic and mitral valves among patients with longer disease duration. The development of hypertension in acromegaly may be attributed to the effects of chronic GH/IGF-1 excess on different organ systems, which act via several mechanisms. The aspect of arrhythmia and CAD complicating acromegaly are currently not fully understood.

Metabolic Profile of People Living with HIV in a Treatment Hub in Manila, Philippines: A Pre- and Post-Antiretroviral Analysis.

Objectives: People living with HIV (PLHIV) are susceptible to develop dyslipidemia and hyperglycemia. This study aims to determine the prevalence of these metabolic derangements among Filipino PLHIV. Methodology: We reviewed 635 medical records in a treatment hub in Manila, Philippines from January 2004 to July 2016. Logistic regression analysis was done to determine factors associated with dyslipidemia and hyperglycemia pre- and post-ART. Results: Among 635 PLHIV, 97.3% were males with mean age of 30 years and median CD4 count of 207 cells/mm3. Pre-ART, prevalence of dyslipidemia was 65.4% and hyperglycemia was 10.4%. Risk factors for dyslipidemia include hyperglycemia (AOR 3.8, p 0.001) and >320 days delay in ART initiation from HIV confirmation (AOR 1.5, p 0.032), while dyslipidemia was associated with hyperglycemia (AOR 3.1, p 0.001). Post-ART, prevalence of dyslipidemia was 48.6% and hyperglycemia was 15.6%. Risk factors for post-ART dyslipidemia include being WHO stage 4 (AOR 2.1, p 0.021), hyperglycemia (AOR 16.1, p<0.001), >36 months ART duration (AOR 8.7, p<0.001) and efavirenz-based ART (AOR 2.8, p<0.001). Low CD4 count post-ART had a negative correlation with dyslipidemia (AOR 0.5, p 0.005). Post-ART hyperglycemia was associated with age >30 years (AOR 2.1, p 0.004), being overweight (AOR 1.8, p 0.023), dyslipidemia (AOR 17.8, p<0.001) and zidovudine-based ART (AOR 1.4, p 0.051). Conclusion: Dyslipidemia and hyperglycemia prevalence was high in Filipino PLHIV. Traditional, HIV and treatment related factors contributed to its development. Intensive monitoring and initiation of appropriate treatment is recommended.

Endothelial Cells Induced Progenitors Into Brown Fat to Reduce Atherosclerosis.

BACKGROUND: Insulin resistance (IR) can increase atherosclerotic and cardiovascular risk by inducing endothelial dysfunction, decreasing nitric oxide (NO) production, and accelerating arterial inflammation. The aim is to determine the mechanism by which insulin action and NO production in endothelial cells can improve systemic bioenergetics and decrease atherosclerosis via differentiation of perivascular progenitor cells (PPCs) into brown adipocytes (BAT). METHODS: Studies used various endothelial transgenic and deletion mutant ApoE-/- mice of insulin receptors, eNOS (endothelial NO synthase) and ETBR (endothelin receptor type B) receptors for assessments of atherosclerosis. Cells were isolated from perivascular fat and micro-vessels for studies on differentiation and signaling mechanisms in responses to NO, insulin, and lipokines from BAT. RESULTS: Enhancing insulin's actions on endothelial cells and NO production in ECIRS1 transgenic mice reduced body weight and increased systemic energy expenditure and BAT mass and activity by inducing differentiation of PPCs into beige/BAT even with high-fat diet. However, positive changes in bioenergetics, BAT differentiation from PPCs and weight loss were inhibited by N(gamma)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of eNOS, in ECIRS1 mice and eNOSKO mice. The mechanism mediating NO's action on PPC differentiation into BAT was identified as the activation of solubilized guanylate cyclase/PKGIα (cGMP protein-dependent kinase Iα)/GSK3ß (glycogen synthase kinase 3ß) pathways. Plasma lipidomics from ECIRS1 mice with NO-induced increased BAT mass revealed elevated 12,13-diHOME production. Infusion of 12,13-diHOME improved endothelial dysfunction and decreased atherosclerosis, whereas its reduction had opposite effects in ApoE-/-mice. CONCLUSIONS: Activation of eNOS and endothelial cells by insulin enhanced the differentiation of PPC to BAT and its lipokines and improved systemic bioenergetics and atherosclerosis, suggesting that endothelial dysfunction is a major contributor of energy disequilibrium in obesity.

Self-reported cultural competency measures among patients with diabetes: A nationwide cross-sectional study in the United States.

Background: Culturally tailored interventions may reduce disparities in diabetes care. We conducted a nationally representative assessment of self-reported cultural competency measures of care among patients with diabetes in the United States. Methods: The 2017 National Health Interview Survey was queried for adults with self-reported diabetes. Sample weight-adjusted multivariable logistic regressions defined adjusted odds ratios and 95% confidence intervals of a positive response to each of the cultural competency measures while controlling for relevant sociodemographic variables. Findings: 2,448 adults were included in the analyses. Black, Latinx, and Asian respondents had greater odds of and individuals with the highest income level had lower odds of placing greater importance in sharing cultures with their provider. Black and Latinx individuals had lower odds of reporting encountering providers who shared or understood their cultures. Asians had lower odds of and respondents aged 40-64 and 65 years and older had greater odds of reporting frequently being treated with respect by their providers. Non-English speakers had lower odds of and individuals from higher income brackets had greater odds of reporting frequently receiving easy-to-understand information about their care. Blacks and respondents not part of the workforce had greater odds of reporting frequently being asked about their opinions or beliefs in care. Interpretation: Disparities in self-reported provider cultural competency measures exist among cultural minorities in the United States. Our findings may inform efforts to reduce disparities and improve care among minorities with diabetes. Funding: No funding was used in the preparation of this work.

Insulin's actions on vascular tissues: Physiological effects and pathophysiological contributions to vascular complications of diabetes.

BACKGROUND: Insulin has been demonstrated to exert direct and indirect effects on vascular tissues. Its actions in vascular cells are mediated by two major pathways: the insulin receptor substrate 1/2-phosphoinositide-3 kinase/Akt (IRS1/2/PI3K/Akt) pathway and the Src/mitogen-activated protein kinase (MAPK) pathway, both of which contribute to the expression and distribution of metabolites, hormones, and cytokines. SCOPE OF REVIEW: In this review, we summarize the current understanding of insulin's physiological and pathophysiological actions and associated signaling pathways in vascular cells, mainly in endothelial cells (EC) and vascular smooth muscle cells (VSMC), and how these processes lead to selective insulin resistance. We also describe insulin's potential new signaling and biological effects derived from animal studies and cultured capillary and arterial EC, VSMC, and pericytes. We will not provide a detailed discussion of insulin's effects on the myocardium, insulin's structure, or its signaling pathways' various steps, since other articles in this issue discuss these areas in depth. MAJOR CONCLUSIONS: Insulin mediates many important functions on vascular cells via its receptors and signaling cascades. Its direct actions on EC and VSMC are important for transporting and communicating nutrients, cytokines, hormones, and other signaling molecules. These vascular actions are also important for regulating systemic fuel metabolism and energetics. Inhibiting or enhancing these pathways leads to selective insulin resistance, exacerbating the development of endothelial dysfunction, atherosclerosis, restenosis, poor wound healing, and even myocardial dysfunction. Targeted therapies to improve selective insulin resistance in EC and VSMC are thus needed to specifically mitigate these pathological processes.