Type 1 diabetes (T1D) represents an autoimmune disease caused by the gradual immune-mediated destruction of the insulin-producing beta cells within the pancreatic islets of Langerhans, resulting in the lifelong need for exogenous insulin therapy. According to recent estimates, T1D currently affects about 8.4 million individuals worldwide. Since a definitive biological cure for this disease is not available yet, there is a great need for novel therapeutic strategies aimed at safely and effectively altering the natural history of the disease during its sequential stages. Ideal therapeutic goals in T1D include the prevention of autoimmune beta-cell destruction, the preservation of residual beta-cell mass and endogenous insulin secretion, the replacement and/or regeneration of beta cells, as well as automated insulin delivery through advanced closed-loop artificial pancreas systems. With this regard, an important research area focused on the identification of a definitive biological cure for T1D is represented by the investigation of immunotherapeutic and beta-cell-protective agents used as disease-modifying therapies to forestall or eliminate insulin dependence. In this commentary, we discuss the reasons why the use of combination therapies targeting the multiple immunometabolic dysfunctions associated with T1D (other than beta-cell autoimmunity) is likely to be more effective in preserving beta cell function in individuals at different stages of T1D, as compared to the use of single therapeutic agents.

The term “democratization of science” describes the process of more evenly allocating epistemic authority between scientists, members of dominant civilizations, and the academic community at large, or members of less dominant societies. This means that it includes initiatives aimed at democratizing the decision-making process by acknowledging the presence of diverse types of “wisdom of crowd” and so reducing the barriers between the various stakeholders. Our purpose is to separate influence from involvement that contributes to the breakdown of conventional closed-circuit authority structures and to prevent future abuses of power by academic institutions, scientific societies, and even individual opinion leaders. A conceptual framework for comprehending the idea of the democratization of science is presented in this perspective piece. Our considerations are pertinent to the politics of widespread academic engagement in scientific decision-making, even though they were spurred by the discussion surrounding the definitions of fatty liver disease.

Aim: Hepatic homocysteine (Hcy) accumulation promotes inflammation and fibrosis in experimental nonalcoholic fatty liver disease (NAFLD), while vitamin B12 and folate reduce hepatic Hcy and protect animals from nonalcoholic steatohepatitis. This suggests clinical implications for preventing/treating patients with NAFLD. Given the known sex-specific regulation of one-carbon metabolism (OCM), the response to various OCM cofactors may vary by sex and reproductive status. We aimed to strategize an effective Hcy-lowering treatment in broader NAFLD patients while discerning disparities in treatment responses.

Methods: We analyzed existing hepatic microarray data relevant to Hcy metabolism with clinical and histologic data from patients with NAFLD (N = 82), while considering potential age/sex disparities. Additionally, we performed computer simulation analyses using a mathematical model of OCM to predict hepatic Hcy-lowering effects of OCM cofactors by sex.

Results: Of 82 patients with NAFLD, 98% had at least one metabolic feature [i.e., metabolic dysfunction-associated steatotic liver disease (MASLD)]. Lower hepatic gene expressions of cystathionine-beta synthase (CBS) and phosphatidyl- ethanolamine N-methyltransferase (PEMT) were associated with more severe fibrosis in NAFLD, while sub-analysis suggested possible variations by age and sex. The simulation analysis demonstrated sex differences in the Hcy-lowering effects of the OCM cofactors (vitamins B6 and B12, folate, and betaine), with the combination of these cofactors consistently showing the maximum Hcy-lowering effect in both sexes.

Conclusion: We theorize that the combination of OCM cofactors would maximize Hcy-lowering effects in the broader MASLD population. Our findings also underscore the importance of considering sex and age in designing future studies on homocysteine metabolism.

Heart disease remains a major health threat in women. Cardiometabolic risk factors such as obesity and diabetes differentially and adversely impact heart disease risk. Although obstructive coronary artery disease is an important cause of ischemic heart disease in women and is prognostic, women are more likely to have angina and myocardial ischemia without obstructive atherosclerosis, which has been attributed to coronary microvascular dysfunction (CMD). Heart failure with preserved ejection fraction (HFpEF) is another condition that predominates in women. CMD and HFpEF are both associated with cardiometabolic risk factors that are prevalent in women. Women are also more likely to have additional risk-enhancing conditions such as autoimmune dysfunction, chronic inflammation, and sex-specific hormonal factors that adversely influence risk. In this review, we focus on cardiometabolic risk factors of obesity and diabetes in heart disease in women, including ischemic heart disease from CMD, HFpEF, and arrythmias. Team-based care to focus on cardiometabolic risk reduction is needed to alter adverse heart disease outcomes in women. Identification, education, treatment, and active surveillance of these dysmetabolic risk factors are imperative in the primary and secondary prevention of heart disease in women.

Metabolic dysfunction-associated steatotic liver disease (MASLD) stands as an independent risk factor for cardiovascular disease (CVD), which is the leading cause of mortality among MASLD patients. The diverse spectrum of cardio-nephro-metabolic and vascular manifestations inherent in MASLD highlights the complex profile of CVD risk associated with this condition. However, current approaches to assessing CVD risk in MASLD lack specificity, predominantly relying on traditional markers. Although it is widely accepted that patients with advanced fibrosis are more prone to CVD risk, recent evidence suggests that this isolated focus may overlook the remarkable phenotypic variability of this CVD risk across the entire MASLD population. Emerging data indicate a progressive escalation of CVD risk in parallel with the severity of MASLD, highlighting the need for precise disease staging to inform accurate risk assessment. To address this challenge, we propose a novel sequential approach to CVD risk assessment in MASLD. While traditional CVD risk factors remain essential, incorporating liver-specific parameters enhances risk stratification and guides targeted interventions to mitigate the substantial burden of cardiovascular disease in this vulnerable population. This approach involves initial screening using FIB-4 and NAFLD fibrosis score, followed by assessment of liver fibrosis with imaging-based non-invasive techniques in individuals at intermediate-high risk for advanced fibrosis and liver fat quantification in low-risk individuals. Future prospective investigations should focus on the simultaneous use of liver biomarkers and imaging modalities to evaluate, in a sex-specific manner, the efficacy of the proposed approach and to determine optimal thresholds of liver fibrosis and steatosis for optimal CVD risk assessment.

Aim: To neurophysiologically characterize the innervation of the sole and assess the diagnostic efficacy of whole plantar nerve (WPN) conduction study in type 2 diabetes mellitus (T2DM) patients and healthy control subjects.

Methods: This single-center prospective observational case-control study involved 51 individuals with T2DM and 34 healthy controls. All subjects underwent validated screening tests for peripheral neuropathy (PN), including proximal and distal sural nerve conduction study and WPN.

Results: The median amplitude of the compound nerve action potentials (CNAPs) and the sensory conduction velocity (SCV) recorded by WPN conduction were significantly lower in patients with T2DM as compared to healthy controls. Sural nerve conduction revealed that both proximal and distal sensory nerve action potentials amplitude and SCV were significantly lower in subjects with diabetes, as compared to healthy controls. As compared with sural nerve conduction, WPN shows a Sensitivity of 77% and a negative predictive value (NPV) of 77%.

Conclusions: WPN conduction study is helpful in characterizing the most distal nerve fibers in patients with T2DM and healthy controls. WPN may represent a useful tool in the diagnosis of length-dependent diabetic polyneuropathy.

Steatotic liver disease (SLD), including metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease (ALD), is the primary cause of illness and mortality. In particular, MASLD affects more than 30% of the global population, while ALD accounts for 5.1% of all diseases and injuries worldwide. The SLD spectrum includes a variety of clinical conditions, from mild fatty liver and inflammation to different stages of liver fibrosis. Additionally, both conditions (MASLD and ALD) can be complicated by hepatocellular carcinoma (HCC), while around one-third of ALD patients can also develop at least one alcohol‐associated hepatitis (AH) episode. Both of these diseases are also associated with multiple extrahepatic complications, such as cardiovascular disease, chronic kidney disease, and malignancies. In MASLD, the rapid rise in global obesity and type 2 diabetes mellitus (T2DM) prevalence due to Westernized lifestyles has led to an increase in the prevalence of MASLD. Thus, the prevention and control of cardiometabolic risk factors (CMRFs) are the cornerstone of its treatment. Hypertension and atherogenic dyslipidemia are also important CMRFs associated with MASLD. Susceptible individuals with MASLD are adversely affected by even a small amount of alcohol consumption (though there is no agreed definition of a small amount), increasing the risk of severe outcomes and a faster progression of liver disease. This review explores factors that play a role in the development of SLD, especially focusing on the management of CMRFs and levels of alcohol use to prevent liver disease progression.

Aim: Obesity is a chronic disease that can lead to many consequences and is directly related to the development of other non-communicable chronic diseases. Since medical treatment for this comorbidity does not always yield satisfactory results, bariatric surgery ends up being the best option for many cases. Thus, the present study aims to analyze long-term weight loss in patients undergoing bariatric surgery, compare weight loss according to the surgical technique performed, and assess the quality of life of patients in the long-term postoperative period.

Methods: This is a descriptive and cross-sectional study analyzing a pre-existing database along with new data collected through telephone interviews according to the modified Bariatric Analysis and Reporting Outcome System (BAROS) questionnaire. Medical records for those who underwent the procedure within the specified period were analyzed.

Results: Records for a total of 208 patients were analyzed, of whom 181 underwent the Bypass surgical technique and 27 underwent the Sleeve technique. Based on the BAROS score, the majority of patients (64.9%) had a "good" or "very good" outcome. Regarding weight loss, 70.68% of the interviewed patients lost over 50% of weight, with this loss occurring in 74.58% of those who underwent Bypass and 44.44% of those who underwent Sleeve. Additionally, 95.2% of respondents reported feeling “better” or “much better” after surgery.

Conclusion: Our results indicate that bariatric surgery is effective both in long-term weight loss and in improving the quality of life of patients. Meanwhile, our study suggests that the BAROS questionnaire may be insufficient to assess long-term quality of life.

Metabolic dysfunction-associated steatotic liver disease (MASLD) [previously termed nonalcoholic fatty liver disease (NAFLD)] is estimated to be the most common chronic liver disease worldwide, affecting 25% of the world’s population and becoming the leading cause of liver transplant in the US. The progression of MASLD from simple hepatic steatosis to the more severe metabolic dysfunction-associated steatohepatitis (MASH) [previously nonalcoholic steatohepatitis (NASH)] has critically important impacts on clinical outcomes. Early detection and staging of disease severity, along with lifestyle modifications and treatment of comorbid conditions, is the best way to prevent the progression or reverse the course of the disease. Although noninvasive imaging and predictive indices are available for the evaluation of hepatic fibrosis, the only way to diagnose MASH remains liver biopsy despite the risk for complications and being less desired by patients. Hence, there is a need to develop noninvasive tests to aid in both the diagnosis and monitoring of MASH, especially with the recent emergence of liver-directed therapy for “at risk” MASH (MASH with NAS ≥ 4 and Stage ≥ F2 Fibrosis). The goal of the current review is to cover the most recent pathophysiology, current diagnostic methods, and recent advances to aid in the diagnosis of MASH.

Bariatric surgery and liver cirrhosis have considerable overlap. Bariatric procedures intend to reduce metabolic dysfunction-associated steatotic liver disease (MASLD); however, these procedures are thought to increase the propensity for alcohol misuse. This may predispose the bariatric surgical patient to a new form of liver insult in the postoperative period. This review explores the complex relationship between obesity and alcohol misuse in the context of the bariatric surgical patient. There is evidence to support the safety of bariatric procedures in compensated cirrhotic patients, with an improvement of liver function and architecture. However, data suggest that after a two-year period, these patients exhibit an increased propensity for alcohol misuse postoperatively, particularly after sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) procedures. A paucity of evidence exists with respect to alcohol-induced liver dysfunction, or MASLD and increased alcohol intake (MetALD) in the post-bariatric surgery patient. This review aims to provide an overview of the current evidence and offer recommendations for further robust studies.