Prevalence of Nonalcoholic Fatty Liver Disease (NAFLD) and Type 2 Diabetes Mellitus (T2DM) are increasing rapidly worldwide, reaching epidemic proportions. Their association, based on common metabolic risk factors (obesity, insulin resistance (IR), unhealthy lifestyle), brings an additional risk of both hepatic and cardiovascular (CV) adverse clinical outcomes. The terminology of “NAFLD” is stigmatizing to some but not all patients, and a more practical one should be announced soon. Medical strategies can address both diseases simultaneously, as they have crossing pathophysiological mechanisms, mainly IR. Strategies vary from lifestyle intervention and pharmacological options, as more molecules designated for T2DM treatment may be helpful in NAFLD, to surgical procedures. This review focuses on the coexistence of NAFLD and T2DM, pointing out the utility of the appropriate terminology, its prevalence, and mortality rates among the diabetic population. Briefly, we have discussed the main pathophysiological mechanisms and the risk stratification algorithm for the development of NAFLD and nonalcoholic steatohepatitis (NASH) as well as the tools for evaluation of fibrosis. Finally, we have focused on the current therapeutic options for the treatment of NAFLD associated with T2DM.

As the pathophysiologic mechanisms of type 2 diabetes mellitus (T2DM) are discovered, there is a switch from glucocentric to a more comprehensive, patient-centered management. The holistic approach considers the interlink between T2DM and its complications, finding the best therapies for minimizing the cardiovascular (CV) or renal risk and benefitting from the treatment‘s pleiotropic effects. Sodium-glucose cotransporter 2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) fit best in the holistic approach because of their effects in reducing the risk of CV events and obtaining better metabolic control. Additionally, research on the SGLT-2i and GLP-1 RA modification of gut microbiota is accumulating. The microbiota plays a significant role in the relation between diet and CV disease because some intestinal bacteria lead to an increase in short-chain fatty acids (SCFA) and consequent positive effects. Thus, our review aims to describe the relation between antidiabetic non-insulin therapy (SGLT-2i and GLP-1 RA) with CV-proven benefits and the gut microbiota in patients with T2DM. We identified five randomized clinical trials including dapagliflozin, empagliflozin, liraglutide, and loxenatide, with different results. There were differences between empagliflozin and metformin regarding the effects on microbiota despite similar glucose control in both study groups. One study demonstrated that liraglutide induced gut microbiota alterations in patients with T2DM treated initially with metformin, but another failed to detect any differences when the same molecule was compared with sitagliptin. The established CV and renal protection that the SGLT-2i and GLP-1 RA exert could be partly due to their action on gut microbiota. The individual and cumulative effects of antidiabetic drugs on gut microbiota need further research.

The increasing prevalence of gestational diabetes mellitus (GDM) requires non-invasive and precise techniques for evaluating the predisposing risk factors such as visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). According to PRISMA, we developed a systematic review and searched after “visceral adipose tissue AND gestational diabetes” and identified 221 articles on the MEDLINE and Word of Science databases. After assessing them for inclusion criteria and two researchers screened them, 11 relevant articles were included. Although evidence is conflicting, more studies favor using US-determined VAT in GDM prediction. VAT may be more valuable than body mass index or SAT in predicting GDM. VAT can represent an additive factor to the prediction tool of the risk of developing GDM when used in conjunction with other anthropometric or biological parameters or maternal risk factors. US measurements are heterogeneous given different evaluation techniques, cut-off values and inter-operator variation. A significant limitation is the lack of a gold standard to identify GDM confidently. Pregnant women may benefit from early monitoring and preventive care if classified as high risk for GDM early in the gestational period. US-measured VAT during the first trimester of pregnancy seems a valuable and inexpensive screening approach to predict GDM development later in pregnancy, either by itself or if used in conjunction with other clinical and biological parameters.

In this paper, we aim to evaluate the efficacy of antidiabetic cardioprotective molecules such as Sodium-Glucose Cotransporter-2 Inhibitors (SGLT-2i) and Glucagon-like Peptide 1 Receptor Agonists (GLP-1 RAs) when used with other glucose-lowering drugs, lipid-lowering, and blood pressure (BP)-lowering drugs in a real-life setting. A retrospective, observational study on 477 patients admitted consecutively in 2019 to the outpatient clinic of a tertiary care unit for Diabetes Mellitus was conducted. Body mass index (BMI), blood pressure (BP) (both systolic and diastolic), and metabolic parameters, as well as A1c hemoglobin, fasting glycaemia and lipid profile, including total cholesterol (C), HDL-C, LDL-C and triglycerides), were evaluated at baseline and two follow-up visits were scheduled (6 months and 12 months) in order to assess the antidiabetic medication efficacy. Both SGLT-2i and GLP-1 RAs were efficient in terms of weight control reflected by BMI; metabolic control suggested by fasting glycaemia and A1c; and the diastolic component of BP control when comparing the data from the 6 and 12-month visits to the baseline, and when comparing the 12-month visit to the 6-month visit. Moreover, when comparing SGLT-2i and GLP-1 RAs with metformin, there are efficacy data for SGLT-2i at baseline in terms of BMI, fasting glycaemia, and HbA1c. In this retrospective study, both classes of cardioprotective molecules, when used in conjunction with other glucose-lowering, antihypertensive, and lipid-lowering medications, appeared to be efficient in a real-life setting for the management of T2DM.

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent in patients with type 2 diabetes (T2D) and is associated with increased cardiovascular risk. However, the relative contribution of traditional cardiometabolic risk factors (CMRFs), hepatic fibrosis markers, and antidiabetic therapies to atherosclerosis remains unclear. Methods: We conducted a cross-sectional study including 46 patients with T2D and MASLD. Atherosclerotic cardiovascular disease (ASCVD) was defined as the presence of carotid atheromatosis, stroke, peripheral arterial disease, or ischemic heart disease, as assessed by imaging-based parameters. Clinical, metabolic, and treatment-related variables were analyzed, including age, Hemoglobin A1c (HbA1c), lipid profile, hepatic fibrosis indices such as Fibrosis-4 index (FIB-4), and antidiabetic therapies (sodium–glucose cotransporter-2 inhibitors (SGLT2is), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and insulin). Multivariable regression models and receiver operating characteristic (ROC) curve analyses were used to evaluate associations and discriminative performance. Results: Traditional CMRFs were more strongly associated with ASCVD than hepatic fibrosis markers or antidiabetic therapies. Age was associated with ASCVD in several exploratory models, although this association was attenuated in the fully adjusted model. HbA1c showed the highest discriminative performance (AUC 0.77), indicating that chronic glycemic exposure is a major determinant of vascular disease in this cohort. In contrast, FIB-4 was not associated with ASCVD and did not improve model performance. Antidiabetic therapies, including SGLT2i and GLP-1 RAs, were not independently associated with ASCVD. Insulin therapy was more frequent among patients with ASCVD, but was not independently associated after adjustment. Conclusions: In patients with T2D and MASLD, ASCVD appears to be associated with traditional CMRFs, particularly chronic glycemic exposure, rather than hepatic fibrosis markers or treatment status. These findings highlight the central role of metabolic control in cardiovascular risk and suggest that the contribution of liver-related markers and therapeutic interventions may be more relevant in longitudinal settings.

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent among patients with type 2 diabetes (T2D) and has been increasingly recognized as a potential contributor to cardiovascular (CV) disease. However, the relationship between MASLD and subclinical/clinical atherosclerosis remains controversial, with inconsistent findings across imaging modalities and study populations. Methods: A systematic review was conducted according to PRISMA guidelines and registered in PROSPERO (CRD420261347480). Literature searches were performed across the PubMed, Scopus, and Web of Science library databases from 1 January 2016 to 27 March 2026, using the terms: “MASLD AND (type 2 diabetes OR type 2 diabetes mellitus OR T2DM) AND atherosclerotic plaque” for each of the three databases. Inclusion criteria comprised original full-text English-language studies, published in the last 10 years and conducted in adults, reporting data regarding the evaluation of atherosclerosis in patients with T2D and MASLD/NAFLD. Exclusion criteria are letters to the editor, expert opinions, case reports, conference or meeting abstracts, reviews, and redundant publications; having unclear or incomplete data; and being performed in vitro (cell cultures) or in animal models. The quality of included studies was assessed using the Newcastle–Ottawa Scale. Results: The included studies, predominantly cross-sectional and a single longitudinal study, as well as different modalities of evaluating atherosclerosis, showed heterogeneous findings. MASLD is associated with increased carotid plaque progression, including in lean individuals. Its relationship with carotid intima-media thickness (CIMT) is inconsistent across studies, with some reporting higher values and others finding no significant association after adjustment. Hepatic fibrosis appears more strongly linked to vascular aging than steatosis alone, with variability likely due to differences in study methods and populations. Conclusions: The presence of both MASLD and T2D may be associated with atherosclerosis across different stages, from subclinical changes to clinically manifest disease, particularly at more advanced stages such as plaque presence or progression, whereas its relationship with early markers like pulse wave velocity or CIMT remains inconsistent. Liver fibrosis may represent a stronger determinant of atherosclerosis than hepatic steatosis alone. Although the evidence base is limited and largely derived from a small number of predominantly cross-sectional studies, further standardized and prospective research is warranted to better define these relationships and evaluate CV risk stratification in patients with T2D.