Diabetes mellitus (DM) is a chronic non-communicable disease associated with macroangiopathy and microangiopathy, with disabling or even life-threatening complications. In the present study, we aimed to analyze the association between insulin resistance (IR) and inflammation biomarkers and peripheral arterial disease (PAD) and diabetic peripheral neuropathy (DPN), respectively. The study had a cross-sectional design and evaluated a panel of IR related indices and inflammatory biomarkers commonly used in clinical and epidemiological research, including the triglyceride-glucose (TyG) index and its obesity related derivates, cholesterol, HDL, glucose (CHG) index, lipid-derived ratios, and composite inflammatory indices, together with interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα) and C-reactive protein (CRP) in 110 subjects, according to the presence or absence of PAD and DPN, respectively. In the PAD (+) group, TyG-waist-to-height-ratio (TyG−WHtR) and CHG recorded significantly increased values (p = 0.042, respectively p < 0.001), compared to PAD (−). CHG recorded significantly increased values in DPN (+) subjects (p = 0.007). In addition, in the PAD (+) subjects, IL-6 and systemic immune inflammation index (SII) recorded significantly increased values (p = 0.026, respectively, p = 0.015) and TNFα, monocyte to lymphocyte ratio (MLR) and C-reactive protein to albumin ratio (CAR) recorded significantly increased values in DPN (+) subjects (p = 0.028, respectively, p = 0.008, and p = 0.038). We developed a score with a good discriminatory performance for PAD and DPN, including DM duration, TyG−WHtR, SII, MLR and CAR (AUROC 0.822 in PAD, respectively 0.848 in DPN, p < 0.001). A composite score combining IR and inflammatory biomarkers showed strong discriminatory performance for lower limb complications in type 2 diabetes, suggesting a valuable tool for early detection and prevention.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as one of the greatest challenges for the modern public health system and serves as the foundation for the development of advanced stages, such as metabolic dysfunction-associated steatohepatitis (MASH), which may progress to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). MASLD and type 2 diabetes mellitus (T2DM) mutually exacerbate one another. MASLD increases the incidence of T2DM and the risk of complications in patients already affected. T2DM accelerates progression to MASH, which has become the second leading cause of liver transplantation and end-stage liver disease, and is associated with hepatic decompensation, cirrhosis, HCC, chronic kidney disease, and cardiovascular disease. MASLD and MASH are strongly linked to T2DM and obesity, pathogenesis including genetic polymorphisms, environmental factors, and multiple metabolic disturbances: insulin resistance (IR), gut dysbiosis, altered adipokine signaling, such as reduced adiponectin alongside increased pro-inflammatory cytokines. Inflammation plays a central role in the development of HCC in MASH, even in the absence of significant fibrosis. The Fibrosis-4 index (FIB-4) should be used as a first-line noninvasive tool to assess fibrosis risk. Additionally, ultrasound-based transient elastography (FibroScan) supports clinicians in assessing steatosis and fibrosis severity. Histologically, MASH is characterized by steatosis, lobular inflammatory changes, and ballooning degeneration of hepatocytes, with or without associated fibrosis. Accurately diagnosing and stratifying MASLD based on fibrosis risk is crucial to identify patients who may benefit from pharmacological treatment or can be managed only with lifestyle interventions. Patients should attain above 10% weight loss through lifestyle modifications. Resmetirom is recommended in F2/F3 fibrosis stages. For treating T2DM, glucagon-like peptide-1 receptor agonists and coagonists, sodium–glucose cotransporter-2 inhibitors, metformin (if glomerular filtration rate exceeds 30 mL/min), and insulin (in decompensated cirrhosis) are preferred. Clinical insights derived from trials are expected to optimize quality of life and long-term outcomes in patients with MASH.

Obstructive sleep apnea (OSA) is strongly associated with hypertension, yet the apnea–hypopnea index (AHI), while it defines the presence and frequency of respiratory events, predicts cardiovascular risk less reliably in the individual patient than metrics that incorporate the depth and duration of hypoxic exposure. Patients with comparable AHI values can differ substantially in nocturnal hypoxemia, sympathetic activation, ambulatory blood pressure behavior, and target-organ damage, exposing a persistent gap between respiratory classification and cardiovascular prognosis. This review synthesizes current evidence on the mechanisms linking OSA to hypertension, intermittent hypoxia, chemoreflex-mediated sympathetic overactivity, renin–angiotensin–aldosterone system activation, hypoxia-associated insulin resistance and examines emerging metrics, including hypoxic burden, oxygen desaturation index, and ambulatory blood pressure monitoring, that capture cardiovascular risk more accurately than AHI alone. We describe six cardiovascular phenotypes of hypertension in OSA: resistant, nocturnal, non-dipping/reverse-dipping, masked, and morning-surge hypertension, alongside hypertension-mediated target-organ damage, each with distinct mechanisms, prognosis, and treatment response. Because intermittent hypoxia and sympathetic activation are also implicated in insulin resistance and MASLD, this shared metabolic pathway is integrated throughout rather than treated as an incidental comorbidity. Building on this evidence, we propose a phenotype-oriented clinical framework spanning cardiovascular screening, multidomain phenotyping, risk stratification, and personalized therapy intended to complement, not replace, AHI-based diagnosis and current hypertension guidelines. This framework is presented as a conceptual, expert-derived proposal intended to structure clinical reasoning, and it has not been derived from or validated in an independent cohort. We conclude with future directions, including digital biomarkers, multimodal imaging, and artificial intelligence-assisted phenotyping, as pathways toward precision cardiovascular medicine in hypertensive patients with OSA.

The coronavirus disease 2019 (COVID-19) pandemic has had an unprecedented impact on public health. In the present study, we aimed to analyze the association of certain inflammatory biomarkers with severe COVID-19 and to explore the role of diabetes mellitus (DM) and vaccination status in relation to COVID-19 severity, intensive care need and mortality. Associated comorbidities (DM, obesity, cardiovascular, neurological, endocrine, hepatic, renal, pulmonary, rheumatological, psychiatric, hematological diseases, cancer and HIV), as well as inflammatory biomarkers, like ferritin, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), fibrinogen, lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) were analyzed in 866 subjects, according to vaccination status. In unvaccinated subjects, the highest AUROC curve for severe COVID-19 was recorded for CRP (0.668), and in the vaccinated group, the highest was recorded for SII (0.694). In age- and comorbidity-adjusted analyses, diabetes mellitus was associated with higher odds of severe COVID-19, ICU admission, and mortality among unvaccinated patients. This analysis was not feasible in the vaccinated group because of the very low number of unfavorable outcomes. These findings emphasize the potential role of vaccination in attenuating the excess risk linked to comorbidities—particularly diabetes mellitus—and support the use of accessible inflammatory biomarkers for early risk stratification. The results should be interpreted within the specific epidemiological phases of the pandemic and in the context of the observational study design.

The disproportionately severe disease course of diabetic patients with SARS-CoV-2 infection was repeatedly observed by clinicians during the COVID-19 pandemic. The overlap between metabolic impairment, viral pathophysiology, and chronic inflammation created a pattern that urged deeper examination. The aim of this paper was to review and synthesize evidence regarding the interaction between diabetes mellitus and COVID-19. We synthesized evidence across mechanistic pathways (immune dysregulation, chronic inflammation, ACE2/DPP-4-related signaling, endothelial dysfunction, and pancreatic involvement) and key clinical outcomes (severity, intensive care unit (ICU) admission, mortality, dysglycaemia/new-onset diabetes, and DKA). This systematic search was conducted in PubMed, Clinical Key, and Google Scholar. The eligibility criteria included papers on adults (≥18 years) with pre-existing diabetes mellitus (type 1 or type 2) or newly diagnosed diabetes/hyperglycemia and confirmed SARS-CoV-2 infection, published between January 2020 and October 2025, in English language. The PRISMA guidelines were used for data extraction. We identified 412 articles, out of which only 30 met all the inclusion criteria. Diabetes was consistently evoked as a major risk factor for severe COVID-19, being associated with higher susceptibility to pneumonia, respiratory failure, ICU admission, and mortality. The explanation lies in the impaired immune system, endothelial dysfunction, and metabolic repercussions imposed by hyperglycemia. Several antidiabetic drugs appeared protective in multiple cohorts. In conclusion, the accumulated evidence underscores the tight interplay between metabolic disease and COVID-19. Essentially, the clinical management of these patients would be a thoughtful selection of antidiabetic therapy and close metabolic monitoring.

Obstructive sleep apnea (OSA) and metabolic dysfunction-associated steatotic liver disease (MASLD) frequently coexist and share a common cardiometabolic substrate through a shared cardiometabolic substrate. This narrative review critically appraises the epidemiological, experimental, and interventional evidence proposed to link chronic intermittent hypoxia (CIH) and sleep fragmentation to hepatic steatosis, steatohepatitis, and fibrosis. We summarize the candidate mechanisms, including mitochondrial oxidative stress, hypoxia-inducible factor 1-alpha signaling, sympathetically driven lipolysis, and Kupffer and stellate cell activation and then examine the limits of the evidence supporting them: hypoxia-induced hypophagia and the scarcity of pair-fed controls in rodent models, species differences in the physiological response to hypoxia, publication bias, common-cause confounding by age and systemic inflammation, and the rarity of progressive liver disease in lean patients with anatomically driven OSA. We further review non-invasive diagnostic tools, polysomnographic hypoxemia indices, transient elastography, METS-IR, FIB-4, and emerging biomarkers, such as omentin-1 and follistatin-like 1, that enable bidirectional screening between sleep and hepatology clinics. Finally, we discuss therapeutic strategies, including continuous positive airway pressure, structured weight loss, and incretin-based pharmacotherapy (GLP-1 and dual GIP/GLP-1 receptor agonists), highlighting recent phase 3 evidence for tirzepatide in OSA and semaglutide in metabolic dysfunction-associated steatohepatitis. Current evidence supports CIH as a context-dependent amplifier of liver injury in patients with pre-existing metabolic dysfunction rather than as an established independent cause of MASH. This interpretation still justifies integrated screening and treatment pathways, while identifying the study designs needed to test causality directly.