RESUMEN
An acute metabolic complication of diabetes mellitus, especially type 1, is diabetic ketoacidosis (DKA), which is due to an increase in blood ketone concentrations. Sodium/glucose co-transporter-2 inhibitor (SGLT2-i) drugs have been associated with the occurrence of a particular type of DKA defined as euglycemic (euDKA), characterized by glycemic levels below 300 mg/dL. A fair number of euDKA cases in SGLT2-i-treated patients have been described, especially in the last few years when there has been a significant increased use of these drugs. This form of euDKA is particularly insidious because of its latent onset, associated with unspecific symptomatology, until it evolves (progressing) to severe systemic forms. In addition, its atypical presentation can delay diagnosis and treatment. However, the risk of euDKA associated with SGLT2-i drugs remains relatively low, but it is essential to promptly diagnose and manage it to prevent its serious life-threatening complications. In this narrative review, we intended to gather current research evidence on SGLT2i-associated euDKA from randomized controlled trials and real-world evidence studies, its diagnostic criteria and precipitating factors.
RESUMEN
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a highly frequent condition in patients with type 2 diabetes (T2D), but the identification of subjects at higher risk of developing the more severe forms remains elusive in clinical practice. The aim of this study was to evaluate the occurrence and severity of liver fibrosis and its predictive factors in T2D outpatients without a known history of chronic liver disease by using recommended non-invasive methods. METHODS: Consecutive T2D outpatients underwent a set of measurements of clinical and laboratory parameters, FIB-4 score (Fibrosis-4 index), and liver stiffness with controlled attenuation-parameter (CAP) performed by transient elastography (FibroScan) after excluding previous causes of liver disease. RESULTS: Among the 205 T2D outpatients enrolled in the study (median age: 64 years, diabetes duration: 11 years, HbA1c: 7.4%, and BMI: 29.6 kg/m2), 54% had high ALT and/or AST levels, 15.6% had liver stiffness value > 10.1 kPa (severe fibrosis), 55.1% had CAP values > 290 dB/m (severe steatosis), and FIB-4 score was >2 in 11.2% of subjects (>2.67 in 15 subjects). Moreover, 49 (23.9%) T2D patients had clinically meaningful liver harm, with either a FIB-4 score > 2 and/or FibroScan > 10.1 kPa. At regression analysis, BMI, HbA1c, creatinine, and triglycerides values were independent predictors of liver fibrosis. CONCLUSIONS: Liver fibrosis is a frequent finding in T2D outpatients without a known history of liver disease, especially in those with obesity, hypertriglyceridemia, worse glycemic control, and high creatinine levels.
RESUMEN
Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder characterized by motor and non-motor disturbances as a result of a complex and not fully understood pathogenesis, probably including neuroinflammation, oxidative stress, and formation of alpha-synuclein (α-syn) aggregates. As age is the main risk factor for several neurodegenerative disorders including PD, progressive aging of the immune system leading to inflammaging and immunosenescence may contribute to neuroinflammation leading to PD onset and progression; abnormal α-syn aggregation in the context of immune dysfunction may favor activation of nucleotide-binding oligomerization domain-like receptor (NOD) family pyrin domain containing 3 (NLRP3) inflammasome within microglial cells through interaction with toll-like receptors (TLRs). This process would further lead to activation of Caspase (Cas)-1, and increased production of pro-inflammatory cytokines (PC), with subsequent impairment of mitochondria and damage to dopaminergic neurons. All these phenomena are mediated by the translocation of nuclear factor kappa-B (NF-κB) and enhanced by reactive oxygen species (ROS). To date, drugs to treat PD are mainly aimed at relieving clinical symptoms and there are no disease-modifying options to reverse or stop disease progression. This review outlines the role of the TLR/NLRP3/Cas-1 pathway in PD-related immune dysfunction, also focusing on specific therapeutic options that might be used since the early stages of the disease to counteract neuroinflammation and immune dysfunction.
