Background This study aims to investigate the differential miRNA expression profile between the visceral white adipose tissue and the skeletal muscle of people with obesity undergoing bariatric surgery. Methods Skeletal muscle and visceral adipose tissue samples of 10 controls and 38 people with obesity (50% also with type 2 diabetes) undergoing bariatric surgery were collected. miRNA expression profiles were analyzed using Next-Generation Sequencing and subsequently validated using RT-PCR. Results Approximately 69% of miRNAs showed similar expression in both tissues, however, 55 miRNAs were preferentially expressed in visceral adipose tissue and 53 in skeletal muscle. miR-122b-5p was uniquely identified in skeletal muscle, while miR-1-3p and miR-206 were upregulated in skeletal muscle. Conversely, miR-224-5p and miR-335-3p exhibited upregulation in visceral adipose tissue. Notably, distinctions related to the presence of type 2 diabetes were observed solely in the expression of miR-1-3p and miR-206 in visceral adipose tissue. Conclusions This is the first study unveiling distinct miRNA expression profiles in paired samples of visceral adipose tissue and skeletal muscle in humans. The identification of obesity-specific miRNAs in these tissues opens up promising avenues for research into potential biomarkers for obesity diagnosis and treatment.

Metformin is a well-established drug for the treatment of type 2 diabetes; however, the mechanism of action has not been well described and many aspects of how it truly acts are still unknown. Moreover, regarding in vitro experiments, the glycaemic status when metformin is used is generally not considered, which, added to the suprapharmacological drug concentrations that are commonly employed in research, has resulted in gaps of its mechanism of action. The aim of this study was to determine how glucose and metformin concentrations influence cell culture. Considering that diabetic retinopathy is one of the most common complications of diabetes, a retinal pigment epithelial cell line was selected, and cell viability and proliferation rates were measured at different glucose and metformin concentrations. As expected, glucose concentration by itself positively influenced cell proliferation rates. When the metformin was considered, results were conditioned, as well, by metformin concentration. This conditioning resulted in cell death when high concentrations of metformin were used under physiological concentrations of glucose, while this did not happen when clinically relevant concentrations of metformin were used independently of glucose status. Our study shows the importance of in vitro cell growth conditions when drug effects such as metformin’s are being analysed.

Aims: Obesity is characterised by pathological alterations in visceral white adipose tissue (vWAT) that may contribute to the development of type 2 diabetes (T2D). While microRNAs (miRNAs) are key post‐transcriptional regulators, comprehensive human vWAT profiling across metabolic states remains limited. This study characterised vWAT miRNA expression in lean, obese and obese+T2D individuals to identify obesity‐driven regulatory networks associated with metabolic dysfunction. Methods: Deep miRNA sequencing was performed on vWAT samples from a discovery cohort comprising lean controls and individuals with obesity (with and without T2D). Findings were validated via RT‐qPCR in an independent replication cohort. Differentially expressed miRNAs were bioinformatically integrated with matched mRNA transcriptomic data to construct putative functional regulatory associations and identify enriched pathways underlying metabolic impairment. Results: The dominant transcriptomic signal was driven by obesity rather than T2D status, with substantial overlap between obese subgroups in principal component analyses. miR‐141‐3p, miR‐200b‐3p, miR‐12 136 and miR‐585‐3p showed consistent differential expression associated with obesity. miR‐141‐3p and miR‐200b‐3p were upregulated and inversely associated with metabolic stress–related genes, including TF and FBXO32. Integrated miRNA–mRNA analyses revealed putative regulatory associations involving inflammation, lipid metabolism, insulin signalling and iron homeostasis. These associations were robust across progressive covariate adjustment models for age and sex. Conclusions: This study provides a comprehensive characterisation of the vWAT miRNA landscape predominantly shaped by obesity, with T2D contributing comparatively subtle additional variation. We identified putative miRNA–mRNA regulatory associations that may contribute to pathological adipose tissue dysfunction. These findings highlight candidate molecular regulators worthy of further functional investigation in the context of obesity and T2D.

Background/Objectives: Cardiovascular disease remains a leading cause of mortality in Spain, with dyslipidemia being a major modifiable risk factor. Lipid-lowering therapy (LLT) is essential for cardiovascular risk reduction, but regional disparities in prescription patterns and LDL-C control persist. This study analyzes LLT prescription trends in Spain in 2019 and 2023, assessing temporal, demographic and regional differences. Methods: A retrospective observational study was conducted using the Spanish Primary Care Clinical Database (BDCAP), which contains 4.8 million anonymized primary care records. LLT prescriptions for primary prevention were analyzed by sex, age, community size, and employment status. Trends from 2019 to 2023 were evaluated, distinguishing between monotherapy and combination therapy. Results: In 2023, 5.8 million individuals received LLT for primary prevention (139.6 per 1000). Women had higher treatment rates than men after age 60. Treatment rates were highest in small communities and among retirees. The use of combination therapies almost doubled from 2019 to 2023, achieving better LDL-C control (56.4% vs. 41.5% with monotherapy, p < 0.001). Regional disparities were evident, with the lowest treatment rates in Cataluña and País Vasco and the highest in Galicia. Conclusion: LLT prescription patterns in Spain show remarkable socioeconomic and regional disparities. The increase in combination therapy suggests a shift towards more intensive lipid management. Standardized guidelines and targeted interventions are needed to ensure equitable and effective dyslipidemia treatment.

Aims: To investigate the association of post‐oral glucose tolerance test (OGTT) hypoglycaemia with clinical features, incident diabetes and mortality. Materials and Methods: This population‐based cohort study included 2924 adults (median age 49 years, 1680 women) without known diabetes who underwent a 75‐g OGTT as part of the Di@bet.es Study. Metabolic, demographic and lifestyle variables were collected. Serum glucose and insulin concentrations at 0, 30 and 120 min during the OGTT were obtained, allowing insulin resistance estimation using the HOMA‐IR and the Matsuda Index. Participants were grouped according to serum glucose at 120 min: < 70 mg/dL (post‐OGTT hypoglycaemia), 70 to < 140 mg/dL (normal result), 140 to < 200 mg/dL, and ≥ 200 mg/dL. The incidence of diabetes (median follow‐up, 7.5 years) and mortality (median follow‐up, 14.5 years) were assessed. Results: Participants with post‐OGTT hypoglycaemia ( n = 327, 11.1%) were younger, leaner, less insulin resistant and more frequently active smokers. Despite having the lowest serum glucose at 0, 30 and 120 min, and the lowest serum insulin at 0 and 120 min, these participants tended to have the highest serum insulin concentrations at 30 min. Participants with post‐OGTT hypoglycaemia had the lowest incidence of diabetes and mortality, although these associations were attenuated after adjusting for confounders (such as age, sex, body mass index and physical activity) and when compared specifically with the normal result group. Conclusions: Post‐OGTT hypoglycaemia is more frequent in smokers, younger individuals, and those with a favourable metabolic profile. Post‐OGTT hypoglycaemia acts as a marker of protection for incident diabetes and mortality. Preserved early insulin secretion together with good insulin sensitivity could explain post‐OGTT hypoglycaemia.

Obesity-driven type 2 diabetes (T2D) is characterized by pathological alterations in visceral white adipose tissue (vWAT). While microRNAs (miRNAs) are key post-transcriptional regulators, comprehensive human vWAT profiling across metabolic states remains limited. This study characterized vWAT miRNA expression in lean, obese, and obese+T2D individuals to identify regulatory networks associated with metabolic failure. Deep miRNA sequencing was performed on vWAT samples from a discovery cohort, followed by validation via qPCR in an independent replication cohort. Differentially expressed miRNAs across the three groups were bioinformatically integrated with matched mRNA transcriptomic data to construct functional regulatory modules and identify enriched pathways underlying metabolic impairment. Several miRNAs exhibited robust and reproducible differential expression between obesity and obesity with T2D. Integrated miRNA–mRNA analyses revealed coherent regulatory modules involving inflammation, lipid metabolism, insulin signaling, and iron homeostasis. Specifically, miR-141-3p, miR-200b-3p, miR-15b-3p, miR-12136, and miR-585-3p showed consistent differential expression. Notably, miR-141-3p and miR-200b-3p were markedly upregulated and inversely associated with metabolic stress–related genes, including TF and FBXO32 . Several miRNAs correlated with clinical markers of metabolic dysfunction, supporting their biomarker potential. By comparing lean, obese, and diabetic populations, this study provides a comprehensive characterization of the vWAT miRNA landscape and identifies specific miRNA–mRNA regulatory circuits that orchestrate the transition from healthy adiposity to pathological adipose tissue dysfunction. These findings pinpoint novel molecular drivers of type 2 diabetes progression and offer potential targets for therapeutic intervention in metabolic endocrine disorders.