David Emilio Barajas Galindo

Background/Objectives: Type 2 diabetes mellitus (T2DM) is a multisystemic disease with overlapping metabolic, renal, and cardiovascular effects. Within the Diabetic@ project, which aims to characterize individuals with T2DM using real-world data extracted from electronic health records (EHRs), this substudy sought to develop a predictive model for two-year heart failure (HF) risk. Methods: Multicenter, retrospective study including T2DM individuals across eight Spanish hospitals (2013–2018). Data were extracted exclusively from EHRs’ unstructured free text using clinical natural language processing (cNLP) and mapped to SNOMED CT. At inclusion, individuals were categorized as having or not prevalent HF (pHF). Predictive modeling was performed in non-pHF to assess two-year risk of developing HF, termed incident HF (iHF). Logistic regression (LR), decision trees, random forest, and XGBoost were compared, selecting for accuracy and interpretability. Results: Of 588,756 individuals with T2DM, 84,197 (14.3%) had pHF. Among non-pHF, 353,371 (60%) were used for model development (90.7% training, 9.3% validation). iHF occurred in 13.6% of the training set and 11.4% of the validation set. Ischemic heart disease was present in 16.2% overall, 37.9% in pHF, and 12.6% in non-pHF. Glycosylated hemoglobin data was rarely reported (<15%). LR achieved the best performance (AUC-ROC 0.73) using 27 predictors. Reduced 12- and clinically refined 9-predictor models performed similarly, with the latter implemented in a web-based tool. Conclusions: Unstructured data from EHRs enabled development of a two-year HF risk model for individuals with T2DM, underscoring the potential of cNLP for risk stratification across the cardiovascular–renal–metabolic spectrum.

This pilot study aimed to investigate the role of the Klotho/FGF (fibroblast growth factor) system in biological features associated with premature aging, particularly inflammation and muscle dysfunction, focusing on its association with inflammatory markers, body composition, and muscle function in middle-aged adults. A total of 45 participants aged 50–60 years were enrolled, including 30 patients with obesity (22F/8M) and 15 healthy controls (11F/4M). Comprehensive assessments were conducted, including body composition analysis and muscle function tests. Evaluations of protein expression of Klotho, β-Klotho, FGF19, FGF21, FGF23, TFN-α and IL-10 were assessed in peripheral blood mononuclear cells (PBMCs). A Principal Component Analysis (PCA) was carried out to explore the relationships among variables. Significant differences were observed between the obese and control groups, with obese individuals exhibiting lower levels of Klotho and higher levels of TFN-α. The PCA revealed that higher Klotho levels were positively associated with better muscle function and lower inflammatory markers. These associations suggest that Klotho-related alterations may reflect biological processes linked to inflammation and muscle dysfunction in obesity. These findings suggest that alterations in the Klotho/FGF system may reflect biological pathways commonly associated with aging-related phenotypes in obesity, rather than direct measures of chronological aging. Given the exploratory design and limited sample size, these findings should be interpreted as hypothesis-generating rather than evidence of causal mechanisms.

The Klotho gene is recognized for its anti-aging properties. Its downregulation leads to aging-like phenotypes, whereas overexpression can extend lifespan. Klotho protein exists in three forms: α-klotho, β-klotho and γ-klotho. The α-klotho has two isoforms: a membrane-bound form, primarily in the kidney and brain, and a secreted klotho protein present in blood, urine, and cerebrospinal fluid. Klotho functions as a co-receptor for fibroblast growth factor-23 (FGF23), regulating phosphate metabolism. The membrane-bound form controls various ion channels and receptors, while the secreted form regulates endocrine FGFs, including FGF19 and FGF21. The interaction between β-klotho and FGF21 in muscle is critical in the development of sarcopenic obesity. This systematic review, registered in PROSPERO and conducted following PRISMA guidelines, evaluates klotho levels in individuals with obesity or sarcopenic obesity. The study includes overweight, obese, and sarcopenic obese adults compared to those with a normal body mass index. After reviewing 713 articles, 20 studies were selected, including observational, cross-sectional, cohort studies, and clinical trials. Significant associations between klotho levels and obesity, metabolic syndrome (MS), and cardiovascular risk were observed. Exercise and dietary interventions positively influenced klotho levels, which were linked to improved muscle strength and slower decline. Klotho is a potential biomarker for obesity, MS, and sarcopenic obesity. Further research is needed to explore its mechanisms and therapeutic potential.

Introduction: This study aimed to compare efficacy and safety of ultra-rapid-acting insulin analogs (URAIs; faster aspart [FAsp], ultra-rapid lispro [URLi], and technosphere insulin [TI]) with rapid-acting insulin analogs (RAI) in individuals with type 1 (T1D) or type 2 diabetes (T2D). Methods: Searching for randomized control trial comparing the effects of URAI versus RAI that lasted at least 12 weeks, we initially selected 15 studies for analysis. Three studies involving TI were excluded due to a high degree of heterogeneity. The final meta-analysis included only 12 studies with either FAsp or URLi. Results: Mealtime URAI significantly reduced overall early 1 h postprandial glycemia in individuals with T1D (−20.230 mg/dL [95% confidence interval, 95% CI −24.040 to −16.421]; P < 0.001; I ² = 33.42%) and those with T2D (−9.138 mg/dL [95% CI −12.612 to −5.663]; P < 0.001; I ² = 0%). However, the significant reduction in 2 h postprandial glucose remained only in individuals with T1D (−17.620 mg/dL [95% CI −26.047 to −9.193]; P < 0.001; I ² = 65.88%). These benefits were lost when URAI was administered postmeal. At 24–26 weeks, there was no significant difference in HbA1c between groups, but at 52 weeks, a slight reduction in HbA1c with mealtime URAI was observed (−0.080% [95% CI −0.147 to −0.013]; P = 0.019; I ² = 0%). No difference in weight or the rate of severe or confirmed hypoglycemia was observed. Only individuals with T1D showed a small, but significant increase in early 1-h hypoglycemia with URAI (1.468 [95% CI 1.235 to 1.747]; P < 0.001; I ² = 0%). Conclusion: Mealtime URAI improves 1 and 2 h postprandial glycemic control compared to RAI without increasing hypoglycemia or weight gain.

Introduction: COVID‐19 has a wide spectrum of clinical severity and there is evidence that SARS‐Cov2 affects several organs and systems. Among the organs affected since the beginning of the pandemic, the relationship between SARS‐CoV‐2 infection and thyroid involvement has been demonstrated. Novel and highly effective messenger RNA and DNA‐based vaccines have been rapidly developed to decrease SARS‐CoV‐2 morbidity and mortality. Early after mass vaccinations, cases of thyroid dysfunction mainly including episodes of subacute thyroiditis, began to be reported like adverse effects. The objective of this study is to determine the impact of the pandemic, both due to SARS‐CoV2 infections and vaccinations, on the incidence of Graves' disease (GD).Methods: Cross‐sectional, observational study comparing incidence of GD in adult population (over 18 years) before (2017–2019) and after (2020–2021) Covid‐19 pandemic. Only patients with new cases of GD, no relapsed diseases, were included. SARS‐CoV‐2 diagnosis was based on nucleic acid amplification tests on nasopharyngeal swabs or measurement of class M and class G antibodies to SARS‐CoV‐2 by highly specific assays. Data on incidence and vaccination related to SARS‐CoV‐2 infection were obtained from the public records from Castilla y León autonomous regional government.Results: A total of 180 subjects were diagnosed and treated for GD during the study period. We observed a notable increase in expected GD cases in 2021 compared to 2017–19. The number of GD cases was higher in the second (Q2) quarter. Among 2021 GD cases, 42/66 patients (63.6%) had been vaccinated in the 90 days before symptom onset, but none of them in the first quarter of the year. A total of 97.7% were women with a mean age of 48.9 (SD 15.6) years. On average they were diagnosed 19.9 (SD 17.6) days after receiving the vaccine. A total of 7/42 (16.67%) had another previously diagnosed autoimmune disease and 11/42 (26.19%) were smokers.Discussion: Our results show a notable increase in the incidence of GD during the year 2021, specially in women with a history of smoking. Hyper activation of the immune system induced by SARS‐CoV2 and by the recently released SARS‐COV‐2 vaccines has been highlighted in recent months. To assess whether this observed increase in the incidence of GD is sustained in the coming years or has simply been a precipitous trigger for individuals who were already predisposed to develop the disease, future studies will be needed.