Association of biomarkers and Barthel Index with occurrence of age-related adverse health outcomes in individuals with diabetes.

AIMS/INTRODUCTION: The clinical significance of age-related biomarkers in patients with diabetes has not been fully elucidated. In this study, we aimed to establish models to predict the progression of aging in patients with diabetes using biomarkers. MATERIALS AND METHODS: This single-center, retrospective cohort study included 115 Japanese patients with diabetes aged ≥60 years. Age-related adverse health outcomes were defined as emergency hospitalization, any increase in the level of nursing care certification, admission to a nursing home or death. The associations of age-related biomarker levels (adiponectin, growth differentiation factor 15 [GDF15], C-X-C motif chemokine ligand 9 and apelin) and clinical indicators with age-related adverse health outcomes were evaluated. Factors that predominantly influenced the occurrence of age-related adverse health outcomes were explored using the Cox proportional hazards model. RESULTS: The mean age of the 115 participants was 73 years, 50.6% were men, the mean body mass index and hemoglobin A1c level were 25.3 kg/m2 and 9.79%, respectively. There were 26 age-related adverse health outcomes during the study period (median 1.93, range 0-4.65 years). In a model combining clinical indicators and biomarkers, including the Barthel Index, GDF15 and adiponectin, the occurrence of age-related adverse health outcomes was found to be significantly associated with GDF15 and Barthel Index. The group with both GDF15 and adiponectin levels higher than the median proved to be significantly higher than the group with both lower. CONCLUSIONS: The measurement of GDF15 and adiponectin levels and the Barthel Index might be useful for predicting age-related adverse health outcomes in patients with diabetes.

Immunohistochemical Profiling of SSTR2 and HIF-2α with the Tumor Microenvironment in Pheochromocytoma and Paraganglioma.

Metastatic pheochromocytomas and paragangliomas (PPGLs) are rare endocrine malignancies with limited effective treatment options. The association between the tumor microenvironment (TME) with somatostatin receptor 2 (SSTR2) and hypoxia-induced factor-2α (HIF-2α) in PPGLs, critical for optimizing combination therapeutic strategies with immunotherapy, remains largely unexplored. To evaluate the association of SSTR2 and HIF-2α immunoreactivity with the TME in patients with PPGLs, we analyzed the expression of SSTR2A, HIF-2α, and TME components, including tumor-infiltrating lymphocytes (CD4 and CD8), tumor-associated macrophages (CD68 and CD163), and PD-L1, using immunohistochemistry in patients with PPGLs. The primary outcome was to determine the association of the immune profiles with SSTR2A and HIF-2α expression. Among 45 patients with PPGLs, SSTR2A and HIF2α were positively expressed in 21 (46.7%) and 14 (31.1%) patients, respectively. The median PD-L1 immunohistochemical score (IHS) was 2.0 (interquartile range: 0-30.0). Positive correlations were observed between CD4, CD8, CD68, and CD163 levels. A negative correlation was found between the CD163/CD68 ratio (an indicator of M2 polarization) and SSTR2A expression (r = -0.385, p = 0.006). HIF-2α expression showed a positive correlation with PD-L1 IHS (r = 0.348, p = 0.013). The co-expression of PD-L1 (HIS > 10) and HIF-2α was found in seven patients (15.6%). No associations were observed between SDHB staining results and the CD163/CD68 ratio, PD-L1, or SSTR2A expression. Our data suggest the potential of combination therapy with immunotherapy and peptide receptor radionuclide therapy or HIF-2α inhibitors as a treatment option in selected PPGL populations.