Insulin resistance (IR), marked by reduced cellular responsiveness to insulin, and obesity, defined by the excessive accumulation of adipose tissue, are two intertwined conditions that significantly contribute to the global burden of cardiometabolic diseases. Adipose tissue, beyond merely storing triglycerides, acts as an active producer of biomolecules. In obesity, as adipose tissue undergoes hypertrophy, it becomes dysfunctional, altering the release of adipocyte-derived factors, known as adipokines. This dysfunction promotes low-grade chronic inflammation, exacerbates IR, and creates a hyperglycemic, proatherogenic, and prothrombotic environment. However, the fundamental cause of these phenomena remains unclear. This narrative review points to hypoxia as a critical trigger for the molecular changes associated with fat accumulation, particularly within visceral adipose tissue (VAT). The activation of hypoxia-inducible factor-1 (HIF-1), a transcription factor that regulates homeostatic responses to low oxygen levels, initiates a series of molecular events in VAT, leading to the aberrant release of adipokines, many of which are still unexplored, and potentially affecting peripheral insulin sensitivity. Recent discoveries have highlighted the role of hypoxia and miRNA-128 in regulating the insulin receptor in visceral adipocytes, contributing to their dysfunctional behavior, including impaired glucose uptake. Understanding the complex interplay between adipose tissue hypoxia, dysfunction, inflammation, and IR in obesity is essential for developing innovative, targeted therapeutic strategies.

Background: Hashimoto’s thyroiditis (HT) is a common autoimmune thyroid disorder characterized by elevated anti-thyroid peroxidase (A-TPO) antibodies. HT frequently coexists with other autoimmune conditions, which are marked by organ-specific and non-organ-specific autoantibodies, reflecting a deregulated immune response. However, the burden and clinical significance of these circulating autoantibodies in adult patients with HT remains unclear. Methods: A cross-sectional study was conducted at the University Hospital “R. Dulbecco” in Catanzaro, Italy, from November 2023 to May 2024, involving 200 euthyroid adults. The study population comprised 100 A-TPO-positive HT patients and 100 A-TPO-negative controls, matched for age and sex. Laboratory assessments included thyroid function tests and detection of autoantibodies [e.g., antinuclear antibodies (ANA), anti-parietal cell antibodies (APCA), and anti-neutrophil cytoplasmic antibodies (ANCA)]. Cytokine profiles were also measured using sensitive chemiluminescent multi-array technology. Results: HT patients were predominantly female (77.0%) with a median age of 56 years. Compared to controls, HT patients had higher median thyroid stimulating hormone (TSH) levels (2.215 vs. 1.705 μIU/mL, p = 0.025). Circulating autoantibodies were more prevalent in the HT group, with higher rates of APCA positivity (16.3% vs. 4.1%, p = 0.008) and atypical ANCA positivity (27.3% vs. 10.2%, p = 0.003). This suggests an increased risk for autoimmune gastritis and systemic inflammation. Additionally, HT patients with positive atypical ANCA showed elevated inflammatory cytokines, particularly interleukin-1 alpha (IL-1α), in female patients (p = 0.035). Conclusions: HT is significantly associated with a higher prevalence of circulating autoantibodies, such as APCA and atypical ANCA, which may indicate a heightened risk for autoimmune gastritis and broader autoimmune involvement. Detecting these autoantibodies in HT patients could serve as markers for more severe autoimmune dysfunction. These findings emphasize the need for proactive screening, especially in older patients and those with elevated A-TPO levels. Further research is essential to better understand the clinical implications and develop targeted management strategies for these patients.

Introduction: Differentiated thyroid carcinoma (DTC) is frequently found in conjunction with autoimmune thyroid disorders, particularly Hashimoto’s thyroiditis (HT). This study investigates the impact of coexisting HT on the persistence of an indeterminate response to therapy due to positive anti-thyroglobulin antibodies (AbTg), measured via competitive immunoassay, in a consecutive patient series from Calabria, Southern Italy. Methods: This retrospective longitudinal study analyzed 259 consecutive DTC patients managed at the Endocrinology Unit of Renato Dulbecco Hospital (Catanzaro, Italy) up to 2023. Patients with medullary and undifferentiated thyroid carcinoma, partial thyroidectomy, less than six months of post-operative monitoring, or missing clinical data were excluded. Demographic information, histological findings, initial tumor stage, and ATA risk category were collected. The response to therapy was assessed based on ATA guidelines. Results: Among the 259 patients, 29% had coexisting HT. Patients with HT exhibited distinct characteristics: a higher proportion of females (87.0% vs. 74.7%), a shorter post-operative monitoring duration (median 3 vs. 5 years), and a higher prevalence of papillary thyroid carcinoma (PTC) (97.4% vs. 86.3%). The tumor size, lymph node involvement, and distant metastasis were similar between the groups, with patients without HT having a higher incidence of extrathyroidal tumor extension. However, the initial TNM stage and ATA risk category did not differ significantly. At the six-month follow-up, HT patients showed a higher rate of indeterminate responses, primarily due to positive AbTg. After 12 months, the response categories aligned, with decreasing AbTg levels in the HT group. After 24 months, most patients with long-term follow-up demonstrated an excellent response to DTC therapy, irrespective of HT coexistence. Conclusions: While HT does not worsen DTC prognosis, it may result in indeterminate responses. AbTg measurements in the peri-operative period should be encouraged to facilitate post-operative monitoring, emphasizing the importance of using standardized assays. Further research in larger populations with extended follow-up is needed to comprehensively understand the HT-DTC relationship.

Background and Objectives: A novel post-translational modification (PTM) fragment derived from the cleavage of Fetuin-A (PTM-FetA) has recently emerged as a sensitive biomarker for kidney damage in diabetic patients, but evidence in other chronic renal diseases is lacking. In this pilot study, we aimed at evaluating the clinical significance of urinary PTM-FetA (uPTM-FetA) in a mixed cohort of patients with non-advanced chronic kidney disease (CKD) secondary to diabetic kidney disease (DKD) or other causes. Materials and Methods: We enrolled 47 adult patients with CKD (mean CKD-Epi 40.10 ± 16.5 mL/min/1.73 m²) due to DKD (n = 34) or other etiology (n = 13). uPTM-FetA was measured in the urine using a commercially available ELISA kit. Fifteen healthy individuals served as controls. Results: Collectively, all CKD patients displayed remarkably higher levels of uPTM-FetA than controls (0.84 [0.10–1.15] vs. 29.68 [2.50–55.16] ng/mL p = 0.0005), but values were lower in non-DKD than in DKD patients (1.66 [0.09–4.19] vs. 13.9 [0.01–45.02] ng/mL; p = 0.01). uPTM-FetA showed a great diagnostic capacity at ROC analyses to identify the presence of CKD (AUC 0.776; p < 0.001) and, within CKD patients, to discriminate the diabetic and non-diabetic etiology (AUC 0.673; p = 0.02). At multivariate correlation analyses, proteinuria (β = 0.442; p = 0.02) and BMI (β = −0.334; p = 0.04) were the sole independent predictors of uPTM-FetA in this study population. Conclusions: uPTM-FetA could be a novel sensitive biomarker at the crossroad of chronic renal damage and metabolic dysfunction. Additionally, this biomarker could also represent a non-invasive, complementary tool for discriminating among different CKD etiologies (DKD vs. non-DKD) in difficult cases or when renal biopsy is not available.

Background and Objectives: Sarcopenia is exceedingly frequent in end-stage kidney disease (ESKD) patients on dialysis, including those undergoing peritoneal dialysis (PD), and is of multifactorial origin. MOTS-c is a mitochondrial-derived peptide that promotes muscle growth whose levels are unbalanced in ESKD. In this study, we evaluated MOTS-c balance and its relationship with sarcopenia risk in an ESKD-PD cohort. Materials and Methods: MOTS-c was measured in serum, urine, and dialysate samples of 32 chronic PD patients. Patients were thus screened for sarcopenia risk by the SARC-F tool, anthropometric measurements, and physical performance tests. Results: PD patients with a very high sarcopenia risk (SARC-F ≥ 2) had significantly lower serum (sMOTS-c) and higher dialysate (dMOTS-c) levels, suggesting an increased peritoneal clearance of this substance (d/s MOTS-c). sMOTS-c levels were directly correlated with muscle performance in physical tests, while an opposite relationship was found with dMOTS-c and d/sMOTS-c. ROC analyses demonstrated the diagnostic potential of MOTS-c, particularly in combination with physical and anthropometric assessments, to identify PD patients at very high risk of sarcopenia. Conclusions: Chronic PD may negatively affect MOTS-c balance, which, in turn, may contribute to enhanced sarcopenia risk. Larger studies are needed to confirm these observations and to validate the potential utility of this substance as a biomarker for improving sarcopenia risk stratification in PD patients.

Background: Women who experience gestational diabetes mellitus (GDM) during their first pregnancy are at a high risk of developing GDM again in subsequent pregnancies. Even mothers with no previous history of GDM may develop the condition in a new pregnancy. Methods: In this retrospective cross-sectional observational study, 759 multiparous women tested for GDM in two successive pregnancies using the 75 g OGTT (IADPSG criteria) were enrolled. The OGTT was performed at 24–28 weeks’ gestation or earlier if there was a history of GDM. Participants were categorized into four groups: women with normal glucose tolerance (NGT) in both pregnancies (n = 493), women with a first occurrence of GDM in their second pregnancy (n = 74), women with non-recurrent GDM in their second pregnancy (n = 92), and women with recurrent GDM in their second pregnancy (n = 100). Results: Intergroup comparisons revealed clinical predictors of GDM in the first pregnancy (family history of type 2 diabetes, PCOS, advanced maternal age, pregravid obesity) and in the second pregnancy (interpregnancy BMI gain), as well as predictors of recurrent GDM (pregravid obesity, PCOS). A positive correlation was observed between the OGTT glucose levels of consecutive pregnancies. Adjusted logistic regression indicated that a higher 1-h post-load glucose level (≥130 mg/dL) during the first pregnancy significantly increased the likelihood of new-onset GDM in the second pregnancy (OR: 2.496), whereas a higher 2-h post-load glucose level (≥153 mg/dL) at the first diagnostic OGTT increased the likelihood of recurrent GDM (OR: 2.214). Conclusions: Clinical risk factors and post-load glucose levels during the first gestational 75 g OGTT can help predict new-onset or recurrent GDM in multiparous women.