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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.

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BACKGROUND: Mortality and cardiovascular (CV) risk prediction in individuals with end-stage kidney disease (ESKD) on chronic hemodialysis (HD) remains challenging due to the multitude of implicated factors. In a multicenter ESKD-HD cohort, we tested the prognostic yield of the assessment of circulating Humanin, a small mitochondrial-derived peptide involved in CV protection, on CV events and mortality. METHODS: We conducted a prospective, observational, pilot study on 94 prevalent HD patients. The prognostic capacity of circulating Humanin levels was tested on a primary composite (all-cause mortality + non-fatal CV events) and a secondary exploratory endpoint (all-cause mortality alone). RESULTS: Baseline Humanin level was comparable in patients reaching the primary or secondary endpoint as compared to others (p = 0.69 and 0.76, respectively). Unadjusted followed by multivariable Cox regression analyses adjusted for age, left ventricular mass index (LVMi), E/e', pulse pressure and diabetes mellitus indicated a non-linear relationship between Humanin levels and the composite outcome with the highest Hazard Ratio (HR) associated with very low (< 450.7 pg/mL; HR ranging from 4.25 to 2.49) and very high (> 759.5 pg/mL; HR ranging from 5.84 to 4.50) Humanin values. Restricted cubic splines fitting univariate and multivariate Cox regression analyses visually confirmed a curvilinear trend with an increasing risk observed for lower and higher Humanin values around the median, respectively. A similar, u-shaped association was also evidenced with the secondary endpoint. CONCLUSIONS: Altered Humanin levels may impart prognostic information in ESKD-HD patients at risk of death or CV events. Future investigations are needed to confirm whether Humanin measurement could improve CV and mortality risk prediction beyond traditional risk models.

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INTRODUCTION: Uremic patients exhibit remarkably increased rates of mortality and cardiovascular (CV) events, but risk prediction in this setting remains difficult. Systemic mitochondrial dysfunction is pervasive in end-stage kidney disease and may contribute to CV complications. We tested the clinical significance of circulating MOTS-c, a small mitochondrial-derived peptide, as a biomarker for improving mortality and CV risk prediction in hemodialysis (HD) patients. METHODS: We conducted a prospective, observational, multicenter study on 94 prevalent HD patients. The study endpoint was a composite of all-cause mortality and non-fatal CV events. The diagnostic and prognostic capacities of predictive models based on cohort-related risk factors were tested before and after the inclusion of MOTS-c. RESULTS: MOTS-c levels were higher in HD patients than in controls (p < 0.001) and even more elevated (p = 0.01) in the 53 individuals experiencing the combined endpoint during follow-up (median duration: 26.5 months). MOTS-c was independently associated with the endpoint at either multivariate logistic (OR 1.020; 95% CI: 1.011-1.109; p = 0.03) or Cox regression analyses (HR 1.004; 95% CI: 1.000-1.025; p = 0.05) and the addition of this biomarker to prognostic models including the other cohort-related risk predictors (age, left ventricular mass, evidence of diastolic dysfunction, diabetes, pulse pressure) significantly improved the calibration, risk variability explanation, discrimination (receiver operating characteristic area under the curve from 0.727 to 0.743; C-index from 0.658 to 0.700), and particularly, the overall reclassification capacity (NRI 15.87%; p = 0.01). CONCLUSIONS: In HD patients, the mitochondrial-derived peptide MOTS-c may impart significant information to refine CV risk prediction, beyond cohort-related risk factors. Future investigations are needed to generalize these findings in larger and more heterogeneous cohorts.

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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 (ß = 0.442; p = 0.02) and BMI (ß = -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.

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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.

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Background and Objectives: The global prevalence of chronic kidney disease (CKD) is on the rise, posing important challenges for healthcare systems. Thus, the search for new factors potentially involved in the pathogenesis, progression and complications of early CKD remains urgent. Marinobufagenin (MBG) is a natriuretic endogenous cardiotonic steroid, and increased circulating levels of it may accelerate kidney damage. In this study, we explored the possible clinical significance of measuring urinary marinobufagenin (uMBG) in patients with non-advanced CKD. Materials and Methods: One hundred and eight adult CKD patients (mean age 71.6 ± 10 years, 70.4% male; mean eGFR 40.54 ± 17 mL/min/1.73 m2) were enrolled in this cross-sectional study. uMBG was measured together with a series of clinical, anthropometric, laboratory and instrumental analyses. Twenty-five healthy matched subjects served as controls for the uMBG measurement. Results: The uMBG values were lower in the patients with CKD as compared to those of the controls (0.37 [IQR: 0.25-0.45] vs. 0.64 [0.46-0.78] nmol/L. p = 0.004), and a significant trend in eGFR levels was noticed across the decreasing uMBG tertiles (p = 0.03). Regarding the correlation analyses, the uMBG values remained robustly associated with the eGFR in multivariate models employing either uMBG or eGFR as the dependent variable (ß = 0.248; p = 0.01 and ß = 0.139; p = 0.04, respectively). Besides the eGFR, the independent predictors of uMBG values in this population were the use of statins (ß = -0.326; p = 0.001), the presence of diabetes (ß = 0.243; p = 0.009) and urine sodium (ß = 0.204; p = 0.01). Conclusions: Reduced uMBG excretion may reflect impaired renal clearance, which may contribute to the detrimental effects attributed to this hormone due to systemic accumulation. Future studies are needed to clarify the biological mechanisms placing uMBG at the crossroad of sodium intake and the presence of diabetes in CKD-suffering individuals and to verify whether a statin treatment may somewhat limit the detrimental effects of MBG in the presence of impaired renal function.

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