Association of Phoenixin-14 with Body Mass Index Categories and Proteinuria in Adults with Type 2 Diabetes.

Background and Objectives: Human data on obesity and type 2 diabetes mellitus (T2DM) remain limited and inconsistent, particularly with respect to adiposity-related phenotypes and renal involvement. We aimed to assess PNX-14 across body mass index (BMI) categories and to investigate its associations with BMI, insulin resistance indicators, and proteinuria in adults with T2DM. Materials and Methods: In this prospective cross-sectional study, participants were classified into four groups according to World Health Organization body mass index (BMI) thresholds: 18.5-24.9, 25.0-29.9, 30.0-34.9, and ≥35.0 kg/m2. Serum PNX-14 was measured using a human ELISA kit. Group comparisons, trend analysis, false discovery rate-adjusted Spearman correlations, HC3-robust multivariable regression, and parsimonious structural equation modeling were performed. Results: PNX-14 differed significantly across BMI categories and increased monotonically with increasing BMI (p < 0.001 for both the overall comparison and the trend). PNX-14 showed a positive correlation with BMI (ρ = 0.491; qFDR < 0.001), whereas no significant relationship was observed with insulin or HOMA-IR after FDR correction (qFDR = 0.795 for insulin and qFDR = 0.793 for HOMA-IR). In the model adjusted for age, sex, and BMI, higher PNX-14 was independently associated with lower proteinuria (β = -0.326, 95% CI -0.584 to -0.067; p < 0.05), whereas BMI was positively associated with proteinuria (β = 0.407, 95% CI 0.132 to 0.682; p < 0.01). Structural equation modeling supported positive BMI→PNX-14 and BMI → proteinuria paths, a negative PNX-14→proteinuria path, and a non-significant PNX-14→HOMA-IR path. Conclusions: In adults with T2DM, PNX-14 appears to be more consistently related to adiposity than to glycemic or insulin resistance indicators. However, when evaluated together with proteinuria, it may offer a testable framework for phenotyping based on renal involvement within the obesity spectrum. Nevertheless, this approach needs to be validated in studies from different centers and with repeated measurements.