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.
Timurkaan et al. (Sat,) studied this question.