Circulating Ghrelin, Nesfatin-1, and Vaspin Levels Across Glycemic Control Categories in Type 2 Diabetes Mellitus: A Cross-Sectional Study

Background/Objectives: Diabetes mellitus is characterized by chronic hyperglycemia, insulin resistance, and low-grade inflammation, and adipose-tissue-derived adipokines are increasingly implicated as regulators of glucose homeostasis. This study compared circulating ghrelin, nesfatin-1, and vaspin levels across three glycemic-control categories defined by HbA1c and evaluated their association with glycemic status. Methods: In this cross-sectional comparative study, serum ghrelin, nesfatin-1, and vaspin were measured by enzyme-linked immunosorbent assay (ELISA) in 161 adults stratified into three groups: HbA1c 6.0–8.4% (n = 55), HbA1c ≥ 8.5% (n = 52), and non-diabetic controls with HbA1c < 6.0% (n = 54). Distributional assumptions were tested with the Kolmogorov–Smirnov and Shapiro–Wilk tests. Because all three adipokines deviated from normality, the primary omnibus comparison was the Kruskal–Wallis test, followed by Dunn’s post hoc test with Bonferroni adjustment; effect sizes are reported with 95% confidence intervals. Group differences were additionally examined after adjustment for age and sex, and HbA1c was analysed as a continuous variable. Results: Ghrelin (Kruskal–Wallis p = 0.726) and vaspin (p = 0.364) did not differ among the three groups. Nesfatin-1 differed significantly (H = 15.16, p < 0.001, ε2 = 0.095) and non-monotonically: concentrations were higher in the HbA1c 6.0–8.4% group than in controls (median 824 versus 650 pg/mL; Dunn p = 0.018) and than in the HbA1c ≥ 8.5% group (824 versus 600 pg/mL; p < 0.001), whereas the HbA1c ≥ 8.5% and control groups did not differ (p = 0.909). The nesfatin-1 difference persisted after adjustment for age and sex (p < 0.001) and after excluding controls with impaired fasting glucose (p < 0.001). Within the diabetic participants, nesfatin-1 correlated inversely with continuous HbA1c (ρ = −0.373, p < 0.001). Conclusions: Nesfatin-1, but not ghrelin or vaspin, differed significantly between HbA1c-defined glycemic-control categories in a non-monotonic manner, with the highest concentrations in the intermediate-HbA1c group. Because body mass index, diabetes duration, and antidiabetic medication were not available, and because the design is cross-sectional, these between-group differences cannot be interpreted as a within-person trajectory or attributed to glycemic status independently of adiposity. These exploratory findings require confirmation in larger, prospective, BMI- and medication-adjusted cohorts before nesfatin-1 can be considered a candidate biomarker.