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.