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Background: Nesfatin-1 is a polypeptide encoded in the N-terminal region of Nucleobindin2 (NUCB2), expressed in the hypothalamus, pancreatic islets, gastric endocrine cells and adipocytes. Recent studies indicate its role in regulation of satiety and stimulation of insulin secretion. We assessed the relationship between serum nesfatin-1/NUCB2 and selected metabolic risk factors in normoglycemic individuals. Materials and Methods: Study included 80 normoglycemic, non-obese (BMI <30 kg/m2) subjects aged 25-40 years (32 women, 48 men). Basic anthropometric parameters (weight, BMI, WHR) and blood pressure measurements were performed. Laboratory tests: fasting plasma glucose, glycated hemoglobin (HbA1c), lipid profile, insulin, CRP, apolipoproteins AI and B were measured on automatic analyzers (Abbott Architect ci8200, Roche Cobas e411). Adiponectin and nesfatin-1/NUCB2 were assayed by commercially available ELISA kits (BioVendor R&D, Phoenix Pharmaceuticals Inc.). Results: Nesfatin-1/NUCB2 levels ranged 0.53- 14.38 ng/mL and were significantly higher in women compared to men (1.28 vs. 0.82 ng/mL; p=0.02). In men nesfatin-1/NUCB2 correlated negatively with glucose (R= -0.51; p=0.009), insulin (R= -0.33; p=0.038) and HOMA-IR (R= -0.42; p=0.027), while inverse relationship was observed in women. Multivariable regression analysis with glucose, insulin and HOMA-IR in females and with glucose, HOMAIR and adiponectin in males explained 87% and 32% of nesfatin-1/NUCB2 variability. Conclusions: Association of serum nesfatin-1/ NUCB2 with metabolic risk factors differs essentially by gender, however this issue requires further investigation in large, population-based study. [ABSTRACT FROM AUTHOR]