Nesfatin-1 in Regulation of Glucose Homeostasis Across Different Stages of Glycaemia: An Observational Cross-sectional Study

Introduction: Nesfatin-1 plays a crucial role in maintaining energy balance and regulating food intake through its action on both central and peripheral pathways. In addition to peripheral organs, including adipocytes, pancreatic islets, and stomach endocrine cells, it is primarily released by the hypothalamus. By encouraging peripheral glucose uptake and inhibiting gluconeogenesis, nesfatin-1 increases insulin sensitivity. Diabetes mellitus is preceded by prediabetes. Aim: To compare nesfatin-1 in the regulation of glucose homeostasis across different stages of glycaemia. Materials and Methods: This is an observational cross-sectional study conducted at the Department of Biochemistry, SRM Medical College Hospital and Research Centre, Kattankulathur, Chennai, Tamil Nadu, India, from May 2024 to March 2025. The study involved 90 adults, both men and women, aged 20 to 45 years. They were divided into three groups based on American Diabetes Association’s (ADA) criteria into euglycaemic (HbA1c <5.7%), prediabetic (HbA1c 5.7-6.4%), and newly diagnosed type 2 diabetes (HbA1c ≥6.5%). Age, sex, height, weight, Body Mass Index (BMI), and Blood Pressure (BP) values were taken into account. Serum samples of the above individuals were separated and stored for analysing nesfatin-1 levels. Nesfatin-1 levels were analysed using the Enzyme-linked Immunosorbent Assay (ELISA) method. Statistical analysis was performed using IBM Statistical Package for Social Sciences (SPSS) software version 20.0. The three groups’ continuous variables were compared using the Kruskal-Wallis test. The relationship between serum nesfatin-1 levels and metabolic markers was evaluated using Spearman’s correlation. Statistical significance was established at a p-value of less than 0.05. Results: Nesfatin-1 levels varied considerably among the three glycaemic groups (p-value=0.003), with newly diagnosed diabetics having median levels of 161.1 pg/mL, prediabetic people having 132.41 pg/mL and euglycaemic people having 149.28 pg/mL. Nesfatin-1 levels were lower in prediabetic individuals when compared to euglycaemic and newly diagnosed diabetic individuals. The prevalence of insulin resistance [Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) ≥2.9] was higher in newly diagnosed diabetics, 17/30 (57%), than in prediabetics, 4/30 (13%) and euglycaemics, 4/30 (13%). All groups had substantial prevalences of obesity (BMI ≥25 kg/m2 ), 17/30 (57%) of euglycaemic people, 17/30 (57%) of prediabetic people, and 19/30 (63%) of newly diagnosed diabetic people. This suggests that insulin resistance and obesity play a part in early glucose dysregulation. Conclusion: Early disruptions in glucose metabolism may be linked to altered nesfatin-1 levels. Increased BMI and HOMA-IR are important markers of type 2 diabetes progression, highlighting the necessity of early identification and individualised treatment plans.