Relationship Between Orexin-A and Insulin Resistance in Patients with Type 2 Diabetes Mellitus

Background: Orexin-A is an orexigenic hormone that plays an important role in the metabolism of blood glucose, insulin, and insulin resistance (IR). The pathogenesis of type 2 diabetes mellitus (T2DM) is related to the abnormality in insulin and IR. However, no sufficient studies to date have clearly shown the association of orexin-A with biochemical parameters related to T2DM. Objectives: The aim of this study was to determine the relation of orexin-A with IR and how they associate with physiological changes in T2DM patients. Understanding this relation will offer some pharmacological tools to reduce some complications in diabetes. Materials and Methods: A total of 41 T2DM and 43 non-DM subjects, aged between 40-60 years with body mass index (BMI) ≤25 kg/m2, participated in the present study. Fasting serum orexin-A, IR, fasting blood glucose (FBG), glycated hemoglobin (HbA1C), lipid profile, liver enzymes (alanine aminotransferase (ALT) and aspartate transaminase (AST)), nitric oxide (NO), and malondialdehyde (MDA) parameters were evaluated. Orexin-A was evaluated by using enzyme-linked immunosorbent assay (ELISA). For statistical analysis, GraphPad Prism 7.0 and SPSS version 24.0 programs were used. Results: Orexin-A was positively correlated with blood pressure, FBG, HbA1c, insulin, and IR but inversely related to insulin sensitivity (IS), leptin, and gender. Stepwise multiple regression presented HOMA-IR, diastolic blood pressure, and very-low-density lipoprotein-cholesterol as predictors for orexin-A. The area under control value showed orexin-A, FBG, HbA1c, HOMA-IR, IS, ALT, AST, NO and MDA as biomarkers for T2DM disease. Conclusion: Orexin-A has a predictive ability to diagnose T2DM, as it is significantly associated with hyperglycemia, IR, and IS.