Serum Orexin A and Anthropometric, Hemodynamic and Lipid Profiles in Newly Diagnosed Treatment-Naïve Type 2 Diabetes: a Case-Control Study.

Background: Orexin A is a neuropeptide from the lateral hypothalamus and is involved in the regulation of energy balance and peripheral metabolic processes. There is extensive mechanistic evidence in animal models, but its circulating behavior during the initial phases of type 2 diabetes mellitus (T2DM) in South Asian populations in general and resource-limited Indian settings in particular is poorly characterized. Objectives: The purpose of this study was to compare serum Orexin A levels in newly diagnosed, treatment-naïve T2DM patients with healthy controls and to investigate possible associations with anthropometric measurements, hemodynamic parameters and serum lipid profile. Materials and methods: A hospital-based cross-sectional case-control study was conducted among 150 participants (100 newly diagnosed T2DM cases and 50 age- and sex-matched healthy volunteers) from Mahatma Gandhi Medical College and Hospital, Jaipur, Rajasthan. Anthropometric measurements, blood pressure measurements and biochemical investigations like fasting blood glucose, HbA1c, lipid profile and liver enzymes were done using standard procedures. Serum Orexin A was quantified by a competitive enzyme-linked immunosorbent assay. Results: Circulating Orexin A concentrations were significantly lower in the T2DM group than in controls (median 26.52, IQR 16.03-37.62 pg/mL versus median 224.21, IQR 205.48-243.88 pg/mL; p < 0.001), with an average decrease of about 85%. Participants with diabetes also had higher body mass index, waist to hip ratio, systolic and diastolic blood pressure (p < 0.001 for each comparison). Lipid assessment showed a typical atherogenic lipid profile in cases with increased triglycerides (193.04 ± 15.64 mg/dL vs 136.19 ± 13.35 mg/dL), total cholesterol (226.56 ± 14.64 mg/dL vs 176.52 ± 12.01 mg/dL) and LDL-cholesterol and decreased HDL-cholesterol (40.15 ± 3.90 mg/dL vs 48.30 ± 5.82 mg/dL). Correlation analyses within the T2DM group did not demonstrate any statistically significant association between Orexin A levels and anthropometric, hemodynamic, or lipid parameters (all p > 0.05). Conclusions: Serum Orexin A levels are significantly lower at the time of clinical presentation of T2DM in this urban Indian cohort. However, in this exploratory analysis, this reduction was not significantly correlated with markers of central obesity, dyslipidemia, or blood pressure. These findings require confirmation in larger prospective studies with direct measures of insulin sensitivity.