Serum Orexin A Levels and Heart Rate Variability Parameters in Newly Diagnosed, Treatment-Naïve Type 2 Diabetes...

Type 2 diabetes mellitus (T2DM) is characterized by metabolic shifts that impact neuroendocrine signals and autonomic performance, yet the direct relationship between circulating neuropeptides and cardiac regulation in early-stage disease is unclear in low-resource settings like India.

This case-control study was performed to compare baseline serum Orexin A levels and heart rate variability (HRV) parameters between newly diagnosed, treatment-naïve T2DM patients and healthy controls, and to assess the linear correlations between serum Orexin A concentrations and HRV indices within the T2DM group.

One hundred newly diagnosed treatment-naïve type 2 DM and 50 age-matched healthy volunteers were recruited in the outpatient department of Endocrinology and General Medicine, Mahatma Gandhi Medical College & Hospital, Jaipur. Serum Orexin A was quantified using a competitive enzyme-linked immunosorbent assay (ELISA) kit, and five-minute resting electrocardiograms were captured to calculate time-domain parameters including the standard deviation of NN intervals (SDNN), root mean square of successive differences (RMSSD), and percentage of successive NN intervals differing by more than 50 milliseconds (pNN50) alongside frequency-domain spectral parameters including low-frequency (LF) power, high-frequency (HF) power, and the LF/HF ratio.

Serum Orexin A concentrations were significantly reduced in the diabetic group compared with the healthy control (33.92 ± 28.45 pg/mL vs. 225.77 ± 20.45 pg/mL), (p < 0.001), representing a significant baseline reduction. Marked reductions were identified across all recorded autonomic components, with the mean overall time-domain tone falling below reference values (SDNN: 46.06 ± 6.16 ms vs. 85.29 ± 13.65 ms), (p < 0.001); (RMSSD: 31.50 ± 3.76 ms vs. 55.74 ± 3.23 ms), (p < 0.001). Pearson correlation revealed near-zero coefficients and no statistically significant linear association between circulating orexin A levels and any time- or frequency-domain parameter within the type 2 DM group (p > 0.05 for all).

In conclusion, newly diagnosed, treatment-naïve patients with T2DM exhibited significantly lower serum Orexin A concentrations and impaired HRV parameters compared with healthy controls. However, no significant linear correlations were observed between serum orexin A concentrations and HRV indices, suggesting that the relationship between circulating orexin A and cardiac autonomic function may be more complex than a simple linear association. Further studies are warranted to elucidate the underlying mechanisms.