5 Diabetes, hyperinsulinemia, and the hypoxic ventilatory response balance and hypoxic reactivity during hyperinsulinemia. Sympathetic excitation may also explain the observed changes in hemodynamic response to hyperinsulinemia and hypoxia, due to different levels of attenuation of peripheral α-adrenergic mediated vasoconstriction, peripheral β-adrenergic vasodilation, myocardial glucose uptake, and β-adrenergic cardiac stimulation.34,35 Apart from the observation of a substantial influence of T2DM on autonomic regulation, our findings suggest a dynamic interaction between the metabolic and respiratory systems, with effects of diabetes on respiratory physiology in the presence of hyperinsulinemia and hypoxia. The carotid body, a primary oxygen-sensing organ, plays an integral role in ventilatory adjustments to hypoxia. Prolonged hyperinsulinemia might exert modulatory effects on the carotid body, potentially altering its sensitivity and responsiveness to hypoxic challenges. Such alterations could, in turn, impact the overall functionality of the autonomic nervous system, given the close interplay between carotid body activity and autonomic regulation. Limitations Our study has several limitations: (1) While the T2DM group refrained from antidiabetic drugs for 24 h, prolonged effects of various medications cannot be ruled out. (2) Data of subjects with poor HEC was disregarded and data of three subjects with insufficient quality HVR was excluded from analysis, resulting in missing data in both groups that affected our sample size. (3) Furthermore, there was significant variability in insulin resistance in both patients with T2DM and HC. This suggests undiagnosed insulin resistance in the “healthy” population, which cannot be detected from fasting glucose measurements, and heterogeneity in T2DM phenotype, with different progression, severity, and drug response.36 A stronger demarcation between patients with and without insulin resistance, irrespective of their diagnosis, could have increased the observed differences. Conclusion In an experimental paradigm, we observed that individuals with T2DM display significant differences in their carotid body function that affects ventilatory and metabolic control and is possibly an important factor in sympathetic tonerelated hemodynamic changes. This study should be considered exploratory and hypothesis-generating. Our study may be used to power future studies on the intricate interaction between metabolic, hemodynamic and ventilatory control. 113
RkJQdWJsaXNoZXIy MTk4NDMw