Role for the Carotid Chemoreceptors in Glucose Tolerance in Human Type 2 Diabetes

Abstract

Objectives: The carotid body (CB) chemoreceptors have been implicated in the development and progression of type 2 diabetes (T2D). CB denervation can prevent the development and worsening of T2D in pre-clinical models — although these data have yet to be translated to humans. We examined CB chemosensitivity in T2D, as well as the contribution of the CB to glucose tolerance. We hypothesized: 1) individuals with T2D would exhibit exaggerated CB sensitivity to hypoxia (hypoxic ventilatory response, HVR), 2) attenuation of CB chemoreceptor activity (i.e., hyperoxia) would improve glucose tolerance in T2D, and 3) the magnitude of the effect of hyperoxia on glucose tolerance would be related to the level of CB chemosensitivity. Methods: HVR was assessed in sixteen adults with T2D (6M/10F, 55±11 yrs, HbA1c 7.7±1.4%) and twenty-one healthy controls (9M/12F, 50±13 yrs, HbA1c 5.2±0.4%)(NCT05219994). A subset (n=9 per group) completed two additional visits randomized to normoxia (0.21 FiO2) and hyperoxia (1.0 FiO2). During each visit, blood glucose and plasma insulin were measured every 15 min for 2 hrs following consumption of a 75 g glucose drink and responses were calculated as area under the curve (AUC). Pearson correlations between HVR and the difference in AUC glucose and insulin between visits (ΔAUC = hyperoxia-normoxia) were conducted. Results: HVR was augmented in T2D compared to control (control, -0.47±0.39; T2D, -0.83±0.50 L/min/%; p=0.02). There was no effect of hyperoxia on AUCglucose (control, p=0.77; T2D, p=0.73) or AUCinsulin (control, p=0.70; T2D, p=0.41). Correlations were observed between HVR and ΔAUCglucose (R=0.67, p=0.047) and ΔAUCinsulin (R=-0.55, p=0.16)] in adults with T2D, but not in controls [ΔAUCglucose (R=-0.32, p=0.40), ΔAUCinsulin (R=-0.18, p=0.67)]. Conclusions: Individuals with T2D exhibit exaggerated CB sensitivity to hypoxia. Glucose tolerance was unaffected by attenuation of CB chemoreceptor activity; however, when examined in relation to CB sensitivity, glucose tolerance improved with hyperoxia in T2D adults with the highest HVR. Present data advance our understanding of the pathophysiology of T2D and support a potential role for the CB chemoreceptors in glucose tolerance in human T2D. MizzouForward Undergraduate Research Training Grant, University of Missouri Research Council, University of Missouri Alumni Association Richard Wallace Research Incentive Fund. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.