(748.3) Peripheral Chemoreflex Sensitivity is Augmented in Human Type 2 Diabetes

Poster Board Number: E406

Eric Lis (University of Missouri), Elizabeth Ott (University of Missouri), Jennifer Harper (University of Missouri), Camila Manrique-Acevedo (University of Missouri), Jacqueline Limberg (University of Missouri)

Introduction:   The peripheral chemoreceptors have been implicated in the pathogenesis of type 2 diabetes. Our main objective was to examine peripheral chemosensitivity in individuals with type 2 diabetes, as well as the contribution of the peripheral chemoreceptors to basal cardiovascular control. We hypothesized individuals with type 2 diabetes exhibit exaggerated peripheral chemoreflex sensitivity to hypoxia compared to healthy, non-diabetic controls. We further hypothesized the peripheral chemoreceptors contribute to cardiovascular dysfunction in type 2 diabetes.  

Methods:   Eight adults with diagnosed type 2 diabetes (3M/5F, 54±3 yrs, HbA1c 8.1±0.6%) and nineteen healthy controls (8M/11F, 50±3 yrs, HbA1c 5.3±0.1%) participated (IRB #2010295 and #2018486).  Ventilatory and hemodynamic responses to acute hypoxia were assessed to determine peripheral chemosensitivity [i.e., hypoxic ventilatory (HVR), heart rate (HHRR) and blood pressure (HBPR) response].  Separately, heart rate, blood pressure and forearm blood flow (Doppler ultrasound) were measured while breathing normoxic or hyperoxic air (100% O2; Modified Dejours test) to acutely attenuate peripheral chemoreceptor activity.  Forearm blood flow was normalized for mean arterial blood pressure for measures of vascular resistance.

Results:   Peripheral chemosensitivity was augmented in adults with type 2 diabetes compared to control as assessed via the HVR (-1.10±0.16 vs -0.50±0.10 L/min/%, plt;0.01) and HBPR (-0.92±0.17 vs -0.42±0.19 mmHg/%, p=0.06), with no differences in HHRR (-0.68±0.22 vs -0.56±0.12 beats/min/%, p=0.64).  Higher HVR and HBPR were associated with higher fasting insulin (R=-0.58, plt;0.01 and R=-0.38, p=0.06) and HbA1c (R=-0.60, plt;0.01 and R=-0.39, p=0.05).  Attenuation of peripheral chemoreceptor activity with acute hyperoxia decreased heart rate (plt;0.01) and blood pressure (p=0.02), with no effect on forearm vascular resistance (p=0.55); any effect of hyperoxia did not differ between adults with type 2 diabetes and controls (pgt;0.05). 

Conclusion:   Individuals with type 2 diabetes exhibit exaggerated peripheral chemoreflex sensitivity which is associated with disease severity (i.e., HbA1c).  In contrast, the contribution of the peripheral chemoreceptors to basal cardiovascular function in type 2 diabetes does not differ from non-diabetic controls. Results advance our understanding of the pathogenesis of type 2 diabetes and related complications.

University of Missouri Alumni Association Richard Wallace Faculty Incentive Grant, University of Missouri Research Council