Carotid body chemosensitivity: early biomarker of dysmetabolism in humans.

João P Cunha-Guimaraes,Mafalda Selas,Ana T Timóteo,Silvia V Conde,Joana F Sacramento,Maria J Ribeiro,Miguel Mota-Carmo,Iolanda Caires,João C P Santiago,Maria P Guarino

doi:10.1530/eje-19-0976

Abstract

The carotid bodies (CBs) are peripheral chemoreceptor organs classically described as being O2 sensors, which are increasingly emerging as core players in metabolic control. Herein we evaluated CB activity in prediabetes patients and determined its correlation with dysmetabolism clinical features. Prediabetes patients were recruited at the Cardiology Service, Hospital Santa Marta, Centro Hospitalar Lisboa Central, EPE (CHLC-EPE). The study was approved by CHLC-EPE and NOVA Medical School Ethics Committee. Thirty-three prediabetic and 14 age-matched, non-prediabetic, volunteers had their peripheral chemosensitivity evaluated by the Dejours test. Serum biomarkers of metabolic disease, insulin sensitivity (HOMA-IR), blood pressure, carotid intima-media thickness (cIMT) and glucose tolerance were assessed. CB chemosensitivity was significantly increased in prediabetic group (P < 0.01). Fasting blood, glucose intolerance, fasting insulin and HOMA-IR were significantly higher in prediabetes patients. Insulin resistance correlated both with peripheral chemosensitivity, assessed by the Dejours test (P < 0.05) and with abdominal circumference (P < 0.01). HbA1c correlated with HOMA-IR (P < 0.05) and left cIMT (P < 0.05) in prediabetes patients. We conclude that CB is overactive in prediabetes subjects and that peripheral chemosensitivity correlates with fasting insulin and insulin resistance representing a novel non-invasive functional biomarker to forecast early metabolic disease.

Highlights

The carotid bodies (CBs) are peripheral chemoreceptors that classically sense changes in arterial blood O2, CO2 and pH levels [1]
The main novel finding is that CB chemosensivity correlates with fasting plasma insulin levels and with HOMA-IR index in prediabetes patients, classical markers of insulin resistance
Being a pilot study, the results are statistically robust and show that prediabetes patients exhibit increased CB chemosensitivity and that disrupted CB activity patterns are linked to circulating insulin and to insulin resistance

Summary

Introduction

The carotid bodies (CBs) are peripheral chemoreceptors that classically sense changes in arterial blood O2, CO2 and pH levels [1]. The classical stimulus for the carotid body is hypoxemia, which leads to an increase in CSN activity. There has been huge debate in the literature on the hypothesis that CBs sense glucose and that hyperglycemia may be the trigger for CB overactivation observed in metabolic diseases. Scientific evidence supports that carotid bodies, having a fundamental role in glucose homeostasis, do not sense glucose directly except in acute hypoglycemic states where there is urgent need to regulate the counterregulatory response and appropriate increase in ventilation. Hyperinsulinemia, rather than hyperglycemia, appears to be the key trigger for CB overactivation [4, 5].

Methods

Results

Conclusion