Carotid body chemosensitivity: early biomarker of dysmetabolism in humans

Abstract

Objective 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. Design and methods 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. Results 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. Conclusions 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.

Sympathetic activation: a potential link between comorbidities and COVID‐19

“…It is widely known that increased sympathetic discharge is associated with chronic obstructive pulmonary disease, obstructive sleep apnea syndrome, cardiovascular diseases (hypertension, heart failure), renal pathologies, and metabolic disturbances (diabetes, obesity, metabolic syndrome). Increase in peripheral hypoxic chemosensitivity is a common mechanism stimulating sympathetic activation in the above conditions [4–9], but other stimulatory mechanisms are present.…”

Exploring the Mediators that Promote Carotid Body Dysfunction in Type 2 Diabetes and Obesity Related Syndromes

“…Taking all these data together, we postulate that, in metabolic diseases, hyperinsulinemia, rather than hyperglycemia, is one of the major stimuli contributing to CB dysfunction [13,14] (Figure 2). Alongside these, increased CB chemosensitivity, measured by the Dejours test, observed in prediabetes patients is directly correlated with plasma insulin levels and with insulin resistance but not with fasting glycemia [21].…”

“…Besides its role as an oxygen sensor, in the last few years, the CB has also been proposed to be a metabolic sensor implicated in the control of carbohydrate and lipid metabolism [ 8 , 9 , 10 , 11 ] and in the regulation of peripheral insulin sensitivity and glucose homeostasis [ 8 , 9 , 12 , 13 , 14 , 15 , 16 , 17 ] ( Figure 1 a). Recently, we showed that CB activity is increased in prediabetes and type 2 diabetes animal models [ 13 , 18 , 19 , 20 ] and patients [ 21 ] ( Figure 1 a) and that the abolishment of CB activity in animals, via chronic resection of the CSN or CB ablation, prevents and reverses dysmetabolism in rodent models of metabolic disease [ 13 , 15 , 16 ] ( Figure 1 b) by positively impacting glucose uptake and insulin signaling in the liver and in the visceral adipose tissue [ 15 ]. Additionally, we have previously shown that CSN resection in animal models prevents and restores the heightened sympathetic activity, measured as increased plasma and adrenal medulla catecholamines levels and increased LF bands and LF/HF ratio in heart rate variability analysis, which is characteristic of metabolic diseases [ 13 , 15 ].…”

“…Alongside the hypothesis that CB dysfunction contributes to metabolic diseases, we described how hypercaloric diet animals [ 13 ] and prediabetes patients [ 21 ] exhibit increased basal ventilation and showed that prediabetic dysmetabolism correlates with increased peripheral chemosensitivity, as evaluated by the Dejours test, which measures the decrease in basal ventilation produced by 100% O 2 (hyperoxia), and that this correlates with abdominal perimeter and insulin resistance [ 21 ]. This increased peripheral chemosensitivity observed both in prediabetes and type 2 diabetes was shown to be associated with increased CB weight, with an increase in the percentage of CB chemoreceptor cells and CB tyrosine hydroxylase activity as well as with augmented CB release of catecholamines and CSN activity in metabolic disease animals [ 13 , 18 , 19 , 22 ] and with an increase in CB size of approximately 25% in type 2 diabetes patients [ 23 ].…”

Carotid Body and Metabolic Syndrome: Mechanisms and Potential Therapeutic Targets

“…The CB is overactivated in prediabetic patients, and the variables related to CB chemosensitivity significantly correlate with fasting plasma insulin levels and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) [ 142 ]. Silencing CB activity via hyperbaric oxygen therapy significantly improved fasting blood glucose and glucose tolerance in patients with type 2 diabetes [ 143 ].…”