Respiratory responses of diabetics to hypoxia, hypercapnia, and exercise.

Williams, Joseph F.; Morris, Alanna; Hayter, R C; Ogilvie, Colin

doi:10.1136/thx.39.7.529

Cited by 64 publications

(48 citation statements)

References 24 publications

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“…There is evidence that carotid body function is impaired in diabetic patients. This is suggested by data that show the ventilatory response to hypoxia, which is mediated by the carotid bodies, is diminished in diabetic patients (35)(36)(37)(38). Impaired carotid body function may result from the increased carotid artery wall intima-media thickness that often accompanies glucose-intolerant or insulin-resistant states (39)(40)(41)(42)(43)(44).…”

Section: Discussionmentioning

confidence: 97%

Evidence that carotid bodies play an important role in glucoregulation in vivo.

et al. 2000

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The carotid bodies are sensitive to glucose in vitro and can be stimulated to cause hyperglycemia in vivo. The aim of this study was to determine if the carotid bodies are involved in basal glucoregulation or the counterregulatory response to an insulin-induced decrement in arterial glucose in vivo. Dogs were surgically prepared >16 days before the experiment. The carotid bodies and their associated nerves were removed (carotid body resected [CBR]) or left intact (Sham), and infusion and sampling catheters were implanted. Removal of carotid bodies was verified by the absence of a ventilatory response to NaCN. Experiments were performed in 18-h fasted conscious dogs and consisted of a tracer ([3-3 H]glucose) equilibration period (-120 to -40 min), a basal period (-40 to 0 min), and an insulin infusion (1 mU · kg -1 · min -1 ) period (0-150 min) during which glucose was infused as needed to clamp at mildly hypoglycemic (65 mg/dl) or euglycemic (105 mg/dl) levels. Basal (8 µU/ml) and clamp (40 µU/ml) insulin levels were similar in both groups. Basal arterial glucagon was reduced in CBR compared with Sham (30 ± 2 vs. 40 ± 2 pg/ml) and remained reduced in CBR during hypoglycemia (peak levels of 36 ± 3 vs. 52 ± 7 pg/ml). Cortisol levels were not significantly different between the 2 groups in the basal state, but were reduced during the hypoglycemic clamp in CBR. Catecholamine levels were not significantly different between the 2 groups in the basal and hypoglycemic periods. The glucose infusion rate required to clamp glucose at 65 mg/dl was 2.5-fold greater in CBR compared with Sham T here is considerable uncertainty as to the site at which decrements in blood glucose are sensed. Sites in the brain (1), portal vein (2,3), liver (4), and pancreas (5) are all sensitive to blood glucose. Despite intensive investigation, however, the physiological role of these glucose-sensitive regions are highly controversial because no one site can completely explain the full counterregulatory response to hypoglycemia.We tested the hypothesis that the carotid bodies (or receptors near this site) are instrumental in detecting a decrement in blood glucose. This hypothesis was based on evidence that 1) the carotid bodies can detect glucose (6-8), 2) the carotid bodies have the "circuitry" to provide input to centers involved in glucoregulation (7-10), and 3) the carotid bodies have unique physiological characteristics making them potentially highly sensitive to changes in blood glucose content (high blood flow and metabolic rate per gram tissue) (11).To examine the role of the carotid bodies (or receptors anatomically near them), carotid body resected (CBR) conscious dogs or dogs having undergone a sham surgery (Sham) were studied in the basal state and during hyperinsulinemic, euglycemic, or hypoglycemic clamps. Isotope dilution methods were used to calculate glucose kinetics. RESEARCH DESIGN AND METHODSAnimal maintenance and surgical procedures. Mongrel dogs (n = 23, mean weight 25.1 ± 0.6 kg) of either sex that had been fed a standard...

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Section: Discussionmentioning

confidence: 97%

Evidence that carotid bodies play an important role in glucoregulation in vivo.

et al. 2000

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“…This suggests that the HPA axis response to this challenge remains intact in diabetic subjects and is independent of peripheral autonomic dysfunction. However, it should be noted that subjects in the present study were matched in terms of glycaemic control and all had relatively normal glucose levels at the time of testing, and previous studies have reported that uncontrolled diabetes and acute hyperglycaemia or hypoglycaemia may be associated with altered HPA axis activity [12,23]. Cortisol responses to graded exercise have been shown to be impaired in diabetic subjects with autonomic neuropathy, albeit only at maximum workload [14,24], and it has been suggested that this is due to an impairment in sympathetic afferent impulses [24].…”

Section: Discussionmentioning

confidence: 99%

A new test for autonomic cardiovascular and neuroendocrine responses in diabetes mellitus: evidence for early vagal dysfunction

2004

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Aims/hypothesis: Diabetic autonomic neuropathy affects many physiological systems, producing a variety of important clinical manifestations. It is associated with high morbidity and mortality, particularly during times of stress. This is thought to be due to an increased risk of cardiac arrhythmias, although the exact mechanisms involved have yet to be fully elucidated. The aim of the present study was to investigate the endocrine, cardiac autonomic and psychological responses of diabetic patients with and without autonomic neuropathy to a single breath of 35% CO 2 . Methods: The 35% CO 2 challenge was performed in 20 male diabetic subjects, 11 of whom had autonomic neuropathy. Results: Baseline and stimulated cortisol, prolactin, systolic blood pressure and emotional arousal were similar in the two groups. However, subjects with autonomic neuropathy failed to demonstrate the expected CO 2 -induced bradycardia seen in the non-neuropathic patients (p<0.0001). Conclusions/ interpretation: The CO 2 challenge can be safely and easily administered to produce hypothalamic-pituitary-adrenal axis and cardiac autonomic activation, as well as emotional arousal. The test clearly distinguishes between subjects with and without cardiac autonomic neuropathy and could be an important adjunct to the methods currently available for the investigation and diagnosis of diabetic autonomic neuropathy.

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“…Animal models with chemically induced diabetes suggest that abnormal ventilatory responses to hypoxia and/or hypercapnia may be partially responsible (195;196). Studies in diabetic patients also show that abnormalities in O 2 ad CO 2 sensitivity may have an important role in increasing respiratory control instability during sleep (197)(198)(199)(200)(201). Whether diabetes also contributes to mechanical alterations in the upper airway and thus increasing upper airway collapsibility during sleep remains an open question.…”

Section: Diabetes As a Risk Factor For Sleep Apneamentioning

confidence: 99%