Depth and duration of hypoglycaemia achieved during the insulin tolerance test.

CONTEXT: The insulin tolerance test (ITT) is the gold standard for assessment of the pituitary adrenal axis but its use is limited because of concerns relating to the risk of hypoglycaemia. OBJECTIVE: This study examined the depth and duration of hypoglycaemia achieved during the test in a large cohort of patients. DESIGN: Two hundred and twenty ITTs were performed from 2005 to 2010. SETTING: A 1200-bed University Teaching Hospital. PATIENTS: Two hundred and twenty ITTs were carried out in patients with suspected or known pituitary disorders. INTERVENTIONS: Intravenous insulin was administered to achieve nadir plasma glucose (NPG) of 2.2 mmol/l (39.6 mg/dl). Blood chemistry to show the cortisol and GH response to hypoglycaemic stress was measured. MAIN OUTCOME MEASURES: Predictors of depth and duration of hypoglycaemia, adverse events and within-subject variability of nadir glucose, peak cortisol and peak GH were studied. RESULTS: Thirty percent of the cohort achieved a nadir glucose of <2.0 mmol/l (36 mg/dl) that lasted for 60 min or more. The NPG correlated positively with fasting plasma glucose (FPG; r=0:56; P<0.0005), insulin dose (r=0.27; P<0.0005) and weight (r=0.21; P<0.004). The within subject variability of nadir glucose was 15.2%, peak cortisol was 11.7% and peak GH was 6.4%. The factors determining nadir blood glucose were FPG (b=0.56, P<0.0005, 20% contribution) and weight (b=0.14, P<0.05, 2% contribution). The five patients with adverse events had NPG and insulin dose comparable with the rest of the population. CONCLUSIONS: The hypoglycaemia achieved during the ITT is much lower than the target required. However, adverse events are few and do not relate to the depth of hypoglycaemia.

Angiotensin stimulates respiration in spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHR) have an activated brain angiotensin system. We hypothesized 1) that ventilation (V) would be greater in conscious SHR than in control Wistar-Kyoto (WKY) rats and 2) that intravenous infusion of the ANG II-receptor blocker saralasin would depress respiration in SHR, but not in WKY. Respiration and oxygen consumption (VO(2)) were measured in conscious aged-matched groups (n = 16) of adult female SHR and WKY. For protocol 1, rats were habituated to a plethysmograph and measurements obtained over 60-75 min. After installation of chronic intravenous catheters, protocol 2 consisted of 30 min of saline infusion ( approximately 14 microliter. kg(-1). min(-1)) followed by 40 min of saralasin (1.3 microgram. kg(-1). min(-1)). V, tidal volume (VT), inspiratory flow [VT/inspiratory time (TI)], breath expiratory time, and VO(2) were higher, and breath TI was lower in "continuously quiet" SHR. In SHR, but not in WKY rats, ANG II-receptor block decreased V, VT, and VT/TI and increased breath TI. During ANG II-receptor block, an average decrease in VO(2) in SHR was not significant. About one-half of the higher V in SHR appears to be accounted for by an ANG II mechanism acting either via peripheral arterial receptors or circumventricular organs.