Interactions of stress hormones on lipid and carbohydrate metabolism in man with partial insulin deficiency

Abstract. The metabolic responses to 4-h infusions of adrenaline (3 μg kg^-1 h^-1) and cortisol (10 mg m^-2 h^-1 for 2 h followed by 5 mg m^-2 h^-1 for 2 h), separately and in combination, have been studied in six healthy subjects with concurrent somatostatin infusion (250 μg h^-1). A combined infusion of adrenaline, cortisol, glucagon (180 ng kg^-1 h^-1) and somatostatin has also been studied. Somatostatin plus adrenaline and somatostatin plus cortisol resulted in hyperglycaemia (at 240 min, somatostatin plus adrenaline 11·4 ± 0·4 mmol l^-1, P < 0·001; somatostatin plus cortisol 6·7 ± 0·3 mmol l^-1, P < 0·05; somatostatin alone 4·9 ± 0·4 mmol l^-1). No synergistic effect on blood glucose was seen with adrenaline and cortisol together. When glucagon was added, blood glucose rose more rapidly than without glucagon (9·3 ± 0·4 mmol l^-1v. 7·2 ± 0·5 mmol l^-1 at 45 min, P < 0·001), but plateau values were similar. Plasma NEFA levels were raised by somatostatin plus adrenaline (0·55 ± 0·04–1·82 ± 0·11 mmol l^-1 at 60 min). Somatostatin plus cortisol had no more effect on plasma NEFA than somatostatin alone. During the combined infusion of somatostatin plus adrenaline plus cortisol, a synergistic effect on plasma NEFA was observed (2·30 ± 0·11 mmol l^-1 at 60 min, P < 0·01 v. somatostatin plus adrenaline). This occurred despite a small escape of insulin secretion. The lipolytic actions of adrenaline are potentiated by elevated circulating cortisol levels in insulin-deficient man. Glucagon does not modify this response, but accelerates the development of hyperglycaemia.     

Reduced cardiac sympathetic autonomic tone after long-term nasal continuous positive airway pressure in obstructive sleep apnoea syndrome

The increased sympathetic activation that occurs in obstructive sleep apnoea (OSA) may play an important role in associated morbidity. We investigated the effect of long-term (3 month) nasal continuous positive airway pressure (CPAP) on the autonomic nervous system assessed by heart rate variability (HRV). Fourteen patients (12 men), mean age 61·4 ± 8·1 years, with OSA underwent continuous synchronized electrocardiographic and polysomnographic monitoring. The apnoea/hypopnoea index (AHI) decreased from 50·6 ± 13·7 to 2·2 ± 2·5 events h^?1 after CPAP. HRV analysis showed significant decreases in low frequency (LF; from 7·12 ± 1·06 to 6·22 ± 1·18 ln ms² Hz^?1; P<0·001), high frequency (HF; from 5·91 ± 0·87 to 5·62 ± 0·92 ln ms² Hz^?1; P<0·05) and LF/HF (from 1·21 ± 0·12 to 1·11 ± 0·15 ln ms² Hz^?1; P<0·001) when the patients were asleep. The decrease in LF/HF was prolonged into the daytime (from 1·33 ± 0·22 to 1·24 ± 0·21 ln ms² Hz^?1; P<0·001). Treatment of OSA by CPAP significantly reduced the parameters of cardiac sympathetic tone, a favourable effect.     

Glucose metabolism in chronic diabetic foot ulcers measured in vivo using microdialysis

Ten subjects with diabetes mellitus and unilateral chronic foot ulcer were investigated. Local tissue concentrations of glucose and lactate were measured using the microdialysis method at a distance of 0·5–1 cm from the edge of the ulcer and in normal skin in the contralateral foot. Subcutaneous blood flow in the area investigated was measured using the ¹³³Xe-washout technique. The interstitial glucose concentration in the ulcer was found to be lower than in intact skin (8·0 ± 1·0 mmol l^?1 vs. 8·5 ± 1·1 mmol l^?1) (P<0·02), and the interstitial lactate concentration was higher in the ulcer than in intact skin (3·2 ± 0·2 mmol l^?1 vs. 2·1 ± 0·3 mmol l^?1) (P<0·01). The subcutaneous blood flow was on average 40% higher in the ulcer than in the intact skin. The calculated local glucose uptake and lactate outputs were twofold higher in the ulcer than in the intact skin. However, the molar ratio between lactate output and glucose uptake was approximately two, both in the ulcer and in the intact skin, indicating that the glucose metabolism was qualitatively the same in the two regions.     

Altered skeletal muscle glucose transport and blood lipid levels in habitual cigarette smokers

We determined whether habitual cigarette smoking alters insulin-stimulated glucose transport and GLUT4 protein expression in skeletal muscle. Vastus lateralis muscle was obtained from 10 habitual cigarette smokers and 10 control subjects using an open muscle biopsy procedure. Basal 3-O-methylglucose transport was twofold higher (P > 0·01) in muscle from habitual smokers (0·05 ± 0·08 vs. 1·04 ± 0·19 μmol ml^?1 h^?1; controls vs. smokers respectively). Insulin (600 pmol l^?1) increased glucose transport 2·6-fold (P > 0·05) in muscle from control subjects, whereas no significant increase was noted in habitual smokers. Skeletal muscle GLUT4 protein expression was similar between the groups. FFA levels were elevated in the smokers (264 ± 49 vs. 748 ± 138 μmol l^?1 for control subjects vs. smokers; P < 0·05), and serum triglyceride levels were increased in the smokers (0·9 ± 0·2 vs. 2·3 ± 0·6 mmol l^?1 for control subjects vs. smokers; P < 0·05). Skeletal muscle carnitine palmitil (acyl) transferase activity was similar between the groups, indicating that FFA transport into the mitochondria was unaltered by cigarette smoking. In conclusion, cigarette smoking appears to have a profound effect on glucose transport in skeletal muscle. Basal glucose transport is markedly elevated, whereas insulin-stimulated glucose transport is impaired. These changes cannot be explained by altered protein expression of GLUT4, but may be related to increased serum FFA and triglyceride levels. These findings highlight the importance of identifying habitual cigarette smokers in studies aimed at assessing factors that lead to alterations in lipid and glucose homeostasis in people with non-insulin-dependent diabetes mellitus (NIDDM).     

Effects of a high‐fat meal on resistance vessel reactivity and on indicators of oxidative stress in healthy volunteers

High fat meals postprandially impair macrovascular endothelial function and a link to increased oxidative stress is suggested. Few information, on the other hand, exists on the effect of postprandial hyperlipidaemia on resistance vessel function. Under normal circumstances this vascular bed regulates tissue perfusion and, by controlling flow, impacts on macrovascular nitric oxide formation. The impact of a high fat meal (1200 kcal, 90 g fat, 46 g protein and 47 g carbohydrates) on postprandial resistance vessel reactivity and on indicators of oxidative stress was studied in 11 healthy subjects by venous‐occlusion plethysmography using another six subjects as time control group. Ingestion of the test meal resulted in a pronounced increase of serum triglycerides from 1·05 ± 0·61 mmol l^?1 in the fasting state to peak postprandial values of 1·94 ± 0·41 mmol l^?1 (P < 0·001) reached after 4 h and a return to baseline after 8 h. Fasting peak reactive hyperaemia (RH) was 19·6 ± 2·4 ml min^?1 (100 ml)^?1. Two hours after ingestion of the test meal peak RH was transiently reduced to 16·8 ± 2·2 ml min^?1 (100 ml)^?1 (P < 0·05). No alteration of resting forearm perfusion was observed. The time course of peak RH suggested a potential biphasic effect of the test meal with an early impairment and a late increase of RH. Ingestion of a lipid rich test meal did not exert any influence on either total plasma antioxidant capacity given in trolox equivalents (513 ± 26 μmol l^?1 at baseline) or on plasma peroxides measured as H₂O₂ equivalents (469 ± 117 μmol l^?1). Our results suggest that ingestion of a meal containing 90 g of fat results in a transient impairment of reactive hyperaemia in healthy subjects but these vascular alterations are not accompanied by signs of systemically increased oxidative stress.     

Intravenous adrenaline infusion causes vasoconstriction close to an intramuscular microdialysis catheter in humans

Aim: To test if a small muscle injury influences the vascular reactivity to adrenaline in human skeletal muscle. Methods: Blood flow was measured by ¹³³Xenon clearance in the gastrocnemius muscle of eight male subjects at basal and during i.v. infusion of adrenaline (0·1 nmol kg^?1 min^?1) or placebo. Measurements were done with (expts 2 and 3) or without (expt 1) the influence of a small muscle injury induced by inserting a microdialysis catheter. ¹³³Xenon was administered either (expt 1) conventionally into the muscle via a fine needle, or (expts 2 and 3) through a fine tube close to the inserted microdialysis catheter. Expt 3 (control expt) was identical to expt 2 except that placebo was infused instead of adrenaline. Mean ± SEM, n = 8. Results: The blood flow tended to increase during the adrenaline infusion in expt 1 (1·17 ± 0·10 to 1·39 ± 0·15, N.S.), whereas it decreased during the adrenaline infusion in expt 2, from 1·39 ± 0·14 to 1·03 ± 0·14 ml min^?1 100 g tissue^?1 (P<0·001). The blood flow change in response to adrenaline infusion was significantly different in expt 1 and expt 2 (P<0·05). Blood flow also decreased during the placebo infusion in expt 3 (1·15 ± 0·10 to 1·00 ± 0·09, P<0·01), but this decrease was significantly smaller than in response to the adrenaline infusion in expt 2, P<0·01. Conclusion: The present results are consistent with the hypothesis that the small muscle injury caused by the inserted microdialysis catheter influences the vascular reactivity to adrenaline in a vasoconstrictive direction.     

Postprandial impairment of resistance vessel function in insulin treated patients with diabetes mellitus type‐2

Reduced postischaemic reactive hyperaemia, is considered a marker of impaired resistance vessel function. Acute postprandial hyperlipidaemia has been shown to induce vascular dysfunction. In the present study, the impact of postprandial hyperglycaemia on resistance vessel reactivity was investigated in insulin treated type‐2 diabetic patients. The study was performed in 16 insulin treated type‐2 diabetics (eight male/eight female, age 47 ± 3 years, HbA1c 7·2 ± 0·2) and 16 controls. Reactive hyperaemia was measured in the forearm by venous occlusion plethysmography after 5 min of ischaemia in the fasting state and 90 min after a test meal. In diabetics, blood glucose increased from 8·7 ± 1·1 to 15·3 ± 1·0 mmol l^?1 (P<0·001) postprandially. This resulted in (i) a significant increase of resting blood flow (3·4 ± 0·3 to 4·8 ± 0·4 ml min^?1 100 ml^?1, P<0·01) and (ii) in a reduced peak reactive hyperaemia (52·3 ± 7·4 to 36·8 ± 4·3 ml min^?1 100 ml^?1, P<0·005). In controls, a similar effect of the meal on resting flow was observed but reactive hyperaemia was unaltered. In the absence of a test meal, basal flow as well as peak reactive hyperaemia remained unchanged in diabetic as well as in non‐diabetic subjects. Our data provide evidence that in the postprandial state resistance vessel reactivity becomes reduced in insulin treated type‐2 diabetic patients.     

The forearm and leg perfusion techniques in man do not give the same metabolic information

Summary. The present study evaluates whether forearm and leg perfusion techniques give the same metabolic information. Seven patients hospitalized for operation of uncomplicated disease were investigated pre-operatively in the fasted state, while seven other patients who were on intravenous nutrition were studied in the fed state. Blood flow and the extremity exchange of glucose, lactate, glycerol, free fatty acids and amino acids were measured simultaneously across the forearm and the leg in all individuals. In the fasted state the arteriovenous difference (a-v) of glucose uptake was statistically significant across the forearm while it was statistically insignificant across the. leg (0·27 ± 0·06 vs. -0·04±0·13 mmol l¹). The a-v differences of glycerol (0·025 ± 0·028 vs. -0·043 ± 0·013 mmol l¹) and free fatty acids (0·10 ± 0·03 vs. -0·10 ± 0·04 mmol l¹) were positive across the forearm while they were negative across the leg (P < 0·01). In the fasted state the a-v difference of oxygen uptake (3·93 ± 0·67 vs. 3·21 ± 0·44 mmol l¹) and blood flow (4·1 ± 1·0 vs. 4·0 ± 0·7 ml min¹ 100 g¹) did not differ between the arm and the leg, but the a-v difference in carbon dioxide production was significantly higher (P<0.05) across the forearm (2·43 ± 0·37 vs. 1·29 ± 0·29 mmol l¹) compared to the leg. In the fed state all the above-mentioned differences between forearm and leg became statistically insignificant. In the fed state the a-v difference of the sum of all amino acids was not significantly different from zero balance across the forearm (-146 ± 103 mmol l¹) while there was a significant release from the leg (-175 ± 6 mmol l¹, P<0.05). In the fed state the flux of the sum of all amino acids became significantly positive across the arm while it was not significantly different from zero balance across the leg. In the fed state, forearm blood flow was significantly higher than leg blood flow (6·2 ± 0·5 vs. 4·0 ± 0·2 ml min¹ 100 g¹, P<0.001). The results in the present study demonstrate that the metabolic balance across regions of peripheral tissues may simultaneously differ considerably, i.e. being positive across the forearm and negative across the leg. This fact may imply that some previous claims may need reconsideration about ‘peripheral tissue metabolism’ associated with a certain clinical condition.     

Persistence of counter-regulatory abnormalities in insulin-dependent diabetes mellitus after pancreas transplantation

Abstract Conventional insulin therapy does not correct the counter-regulatory abnormalities of insulin-dependent diabetes mellitus. Pancreas transplantation is an alternative therapy that restores the endogenous insulin secretion in diabetes. In this study, the effects of segmental pancreas transplantation on counter-regulation to mild hypoglycaemia were evaluated. Glucose kinetics and the counter-regulatory hormonal responses were assessed in eight insulin-dependent diabetics with end-stage renal failure who had received pancreas and kidney transplantation 1 year previously, seven diabetic uraemic subjects (candidates for combined transplantation), five patients with chronic uveitis on immunosuppressive therapy comparable to pancreas recipients and 10 normal subjects. Insulin (0·3 mU kg^-1 min^-1) was infused for 2h to induce mild hypoglycaemia (plasma glucose 3·2–3·5-mmol l^-1) and exogenous glucose was infused as required to prevent any glucose decrease below 3·1 mmol l^-1. After transplantation, two of eight recipients had hypoglycaemic episodes reported in their medical records. During the study, hepatic glucose production was rapidly suppressed in the controls and in the patients on immunsuppression (–80 ± 7 and –54 ± 7%, P < 0·001 vs. basal), and rebounded to the baseline values within 1 h (–3 ± 1 and –6 ± 2%, P= NS vs. basal). The transplant recipients had similar suppression in the first hour (–88 ± 8%, P < 0·001 vs. basal), but the suppression persisted in the second hour (–69 ± 11%, P < 0·001 vs. basal) indicating a lack of glucose counter-regulatory response. The uraemic-diabetics had reduced suppression of hepatic glucose production (–45 ± 14%, P < 0·001 vs. basal) with respect to the recipients (P < 0·001), but had the same lack of response in the second hour (suppression: –39 ± 12%, P < 0·001 vs. basal). In addition, the response of glucagon to hypoglycaemia was blunted in both the recipients and in the diabetic subjects. In conclusion, the alterations in glucose counter-regulation of insulin-dependent diabetes persists after segmental pancreas transplantation. Specifically, the increased sensitivity of hepatic glucose production to the action of insulin renders this defect more evident after transplantation.     

Osteocalcin metabolism in the pulmonary circulation

The aim of this study was to evaluate the role of the pulmonary vessel endothelium in the removal of circulating osteocalcin, by measuring the osteocalcin levels in serum from pulmonary and radial artery blood from 39 patients undergoing aorto‐coronary bypass. Because of the discrepancies between methods of measurement, two methods were used. Significant differences were observed in group A (n = 18), tested with heterologous radioimmunoassay (2·85 ± 0·67 μg l^?1 in the pulmonary versus 2·69 ± 0·67 μg l^?1 in the radial artery serum, P<0·001) and in group B (n = 21), tested with a two‐site immunoradiometric assay (5·22 ± 1·46 versus 4·93 ± 1·36 μg l^?1, P<0·01). The percentage differences were –5·54 ± 4·76% (P<0·001) in group A and –4·99 ± 8·13% (P<0·01) in group B; the comparison between the percentage differences was not significant. These different osteocalcin concentrations between the two vascular compartments were considered a marker of osteocalcin degradation. Therefore, the study seems to demonstrate that, as well as kidney, liver and bone, the lung is a relevant site of osteocalcin catabolism. The proteolytic activity of pulmonary vessel endothelium seems to involve about 5% of the circulating peptide.     

Impaired responses of plasma catecholamines to exercise in diabetic patients with abnormal heart rate reactions to tilt

Summary. The plasma catecholamine response to a standardized bicycle exercise test was evaluated in 24 insulin-dependent diabetic (IDDM) patients in whom the heart rate reactions to deep breathing (E/I ratio) and to tilt, the immediate acceleration and the transient deceleration (acceleration and brake indices), had been assessed as tests of autonomic neuropathy. Patients with an abnormal acceleration index (n= 8) showed, compared with non-diabetic (n= 18) controls who had participated in previous studies, an impaired increment in noradrenaline during exercise (80% of maximal working capacity) (MWC) (12·38 ± 1·46 nmol l^-1 vs. 18·74 ± 1·45 nmol I^-1; P<0·01) and adrenaline (50% of MWC: 0·25 ± 0·04 nmol I^-1 vs. 0·54 ± 0·08 nmol I^I–1; P<0·05). Similarly, patients with an isolated abnormal brake index (n= 6), i.e. with a normal acceleration index and a normal E/I ratio, showed compared with controls an impaired increment in noradrenaline (9·53 ± 1·66 nmol I^-1 vs. 18·74 ± 1·45 nmol I^-1; P<0·01) and adrenaline (1·41 ± 0·22 nmol I^-1 vs. 2·92 ± 0·51 nmol I^-1; P<0·05) during 80% of MWC. IDDM patients with abnormal heart rate reactions to tilt, an abnormal acceleration index or an abnormal brake index show impaired catecholamine responses to exercise, which can be demonstrated also in patients without signs of parasympathetic neuropathy.     

Autonomic nervous function at rest in aerobically trained and untrained oldermen

Therelationship between aerobictraining, vagal influence on the heart and ageing was examined by assessing aerobic fitness andresting heart rate variability in trained and untrained older men. Subjects were 11 trained cyclistsand runners (mean age=6±61·6 years) and 11 untrained, age-matchedmen (mean age=66±1·2 years). Heart rate variability testing involvedsubjects lying supine for 25 min during which subjects’ breathing was paced andmonitored (7·5 breaths min^?1). Heart rate variability was assessedthrough time series analysis (HRV_ts) of the interbeat interval. Results indicated thattrained older men (3·55±0·21 l min^?1) hadsignificantly (P<0·05) greater VO _2maxthan that of control subjects (2·35±0·15 l min^?1).Also, trained older men (52±1·8 beats min^?1) hadsignificantly (P<0·05) lower supine resting heart rate than that of controlsubjects (65±4·2 beats min^?1). HRV_ts at highfrequencies was greater for trained men (5·98±0·22) than for untrainedmen (5·23±0·32). These data suggest that regular aerobic exercise inolder men is associated with greater levels of HRV_ts at rest.     

Cardiac vagal activity following three intensities of exercise in humans

Cardioprotective benefits of exercising at vigorous intensities are known, but reservations remain in prescribing such activity to the untrained population, due to a perceived risk of cardiac events. Few studies have investigated the recovery of the autonomic nervous system (ANS) after a single exercise bout, especially following vigorous exercise in healthy, young but untrained individuals. In this study, the recovery of the ANS, in particular indices of vagal activity were measured postexercise, at three intensities similar to current international recommendations for health. Thirteen individuals (six females, 22·2 ± 3·1 years) performed three 20‐min constant load tests lying supine on a modified bicycle ergometer at the following intensities: moderate (2 mmol l^?1 blood lactate concentration, BLC); hard (3 mmol l^?1BLC); and vigorous (4 mmol l^?1BLC) as derived from a maximal test. ECG data were collected during 5‐min epochs at baseline then at: 5, 15, 30, 45 and 65‐min postexercise. Heart rate variability (HRV) analysis was performed to obtain R–R interval, standard time [root mean square of successive differences (RMSSD)] and frequency measures [natural logarithm of high (lnHF) and low frequency (lnHF)]. RMSSD, lnHF, lnLF and total power were reduced 5‐min postexercise following all three intensities (P<0·01). Decreases persisted up to 15‐min postexercise following hard and vigorous exercise only (P<0·01). In untrained young adults, parasympathetic reactivation is reduced up to 5‐min postexercise regardless of intensity, returning to baseline by 30 min even after vigorous exercise. In this population, the benefits of exercise outweigh any risks of cardiac events that may be evoked by a reduction in the influence of vagal activity.     

Interstitial lactate levels in human skin at rest and during an oral glucose load: a microdialysis study

In vitro data have suggested that the skin is a significant lactate source. The purpose of the present study was to measure lactate and glucose concentrations in intact human skin in vivo using the microdialysis technique. Microdialysis fibres of 216 μm were inserted intradermally and perfused at a rate of 3 μl min^–1. In the first experimental protocol, dialysis fibres were calibrated by the method of no net flux in eight subjects. Skin lactate concentrations of 2·48 ± 0·17 mmol l^–1 were significantly greater than lactate concentrations of 0·84 ± 0·15 mmol l^–1 in venous plasma (P<0·01). Glucose concentrations in skin and venous plasma were similar (5·49 ± 0·18 vs. 5·26 ± 0·24 mmol l^–1). In the second experimental protocol, changes in lactate and glucose levels were studied in 10 subjects after an oral glucose tolerance test (OGTT). After the OGTT, plasma glucose and lactate levels increased by 54% and 39% to peak levels at 30 and 60 min respectively. In comparison, skin glucose and lactate increased by 41% and 18% at 60 and 90 min. No changes in skin blood flow were observed during the OGTT. The data suggest that resting skin is a significant lactate source with no significant lactate production during OGTT. The cellular source of lactate in the skin remains undetermined to date.     

Inter-relations between the calcium set-points of Parfitt and Brown in primary hyperparathyroidism: a sequential citrate and calcium clamp study

Abstract. The objective of the present study was to compare the calcium set-points of E. M. Brown and A. M. Parfitt obtained by sequential citrate and calcium clamp in patients with primary hyperparathyroidism and healthy controls. Twenty-six patients with primary hyperparathyroidism were investigated and compared to 22 healthy volunteers. All participants were investigated by sequential calcium lowering and raising comprising the following four phases: Phase (1) blood ionized calcium lowering of about 0·20 mmol l^-1; phase (2) steady-state (relative) hypocalcaemia of blood ionized calcium 0·20 mmol l^-1 below baseline; phase (3) blood ionized calcium is raised to about 0·20 mmol l^-1 above baseline; and phase (4) (relative) hypercalcaemia of blood ionized calcium 0·20 mmol l^-1 above baseline. Serum parathyroid hormone (1–84) was measured by an immunoradiometric assay. Blood ionized calcium was measured by a calcium selective electrode. We found the calcium set-points of Parfitt to be 1·42 mmol l^-1 (SD 0·12, n= 52) vs. 1·25 mmol l^-1 (SD 0·04, n= 44) in patients and controls, respectively (P < 0·001). The calcium set-points of Brown were 1·32 mmol l^-1 (SD 0·10, n= 26) vs. 1·13 mmol l^-1 (SD 0·04, n= 22), respectively (P < 0·001). By comparing the calcium set-points of Parfitt and Brown, a strikingly good correlation was observed, in patients (r= 0·91, P < 0·001) and in controls (r= 0·85, P < 0·001). We demonstrate in this paper in vivo that Brown's and Parfitt's calcium set-points are raised in primary hyperparathyroidism and return to normal following parathyroidectomy. The values for Brown's and Parfitt's calcium set-points are significantly different, but strikingly well correlated, supporting the view that Brown and Parfitt describe two different points on the same sigmoidal curve, corresponding to 50% and about 85% inhibition of PTH maximum, respectively. The mathematical form of the sigmoidal curve between blood ionized calcium and parathyroid hormone is very similar in primary hyperparathyroidism and normal humans.     

Forearm metabolism during infusion of adrenaline: comparison of the dominant and non‐dominant arm

Human skeletal muscle metabolism is often investigated by measurements of substrate fluxes across the forearm. To evaluate whether the two forearms give the same metabolic information, nine healthy subjects were studied in the fasted state and during infusion of adrenaline. Both arms were catheterized in a cubital vein in the retrograde direction. A femoral artery was catheterized for blood sampling, and a femoral vein for infusion of adrenaline. Forearm blood flow was measured by venous occlusion strain‐gauge plethysmography. Forearm subcutaneous adipose tissue blood flow was measured by the local ¹³³Xe washout method. Metabolic fluxes were calculated as the product of forearm blood flow and a‐v differences of metabolite concentrations. After baseline measurements, adrenaline was infused at a rate of 0·3 nmol kg^?1 min^?1. No difference in the metabolic information obtained in the fasting state could be demonstrated. During infusion of adrenaline, blood flow and lactate output increased significantly more in the non‐dominant arm (8·12 ± 1·24 versus 6·45 ± 1·19 ml 100 g^?1 min^?1) and (2·99 ± 0·60 versus 1·83 ± 0·43 μmol 100 g^?1 min^?1). Adrenaline induced a significant increase in oxygen uptake in the non‐dominant forearm (baseline period: 4·98 ± 0·72 μmol 100 g^?1 min^?1; adrenaline period: 6·63 ± 0·62 μmol 100 g^?1 min^?1) while there was no increase in the dominant forearm (baseline period: 5·69 ± 1·03 μmol 100 g^?1 min^?1; adrenaline period: 4·94 ± 0·84 μmol 100 g^?1 min^?1). It is concluded that the two forearms do not respond equally to adrenaline stimulation. Thus, when comparing results from different studies, it is necessary to know which arm was examined.     

Early activation of the coagulation system during lower body negative pressure

We considered that a moderate reduction of the central blood volume (CBV) may activate the coagulation system. Lower body negative pressure (LBNP) is a non‐invasive means of reducing CBV and, thereby, simulates haemorrhage. We tested the hypothesis that coagulation markers would increase following moderate hypovolemia by exposing 10 healthy male volunteers to 10 min of 30 mmHg LBNP. Thoracic electrical impedance increased during LBNP (by 2·6 ± 0·7 Ω, mean ± SD; P < 0·001), signifying a reduced CBV. Heart rate was unchanged during LBNP, while mean arterial pressure decreased (84 ± 5 to 80 ± 6 mmHg; P < 0·001) along with stroke volume (114 ± 22 to 96 ± 19 ml min^?1; P < 0·001) and cardiac output (6·4 ± 2·0 to 5·5 ± 1·7 l min^?1; P < 0·01). Plasma thrombin–antithrombin III complexes increased (TAT, 5 ± 6 to 19 ± 20 μg l^?1; P < 0·05), indicating that LBNP activated the thrombin generating part of the coagulation system, while plasma D‐dimer was unchanged, signifying that the increased thrombin generation did not cause further intravascular clot formation. The plasma pancreatic polypeptide level decreased (13 ± 11 to 6 ± 8 pmol l^?1; P < 0·05), reflecting reduced vagal activity. In conclusion, thrombin generation was activated by a modest decrease in CBV by LBNP in healthy humans independent of the vagal activity.     

Decreased leg glucose uptake during exercise contributes to the hyperglycaemic effect of octreotide

Aim: During prolonged infusion of somatostatin, there is an increase in arterial glucose concentration, and this increase persists even during prolonged exercise. The aim of the study was to measure glucose uptake in the leg muscles during infusion of the somatostatin analogue octreotide before and during leg exercise. Material and methods: Eight healthy male subjects were investigated twice in the fasting state: during 3 h infusion of octreotide [30 ng (kg min)^?1] or sodium chloride with exercise at 50% of maximal VO₂ in the last hour. Glucose uptake and oxygen uptake in the leg were measured using Fick’s principle by blood sampling from an artery and a femoral vein. Blood flow in the leg was measured using the indicator (indocyanine green) dilution technique. Results: After an initial decrease during rest, octreotide infusion resulted in a significant increase in arterial glucose concentrations compared to control conditions during exercise (mean ± SEM: 7·6 ± 0·6 versus 5·6 ± 0·1 mmol l^?1, P<0·01). During rest, octreotide did not change the leg glucose uptake (59 ± 10 versus 55 ± 11 μmol min^?1). In contrast, leg glucose uptake was significantly lower during exercise compared to control conditions (208 ± 79 versus 423 ± 87 μmol min^?1, P<0·05). During exercise, leg oxygen uptake was not different in the two experiments (20·4 ± 1·3 versus 19·5 ± 1·1 μmol min^?1). Conclusion: In conclusion, infusion of octreotide reduced leg glucose uptake during exercise, despite the same leg oxygen consumption and blood flow compared to control conditions. The hyperglycaemic effect of octreotide can partly be explained by the reduction in leg glucose uptake. Furthermore, the results suggest that a certain level of circulating insulin is necessary to obtain sufficient stimulation of glucose uptake in the exercising muscles.     

Successive deep dives impair endothelial function and enhance oxidative stress in man

The aim of this study was to assess the effects of successive deep dives on endothelial function of large conduit arteries and plasma pro‐oxidant and antioxidant activity. Seven experienced divers performed six dives in six consecutive days using a compressed mixture of oxygen, helium and nitrogen (trimix) with diving depths ranging from 55 to 80 m. Before and after first, third and sixth dive, venous gas emboli formation and brachial artery function (flow‐mediated dilation, FMD) was assessed by ultrasound. In addition, plasma antioxidant capacity (AOC) was measured by ferric reducing antioxidant power, and the level of oxidative stress was assessed by thiobarbituric acid‐reactive substances (TBARS) method. Although the FMD was reduced to a similar extent after each dive, the comparison of predive FMD showed a reduction from 8·6% recorded before the first dive to 6·3% before the third (P = 0·03) and 5·7% before the sixth dive (P = 0·003). A gradual shift in baseline was also detected with TBARS assay, with malondialdehyde values increasing from 0·10 ± 0·02 μmol l^?1 before the first dive to 0·16 ± 0·03 before the sixth (P = 0·005). Predive plasma AOC values also showed a decreasing trend from 0·67 ± 0·20 mmol l^?1 trolox equivalents (first day) to 0·56 ± 0·12 (sixth day), although statistical significance was not reached (P = 0·08). This is the first documentation of acute endothelial dysfunction in the large conduit arteries occurring after successive deep trimix dives. Both endothelial function and plasma pro‐oxidant and antioxidant activity did not return to baseline during the course of repetitive dives, indicating possible cumulative and longer lasting detrimental effects.     

The effect of a very low-calorie diet-induced weight loss on the severity of obstructive sleep apnoea and autonomic nervous function in obese patients with obstructive sleep apnoea syndrome

The aim of this study was to examine the effect of a very low-calorie diet (VLCD)-induced weight loss on the severity of obstructive sleep apnoea (OSA), blood pressure and cardiac autonomic regulation in obese patients with obstructive sleep apnoea syndrome (OSAS). A total of 15 overweight patients (14 men and one woman, body weight 114 ± 20 kg, age 52 ± 9 years, range 39–67 years) with OSAS were studied prospectively. They were advised to follow a 2·51–3·35 MJ (600–800 kcal) diet daily for a 3-month period. In the beginning of the study, the patients underwent nocturnal sleep studies, autonomic function tests and 24-h electrocardiograph (ECG) recording. In addition, 15 age-matched, normal-weight subjects were studied. They underwent the Valsalva test, the deep-breathing test and assessment of heart rate variability at rest. The sleep studies and autonomic function tests were repeated after the weight loss period. There was a significant reduction in weight (114 ± 20 kg to 105 ± 21 kg, P<0·001), the weight loss being 9·2 ± 4·0 kg (range 2·3–19·5 kg). This was associated with a significant improvement in the oxygen desaturation index (ODI4) during sleep (31 ± 20–19 ±18, P<0·001). Before the weight loss the OSAS patients had significantly higher blood pressure (150 ± 18 vs. 134 ± 20, P<0·05, for systolic blood pressure, 98 ± 10 vs. 85 ± 13, P<0·05, for diastolic blood pressure) and heart rate (67 ± 10 beats min^?1 vs. 60 ± 13, P<0·05) at rest than the control group. They had also lower baroreflex sensitivity (4·7 ± 2·8 ms mmHg^?1 vs. 10·8 ± 7·1 ms mmHg^?1, P<0·01). During the weight reduction, the blood pressure declined significantly, and the baroreflex sensitivity increased by 49%. In conclusion, our experience shows that weight loss with VLCD is an effective treatment for OSAS. Weight loss improved significantly sleep apnoea and had favourable effects on blood pressure and baroreflex sensitivity that may have prognostic implications.