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Biomedical subjects

I Macdonald

Publications and source records attributed to I Macdonald.

At least 37 records · Page 2Linked to original sources
PubMed1998

The impact of early and late shift changeovers on sleep, health, and well-being in 8- and 12-hour shift systems.

The effects on industrial shift workers of the timing of the changeover from the night to morning shift and of the length of the shift were examined. Two groups changed over at 6 a.m. and worked either 8-hr or 12-hr shift systems; the other 2 groups changed over at 7 a.m., working either 8- or 12-hr systems. Night sleeps between consecutive shifts that started at 6 a.m. were shorter and more disrupted than those starting at 7 a.m. Day sleeps following night shifts that finished at 6 a.m. were longer and less disrupted than those finishing at 7 a.m. Early starts were associated with poorer psychological and physical health. These effects of changeover time are considered in relation to the circadian rhythms in sleep duration and propensity. Although several measures favored 12-hr shifts, physical health indicators appeared to favor 8-hr systems, especially in combination with late changeovers. However, the observed effects of shift length on chronic outcome measures are somewhat inconsistent with previous research findings.

Adaptation, Psychological↗
PubMed1998

Work shift duration: a review comparing eight hour and 12 hour shift systems.

OBJECTIVES: Shiftwork is now a major feature of working life across a broad range of industries. The features of the shift systems operated can impact on the wellbeing, performance, and sleep of shiftworkers. This paper reviews the current state of knowledge on one major characteristic of shift rotas-namely, shift duration. Evidence comparing the relative effects of eight hour and 12 hour shifts on fatigue and job performance, safety, sleep, and physical and psychological health are considered. At the organisational level, factors such as the mode of system implementation, attitudes towards shift rotas, sickness absence and turnover, overtime, and moonlighting are discussed. METHODS: Manual and electronic searches of the shiftwork research literature were conducted to obtain information on comparisons between eight hour and 12 hour shifts. RESULTS: The research findings are largely equivocal. The bulk of the evidence suggests few differences between eight and 12 hour shifts in the way they affect people. There may even be advantages to 12 hour shifts in terms of lower stress levels, better physical and psychological wellbeing, improved durations and quality of off duty sleep as well as improvements in family relations. On the negative side, the main concerns are fatigue and safety. It is noted that a 12 hour shift does not equate with being active for only 12 hours. CONCLUSIONS: There can be considerable extension of the person's time awake either side of the shift. However, the effects of longer term exposure to extended work days have been relatively uncharted in any systematic way. Longitudinal comparative research into the chronic impact of the compressed working week is needed.

Absenteeism↗
PubMed1998

Reduced counterregulation during hypoglycemia with raised circulating nonglucose lipid substrates: evidence for regional differences in metabolic capacity in the human brain?

We have investigated the potential for the human brain to use lipid fuels during acute hypoglycemia. Nine healthy male subjects underwent hyperinsulinemic (1.5 mU/kg x min) stepped hypoglycemic clamps on two occasions, infusing Intralipid (20%) and heparin (0.1 U/kg x min) on one occasion only (ILH), with an identical study without infusion of ILH acting as a control. Five subjects also underwent euglycemic clamping with Intralipid/heparin infusion. During hypoglycemia, ILH raised circulating levels of nonesterified fatty acids, glycerol, and beta-hydroxybutyrate, although the latter did not rise until after the onset of counterregulation. With ILH, epinephrine responses [area under the curve (AUC), 127.9 +/- 31.7 vs. 175.1 +/- 27.4 nmol/L x 180 min; P = 0.03] and GH responses (AUC, 260 +/- 91 vs. 1009 +/- 150, P < 0.01) were reduced and delayed (glucose thresholds, 2.8 +/- 0.04 vs. 3.0 +/- 0.1 mmol/L; P = 0.04), with a trend toward reduced cortisol responses. Similarly, hypoglycemic symptom scores were diminished during ILH (AUC, 647 +/- 162 vs. 1222 +/- 874; P = 0.03). However, there was no significant effect on the deterioration in four-choice reaction time, one measure of cognitive deterioration [glucose thresholds, 2.6 +/- 0.1 vs. 2.7 +/- 0.1 mmol/L, ILH vs. control (P = 0.75); AUC, 1420 +/- 710 vs. 2250 +/- 1080 ms/min (P = 0.59)]. During euglycemic clamping with Intralipid/heparin infusion studies, there was no rise in hormones, four-choice reaction time, or symptoms other than hunger and tiredness. Both nonesterified fatty acids and glycerol can penetrate the mammalian brain and be metabolized. Raised levels were able to reduce neurohumoral responses to hypoglycemia, but could not protect cognitive function. This suggests that regional differences exist in human brain metabolism between glucose-sensing and cognitive areas of brain, which may be important in the understanding of the mechanisms of glucose sensing and in the genesis of hypoglycemia unawareness in insulin-dependent diabetes.

3-Hydroxybutyric Acid↗
PubMed1998

Effects of glycemic control on protective responses against hypoglycemia in type 2 diabetes.

OBJECTIVE: To determine the effects of glycemic control on the counterregulatory responses to hypoglycemia in type 2 diabetes. RESEARCH DESIGN AND METHODS: Seven poorly controlled type 2 diabetes patients (mean HbA1c, 11.3 +/- 1.1%) were studied by stepped hyperinsulinemic hypoglycemic clamp (nadir, 2.4 mmol/l) before and after improving glycemic control with insulin treatment. Counterregulatory hormones, symptoms, and four-choice reaction time were measured at each glucose plateau. RESULTS: In patients with poorly controlled type 2 diabetes, counterregulatory hormone responses began at higher plasma glucose levels than did those in healthy subjects (epinephrine, 4.4 +/- 0.2 vs. 3.7 +/- 0.2 mmol/l, P = 0.011). After significant improvement in glycemic control (mean HbA1c, 8.1 +/- 0.9%, P < 0.001) was achieved without severe hypoglycemia, hormonal responses started at much lower plasma glucose levels (e.g., epinephrine, 3.5 +/- 0.3 mmol/l, P = 0.005) and were significantly reduced in magnitude (e.g., area under epinephrine response curve, 306 +/- 93 vs. 690 +/- 107 nmol.min-1.l-1, P = 0.012). This was accompanied by a change in the plasma glucose threshold at which hypoglycemic symptoms first developed from 3.6 +/- 0.2 to 3.0 +/- 0.2 mmol/l (P = 0.019). In contrast, the plasma glucose threshold at which four-choice reaction time deteriorated did not change significantly (3.1 +/- 0.1 vs. 2.9 +/- 0.1 mmol/l, P = 0.125). CONCLUSIONS: Counterregulatory responses begin at normoglycemia in poorly controlled type 2 diabetes. Improving glycemic control with insulin therapy normalizes hormonal responses but lowers the plasma glucose levels at which hypoglycemic symptoms develop to levels associated with impairment of four-choice reaction time, a marker of cognitive function. This process potentially increases the risk of severe hypoglycemia, but to a lesser extent than occurs in type 1 disease.

Blood Glucose↗
PubMed1998

Shift length as a determinant of retrospective on-shift alertness.

OBJECTIVES: This study examined the combined effects of shift length (8 versus 12 hours) and night-to-morning-shift changeover time (0600 versus 0700) on retrospective on-shift alertness ratings. METHODS: An abridged version of the Standard Shiftwork Index, which included retrospective alertness ratings, was completed by 4 groups of industrial shift workers. Two groups worked 8-hour shift systems and started their morning shifts at either 0600 or 0700; the other 2 groups worked 12-hour systems, starting their day shifts at either 0600 or 0700. RESULTS: The 8-hour workers reported considerably higher levels of alertness in the afternoon, while the 12-hour workers were more alert than the 8-hour workers in the morning and at 2200. Workers who started their shift around 0600 were less alert during the morning than those who started around 0700. The data suggested that the combined effects of working 8-hour shifts and starting the morning shift at around 0600 have particularly deleterious effects upon alertness. CONCLUSIONS: Effects on alertness can be explained in terms of differences in elapsed time on duty, sleep duration, sleep disruption, and chronic fatigue. The findings of this study appear to contradict previous research demonstrating that the major deleterious effects of extended shifts and delayed changeovers upon alertness occur at night. However, it is acknowledged that the absence of a difference in alertness at night may have been due to floor effects. Nevertheless, the implications of the alertness ratings for performance and safety, particularly during the afternoon, should not be ignored.

Adult↗
PubMed1998

Diurnal trends in mood and performance do not all parallel alertness.

OBJECTIVES: This study examined the hypothesis that alertness can be used to predict time-of-day effects on performance. METHODS: For 6 or 7 days the volunteers (24, highly practiced young women) were required to retire to bed at 0000 and were awakened at 0800. A battery of mood and performance tests was completed every 2 hours while the women were awake; the result was 9 equally spaced measures per day. Measures of mood, serial reaction time, and memory scanning were recorded. Rectal temperature was recorded continuously. RESULTS: After omitting the data from the first day to avoid any carry-over from the "first-night" effect on sleep, average time-of-day functions were calculated for each subject, for each variable, and were then z-transformed. Cross-correlations between the pooled time-of-day trends indicated that, while alertness was a reasonably good "predictor" of the simple perceptual-motor speed measures, it fared less well for some of the other measures. Two-way analyses of variance indicated that the time-of-day trend for all measures differed from that for alertness, although the magnitude of this difference varied substantially and, for some measures, was very largely due to the last reading of the day (0000). CONCLUSION: It is clear from these results that, while alertness may successfully "predict" variations in some measures of performance capability, and especially those of simple perceptual motor speed, care should be exercised in extrapolating to other performance measures.

Adolescent↗
PubMed1997

Construction and biological characterization of an interleukin-12 fusion protein (Flexi-12): delivery to acute myeloid leukemic blasts using adeno-associated virus.

Interleukin-12 (IL-12) is a cytokine that exhibits pleiotropic effects on lymphocytes and natural killer cells and has been shown to have promise for the immunotherapy of cancer. The combination of the immune costimulatory molecule B7.1 and IL-12 has been shown to be synergistic for T cell activation. By transfecting tumor cells with both IL-12 and B7.1 cDNAs, it may be possible to use these modified targets as vaccines. A major obstacle in designing a vector to deliver these genes results from the structure of IL-12. Functional IL-12 is a heterodimer composed of two distinct subunits that are encoded by separate genes on different chromosomes. Production of functional IL-12 requires the coordinated expression of both genes. This presents several problems in vectors, particularly those in which additional genes, either a co-stimulatory gene or a selectable marker, are inserted. Therefore, we have constructed a single cDNA that encodes a single-chain protein, called Flexi-12, which retains all of the biological characteristics of recombinant IL-12 (rIL-12). The monomeric polypeptide Flexi-12 is able to induce the proliferation of phytohemagglutinin (PHA) blasts, induce PHA blasts to secrete interferon-gamma (IFN-gamma) and additionally, by preincubation, enhance the killing of K562 targets by PBLs. These phenomena are in a dose-dependent manner comparable to that seen with rIL-12. We have also shown that tyrosine phosphorylation of the STAT 4 transcription factor, which has been shown to be unique to the IL-12 signaling pathway, occurs with Flexi-12 at levels similar to those seen with rIL-12. We have packaged Flexi-12 into a recombinant adeno-associated virus (AAV) and used this vector to infect acute myeloid leukemic (AML) blasts. Infected AML blasts produced between 2 and 6 ng of IL-12/10(6) cells per ml per 48 hr. These studies also confirm that AAV is an efficient delivery vehicle for cytokines to leukemic cells. Direct analysis of these modified cells acting as tumor vaccines is underway.

Amino Acid Sequence↗
PubMed1997

Replacement of dietary fat by sucrose or starch: effects on 14 d ad libitum energy intake, energy expenditure and body weight in formerly obese and never-obese subjects.

OBJECTIVE: To investigate the impact of a high-sucrose diet vs a high-starch and a high-fat diet on 14 d ad libitum energy intake, body weight, energy expenditure and sympathoadrenal activity. MEASUREMENTS: Food intake; body weight and composition (bioelectrical impedance); 24 h energy expenditure, substrate oxidation rates, spontaneous physical activity, heart rate and appetite sensations in a respiration chamber (VAS scores); plasma catecholamine concentration and blood pressure. SUBJECTS: Twenty normal-weight, healthy women, 9 post-obese (body mass index (BMI): 22.9 +/- 0.7 kg/m2) and 11 closely matched controls (BMI: 22.6 +/- 0.4 kg/m2). RESULTS: Average 14 d ad libitum energy intake was 13% and 12% lower on the starch diet compared with the sucrose and fat diets, respectively (P < 0.05). In both post-obese and normal-weight subjects, body weight and fat mass decreased significantly on the starch diet (by 0.7 +/- 0.2 kg and 0.4 +/- 0.1 kg, respectively, P < 0.05). No changes were observed on the fat or sucrose diets. After 14 d on the sucrose diet, 24 h energy expenditure as well as postprandial plasma adrenaline and noradrenaline concentrations, were significantly increased compared with the other two diets. Overall satisfy and palatability ratings were also highest on the sucrose diet. CONCLUSION: Intake of a 14-d ad libitum high-starch diet decreased energy intake and body weight compared with a high-fat or high-sucrose diet. The increased energy expenditure observed on the sucrose-rich diet can probably be explained both by the increased intake of energy and fructose (mainly from sucrose) on this diet.

Adult↗
PubMed1997

Altered hierarchy of protective responses against severe hypoglycemia in normal aging in healthy men.

OBJECTIVE: To investigate the effect of normal aging on the protective responses against hypoglycemia, in view of the fact that type II diabetes is primarily a disease of aging, and its treatment is associated with risk of hypoglycemia with cognitive impairment. RESEARCH DESIGN AND METHODS: Plasma glucose was lowered stepwise from 5 to 2.4 mmol/l and restored by manipulation of an infusion of 20% glucose during 220-min intravenous infusion of 1.5 mU.kg-1.min-1 soluble insulin in 14 men; 7 were aged 60-70 years and the other 7 were 22-26 years. Changes in neurohumoral responses, subjective awareness, and choice reaction time were assessed. RESULTS: Hormonal responses were similar in the two groups, but symptoms began earlier in the younger men (at a plasma glucose of 3.6 +/- 0.1 vs. 3.0 +/- 0.2 mmol/l, P = 0.02) and were more intense (P = 0.03). Four-choice reaction time, a measure of psychomotor coordination, deteriorated earlier in the older men (at a plasma glucose of 3.0 +/- 0.1 vs. 2.6 +/- 0.1 mmol/l, P = 0.07) and to a greater degree. The difference between the glucose level for subjective awareness of hypoglycemia and the onset of cognitive dysfunction was lost in the older men (0.0 +/- 0.2 vs. 0.8 +/- 0.1 mmol/l, P < 0.007). CONCLUSIONS: Older men are prone to more severe cognitive impairment during hypoglycemia than younger men and are less likely to experience prior warning symptoms if blood glucose falls. This effect of normal aging may contribute to the risk of severe hypoglycemia in older diabetic patients treated with sulfonylureas and insulin.

Adult↗
PubMed1996

Short-term diabetic ketosis alters n-6 polyunsaturated fatty acid content in plasma phospholipids.

At present, no information is available about the possibility that acute loss of metabolic control might be able to modify fatty acid composition in IDDM patients. Therefore, the aim of this study was to determine whether a short-term period of ketosis has any effect on the composition of fatty acid of plasma phospholipids in a group of insulin-dependent diabetes mellitus (IDDM) patients. Eleven IDDM patients and nine healthy volunteers were studied. Patients were studied over a 2-day period; each 2-day period consisted of initial baseline measurements followed by a day of hyperglycemia and mild ketosis, which was promptly alleviated by insulin infusion. No significant difference in baseline percent fatty acid composition was observed between normal controls and IDDM patients. In IDDM patients, ketosis induced a significant decrease in percent arachidonic acid (20:4 n-6) content, with a significant parallel decline in n-6 total polyunsaturated fatty acids. A significant inverse correlation between the prevailing plasma glucose and the relative content of arachidonic acid in plasma phospholipids was observed (r = -0.35; P = 0.0488). A highly significant inverse correlation was observed between the change from baseline condition to ketosis of the ratio C20:4/C20:3, the product/precursor ratio for the reaction catalyzed by delta5-desaturase, and the values of hemoglobin A1c,(r = -0.855; P = 0.0015). In conclusion, short term diabetic ketosis is associated with a significant decrease in n-6 polyunsaturated fatty acid content in plasma phospholipids, especially arachidonic acid. This decrease in arachidonic acid appears to be related to the degree of metabolic derangement, whereas the influence of short-term diabetic ketosis on the ratio of C20:4 to C20:3 seems to be due to the degree of long-term metabolic control.

Adult↗
PubMed1996

The hemodynamic abnormalities in short-term insulin deficiency: the role of prostaglandin inhibition.

It has been suggested that the hemodynamic derangements present in diabetic ketoacidosis are the results not only of profound volume depletion but also of the effects of increased production of vasodilating prostaglandins (PGs), principally PGI2, released by adipose tissue. In animal and in vitro models, prostaglandin synthesis is increased during insulin deficiency. We assessed the effects of short-term ketosis on the metabolic and hemodynamic variables of 10 IDDM patients free from long-term complications and of 9 normal control subjects after a 7-day randomized double-blind indomethacin (INDO) (50 mg q.i.d.) or placebo treatment period. Calf blood flow (CBF), postocclusive reactive hyperemia (PORH), and recovery half-time (an index of overall perfusion) after PORH were measured by plethysmography. Left ventricular and myocardial functions were also studied in each different condition during placebo and INDO treatment in IDDM patients. During placebo treatment, the increase in CBF during ketosis was higher (1.75 +/- 0.29 ml / min / 100 ml muscle) than during INDO (0.85 +/- 0.17 ml / min) / 100 ml muscle; P = 0.007). PORH was similar in baseline conditions, during ketosis, and in recovery in both the placebo and INDO arms. Recovery half-time significantly increased during placebo (10 +/- 2; 200%; P < 0.01) but not during INDO (1 +/- 1; 106%; NS) treatment. In normal control subjects, insulin deficiency did not induce any significant effect on hemodynamic variables. In IDDM patients, during placebo treatment, ketosis increased both the cardiac index (from 3.4 +/- 0.7 to 4.1 +/- 0.81 / min / m; P < 0.01) and the stroke index (from 42 +/- 8 to 49 +/- 7 ml/m2; P < 0.01) without changes in left ventricular ejection fraction but with a significant increase in both left and right ventricular end-diastolic volumes. Metabolic recovery induced a normalization of these parameters. INDO treatment significantly blunted these alterations. In summary, we showed that during acute insulin deficiency, INDO-sensitive mechanisms mediate vascular disturbances. Moreover, INDO treatment was capable of completely preventing the cardiac venous return and the left ventricular alterations. INDO does not interfere with the overall ketogenetic process or with insulin-induced metabolic recovery.

3-Hydroxybutyric Acid↗
PubMed1996

A preliminary investigation into individual differences in the circadian variation of meal tolerance: effects on mood and hunger.

A forced desynchrony methodology was used to assess postprandial blood glucose in 9 female volunteers during a 3-h period following a mixed meal presented at four times of day (08:00, 14:00, 20:00, 02:00). The influence of time of day on the postmeal glucose responses was evaluated by calculating the area under the curve, largest increase, time taken to reach peak, and fasting level. Circadian variations in meal tolerance were found for the area under the curve and largest increase, responses were greater (indicating poorer meal tolerance) in the evening than the morning. Fasting blood glucose exhibited diurnal variation although in the opposite direction to meal tolerance; levels were higher in the morning than the evening. Time taken to reach peak levels was not modulated by circadian rhythmicity. Estimates of the timing of poorest meal tolerance and the magnitude of this intolerance were computed for each subject. Individual differences in the magnitude of meal intolerance were found to influence hunger and self-reported calmness. Subjects with good tolerance had rhythms in both calmness and hunger, which were not found in those with poor tolerance. Subjects with good tolerance also tended to rate themselves as feeling more calm. These mood and hunger effects may result from differences in insulin resistance, which is hypothesized to underlie the circadian variations in meal tolerance.

Adult↗
PubMed1996

Congenitally corrected transposition of the great arteries and exercise-induced ventricular tachycardia.

Congenitally corrected transposition of the great arteries (CCTGA) is an uncommon condition. Few patients survive past 50 years of age, because of associated congenital defects, systemic (morphological right) ventricular dysfunction, atrioventricular valvular insufficiency or complete heart block. A unique case is presented of exercise-induced ventricular tachycardia, which led to the diagnosis of CCTGA, without atrioventricular block or other cardiac anomalies.

Age Factors↗
PubMed1995

Haemodynamic responses in muscle and adipose tissue and whole body metabolic responses during norepinephrine infusions in man.

Circulatory metabolic and cardiovascular responses to 1-h-long infusions of norepinephrine (NE) (approx. 0.2 and 0.4 nmol/kg body weight per min) were measured on two separate occasions in six subjects. The infusions increased circulating NE concentrations 6- and 13-fold, respectively. Blood flow to adipose tissue, measured with the 133Xe clearance technique, increased from a basal value of about 3 ml/100 g per min, to about twice this value at 60 min with both doses of NE. In contrast muscle blood flow was unaffected. The higher dose of NE produced significant increments at 60 min in whole body oxygen consumption (approx. 9%), and circulating concentrations of glucose (approx. 18%), non-esterified fatty acids (approx. 200%) and glycerol (approx. 32%) which were greater than those observed with the low-dose infusion. Changes in blood pressure, pulse and CO2 exchange were observed within 5-10 min after the start of the infusion, whilst changes in adipose tissue blood flow were observed after 15-30 min. It is concluded that in humans (i) a dose of NE as low as 0.2 nmol/kg per min is sufficient to evoke both circulatory and metabolic responses; (ii) the pattern in the adipose tissue blood flow response to NE may help explain some of the conflicting reports about the haemodynamic effects of this hormone in adipose tissue; and (iii) blood flow and vascular resistance in different tissues may be affected in different ways by norepinephrine.

Adipose Tissue↗
PubMed1995

Cardiovascular and metabolic responses to adrenaline infusion in patients with short-term hypothyroidism.

OBJECTIVE: The relation between the clinical manifestations of thyroid disease (both hypo and hyper-thyroidism) and tissue sensitivity to catecholamines remains uncertain. It has been suggested that tissue adrenergic responsiveness is decreased in hypothyroidism, but the reports have been conflicting and have invariably focused on a single physiological response. Therefore the aim of the present study was to determine in patients with moderate, short-term, symptomatic hypothyroidism the responses of heart rate, systolic and diastolic blood pressure, forearm blood flow and metabolic rate to adrenaline infused at a rate known to achieve plasma concentrations in the middle of the physiological range. PATIENTS: Ten subjects (5M, age 43 +/- 3 years, mean +/- SEM) were studied. All were on thyroxine replacement for hypothyroidism following either thyroidectomy or radioactive iodine and had been biochemically euthyroid for at least 6 months. DESIGN: Studies were performed in random order. One study was undertaken on full replacement therapy and the other after 50 micrograms thyroxine daily for 2 weeks. After basal, supine measurements adrenaline was infused at 25 ng/kg/min for 30 minutes. MEASUREMENTS: Heart rate, blood pressure, blood glucose, metabolic rate and forearm blood flow were measured at rest and at 10-minute intervals throughout the adrenaline infusion. RESULTS: Free T4 (10.6 +/- 1.3 vs 17.6 +/- 2.0 pmol/l, P < 0.001) and free T3 (3.6 +/- 0.2 vs 4.6 +/- 0.3 pmol/l, P < 0.01) concentrations were significantly lower on 50 micrograms thyroxine than full replacement therapy. Fasting blood glucose concentrations (4.7 +/- 0.2 vs 4.7 +/- 0.1 mmol/l) were similar. The resting adrenaline concentrations were comparable, 0.29 +/- 0.18 and 0.24 +/- 0.14 nmol/l on 50 micrograms thyroxine and full replacement therapy respectively, and increased to a similar level (2.36 +/- 0.39 and 2.36 +/- 0.35 nmol/l) throughout the adrenaline infusion. The resting heart rate and metabolic rate were significantly lower on 50 micrograms thyroxine than full replacement therapy (68 +/- 2 vs 72 +/- 3 beats/min, P < 0.01; and 4.48 +/- 0.35 vs 4.88 +/- 0.39 kJ/min, P < 0.01) respectively, but the increase in heart rate (7 +/- 2 vs 8 +/- 2 beats/min) and metabolic rate (0.43 +/- 0.09 vs 0.43 +/- 0.06 kJ/min) did not differ on the two study days. Resting systolic blood pressure, diastolic blood pressure and forearm blood flow were comparable on 50 micrograms thyroxine and full replacement therapy as were the changes in systolic blood pressure (1 +/- 1 vs 1 +/- 1 mmHg), diastolic blood pressure (-7 +/- 2 vs -7 +/- 1 mmHg), forearm blood flow (1.4 +/- 0.1 vs 1.7 +/- 0.2 ml/min/100ml forearm) and blood glucose concentration (0.7 +/- 0.1 vs 0.7 +/- 0.1 mmol/l). CONCLUSIONS: Patients with short-term hypothyroidism appear to have a normal response to adrenaline infusion despite reduced baseline heart rate and metabolic rate. Thus, under physiological and mild pathophysiological conditions there appears to be no evidence of any synergy between thyroid status and sensitivity to catecholamines.

Adult↗
PubMed1994

Restoration of hypoglycaemia awareness in patients with long-duration insulin-dependent diabetes.

Hypoglycaemia without warning is a dangerous complication of insulin-dependent diabetes mellitus and it limits the use of intensified insulin therapy to reduce chronic diabetic complications. To investigate the possibility of restoring awareness; symptomatic, cognitive, and hormonal responses to controlled hypoglycaemia were studied in insulin-dependent diabetic patients with long disease duration (6 with good glycaemic control and 6 with poor control) before and after hypoglycaemia avoidance. At the start of the study, all had loss of hypoglycaemia awareness. Responses to the initial challenge were small (pooled area under curve [AUC] adrenaline 5.75 [SE 0.07] nmol/L per 260 min, pooled AUC symptom score 80 [1.3]) and only started when plasma glucose was significantly lower than the 2.8 (0.1) mmol/L at which cognitive function deteriorated. After 4.1 (1.1) months' scrupulous hypoglycaemia avoidance, hormone and symptom responses to the challenge were increased (AUC adrenaline 15.9 [0.1] nmol/L per 260 min, p = 0.01; AUC symptom score 275 [7], p < 0.001), starting at plasma glucose concentrations significantly higher than that causing cognitive dysfunction. Glycosylated haemoglobin did not deteriorate significantly. We conclude that the normal hierarchy of subjective awareness before cognitive dysfunction during hypoglycaemia can be restored by avoiding hypoglycaemia. This is independent of disease duration or initial metabolic control.

Adult↗
PubMed1994

Protection by lactate of cerebral function during hypoglycaemia.

Severe hypoglycaemia with brain dysfunction limits intensified therapy in patients with insulin-dependent diabetes mellitus, despite evidence that such therapy reduces the risk of chronic complications of the disease. We have investigated the effect of infusing lactate (a potential non-glucose fuel for brain metabolism) on protective, symptomatic neurohumoral responses and on brain function during hypoglycaemia in seven healthy men. Elevation of lactate (within a physiological range) substantially diminished catecholamines, growth hormone, cortisol, and symptomatic responses to hypoglycaemia and lowered the glucose level at which these responses began. Glucagon responses were unaffected. Lactate was also associated with a significant lowering of the glucose level at which brain function deteriorated, suggesting that brain function was protected during the hypoglycaemia. The defect in counter-regulation is similar to that seen in hypoglycaemia-prone diabetic patients. Initiation of the protective responses to hypoglycaemia (except glucagon) can be delayed by supporting metabolism with an alternative metabolic fuel. Cerebral cortical dysfunction of severe hypoglycaemia is also delayed. Our demonstration that higher brain function can be protected during hypoglycaemia may have therapeutic potential.

Adult↗