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Biomedical subjects

J Hilsted

Publications and source records attributed to J Hilsted.

At least 55 records · Page 3Linked to original sources
PubMed1994

Theophylline enhances glucose recovery after hypoglycemia in healthy man and in type I diabetic patients.

The principal mediators of glucose counterregulation (glucagon and epinephrine) use intracellular cyclic adenosine monophosphate (cAMP) to mediate glucose release. Since theophylline increases cAMP (by inhibiting its decomposition), we investigated the effect of theophylline on glucose recovery after insulin-induced hypoglycemia. Eleven healthy subjects and nine type I (insulin-dependent) diabetic patients each participated in two experiments in randomized order, receiving on both days an insulin bolus of 0.15 IU/kg soluble insulin. On one day, theophylline (intravenous [IV] bolus of 220 mg followed by IV infusion of 1 mg/kg/h) was administered from 1 hour before induction of hypoglycemia until the end of the study period. On the other day, NaCl was administered. Plasma glucose before induction of hypoglycemia was equal on the 2 study days. The plasma glucose area under the curve (AUC) was larger with theophylline than with NaCl (P = .04 for diabetic patients and P = .003 for healthy subjects). During the most active phase of glucose counterregulation, the rate of increase of plasma glucose was larger with theophylline (P = .003 for diabetic patients and P = .03 for healthy subjects). The incremental AUC for cAMP was larger with theophylline for diabetic patients (P = .01). For healthy subjects, cAMP was greater with theophylline 30 minutes after insulin (P = .03). In conclusion, glucose recovery after hypoglycemia is significantly increased when theophylline is administered in an asthma dosage before hypoglycemia is induced. This may be due to a significant enhancement of the cAMP response.

Adult↗
PubMed1994

Effect of glucagon-like peptide-1 (proglucagon 78-107amide) on hepatic glucose production in healthy man.

The newly discovered intestinal hormone, glucagon-like peptide-1 (GLP-1) (proglucagon 78-107amide), stimulates insulin secretion and inhibits glucagon secretion in man and may therefore be anticipated to influence hepatic glucose production. To study this, we infused synthetic GLP-1 sequentially at rates of 25 and 75 pmol.kg-1.h-1 into eight healthy volunteers after an overnight fast and measured plasma concentrations of glucose, insulin, and glucagon and glucose turnover by a technique involving infusion of 3-3H-glucose. Plasma levels of GLP-1 increased by 21.3 +/- 3.1 and 75.4 +/- 3.2 pmol/L during the infusion, changes that were within physiologic limits. In a control experiment only saline was infused. During GLP-1 infusion, plasma glucose level decreased significantly (from 5.3 +/- 0.1 to 4.7 +/- 0.1 and 4.3 +/- 0.1 pmol/L at the end of the two infusion periods). Despite this, plasma insulin level increased significantly (from 20.5 +/- 2.9 to a peak value of 33.5 +/- 5.2 pmol/L during the second period), and plasma glucagon level decreased (from 9.3 +/- 1.7 to 7.1 +/- 1.0 pmol/L). Glucose rate of appearance (Ra) decreased significantly to 75% +/- 6% of the preinfusion values during GLP-1 infusion. Glucose disappearance rate (Rd) did not change significantly, but glucose clearance increased significantly compared with saline. All parameters of glucose turnover remained constant during saline infusion. We conclude that GLP-1 may potently control hepatic glucose production and glucose clearance through its effects on the pancreatic glucoregulatory hormones. The effect of GLP-1 on glucose production is consistent with its proposed use in the treatment of type II diabetes.

Adult↗
PubMed1993

[Diabetic neuropathy: prevention and treatment].

Considerable progress has been made regarding symptomatic treatment of diabetic neuropathy. Apart from causal treatment (optimising metabolic control) a number of treatment modalities are now available for symptomatic diabetic neuropathy. The principles of symptomatic treatment depend very much upon which area of innervation is primarily affected. The optimal treatment of symptomatic diabetic neuropathy often requires the intervention of several clinical and paraclinical subspecialties.

Diabetic Neuropathies↗
PubMed1993

Cimetidine suspension as adjuvant to energy restricted diet in treating obesity.

OBJECTIVE: To study the effect of cimetidine suspension compared with placebo suspension on weight loss in moderately obese patients taking a 5 MJ/day diet supplemented with dietary fibre. To determine the relation between the effectiveness of the blinding and weight loss. DESIGN: Randomised double blind study with an eight week parallel group phase and a subsequent eight week crossover or continuation phase. SETTING: Outpatient clinic. SUBJECTS: 60 patients (51 women) aged 18-60. MAIN OUTCOME MEASURE: Weight loss. RESULTS: After eight weeks of treatment the mean weight loss in the cimetidine group (5.7 kg) was similar to that of the placebo group (5.9 kg; p = 0.78, 95% confidence interval -2.0 to 1.5 kg). Body mass index, waist and hip measurements, waist-hip ratio, and systolic and diastolic blood pressures decreased similarly in the two groups. No association was found between weight loss and the patients' ability to guess if they were being given drug or placebo. Correct guesses of current drug were more prevalent than expected by chance (25/37 correct, p = 0.05 for the parallel group phase; 26/30, p = 0.0001 for the crossover phase). CONCLUSIONS: Cimetidine had no effect on weight loss in moderately obese patients. The study underlines the potential problem that blinding of patients to treatment can be compromised.

Adolescent↗
PubMed1993

Impaired pancreatic polypeptide response to a meal in type 1 diabetic patients: vagal neuropathy or islet cell dysfunction?

The pancreatic polypeptide (PP) response to a mixed meal was investigated in seven insulin-dependent diabetics without measurable signs of diabetic autonomic neuropathy, and in seven healthy subjects. Since acute changes in metabolic regulation might influence the meal-induced PP response, the insulin-dependent diabetic patients were studied during normo- and hyperglycemic experimental conditions at blood glucose levels of 5 and 15 mmol/l, respectively. The PP response was identical on the two occasions, the response being significantly smaller than in the healthy subjects. Thus, PP response is independent of short-term changes in metabolic control. Since the response was attenuated in the insulin-dependent diabetic patients, who had no otherwise measurable signs of neuropathy, the PP response to a meal could be a sensitive indicator of dysfunction of the reflex arc controlling PP secretion in insulin-dependent diabetic patients. Alternatively, the reduction in PP secretion in these patients reflects dysfunction of the PP secreting cells of the pancreas. Iv injection of cholecystokinin-8 elicited a small but significant increase in PP concentrations, while iv secretin did not increase PP concentrations at all in healthy subjects. These stimuli are therefore less suitable in the assessment of vagal neuropathy.

Adult↗
PubMed1993

Insulin facilitates transport of macromolecules and nutrients to muscles.

We previously showed that intravenous insulin increased plasma noradrenaline during euglycemia and without concomitant changes in plasma adrenaline. Insulin decreased plasma volume and increased the fractional escape rate of albumin from plasma. In normal subjects, oral glucose increased heart rate, systolic blood pressure and plasma noradrenaline. These changes were absent or attenuated in diabetic patients (without neuropathy) after an oral glucose load. These responses were normalized by insulin infusion. Our results suggest that insulin facilitates the transfer of macromolecules and nutrients from the blood to the extracellular space after food intake. This process may be greatly disturbed in insulin-dependent diabetic patients.

Biological Transport↗
PubMed1993

Observer variation in measurements of waist-hip ratio and the abdominal sagittal diameter.

In an out-patient weight loss study of 63 patients (54 female, 9 male), 53 completed a 16 week treatment with a low calorie diet and a 9 g/day fibre supplement. In these 53 patients, the average weight loss was 8.3 kg (s.e.m. 0.8). Waist-hip ratio (WHR) and abdominal sagittal diameter (SagD) were measured as indicators of fat distribution and visceral adipose tissue (visceral AT) was estimated by anthropometric computerized tomography calibrated equations. Four observers measured WHR and SagD ten times in eight patients. Two dietitians examined the patients throughout the clinical trial at weeks 0, 4, 8 and 16. Furthermore, two physicians examined the patients at week 12 in the trial. Two- and three-way analyses of variance were performed to estimate the contribution of single factors to the total variance. The contribution of observers, 3.2% and 3.8%, respectively, was of the same magnitude as the error variance (2.9% and 4.8% respectively) which is a measure of the intra-observer variation. The two dietitians had very similar recordings and contributed only 0.3% and 0.9% to the total variance for WHR and SagD, respectively. The contributions of the two physicians to the total variance were 0.0% for WHR and 0.4% for SagD. It is concluded that there is no need to use several observers or repeated measurements of waist, hip and SagD in clinical anti-obesity trials.

Adipose Tissue↗
PubMed1992

Dual effect of insulin on plasma volume and transcapillary albumin transport.

During the past decade it has been demonstrated that insulin, apart from its effects on metabolism and ion fluxes, has acute effects on the cardiovascular system and capillary permeability. Intravenous infusion of insulin in doses which increase plasma insulin to physiological levels, induced vascular dilatation and increased muscle sympathetic nerve activity during a euglycaemic glucose clamp. During similar conditions insulin increased the transcapillary escape rate of albumin and reduced plasma volume. Insulin has also an indirect effect on vascular permeability during hypoglycaemia, which is mediated by the increase in plasma adrenaline. Adrenaline infusion increased haematocrit and decreased plasma volume and intravascular albumin mass. In contrast to insulin adrenaline did not increase the transcapillary escape rate of albumin. Total autonomic blockade during insulin-induced hypoglycaemia abolished the increase in haematocrit, but did not influence the decrease in plasma volume and the increase in the transcapillary escape rate of albumin. Insulin administration may also increase urinary albumin excretion, and this effect was observed during a euglycaemic clamp. The mechanism of the increase in capillary permeability after insulin has not been elucidated. A number of morphological studies indicate that insulin may have effects on endothelial cell morphology and paraendothelial cell permeability. These results indicate that insulin, apart from its effect on peripheral blood flow, may play a role in a normal transfer of macromolecules from the blood to the extracellular space after food intake. This process may be greatly disturbed in insulin-dependent diabetic patients.

Capillaries↗
PubMed1992

Effects of alpha-adrenoceptor and of combined sympathetic and parasympathetic blockade on cardiac performance and vascular resistance.

1. Cardiac performance and vascular resistance was studied in seven healthy men by radionuclide cardiography and venous plethysmography before and after alpha-adrenoceptor blockade with phentolamine and after combined alpha-adrenoceptor, beta-adrenoceptor (propranolol) and parasympathetic (atropine) blockade. 2. During alpha-adrenoceptor blockade heart rate and cardiac output increased considerably and left ventricular ejection fraction increased because of increased contractility. Systemic vascular resistance fell both during alpha-adrenoceptor blockade alone and during combined blockade. The increase in calf blood flow was of the same magnitude after combined blockade and after alpha-adrenoceptor blockade alone, and was considerably higher than the fall in systemic vascular resistance. Plasma catecholamine concentrations increased after phentolamine, but the changes were blunted when propranolol and atropine were added. 3. These results indicate that peripheral vasoconstriction especially that exerted by alpha-adrenoceptor nervous tone in skeletal muscle restricts left ventricular emptying of the intact heart. During pharmacologic blockade of the sympathetic and parasympathetic nervous system at rest the chronotropic state is augmented, whereas preload and inotropy are unaffected.

Adrenergic alpha-Antagonists↗
PubMed1992

The effect of genetically engineered glucagon on glucose recovery after hypoglycaemia in man.

To compare the effect on glucose recovery after insulin-induced hypoglycaemia of intramuscular genetically engineered glucagon, intramuscular glucagon from pancreatic extraction and intravenous glucose, we examined 10 healthy subjects during blockage of glucose counterregulation with somatostatin, propranolol and phentolamine. Each subject was studied on three separate occasions. Thirty min after a bolus injection of 0.075 iu soluble insulin per kilogram body weight the subjects received one of the following treatments: 1 mg glucagon from pancreatic extraction intramuscularly; 1 mg genetically engineered glucagon intramuscularly; and 25 g glucose intravenously, respectively. The two glucagon preparations induced an equally rapid increase in plasma glucose. This was due to an abrupt (within 4 min) and equal increase in glucose appearance rate. The increases in both plasma glucose and in glucose appearance rate were far more protracted after i.m. glucagon than after i.v. glucose. These results suggest that genetically engineered glucagon and glucagon from pancreatic extraction have a similar effect on hepatic glucose production rate. Due to the protracted effect of intramuscular glucagon, a combined treatment consisting of both intravenous glucose and intramuscular glucagon may be more effective in the treatment of hypoglycaemia than any of these given alone.

Adult↗
PubMed1991

Plasma volume changes during hypoglycaemia: the effect of autonomic blockade.

To investigate the role of the autonomic nervous system in changes in blood volume and composition induced by acute hypoglycaemia in man, seven healthy subjects participated in three experiments on separate days: insulin-induced hypoglycaemia with concomitant alpha-adrenoceptor blockade; insulin-induced hypoglycaemia with total autonomic blockade (alpha-adrenoceptor blockade combined with beta-adrenoceptor blockade and atropine); and insulin-induced hypoglycaemia without any autonomic blockade. In the experiments without autonomic blockade the peripheral venous hematocrit increased, plasma volume decreased, intravascular albumin content decreased and the transcapillary escape rate of albumin increased. In both experiments with autonomic blockade the increase in venous haematocrit was abolished, yet plasma volume decreased, intravascular albumin content decreased and the transcapillary escape rate of albumin increased in these experiments. Thus, the changes in plasma volume and composition in response to hypoglycaemia are due to the combined actions of adrenaline and of insulin.

Adult↗
PubMed1991

The effect of insulin withdrawal on intermediary metabolism in patients with diabetes secondary to chronic pancreatitis.

Insulin was withdrawn from 7 patients with Type I (insulin-dependent) diabetes and 4 patients with insulin-dependent diabetes secondary to chronic pancreatitis, both groups without residual beta-cell function. Median plasma glucagon concentrations rose slightly, but significantly after withdrawal of insulin in Type I diabetic patients (from 14 (range: 11-16) to 19 (14-25) pmol/l by 6 h), but not in the patients with secondary diabetes. This was accompanied by a significantly higher increase in blood glucose concentration from 5.1 (4.9-5.7) to 15.2 (12.9-18.1) mmol/l by 6 h in Type I diabetic patients compared with patients with secondary diabetes (from 4.9 (4.3-6.7) to 13.1 (10.9-13.5) mmol/l) (p less than 0.01). Beta-hydroxybutyrate increased to a similar extent in the two groups, whereas no significant increases were found in glycerol and lactate in any of the groups. Increased secretion of glucagon is not essential for the development of hyperglycemia and ketonemia in patients with diabetes secondary to chronic pancreatitis, but may augment the degree of hyperglycemia in Type I diabetic patients compared with patients having secondary diabetes.

3-Hydroxybutyric Acid↗
PubMed1991

Plasma glucagon and glucose recovery after hypoglycemia: the effect of total autonomic blockade.

The role of the autonomic nervous system in the glucagon response to hypoglycemia has not been fully clarified. We have studied the effect of total pharmacological blockade of the autonomic nervous system (concomitant alpha- and beta-adrenergic blockade with simultaneous atropine injection) and of isolated alpha-adrenergic blockade on hormonal responses to hypoglycemia and on blood glucose recovery after hypoglycemia in healthy subjects. Neither of the pharmacological blockades had any significant effects on plasma glucagon responses to hypoglycemia nor had they any effect on the rate of blood glucose recovery after hypoglycemia. We conclude that the autonomic nervous system has no major influence on the glucagon response to hypoglycemia in healthy man. Changes in autonomic nervous activity are not essential for blood glucose recovery after hypoglycemia in healthy man.

Adult↗
PubMed1991

Adrenergic receptors are a fallible index of adrenergic denervation hypersensitivity.

In view of evidence that neither interindividual nor induced intra-individual variations of adrenergic receptor status are related to metabolic or haemodynamic sensitivity to adrenaline in vivo, we took an alternative approach to assessment of the relevance of adrenergic receptor measurement by measuring these in a group of subjects with well-documented adrenergic denervation hypersensitivity, patients with diabetic autonomic neuropathy. Mononuclear leukocyte beta 2-adrenergic receptor densities (and binding affinities), measured with 125I-labelled pindolol, and isoproterenol-stimulated cyclic AMP accumulation, in samples from patients with insulin-dependent diabetes mellitus (IDDM) with diabetic autonomic neuropathy (n = 8), were no different from those in samples from patients with IDDM without neuropathy (n = 8), or from non-diabetic subjects (n = 8). In addition, platelet alpha 2-adrenergic receptor densities (and binding affinities), measured with 3H-labelled yohimbine, and adrenaline-induced suppression of cyclic AMP contents did not differ among the three groups. Thus, in contrast to idiopathic autonomic failure, there is no generalized increase in adrenergic receptors in autonomic failure due to diabetic autonomic neuropathy. Regardless of the mechanism of adrenergic denervation hypersensitivity in such patients, these data provide further evidence that measurements of cellular adrenergic receptors (and adenylate cyclase) in vitro are a fallible index of sensitivity to catecholamines in vivo.

Adult↗
PubMed1991

Scintigraphic determination of gastrointestinal transit times. A comparison with breath hydrogen and radiologic methods.

A scintigraphic method for determination of gastrointestinal transit times was compared with the breath hydrogen test and a multiple-bolus, single-radiograph technique. A close temporal association was found between the caecal appearance of radioactivity and the onset of breath hydrogen excretion in eight healthy subjects. Neither mean small-intestinal nor mean orocaecal transit times of the radiolabelled marker were correlated with the magnitude of hydrogen peak, hydrogen peak time, or the area under hydrogen curve. No correlation was noted between whole-gut transit time of the radiolabelled marker and mean whole-gut transit time calculated from a 6-day administration of the radiopaque marker in 16 healthy subjects. The stool weight was inversely correlated with the mean colonic (r = -0.46, p = 0.009) and the mean whole-gut (r = -0.45, p = 0.011) transit times of the radiolabelled marker. In conclusion, inadequate delineation of the caecal region seems to be an unimportant drawback of the scintigraphic measurements, whereas day-to-day variation in gastrointestinal transit rates may influence the reliability of the assessments. Probably, quantitative transit data cannot be obtained from the breath hydrogen concentration profiles.

Adult↗
PubMed1991

Peripheral blood flow control in diabetes mellitus.

Long term diabetes has a profound effect on the peripheral circulation. This has been demonstrated to be due to the presence of angiopathy and autonomic neuropathy, affecting autoregulation and distensibility of the vessels as well as local and central reflex regulation of the vascular resistance. Whereas the hemodynamic consequences of vascular denervation are well known (causing blood pressure maladaptation to a number of stimuli such as standing, exercise and agonist infusion) (Hilsted 1985), the consequences of disturbances in autoregulation and distensibility remain to be established.

Diabetes Mellitus↗
PubMed1990

Glucose counterregulation in diabetes secondary to chronic pancreatitis.

Glucose counterregulation and hormonal responses after insulin-induced hypoglycemia were investigated in six patients with diabetes mellitus secondary to chronic pancreatitis, in seven with insulin-dependent (type I) diabetes mellitus, and in seven healthy subjects. Glucose counterregulation was identical in type I patients and in the patients with chronic pancreatitis, whereas both groups had impaired glucose recovery compared with the healthy subjects. The patients with chronic pancreatitis had no glucagon response to hypoglycemia, whereas epinephrine increased significantly. In an additional experiment, glucose recovery did not occur after hypoglycemia during concomitant beta-adrenoceptor blockade in these patients. In conclusion, glucose counterregulation is preserved but slightly impaired in patients with diabetes secondary to chronic pancreatitis, and the combination of total glucagon deficiency and pharmacological blockade of the metabolic actions of circulating epinephrine abolishes glucose counterregulation after hypoglycemia.

Adrenergic beta-Antagonists↗