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Biomedical subjects

C Berne

Publications and source records attributed to C Berne.

At least 109 records · Page 6Linked to original sources
PubMed1993

Inhibition of insulin secretion, but normal peripheral insulin sensitivity, in a patient with a malignant endocrine pancreatic tumour producing high amounts of an islet amyloid polypeptide-like molecule.

Islet amyloid polypeptide or amylin is a polypeptide secreted mainly from the pancreatic beta cells together with insulin upon stimulation. High levels of islet amyloid polypeptide have also been shown to increase the peripheral insulin resistance and consequently a role for islet amyloid polypeptide in the glucose homeostasis has been suggested. We have studied the glucose homeostasis in a patient with a malignant endocrine pancreatic tumour producing large amounts of an islet amyloid polypeptide-like molecule (about 400 times the upper reference level for islet amyloid polypeptide). This patient developed insulin-requiring diabetes mellitus shortly after the tumour diagnosis. Both intravenous and oral glucose tolerance tests revealed inhibited early responses in insulin and C-peptide release, but the insulin and C-peptide response to glucagon stimulation was less affected. Aneuglycaemic insulin clamp showed normal insulin-mediated glucose disposal. In vitro experiments, where isolated rat pancreatic islets were cultured with serum from the patient, showed a moderately decreased islet glucose oxidation rate and glucose-stimulated insulin release compared to islets cultured with serum from healthy subjects. However, culture of rat islets with normal human serum supplemented with synthetic rat islet amyloid polypeptide did not affect the glucose-stimulated insulin release. In conclusion, the observed effects show that the diabetic state in this patient was associated with an impaired glucose-stimulated insulin release but not with an increased peripheral insulin resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Amyloid↗
PubMed1993

Metabolic regulation of sympathetic nervous system activity: lessons from intraneural nerve recordings.

Intraneural recordings of sympathetic nerve discharge give access to two subdivisions of the sympathetic nervous system: muscle nerve sympathetic activity and skin nerve sympathetic activity. Muscle nerve sympathetic activity (MSA) involves baroreceptor-controlled vasoconstrictor impulses to the resistance vessels in skeletal muscles. MSA is time-locked to the heart rhythm, correlates at rest to plasma noradrenaline concentrations and increases with age, but displays large inter-individual variations, the causes of which are poorly understood. Skin nerve sympathetic activity (SSA) is irregular with no relation to the pulse, is composed of sudomotor and cutaneous vasoconstrictor impulses and is practically absent in relaxed subjects in a thermoneutral environment. MSA and the sudomotor component of SSA are stimulated by acute insulin-induced hypoglycaemia, whereas the vasoconstrictor component of SSA is inhibited. MSA is stimulated by oral D-glucose but not by intravenous D-glucose or water. Under euglycaemia, insulin stimulates MSA in a dose-dependent fashion. Neither oral glucose nor insulin stimulate SSA. Exposure to carbohydrate intake and insulin have variable influences on the sympathetic nerve discharge. Various mechanisms are likely to operate in these interactions, including stimulation of central sympathetic motoneurons, baroreceptor control, and input from peripheral receptors in the vasculature or the gastrointestinal tract.

Glucose↗
PubMed1993

[Cost benefits of intensive insulin therapy using injections, external pumps and implantable pumps].

Since feasibility is now proven, cost-efficacy of external sub-cutaneous (EXT) and implantable programmable (IMP) insulin pumps needs to be compared to those of intensified conventional insulin therapy (CONV). Only metabolic efficacy and short-term direct costs are easily evaluable. We (WHO-CSII Study) and others have shown that glycemic control and severe hypoglycemia risk are slightly improved, while ketoacidosis risk and costs are aggravated with EXT vs CONV. We (CEDIT Study) and others have shown that glycemic control, mild and severe hypoglycemic risks are improved, with no increase in ketoacidosis rates although a doubling in costs with IMP vs CONV. Rigid interpretation of the above data would limit indications of insulin pumps to patients experiencing frequent hypoglycemias while on intensified conventional insulin therapy.

Blood Glucose↗
PubMed1992

The sympathetic response to euglycaemic hyperinsulinaemia. Evidence from microelectrode nerve recordings in healthy subjects.

Sympathetic nervous system activation by insulin has been suggested as a mechanism explaining the association between insulin resistance and hypertension. We further examined the effect of insulin by direct microneurographic muscle and skin nerve sympathetic activity recordings during euglycaemic insulin clamps in healthy subjects. The mean plasma insulin level was elevated from 5.3 +/- 0.7 to 92.2 +/- 2.2 mU/l in seven subjects during a 90-min one-step clamp. In six other subjects plasma insulin was further raised from 85.7 +/- 4.0 mU/l to 747 +/- 53 mU/l between 45-90 min (two-step clamp). Four of the latter subjects received a sham clamp with NaCl infusions only on a second recording session. At the low dose of insulin muscle nerve sympathetic activity increased from a resting level of 22.7 +/- 5.0 bursts per min to 27.7 +/- 5.0 bursts per min at 15 min (p less than 0.05). The increases in muscle nerve sympathetic activity were significant (p less than 0.001; ANOVA) throughout insulin infusion, with a slight further increase (from 29.2 +/- 1.6 to 32.3 +/- 1.9 bursts per min) at the supraphysiological insulin concentration. During sham clamps muscle nerve sympathetic activity did not increase. Both insulin clamps induced minor, but significant, increases in forearm venous plasma noradrenaline concentrations. Skin nerve sympathetic activity (n = 3) did not change during insulin infusions. Heart rate increased slightly but significantly (p less than 0.005), during the insulin clamps. Blood pressure was not notably affected. In conclusion, hyperinsulinaemia was associated with increased vasoconstrictor nerve activity to skeletal muscle and with no change of sympathetic outflow to skin.

Adult↗
PubMed1992

Impaired cutaneous reactive hyperaemia during hypoglycaemia in young insulin-dependent diabetic patients and healthy controls.

The aim of the present study was to compare the cutaneous postischaemic hyperaemic response in young insulin-dependent diabetic patients and healthy subjects during normoglycaemia, acute insulin-induced hypoglycaemia and in the posthypoglycaemic state. After a night of normoglycaemia the cutaneous postischaemic hyperaemic response in the forearm skin, measured by the transcutaneous PO2 method, was the same in both groups. A reduction of the maximal postischaemic vasodilatory response was observed in diabetic patients from 2.4 +/- 0.3 to 2.0 +/- 0.2 kPa (P less than 0.05) and in control subjects from 2.7 +/- 0.3 to 1.8 +/- 0.2 kPa (P less than 0.02) during insulin-induced hypoglycaemia (plasma glucose less than 2 mmol/l). Complete recovery of the vasodilatory response occurred in subjects in the posthypoglycaemic state. We conclude that hypoglycaemia induced a transient reduction of the vasodilatory response, which was rapidly reversed after glucose counter-regulation, in both diabetic patients and healthy controls. Thus, the prevailing blood glucose concentration must be taken into account when the postischaemic vasodilatory response is investigated in diabetic patients.

Adult↗
PubMed1992

Cutaneous blood flow during a hypoglycaemic clamp in insulin-dependent diabetic patients and healthy subjects.

1. A marked cutaneous vasodilatation has been shown to occur in healthy subjects, but not in insulin-dependent diabetic patients, in response to hypoglycaemia induced by a rapid intravenous bolus injection of insulin. 2. In the present study cutaneous blood flow in response to a gradual decline in blood glucose concentration was investigated in eight young adult diabetic patients and in eight age- and sex-matched control subjects. After a hyperinsulinaemic euglycaemic clamp for 40 min, hypoglycaemia was induced (plasma glucose concentration 2 mmol/l) by a standardized stepwise reduction in the intravenous glucose infusion. 3. Blood flow was measured by using a laser Doppler sensor and a cutaneous O2 electrode placed on the medial aspect of the forearm, and a laser Doppler sensor placed on the forehead. 4. No significant change in cutaneous blood flow occurred during euglycaemic hyperinsulinaemia. 5. In control subjects a marked increase in blood flow during hypoglycaemia was observed in the forearm by both methods. No corresponding change was observed in the forehead. 6. In the diabetic patients the increase in cutaneous blood flow was absent in both the forearm and forehead. 7. It is concluded that hypoglycaemia, but not hyperinsulinaemia, is associated with a regional cutaneous vasodilatation in healthy control subjects. This cutaneous vasodilatation is absent in diabetic patients.

Adult↗
PubMed1992

Polyunsaturated fatty acids may impair blood glucose control in type 2 diabetic patients.

Fifteen patients with Type 2 diabetes were given two diets rich in either saturated fat or polyunsaturated fat in alternate order over two consecutive 3-week periods on a metabolic ward. Both diets contained the same amount of fat, protein, carbohydrates, dietary fibre, and cholesterol. The proportions of saturated, monounsaturated and polyunsaturated fatty acids in the saturated fat diet were 16, 10, and 5%-energy and in the polyunsaturated fat diet (PUFA) 9, 10, and 12%-energy. The PUFA diet contained a high proportion of n-3 fatty acids. Metabolic control improved significantly in both dietary periods, due to both qualitative dietary changes and a negative energy balance. The serum lipoprotein concentrations decreased on both diets but the serum lipids were significantly lower after the PUFA diet (serum triglycerides -20%, p = 0.001; serum cholesterol -5%, p = 0.03; VLDL-triglycerides -29%, p less than 0.001; and VLDL-cholesterol -31%, p = 0.001) than after the saturated fat diet. Average blood glucose concentrations during the third week were significantly higher fasting (+15%, p less than 0.01), and during the day at 1100 h (+18%, p less than 0.001) and 1500 h (+17%, p = 0.002) on PUFA than on the saturated fat diet. Significantly higher blood glucose levels were also recorded with a standard breakfast, while the sum of the insulin values was lower (-19%, p = 0.01). HbA1c did not differ significantly between the two dietary periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1992

The metabolic and circulatory response to beta-blockade in hypertensive men is correlated to muscle capillary density.

Both haemodynamic and metabolic variables have been shown to be related to the fibre composition and capillary density of skeletal muscle in man. In the present study, the change of several metabolic variables during beta-blockade was investigated and related to muscle fibre composition and capillary density in 28 men with essential hypertension. They had been given atenolol (50 mg/day) or metoprolol (200 mg/day) or propranolol (160 mg/day) for 4-12 months. Serum triglycerides increased during treatment and individual changes were significantly inversely correlated with capillary density. Insulin concentrations in the fasting state and at the end of an i.v. glucose tolerance test were significantly higher during beta-blockade, and individual changes were inversely correlated with capillary density. Furthermore, body weight increased and heart rate decreased, changes that were also correlated with capillary density. It is concluded that many of the previously but poorly understood large interindividual differences in response to beta-blocker treatment may be explained by the degree of development of the capillary net in muscle tissue. Obesity, physical training as well as genetic factors are known determinants of capillary density.

Adrenergic beta-Antagonists↗
PubMed1992

[Diabetic coma--an unnecessary death].

Diabetic ketoacidosis remains a significant cause of death in cases of insulin-dependent diabetes mellitus (IDDM). Among patients hospitalised for diabetic ketoacidosis, the death rate is 5-10 per cent, cardiovascular disease, infection, and ARDS (adult respiratory distress syndrome) being major contributory factors, whereas the degree of acidosis does not differ from that among survivors. Ketoacidosis is a major determinant of the two-fold higher mortality among the youngest age-groups of IDDM patients. The age-specific incidence of ketoacidosis among patients under 20 years of age is several time higher than that among patients over 50. Intensified insulin treatment, using multiple injections or insulin pumps, probably results in an increased risk of insulin deficiency owing to the smaller insulin depots. Thus, there is a need of intensified testing for ketonuria and improved education of patients, physicians and other health care personnel, in order to promote the prevention or rapid, effective treatment of diabetic ketoacidosis.

Adolescent↗
PubMed1991

Cancer risk in patients with diabetes mellitus.

Cancer incidence was ascertained in a population-based cohort of 51,008 patients in Uppsala, Sweden, who were given a discharge diagnosis of diabetes mellitus during 1965-83. Complete follow-up through 1984 with exclusion of the first year of observation showed that the observed number of cancers in females (1,294) was eight percent higher than expected (relative risk [RR] = 1.1, 95 percent confidence interval = 1.0-1.1), whereas in males the observed number (1,123) was close to the expected (RR = 1.0, 0.9-1.1). Significantly increased risks of pancreatic (RR = 1.4, 1.2-1.7), primary liver (RR = 1.5, 1.2-1.7), and endometrial (RR = 1.5, 1.2-1.8) cancers and a lower than expected number of prostatic cancers (RR = 0.7, 0.7-0.9) were found in this cohort of diabetic patients. The excess risk of pancreatic cancer was similar in females and males and evident both during one through four years (RR = 1.7, 1.4-2.1) and five through nine years (RR = 1.3, 0.9-1.7) of follow-up, but not thereafter. A similar pattern was found for primary liver cancer, but the RRs were generally higher in males than in females.

Adult↗
PubMed1991

Rapid resetting of human baroreflex working range: insights from sympathetic recordings during acute hypoglycaemia.

1. Human muscle nerve sympathetic activity (MSA), which is governed by baroreflexes and involved in blood pressure homeostasis, is increased during acute insulin-induced hypoglycaemia. 2. To elucidate the detailed relationship between MSA and blood pressure during hypoglycaemia, 0.15 i.u. (kg body weight)-1 regular human insulin was given intravenously to eight fasting, healthy volunteers. Microneurographic recording of MSA in the peroneal nerve was made with simultaneous monitoring of arterial blood pressure by a finger cuff (Finapres). The course of MSA and blood pressure was monitored for 30 min before and 60 min after insulin injection. In three subjects control recording without insulin injection was made for the same duration. 3. Stimulus-response regression lines were constructed by plotting diastolic blood pressure against the occurrence frequency of MSA for the period of initial rest, the period of maximal MSA outflow during hypoglycaemia and the period of glucose counter-regulation. The control experiments were analysed for the corresponding periods. 4. The stimulus-response line was stable throughout the control experiments, whereas it was shifted either to the left or to the right during hypoglycaemia, and regularly shifted to the left (i.e. towards a lower blood pressure) during glucose counter-regulation, without change of slope. 5. It is concluded that the changes in MSA during acute hypoglycaemia are not secondary to baroreflex regulation but instead are characterized by acute resetting of the baroreflex working range without change of sensitivity.

Adult↗
PubMed1991

Effects of antihypertensive treatment on insulin sensitivity with special reference to ACE inhibitors.

In 1984, the suspicion that pharmacological treatment may worsen the insulin resistance and associated metabolic abnormalities in lipid and carbohydrate metabolism and contribute to the relative failure of antihypertensive treatment to produce more than marginal reductions in cardiovascular morbidity and mortality led us to start a series of trials aimed at elucidating how antihypertensive drugs affect insulin sensitivity. These trials, which included assessment of insulin sensitivity by the euglycemic insulin clamp, showed that beta-adrenergic blockade and thiazide diuretic treatment (hydrochlorothiazide) increase insulin resistance and basal plasma insulin, whereas Ca(2+)-channel antagonists (verapamil and diltiazem), with the exception of the negative effect of nifedipine, are metabolically neutral. alpha-Adrenergic blockade with prazosin and angiotensin-converting enzyme (ACE) inhibition with captopril enhance insulin sensitivity. The mechanisms underlying the positive effects of ACE inhibition and beta-adrenergic blockade are largely unknown, but hemodynamic factors (vasodilation) may contribute by improving the access of glucose and insulin to skeletal muscle. The drugs, which were favorable or neutral with respect to insulin sensitivity, caused no changes in lipids or glucose homeostasis. In contrast, beta-blockers, except pindolol, had negative effects on triglycerides and high-density lipoprotein cholesterol, and thiazide diuretics caused adverse effects on total serum cholesterol, low-density lipoprotein cholesterol, and total and very-low-density lipoprotein triglyceride. The metabolic action of antihypertensive drugs is an important factor to consider in the choice of a proper treatment strategy in both diabetic and nondiabetic patients with hypertension.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Gestational diabetes-perinatal outcome with a policy of liberal and intensive insulin therapy.

During 3 years of continuous screening for gestational diabetes mellitus in the county of Uppsala, 133 pregnant women (1.2%) were given this diagnosis. Maternal characteristics and the perinatal outcome of the pregnancies were examined retrospectively. Maternal overweight [body mass index greater than 23.9 kg/(m)2] was noted in 54.9% of the 133 women. Insulin therapy, with a mean daily dose of 42 U, was given to 62.4% of the patients, whereas the others were given dietary instructions alone. The frequency of infants with a birth weight greater than 2 SD was 24.1% and was significantly (p less than 0.025) related to pre-pregnancy overweight and also to pregnancy weight gain 18kg (p less than 0.01). Caesarean section was performed in 27% of the pregnancies complicated by diabetes, compared with the overall figure of 11% in Uppsala during the study period. Neonatal hypoglycaemia (blood glucose greater than or equal to 1.6 mM) was noted in 17.3% of the infants and was significantly (p less than 0.01) related to maternal sympathomimetic therapy. Despite liberal and intensive insulin therapy, there was a considerable rate of perinatal complications. Although not severe, they indicate a need for further improvement in the care of women with gestational diabetes.

Diabetes, Gestational↗
PubMed1991

Incidence of symptomatic mild hypoglycaemic events: a prospective study in adult patients with insulin-treated diabetes mellitus using a portable microcomputer-based data-logger.

A new method for recording mild symptomatic hypoglycaemic events was evaluated. A pilot study was conducted using a portable microcomputer-based data-logger which was carried for 10 days by 38 adult patients with insulin-treated diabetes mellitus. The patients recorded symptomatic hypoglycaemic events, meals and sleeping-hours. The recording was prospective and continuous and did not allow any corrections afterwards. No patients had any problems in carrying or handling the data-logger and compliance was good. A total of 76 hypoglycaemic events were recorded in 29 patients. Two patients had hypoglycaemic events that they were unable to manage without help from another person. There was a peak in the incidence of hypoglycaemic events late postprandially, particularly in patients treated with a four-dose insulin regime with fast-acting insulin before meals. A portable microcomputer-based data-logger is a reliable new method for recording symptomatic mild hypoglycaemic events. The incidence of mild hypoglycaemic events was higher than previously reported.

Adult↗
PubMed1991

Metabolic effects of ACE inhibitors.

More than 10 years of clinical experience using angiotensin-converting-enzyme (ACE) inhibitors have shown that this class of drug does not have any adverse metabolic effects on carbohydrate and lipid metabolism. Rather, a number of studies on patients with essential hypertension or non-insulin-dependent diabetes mellitus have indicated minor improvements in glucose homeostasis and correction of dyslipidaemia. Some recent studies using the euglycaemic insulin clamp technique have indicated that the beneficial effect of captopril, the most extensively studied drug, is exerted on insulin sensitivity, a site with the potential to influence glucose and lipid metabolism. There is no uniform explanation for this action of captopril, but increased blood flow in skeletal muscle, accumulation of bradykinin or more efficient insulin release may be suggested as potential modes of action. It remains to be established whether this effect of captopril can be extrapolated to other ACE inhibitors, and the extent to which effects on insulin sensitivity will influence the long-term consequences for future risk of diabetes mellitus and coronary heart disease in patients with essential hypertension.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Insulin resistance in hypertension--a relationship with consequences?

Resistance to the action of insulin on glucose metabolism, with the ensuing compensatory hyperinsulinaemia, is closely linked to essential hypertension. The decreased insulin sensitivity observed in hypertensive patients is independent of obesity. Hyperinsulinaemia is likely to promote the dyslipidaemia that frequently accompanies the hypertensive state, and often presents as increased total and very low density lipoprotein (VLDL)-triglycerides, low high density lipoprotein (HDL)-cholesterol and, in some studies, elevated levels of low density lipoprotein (LDL)-cholesterol. Lipid abnormalities, hypertension and possibly hyperinsulinaemia act together to increase the risk of atherosclerotic disease manifestations in hypertensive patients. Acutely, insulin has been shown to stimulate sympathetic nervous system activity and transmembrane electrolyte transport, to promote sodium retention and to cause vascular wall changes, including increased cholesterol biosynthesis and smooth muscle proliferation. If these mechanisms operate on a chronic basis, the continuous exposure to elevated plasma insulin levels may play a pathogenetic role in the development of high blood pressure, and also of a predisposition toward atherosclerosis in patients with hypertension. Further studies are necessary to establish these hypothetical cause-effect relationship which, if shown to be true, will contribute to a more wide-ranging view of essential hypertension and the optimum strategy for antihypertensive treatment.

Cardiovascular Diseases↗
PubMed1990

Insulin resistance is a characteristic feature of primary hypertension independent of obesity.

The relationship between abnormalities in carbohydrate metabolism and hypertension was studied in 143 newly detected hypertensive patients (59% obese) of both sexes (90 males, 53 females) and compared with 51 normotensive controls. Insulin-mediated glucose disposal assessed with the euglycemic insulin clamp technique was significantly decreased in both non-obese (7.2 +/- 2.1 mg/kg/min; P less than .05) and obese hypertensives (5.1 +/- 2.1 mg/kg/min; P less than .01) compared with the controls (8.4 +/- 1.8 mg/kg/min). The decrease in insulin sensitivity and increase in basal insulin as well as a decreased rate of glucose disposal after an intravenous glucose tolerance test (IVGTT) were verified also after statistical adjustment for sex, age, body mass index, and waist-hip ratio. The insulin index (ratio between peak and basal insulin) during IVGTT was significantly decreased in the hypertensive patients (P less than .001). After the statistical adjustment for the factors mentioned the following lipid abnormalities were still significant: total cholesterol (6.25 +/- 1.12 mmol/L non-obese; 6.06 +/- 1.20 mmol/L obese; 5.41 +/- 1.02 mmol/L controls), triglycerides (1.70 +/- 0.74 mmol/L nonobese; 2.26 +/- 1.13 mmol/L obese; 1.24 +/- 0.53 mmol/L controls) and free fatty acids (0.57 +/- 0.20 mmol/L nonobese; 0.59 +/- 0.20 mmol/L obese; 0.48 +/- 0.15 mmol/L controls). This study shows that after correction for a series of probable confounding variables, hypertension emerges as part of a syndrome characterized by major abnormalities of carbohydrate, insulin, and lipid metabolism, which independently or in concert may act as important risk factors for cardiovascular disease.

Blood Glucose↗