PubMed Health⌕ Search

Biomedical subjects

L Sestoft

Publications and source records attributed to L Sestoft.

At least 37 records · Page 2Linked to original sources
PubMed1985

Diffusion and polymerization determines the insulin absorption from subcutaneous tissue in diabetic patients.

In 23 diabetic patients, the disappearance from subcutaneous tissue of 125I-labelled short-acting insulin and of 133Xe (measuring subcutaneous blood flow (SBF] were registered simultaneously. Alterations in the SBF were produced either by orthostatic changes or by application of local heat or cold. The insulin absorption rate was related to the SBF in a curvilinear way with an almost linear relation at SBF below 2-3 ml . (min . 100 g)-1, whereas at SBFs above the value the insulin absorption rate increased less than proportional to SBF. Capillary diffusion capacity of the injected insulin was 0.0145-0.0874 ml . (min . 100 g)-1; indicating that insulin is absorbed in a polymeric form. This was supported by studies of insulin diffusion in agar gel at 37 degrees C, showing that insulin in the normal pharmacological concentration diffuses as a molecule of about 46,000 MW. In conclusion, the absorption of short-acting soluble insulin is curvilinearly related to the SBF. This can be explained by a diffusion-limited transport of insulin in the interstitial space, and increasing transcapillary transport of insulin at increasing blood flow rates caused by recruitment of capillaries, thus increasing exchange surface area and decreasing diffusion distance.

Absorption↗
PubMed1985

Mild mental stress in diabetes: changes in heart rate and subcutaneous blood-flow.

A TV-game of tennis of 20 min duration was used to study the influence of mild mental stress on subcutaneous blood-flow (SBF), blood-pressure and heart rate in nine insulin-dependent diabetics and nine healthy subjects. SBF was measured on the thigh by local clearance of xenon-133. Measurements were made before, during and after the period of stress. During stress, SBF increased significantly by 26% in the healthy subjects, while SBF remained unchanged in the diabetics. The difference between the two groups was significant (P less than 0.05). Following stress, SBF returned to pre-stress level in the healthy subjects, while a significant decrease of 33% was observed in the diabetics. The pre-stress heart rate level was higher and the stress-induced increase in heart rate was less in the diabetics compared with the healthy subjects (P less than 0.05). During the stress a slight--but insignificant--increase in blood-pressure was observed in both groups. In conclusion, we found that even mild mental strain influences SBF in both normal subjects and in diabetics. The induced alterations in the two groups are different, probably because of a slight parasympathetic dysfunction in the diabetics.

Adult↗
PubMed1985

The importance of plasma free insulin and counterregulatory hormones for the recovery of blood glucose following hypoglycaemia in type 1 diabetics.

After induction of hypoglycaemia in 31 Type 1 (insulin-dependent) patients, the 10 patients with the slowest recovery of blood glucose from hypoglycaemia were arbitrarily compared with the 10 patients with the fastest recovery of blood glucose. No differences were found between the two groups regarding response of glucagon to hypoglycaemia, whereas the epinephrine (2-fold), norepinephrine (2.4-fold) and cortisol responses were significantly greater in the group with the slow recovery. The plasma free insulin concentrations were higher (2-fold) in the group with slow recovery from 30 min after stop of insulin and throughout the study. This may be explained by a 3-fold greater amount of insulin binding antibodies in this group compared to the group with fast recovery from hypoglycaemia. An inverse significant correlation was demonstrated between the rates of recovery and the amounts of insulin binding antibodies in all the patients (P less than 0.02). This implicates that enhanced counterregulatory hormone responses in the group with the slow recovery from hypoglycaemia could not compensate for the hypoglycaemic effect of a concomitant higher plasma free insulin concentration. Insulin binding antibodies, acting as a depot of circulating insulin, may be a risk factor of prolonged hypoglycaemia in Type 1 diabetics.

Adolescent↗
PubMed1985

High-carbohydrate, low-fat diet: effect on lipid and carbohydrate metabolism, GIP and insulin secretion in diabetics.

The effects of increasing the dietary polysaccharide content from the customary 40 percent to 50 percent of total energy intake were examined in a metabolic ward-cross-over study of eight noninsulin dependent diabetic patients with normal fasting C-peptide concentration. The aim was to study the effect of a raised carbohydrate content; therefore, the fibre content of the diet was kept approximately constant. Patients had been treated with diet alone, and the high carbohydrate (HC) observation period lasted for two weeks. Blood glucose was significantly increased postprandially in the HC period (11.8 +/- 0.3 versus 10.7 +/- 0.4 mmol/l), and this was accompanied by significantly raised immunoreactive insulin (IRI) concentrations. The secretion of IRI, C-peptide and gastric inhibitory polypeptide (GIP) after a standard meal-challenge at the end of each period were unaffected by the preceding diets. The HC diet was accompanied by increasing values of plasma triglyceride (1.13 +/- 0.06 versus 0.97 +/- 0.06 mmol/l) and VLDL-triglyceride (0.69 +/- 0.04 versus 0.50 +/- 0.04 mmol/l), whereas the ketone body concentration was decreased (0.25 +/- 0.03 versus 0.36 +/- 0.05 mmol/l). Both HDL- and LDL cholesterol were decreased by the HC-diet (1.07 +/- 0.02 versus 1.18 +/- 0.02; 3.45 +/- 0.09 versus 3.89 +/- 0.09 mmol/l, respectively), while the LDL to HDL cholesterol concentration ratio remained unaffected. Thus, in two weeks, a HC diet resulted in hyperglycaemia, hyperinsulinaemia, hypertriglyceridemia and a state of antiketogenesis, without any apparent change in the capacity of mealinduced insulin release. LDL- and HDL-cholesterol were lowered to the same extent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

Orthostatic changes in subcutaneous blood flow and insulin absorption.

Subcutaneous blood flow (SBF), measured by the 133Xenon local clearance technique, and absorption of subcutaneously injected 125I-labelled short-acting insulin from the femoral and abdominal regions were studied in 17 diabetic patients during supine and sitting position. Sitting up induced vasoconstriction with a 28.7-47.0% fall in SBF and a 19.2-43.6% fall in the insulin absorption rate. These findings imply that the SBF of the thighs and abdomen participate in the cardiovascular adjustments to postural changes. The change in the insulin absorption rate during the change of position probably contributes to the great day-to-day variation of insulin absorption. Furthermore, the observation stresses the importance of well defined experimental conditions in insulin absorption studies.

Abdomen↗
PubMed1984

Dose-dependent subcutaneous absorption of porcine, bovine and human NPH insulins.

The absorption of 125I-labelled porcine, bovine and human neutral protamine Hagedorn (NPH) insulins was compared in 40 diabetic patients after subcutaneous injections in the thighs using doses of 6 and 24 IU (40 IU/ml). Furthermore, the absorption of porcine NPH insulin was compared with bovine NPH insulin and porcine lente type insulin in the same dose (6 IU). All these intermediately acting insulins showed similar absorption rates when administered in the same dose. However, an increase in the injected dose from 6 to 24 IU resulted in a decrease of approximately 30% in the absorption rate of all NPH insulins.

Absorption↗
PubMed1984

The effect of continuous subcutaneous insulin infusion on cardiac performance during exercise in insulin-dependent diabetics.

To assess the effects of improved glycaemic control on the right and left ventricular ejection fraction (RVEF and LVEF), we performed radionuclide angiocardiography at rest and during exercise in nine insulin-dependent diabetics with a diabetes duration between 2 and 35 years (mean 12 years) and in 10 control subjects. The diabetics were investigated before and after 7 days' treatment with continuous subcutaneous insulin infusion (CSII). The diabetics had a significantly smaller rise in exercise-induced LVEF during normoglycaemia than in the hyperglycaemic state. In contrast to the control subjects, the diabetics, independent of glycaemic control, did not increase the end-diastolic volume and did not decrease the end-systolic volume during exercise. Our data indicate a preclinical abnormal left ventricular function in young diabetics without long-term diabetic complications. The dysfunction seems unrelated to changes in the loading of the heart and appears to be caused by decreased contractile reserve of the myocardium.

Adult↗
PubMed1984

The onset of liver glycogen synthesis in fasted-refed rats. Effects of streptozocin diabetes and of peripheral insulin replacement.

The mechanism of liver glycogen synthesis after refeeding has been investigated in diabetic rats, diabetic insulin-treated rats, and in control rats fasted for 48 h. The accumulation of liver glycogen was the same in diabetic rats and in control rats after 2 h of feeding, but did not proceed any further in the diabetic group during the next 2 h. Insulin-treated diabetic rats synthesized five times more hepatic glycogen than the control rats after 1 h of refeeding, but the amount accumulated at the end of the refeeding period was the same. Feeding resulted in a transient activation of glycogen synthase in untreated as well as in treated diabetic rats. In control rats, however, glycogen synthase was already partially in the active form before access to food, and the onset of glycogen synthesis occurred without further activation of the enzyme. A transient inactivation of phosphorylase was observed in all groups during the meal, but was very slight in the untreated diabetic rats in which phosphorylase a values were already reduced before the access to food. Peripheral glycemia was markedly increased upon refeeding in treated and untreated diabetic rats, but remained normal in control rats. Peripheral insulinemia was increased by feeding in the control rats and remained low in the diabetic rats and high in the insulin-treated diabetic rats. The results indicate that, in normal controls in contrast to diabetic rats, synthase activation is not a prerequisite for the initiation of glycogen synthesis after a meal; phosphorylase inactivation may be of major importance in normal controls, but also appears to play a role in the diabetic animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Human Monotard insulin: dose-dependent subcutaneous absorption.

The aim was to study the effect of dose on subcutaneous absorption of semisynthetic human Lente-type insulin (Monotard HM) in IDDM patients. The absorption was evaluated by measurements of residual radioactivity of 125-I labelled insulin at the injection sites. In 9 patients, on consecutive days, 6, 12, 24 and 36 IU of Monotard HM was given subcutaneously. The residual radioactivity was measured up to 49 hr after injections. A dose-dependent absorption was found with significantly decreasing absorption rates for increasing doses. The times for 50% of initial activity to disappear were (doses given in parentheses): 9.0 hr (6 IU), 8.9 hr (12 IU), 10.9 hr (24 IU), 14.8 hr (36 IU).

Absorption↗
PubMed1983

Abnormal regulation of sympathetic nervous activity and heart rate after oral glucose in type 1 (insulin-dependent) diabetic patients.

Oral glucose administration increased plasma noradrenaline concentration significantly in seven normal subjects (p less than 0.02), whereas in six young short-term Type 1 diabetic patients without complications plasma noradrenaline did not change. Basal plasma noradrenaline did not differ between the two groups. In the first 3 h after oral glucose administration, the mean heart rate in eight normal subjects was increased 3.5% above basal levels (p less than 0.05). In contrast, no such increase was found in eight Type 1 diabetic patients after glucose administration. In two normal subjects thoroughly examined before and after oral glucose administration, we observed a significant correlation between heart rate and systolic blood pressure (p less than 0.001) but this was not seen in two diabetic patients in whom neither heart rate nor systolic blood pressure increased. Our findings indicate that sympathetic nervous activity and cardiovascular function is abnormal in early diabetes during an oral glucose load.

Adolescent↗
PubMed1983

Biochemistry and differential diagnosis of metabolic acidoses.

This paper reviews the biochemical background of metabolic acidoses. The rate of development is judged from production and/or elimination rate of organic acids, particularly carboxylic acids, namely lactate, ketoacids, acetate, formate and glycollate. Further, acid production from changes in the chemical state of phosphate in tissue is evaluated. The main conclusion is that pathological conditions with acidoses are always accompanied by changes in the rate of elimination of the carboxylic acids, whereas changes in the chemical state of phosphate is of quantitatively minor importance. Further, metabolic effects of metabolic acidoses are described with special reference to the effect of low pH in the extra cellular fluid on glycolysis, gluconeogenesis, lipolysis and ketogenesis. A short outline of the differential diagnostic problems in metabolic acidoses due to changes in carbohydrate and lipid metabolism or intoxication is given.

Acidosis↗
PubMed1983

Plasma somatostatin increases during hypoglycaemia in insulin-dependent patients with and without B-cell function.

Responses of somatostatin-like immunoreactivity (SLI) to hypoglycaemia were investigated in seven type 1 (insulin-dependent) patients with residual B-cell function, eight patients without B-cell function, and six healthy controls. A higher basal level of SLI was found in the group with B-cell function when compared with the group without B-cell function. The basal level in the normal subjects was in between the two diabetic groups. All the diabetics had a somatostatin response to hypoglycaemia which was independent of residual B-cell function and no different from that of normal subjects.

Adolescent↗