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  • 1
    ISSN: 1432-0428
    Keywords: Type 1 diabetes ; interferon ; insulin therapy ; remission
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We studied the effect of interferon as an adjunct to conventional insulin therapy on the early course of Type 1 diabetes in 43 newly diagnosed patients. Compared with conventional therapy, interferon administration slightly delayed the improvement of glucose homeostasis and the rise of high density lipoprotein cholesterol, while C-peptide secretion was unaffected. Independent of the type of therapy, 18 patients (42%) entered partial remission. The remission began 2.0±0.6 months (mean±SEM) from the start of therapy and lasted for 4.1±1.1 months. Seven patients (16%) were still in remission 1 year after diagnosis. The patients who entered remission had higher initial C-peptide secretion, lower glycosylated haemoglobin levels and better initial control than patients without remission. Thus, interferon provided no benefits as an adjunct to conventional insulin therapy in unselected patients with newly diagnosed Type 1 diabetes. An important factor for the development of remission was the presence of C-peptide secretion at the time of diagnosis.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Diabetes ; insulin ; non-esterified fatty acids ; lipid metabolism ; lung ; phospholipids ; pulmonary artery ; rat ; streptozotocin ; triglycerides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of insulin on the triglyceride deposits found in the pulmonary artery branches of streptozotocin-diabetic rats was investigated by treating the animals for two, five, nine or 14 days with insulin (3–8 units/day). Histochemical analysis showed that the triglyceride deposits in the pulmonary artery developed within three to four days after the induction of diabetes, but were not present in any animals five days from the initiation of insulin therapy. Plasma triglycerides, non-esterified fatty acids, phospholipid and total cholesterol concentrations were within the normal range within two days of the inception of insulin therapy and random plasma glucose levels were normal within five days. Analysis of lung lipids showed that after 14 days of insulin treatment the decreased content of phospholipids and the increased content of non-esterified fatty acids found in diabetic rats were also normalized. These findings suggest that insulin has an important role in the regulation of lipid metabolism in the pulmonary artery and lung tissue in the diabetic state.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 13 (1977), S. 305-310 
    ISSN: 1432-0428
    Keywords: Diabetes ; non-esterified fatty acids ; lipid metabolism ; lung ; phospholipids ; pulmonary artery ; rat ; streptozotocin ; triglycerides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To investigate the effect of diabetes on the lipid composition of the lungs and of the pulmonary artery, 43 streptozotocin diabetic rats and 43 control rats were examined. Triglyceride deposits were observed by a histochemical method in the branches of the pulmonary artery in 10 diabetic rats but in none of the controls. In the pulmonary tissue of the diabetic rats the total lipid content was not different from that of control animals, but the relative amount of phospholipids was decreased (p〈0.001), and that of non-esterified fatty acids (p〈0.001) and triglycerides (p〈0.05) increased as compared to the control rats. These results indicate abnormalities in the lipid metabolism of the pulmonary artery and lungs during insulin deficiency.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Adipose tissue ; catecholamines ; diabetes ; exercise ; free fatty acids ; glycerol ; lipolysis ; rat ; streptozotocin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The lipolytic effect of norepinephrine (NE) in adipose tissue in vitro was studied before and after exercise in non-fasted rats with severe, untreated streptozotocin diabetes. It was observed that: 1. NE in increasing concentrations stimulated glycerol release in vitro to an equal extent from the adipose tissue of nondiabetic and diabetic rats. However, the re-esterification of free fatty acids (FFA) in adipose tissue in vitro was decreased by NE in diabetic rats as compared to normal rats. 2. During exercise NE further decreased the re-esterification of FFA in vitro in adipose tissue of diabetic rats. 3. Exercise did not change NE-induced glycerol release in vitro in the adipose tissue of diabetic rats. 4. In diabetic animals the increase in plasma glycerol and FFA during exercise was correlated inversely with the NE-induced release of glycerol and FFA from the adipose tissue of the same animals after exercise. The lipolytic effect of NE is not significantly different in adipose tissue of diabetic and nondiabetic rats. By decreasing the re-esterification of FFA in vitro, NE is probably responsible for the observed increase in the release of FFA in vivo, a likely energy source in severely diabetic animals.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Adipose tissue lipoprotein lipase ; insulin ; glucose ; insulin sensitivity ; lipoproteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to assess the short-term effects of hyperinsulinaemia and hyperglycaemia on adipose tissue lipoprotein lipase activity and on serum lipoproteins, we measured these variables in ten normal subjects during euglycaemic and hyperglycaemic hyperinsulinaemic clamps. The mean steady-state plasma glucose and insulin concentrations, respectively, were 4.7 mmol/l and 101 mU/l during euglycaemic moderate-insulin clamp, 4.9 mmol/l and 565 mU/l during euglycaemic high-insulin clamp, and 8.8 mmol/l and 148 mU/l during hyperglycaemic clamp. Saline infusion was used as control. The adipose tissue lipoprotein lipase activity rose significantly over 5 h during high-insulin clamp (p〈0.01) and during hyperglycaemic clamp (p〈0.05), but did not change during the moderate-insulin clamp. The magnitude of change of lipoprotein lipase activity from baseline (either rise or fall) was inversely related to the preclamp activity during euglycaemic moderate-insulin clamp (r= -0.67), during hyperglycaemic clamp (r= -0.68) and during infusion of saline (r= -0.75, p〈0.05). Total serum triglyceride concentration decreased significantly during all clamp studies compared with the control experiment. This change was mainly accounted for by a decrease of VLDL triglyceride. The LDL cholesterol level fell by an average of 5% (p〈0.05) during the high-insulin clamp and by 10% (p〈0.05) during the hyperglycaemic clamp. The HDL cholesterol level did not change significantly. It is concluded that adipose tissue lipoprotein lipase activity in man is increased by physiological insulin levels during hyperglycaemia and also by supraphysiological insulin levels during euglycaemia, but is not influenced by physiological hyperinsulinaemia without hyperglycaemia. Low basal lipoprotein lipase activity is more sensitive to insulin-glucose stimulation than primarily high lipoprotein lipase activity. Acute hyperinsulinaemia decreases VLDL triglyceride and LDL cholesterol concentrations.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: Cyclosporin A ; Type 1 (insulin-dependent) diabetes mellitus ; immunotherapy ; C-peptide ; islet function ; remission of Type 1 diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the Canadian/European randomized controlled study on cyclosporin A (CsA) in recent onset Type 1 (insulin-dependent) diabetes, treatment with the immunosuppressive drug had increased and maintained Beta-cell function and clinical remission during the first 12 months. Following discontinuation of the study drug and double-blinding after a mean of 13.8 months former CsA patients doubled the daily insulin dose within 6 months reaching the level of former placebo patients. The difference in Beta-cell function between the two groups was also lost. Metabolic control (HbA1c) was transiently worse in the former CsA group. Adverse effects of cyclosporin A on systolic blood pressure, haemoglobin levels, serum potassium and creatinine levels also remitted during that time. We conclude that treatment with cyclosporin A for a mean of 13.8 months had no long-lasting effect on the course of Type 1 diabetes persisting beyond drug discontinuation.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: Type 1 (insulin-dependent) diabetes mellitus ; HDL cholesterol ; apolipoprotein A-I ; apolipoprotein A-II ; kinetic analyses ; VLDL triglyceride ; lipolytic enzymes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Concentrations of HDL cholesterol and apolipoprotein A-I are commonly increased in Type 1 (insul-independent) diabetes mellitus but the mechanisms whereby diabetes influences HDL metabolism have not been studied. We investigated the metabolism of HDL apoproteins A-I and II in normolipidaemic Type 1 diabetic men (n=17, HbA1 6.4–11.9%) without microalbuminuria but with a wide range of HDL cholesterol (0.85–2.10 mmol/l) and in nondiabetic men (n=18) matched for body mass index and the range of HDL cholesterol. Input rates and fractional catabolic rates for apolipoproteins A-I and II were determined following injection of 125I-apolipoprotein A-I and 131I-apolipoprotein A-II tracers. Additional multicompartmental analysis was performed using a model to describe the kinetics of HDL particles containing only apolipoprotein A-I (Lp A-I) and apolipoprotein A-I and apolipoprotein A-II (Lp A-I/ A-II). No gross differences from normal subjects were observed in the mean levels of lipids, lipoproteins, apoproteins and the lipolytic enzymes in the diabetic men as a result of the selection process. Furthermore, the relationship between apolipoprotein A kinetics and plasma HDL cholesterol levels appeared to be preserved in the diabetic group. However, some normal interrelationships were disrupted in the diabetic men. Firstly, the rate of apolipoprotein A-II synthesis was 22% lower than in control subjects (p〈0.05). Modelling indicated that this was due to decreased input of Lp A-I/A-II particles whereas the input of Lp A-I particles was similar in the two groups. Secondly, there was no correlation between VLDL triglyceride and HDL cholesterol or VLDL triglyceride and the fractional catabolic rate of apolipoproteins A-I and A-II in diabetic men in contrast to that seen in control subjects. We conclude that there is a disruption in the normal association between VLDL and HDL metabolism in Type 1 diabetic men and postulate that the observed differences may be due to the therapeutic use of exogenous insulin.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0428
    Keywords: Glucose transport ; insulin ; muscle ; euglycaemic clamp ; GLUT4
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The content of GLUT4 glucose transporter mRNA and protein were measured in samples of the vastus lateralis muscle of normal volunteers subjected to a 4-h hyperinsulinaemic, euglycaemic clamp. Plasma glucose concentration was clamped at 5.3±0.1 mmol/l, and serum insulin concentration was maintained at 740±5 pmol/l. Whole body glucose uptake averaged 38.3±2.2 μmol · kg−1 · min−1, 62% of this being due to disposal via non-oxidative pathways. A significant correlation existed between basal levels of GLUT4 protein and the rate of whole body glucose disposal (r=0.77, p〈0.02) and non-oxidative glucose disposal (r=0.80, p〈0.02). There was no correlation between GLUT4 protein content and oxidative glucose disposal (r=0.08, NS). These observations are consistent with an important role for skeletal muscle GLUT4 protein in whole body glucose disposal.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0428
    Keywords: Key words Exercise ; insulin analogue ; hypoglycaemia ; IDDM.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to examine the effect of short-acting insulin analogue on the exercise-induced hypoglycaemia in insulin-dependent diabetes mellitus (IDDM) patients we compared the glycaemic response of 40 min cycle ergometer exercise performed either shortly (40 min) or later (180 min) after a breakfast meal and subcutaneous injection of either short-acting insulin analogue [Lys(B28) Pro(B29)] or soluble human insulin (Humulin Regular) in ten IDDM patients with long duration of the disease. Both preparations had been used 1 month before respective studies. Changes in blood glucose, insulin and counterregulatory hormones were assayed. As compared to human insulin, after the analogue injection the peak insulin concentration came earlier, was 56 % higher (p 〈 0.05) and disappeared faster, and the postprandial blood glucose response was lower (p 〈 0.05). In the analogue-treated patients the exercise-induced hypoglycaemia was 2.2-fold greater (p 〈 0.01) during the early exercise, but 46 % less (p 〈 0.05) during late exercise as compared to the treatment with human insulin. Serum insulin or analogue concentration at the beginning of the exercise correlated closely with the fall in blood glucose during exercise (r = 0.74, p 〈 0.01; r = 0.73, p 〈 0.02, respectively). In the analogue-treated patients, fasting serum glucagon and adrenalin concentrations were higher than during human insulin therapy (p 〈 0.05) and remained so throughout the study. As compared to soluble human insulin, a much faster absorption of insulin analogue: 1) reduces post-prandial hyperglycaemia, 2) can either augment or reduce exercise-induced hypoglycaemia depending on the time interval between insulin injection and the time of exercise. Since exercise is usually not performed until 2–3 h after a meal, short-acting insulin analogue may be more feasible than soluble human insulin for active IDDM patients. [Diabetologia (1995) 38: 106–111]
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0428
    Keywords: Exercise ; insulin analogue ; hypoglycaemia ; IDDM
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to examine the effect of shortacting insulin analogue on the exercise-induced hypoglycaemia in insulin-dependent diabetes mellitus (IDDM) patients we compared the glycaemic response of 40 min cycle ergometer exercise performed either shortly (40 min) or later (180 min) after a breakfast meal and subcutaneous injection of either short-acting insulin analogue [Lys(B28) Pro(B29)] or soluble human insulin (Humulin Regular) in ten IDDM patients with long duration of the disease. Both preparations had been used 1 month before respective studies. Changes in blood glucose, insulin and counterregulatory hormones were assayed. As compared to human insulin, after the analogue injection the peak insulin concentration came earlier, was 56% higher (p〈0.05) and disappeared faster, and the postprandial blood glucose response was lower (p〈0.05). In the analogue-treated patients the exercise-induced hypoglycaemia was 2.2-fold greater (p〈0.01) during the early exercise, but 46% less (p〈0.05) during late exercise as compared to the treatment with human insulin. Serum insulin or analogue concentration at the beginning of the exercise correlated closely with the fall in blood glucose during exercise (r=0.74,p〈0.01;r=0.73,p〈0.02, respectively). In the analogue-treated patients, fasting serum glucagon and adrenalin concentrations were higher than during human insulin therapy (p〈0.05) and remained so throughout the study. As compared to soluble human insulin, a much faster absorption of insulin analogue: 1) reduces post-prandial hyperglycaemia, 2) can either augment or reduce exercise-induced hypoglycaemia depending on the time interval between insulin injection and the time of exercise. Since exercise in usually not performed until 2–3 h after a meal, short-acting insulin analogue may be more feasible than soluble human insulin for active IDDM patients. [Diabetologia (1995) 38: 106–111]
    Type of Medium: Electronic Resource
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