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  • 1
    ISSN: 1432-0428
    Keywords: Juvenile type diabetes ; muscular exercise ; blood glucose ; ketosis ; free fatty acids ; amino acids ; insulin ; glucagon ; growth hormone ; cortisol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Metabolic and hormonal effects of muscular exercise were studied in juvenile-type diabetics in relation to the prevailing degree of metabolic control and compared with those in healthy control subjects. Two groups of diabetic patients, one in moderate metabolic control and one in ketosis due to insulin withdrawal, were subjected to a 3 hour bicycle ergometer test of comparable, mild work intensity. In both groups of diabetics the exercise-induced rise in blood lactate was similar, but was significantly higher than in control subjects. Blood alanine levels showed a transient, significant rise in both diabetic groups, but not in controls. Blood concentrations of branch-chained amino acids remained unchanged. In the moderately controlled diabetics, exercise induced a marked fall of blood glucose and increases in blood levels of free fatty acids (FFA), ketone bodies and glucagon, which were comparable to the exercise effects in normal controls. In ketotic diabetics, however, exercise led to an additional rise in blood glucose concentration and to increases in ketone body, glucagon and cortisol levels. Significant correlations were found between the exercise effect on blood glucose and initial blood levels of glucose, FFA, ketone bodies and branch chained amino acids: pre-exercise values of above 325 mg/dl glucose, 1173 μmol/l FFA, 2.13 mmol/l ketone bodies and 0.74 mmol/l branch chained amino acids led to increased blood glucose levels on exercise, whereas below these limits glucose fell during the exercise test. These findings seem to be, at least in part, explained by the hypothesis of a permissive effect of insulin during stimulation of muscle glucose uptake by exercise. The increased circulating levels of glucagon and cortisol during exercise in ketotic diabetics might represent additional hyperglycaemic and, probably more important, lipolytic and ketogenic stimuli. The results suggest that in moderately controlled, non-ketotic diabetics blood glucose falls during exercise; in ketotic, relatively insulin deficient patients, muscular activity has adverse metabolic and hormonal effects: a further increase in blood glucose, plasma glucagon and cortisol and a rapid aggravation of ketosis.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Type 2 diabetes ; very low molecular weight serum growth peptide ; human arterial smooth muscle cells ; fibroblasts ; cell culture ; diabetic angiopathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Diabetic angiopathy may be due, in part, to increased growth in vascular cells. We have investigated serum growth factors in Type 2 (non-insulin-dependent) diabetic and healthy subjects and their effect on cultured human arterial smooth muscle cells and fibroblasts. Removal of the dialyzable serum fraction (mol. wt. 〈12,000) reduced the growth effect of the diabetic sera by 37% (2p〈0.005) and of the nondiabetic sera by only 8% (2p〈0.01). In contrast, there was no difference in growth stimulation between the dialyzed diabetic or non-diabetic sera. Complete recovery of the dialyzable serum growth fraction was also obtained at a mol. wt. below 3,500. Ten times the concentration of the low molecular weight growth factor (mol. wt. 〈3,500) from diabetic sera stimulated growth of fibroblasts or arterial smooth muscle cells by a mean of 243% or 174% and from non-diabetic sera by a mean of 146% or 137%, respectively (2p〈0.01). The growth stimulating potency of this serum fraction (mol. wt. 〈3,500) contained in 10% diabetic sera, was two to ten times higher than that of human growth hormone or insulin, added in amounts equivalent to 10% or physiological serum concentrations. This diabetic serum growth factor was further characterized by: (1) linear dependence of growth stimulation over a concentration range of twenty times and by (2) reduction of the growth stimulating activity to control levels by pretreatment: (a) at 95 °C for 30 min, or (b) with two different proteases: Serva pronase E (Streptomyceus griseus) or Calbiochem protease (Subtilisin calsberg). Increased amounts of the very low molecular weight serum growth peptide in Type 2 diabetes might easily penetrate the arterial wall, thus contributing to the genesis of angiopathy.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Physical training ; obesity ; diabetes ; hypertriglyceridaemia ; glucose intolerance ; Zucker rat ; insulin resistance ; perfused hindquarter
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of treadmill training on intravenous glucose tolerance and insulin sensitivity was investigated in Zucker rats (fafa). In 25-week-old fafa animals with the typical metabolic syndrome of massive obesity, glucose intolerance, hypertriglyceridaemia and insulin resistance, treadmill exercise of only very mild intensity was carried out for 6 weeks. The training programme induced a marked reduction in basal and post-glucose challenge plasma insulin levels and a slight but significant improvement of intravenous glucose tolerance. No alteration in insulin sensitivity of the isolated perfused hindquarter was demonstrable. In another study a 9-week training programme was started in 7-week-old fafa rats before the development of their metabolic syndrome. In the sedentary control animals glucose intolerance and insulin resistance developed during the study period; in the training group, both the deterioration of glucose tolerance and the decrease of insulin sensitivity were prevented. This study demonstrates in fafa rats that (a) in young animals physical training may prevent a genetically predisposed deterioration of glucose tolerance and insulin sensitivity and (b) in adult animals mild physical training may improve intravenous glucose tolerance and insulin sensitivity.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Diabetic neuropathy ; glycaemic control ; nerve conduction ; autonomic function ; sensory thresholds
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The natural evolution of neural dysfunction was studied prospectively over 5 years following diagnosis of Type 1 (insulin-dependent) diabetes in 32 patients aged 12–36 years. Motor and sensory nerve conduction velocities, heart rate variation at rest and during deep breathing, and pupillary function were measured at diagnosis and after 3,12, 24,48, and 60 months. Thermal and vibration sensation thresholds were determined after 24, 48, and 60 months of diabetes. Mean HbA1 levels of months 3–60 within the normal range of 〈8.3% (7.3±0.2%) were observed in 13 patients (Group 1), while a mean HbA1 of months 3–60≥8.3% (10.0±0.3%) was found in 19 patients (Group 2). Mean nerve conduction was significantly diminished in Group 2 as compared with Group 1 in at least 4 out of 6 nerves tested during months 12–60 (p〈0.05). Both tests of heart rate variation were significantly impaired in Group 2 as compared with Group 1 after 24 and 60 months (p〈0.05), but no differences in pupillary function were observed between the groups. Thermal discrimination but not vibration perception thresholds on the foot were significantly higher in Group 2 than in Group 1 at 40 and 60 months (p〈0.05). Abnormalities in nerve conduction, thermal discrimination, and heart rate variation, but not vibration perception threshold and the pupillary function tests were significantly more frequent in Group 2 than in Group 1 at 60 months (p〈0.05). After 60 months, none of the patients of Group 1, but 6 and 4 patients of Group 2 developed subclinical or symptomatic neuropathy, respectively (p〈0.05). These findings suggest that the evolution of subclinical and symptomatic neuropathy during the first 5 years after diagnosis of Type 1 diabetes may be predicted by poor glycaemic control and prevented by near-normoglycaemia.
    Type of Medium: Electronic Resource
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  • 5
    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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  • 6
    ISSN: 1432-0428
    Keywords: Autoreactive T cells ; self-tolerance ; beta cell ; pancreatectomy ; regeneration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We studied the effect of severe reduction of beta-cell mass by 90% pancreatectomy on the immune tolerance to the endocrine pancreas. Four months after subtotal pancreatectomy all LEW.Han rats had developed mononuclear infiltration of islets and 9 of 14 rats were positive for islet-cell antibodies. Electron microscopy revealed lymphocytic invasion of endocrine tissue, lysis of beta cells and phagocytotic macrophages. None of these changes were seen 2 weeks after 90% pancreatectomy or 4 months after 10% pancreatectomy. Weekly substitution of islet antigens in the form of a homogenate of 100 islets into 90% pancreatectomized LEW.Han rats almost completely prevented the development of insulitis and autoantibodies. The dependence of insulitis on T cells was shown when 90% pancreatectomy in LEW.rnu rats (i.e., the congenic athymic nude strain), did not result in islet infiltration. The exocrine tissue remained normal in all experimental groups. During the observation period insulitis was not associated with overt diabetes but was accompanied by substantial enlargement of islets and of beta-cell mass, as shown by morphometry. Suppression of islet inflammation by injection of islet antigens abolished beta-cell regeneration, despite continuing metabolic stress in rats with 90% pancreatectomy. The findings indicate induction of islet autoimmunity in response to 90% but not to 10% pancreatectomy. We conclude that severe reduction of the islet-antigen mass allows the development of T-cell-dependent islet autoimmunity which indicates a loss of immune tolerance. In addition, the data suggest the existence of islet-antigen autoreactive immune cells in rats not genetically predisposed to autoimmune diabetes. Finally, we conclude that selective beta-cell regeneration occurs in association with insulitis.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: Insulin-dependent diabetes mellitus ; nutrition surveys ; diet records ; Europe ; diet recommendations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The EURODIAB IDDM Complications Study, a cross-sectional, clinic-based study, was designed to measure the prevalence of diabetic complications in stratified samples of European insulin-dependent diabetic (IDDM) patients. As diet may be related to diabetic complications, nutritional intake was analysed in the study population. The aims of this first nutritional paper are to describe the nutrient intake in 2868 IDDM patients from 30 centres in 16 countries throughout Europe, to investigate the degree of regional differences in nutrient intake and to compare current intakes with recommended levels. Nutritional intake from 1458 male and 1410 female IDDM patients was assessed by a validated 3-day record (two weekdays, Sunday) and centrally analysed. Mean energy intake for all patients was 2390±707 kcal/day. Mean protein intake was 1.5±0.5 g/kg body weight. Carbohydrate intake was 43% and fibre intake 18 g/day. Alcohol intake for the total cohort was 2% of energy. Total fat contributed 38% of energy, with 14% from saturated fat. The Italian centres reported lower total and saturated fat intakes compared with other centres. Recommendations from the Diabetes and Nutrition Study Group of the EASD for total fat, saturated fatty acids and carbohydrate were only achieved by 14%, 14% and 15% of patients, respectively. The data of the present study clearly indicate current problems in the nutritional intake of European IDDM patients. These findings contribute to the definition of future targets in the nutritional management of IDDM patients, to be achieved as part of the initiatives taken by the St. Vincent Declaration action programme.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0428
    Keywords: Keywords Insulin-dependent diabetes mellitus ; protein intake ; urinary albumin excretion rate ; diabetic nephropathy ; diet recommendations ; Europe.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary For people with insulin-dependent diabetes mellitus (IDDM) renal disease represents a life-threatening and costly complication. The EURODIAB IDDM Complications Study, a cross-sectional, clinic-based study, was designed to determine the prevalence of renal complications and putative risk factors in stratified samples of European individuals with IDDM. The present study examined the relationship between dietary protein intake and urinary albumin excretion rate (AER). Food intake was assessed centrally by a standardized 3-day dietary record. Urinary AER was determined in a central laboratory from a timed 24-h urine collection. Complete data were available from 2696 persons with IDDM from 30 centres in 16 European countries. In individuals who reported protein consumption less than 20 % of total food energy intake, mean AER was below 20 μg/min. In those in whom protein intake constituted more than 20 %, mean AER increased, a trend particularly pronounced in individuals with hypertension and/or poor metabolic control. Trends reached statistical significance for intakes of total protein (% of energy, p = 0.01) and animal protein (% of energy, p = 0.02), while no association was seen for vegetable protein (p = 0.83). These findings support the current recommendation for people with diabetes not to exceed a protein intake of 20 % of total energy. Monitoring and adjustment of dietary protein appears particularly desirable for individuals with AER exceeding 20 μg/min (approximately 30 mg/24 h), especially when arterial pressure is raised and/or diabetic control is poor. [Diabetologia (1997) 40: 1219–1226]
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0428
    Keywords: Obesity ; glucose tolerance ; weight reduction ; long-term prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 4 years after controlled clinical treatment with a 1000 calorie mixed diet, 24 patients were reinvestigated to assess (1) whether the improved metabolism, as observed during therapy, is merely the result of starvation and (2) to what extent this improvement continues beyond the time of dietary treatment. — The following tests were carried out: Oral G.T.T. (100 g), immunoreactive insulin, free fatty acids, free glycerol, triglycerides, cholesterol, acetoacetate and beta-hydroxybutyrate. — 12 patients had been able to maintain their weight or reduce further. They showed a slightly improved glucose tolerance and a more normal secretion kinetic for insulin release. However, 12 individuals who were found to have a 35% weight gain (Broca), returning almost to their initial weight, showed a decreased glucose tolerance compared with previous examination, while insulin levels were slightly elevated, with a typically delayed secretion. Both groups showed a weight-independent elevation of cholesterol and triglyceride levels and a marked decline of plasma FFA, free glycerol and ketone bodies. The parameters of lipid metabolism may possibly be influenced by the composition of the diet, while a change of weight after reduction primarily affects blood sugar levels and, to a lesser extent, insulin levels.
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