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  • 1
    ISSN: 1432-0428
    Keywords: Biguanide (metformin) ; obesity ; non-ketotic diabetes ; Schilling-test ; d-xylose-test ; intestinal absorption ; blood lipids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Chez 21 patients atteints de diabète sucré clinique ou chimique et d'obésité, on a déterminé l'excrétion urinaire de vitamine B12 et de D-xylose, ainsi que les taux de lipides sanguins, avant et après un traitement de 10 jours à la metformine. En outre, des études de la tolérance aux graisses et du bilan lipidique ont été effectuées chez 7 patients. Au cours d'une étude prolongée de 9 patients, le test de Schilling a été répété 2–3 mois après le début du traitement à la metformine chez a) 7 patients sous traitement permanent à la metformine, et b) 2 patients après cessation du traitement initial à la metformine. Les résultats étaient les suivants: l'absorption de vitamine B12 et de D-xylose était pathologiquement basse après traitement à la metformine. Les lipides sanguins et le poids corporel étaient réduits. Il y avait également certains signes de trouble de l'absorption des graisses, qui n'ont pas pu cependant être démontrés. D'après nos résultats, il est possible que la chute de la glycémie après le traitement à la. metformine, soit en partie provoquée par une mauvaise absorption du glucose. L'opinion de Sadow concernant l'effet de la metformine sur le métabolisme des hydrates de carbone doit donc être reconsidérée. Les implications cliniques de ces résultats, particulièrement en ce qui concerne l'absorption de la vitamine B12 sont discutées.
    Abstract: Zusammenfassung Bei 21 Patienten wurden vor und 10 Tage nach Biguanidtherapie die Vitamin B12- und Xyloseausscheidung im Urin, sowie die Blutlipide bestimmt. Bei 7 Patienten wurden zusätzlich eine Fettbilanzstudie und ein Fettbelastungstest vor und während Biguanidtherapie durchgeführt. Bei 5 Patienten wurde der Schillingtest 2–3 Monate nach Beginn der Biguanidtherapie erneut bestimmt, bei 2 Patienten zur gleichen Zeit nach Absetzen der initialen Therapie. Die Resultate sind folgende: Vitamin B12- und Xyloseabsorption sind während der Biguanidtherapie pathologisch erniedrigt, der Schillingtest kann sich nach der Langzeittherapie normalisieren. Die Blutlipide und das Körpergewicht fallen nach 10-tägiger Therapie ab. Die Resultate lassen auch eine Fettabsorptionsstörung vermuten. Die Ergebnisse berechtigen zur Annahme, daß die Blutzuckersenkung nach Biguanidtherapie z.T. ebenfalls die Folge einer Absorptionsstörung ist und sprechen dafür, daß das Konzept über die Wirkungsweise der Biguanide von Sadow, welches in der Einleitung besprochen wird, in diesem Sinne erweitert werden muß. Die sich für die Klinik ergebenden Konsequenzen dieser biguanidbedingten Absorptionsstörung, insbesondere auch von Vitamin B12 werden diskutiert.
    Notes: Summary Urinary excretion of vitamin B12 and D-xylose, and the levels of blood lipids were determined in 21 patients with clinical or chemical diabetes mellitus and obesity, before and 10 days after metformin treatment. In addition, fat tolerance and fat balance studies were carried out in 7 patients. In a long term study of 9 patients, the Schilling test was repeated 2–3 months after the beginning of the metformin treatment in a) 7 patients with permanent metformin treatment, and b) 2 patients after cessation of initial metformin treatment. The results were as follows: vitamin B12 and D-xylose absorptions were pathologically low after metformin treatment. Blood lipids and body weight were reduced. There was also some indication of disturbed fat absorption, which, however, could not be proved. Based on our results, it is possible that the decrease in blood sugar after treatment with metformin is partly induced by malabsorption of glucose. Thus the concept of Sadow on the effect of metformin on carbohydrate metabolism has to be reëvaluated. The clinical implications of the results, especially with respect to vitamin B12 absorption are discussed.
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  • 2
    ISSN: 1432-0428
    Keywords: Oral tolbutamide test ; intravenous tolbutamide test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé La durée de l'oTT a été prolongée à 140 min pour permettre l'observation de la remontée (rebound) qui suit la chute de la glycémie et la comparaison avec PivTT. Les effets indésirés de l'hypoglycémie, observés après l'ingestion de 2 g de tolbutamide, ont été évités en réduisant la dose à 1 g chez 18 patients et à 1.5 g chez 31 autres. Le tolbutamide a été administré en même temps qu'une dose double de bicarbonate de sodium. La concordance entre l'ivTT et l'oTT était bonne dans 35%, moyenne dans 38% et mauvaise dans 27% des cas, On suggère que ces résultats insatisfaisants sont dus à des vitesses différentes d'absorption du tolbutamide. L'utilisation de l'oTT prolongé n'est pas recommandé en tant que procédé pour diagnostiquer le diabète.
    Abstract: Zusammenfassung Der oTT wird auf 140 min verlängert, um gleich wie beim ivTT den Wiederanstieg des Blutzuckers beurteilen zu können. Um die mit 2g Tolbutamid beobachteten Hypoglykämien auszuschließen, wurde die Dosis bei 18 Patienten auf 1 g und bei 31 Patienten auf 1.5 g gesenkt und zusammen mit der doppelten Dosis Natrium-Bicarbonat oral verarbeitet. Gute Übereinstimmung zwischen oTT und ivTT wurde in 35%, mäßige in 38% und schlechte Übereinstimmung in 27% der Fälle gefunden. Es wird vermutet, daß die ungenügende Übereinstimmung der beiden Teste auf unterschiedlichen Absorptionsraten von Tolbutamid beruht. Der verlängerte oTT wird für die Zusatzdiagnostik des Diabetes mellitus nicht empfohlen.
    Notes: Summary The duration of the oral tolbutamide Test (oTT) was extended to 140 min to allow the observation of the rebound following the blood sugar fall and the comparison with the ivTT. The undesired effects of the hypoglycaemia observed after the ingestion of 2g tolbutamide were prevented by reducing the dose of the drug to 1 g in 18 patients and to 1.5 g in 31 others. Tolbutamide was given together with the double amount of sodium bicarbonate. The agreement of ivTT and oTT was good in 35%, fair in 38% and poor in 27% of the cases. It is suggested that these unsatisfactory results are due to different tolbutamide absorption rates. The use of the prolonged oTT is not recommended as a tool for the diagnosis of diabetes.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Intravenous tolbutamide test ; oral tolbutamide test ; glucose ; serum-insulin ; serum tolbutamide ; tolbutamide action
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Chez 12 sujets normaux l'oTT et l'ivTT ont été étudiés en déterminant simultanément la glycémie, l'insuline sérique (IRI) et le tolbutamide du sérum. D'après les résultats il est possible de déduire deux mécanismes d'action différents du tolbutamide administré oralement. Ils dépendent de la vitesse d'absorption de la drogue. Quand le tolbutamide est absorbé rapidement, il se produit une sécretion d'insuline quiest responsable de la chute de la glycémie. Quand l'absorption du tolbutamide est lente, la sécrétion d'insuline est faible, mais le taux de la glycémie diminue quand même. Les trois hypothèses suivantes sont proposées: soit l'insuline qui apparaît dans la veine pancréatique ne peut pas être mesurée á la périphérie et agit surtout dans le foie, soit la faible concentration de tolbutamide dans le sérum ne provoque qu'une légère sécrétion d'insuline, mais une inhibition importante de la sécrétion de glucagon, qui est responsable de l'hypoglycémie observée. L'action extra-pancréatique des sulfonylurées, en particulier sur le tissu musculaire, peut également jouer un rôle important dans l'explication de ces résultats.
    Abstract: Zusammenfassung Bei 12 normalen Probanden wurde mittels der Bestimmung von Glucose, Serum-Insulin und Serum-Tolbutamid der orale und der intravenöse Tolbutamidtest vergleichend untersucht. Aus den Resultaten ergeben sich zwei verschiedene Wirkungsmechanismen, die von der Tolbutamid-Resorptionsrate abhängig sind. Wird Tolbutamid rasch resorbiert, so erfolgt eine Insulinsekretion, die für den Blutzuckerabfall verantwortlich ist. Geht die Tolbutamidresorption langsam vor sich, so ist die Insulinsekretion gering, aber der Blutzucker fällt trotzdem ab. Zur Erklärung werden drei Hypothesen diskutiert: Entweder ist das Insulin, das in die Pankreasvene sezerniert wird, peripher nicht meßbar und entfaltet seine Wirkung allein an der Leber, oder die niedere Serum-Tolbutamidkonzentration verursacht nur eine unwesentliche Insulinsekretion, dafür eine Hemmung der Glucagonsekretion, die ihrerseits für die Hypoglykämie verantwortlich ist. Auch extrapancreatische Wirkungen der Sulfonylharnstoffe, besonders die auf das Muskelgewebe, werden diskutiert.
    Notes: Summary In 12 normal subjects the oTT and ivTT were studied by simultaneous determination of blood glucose, serum insulin (IRI) and serum tolbutamide. From the results it is possible, to deduce two different mechanisms for the action of the orally administred tolbutamide. They are dependent of the absorption rate of the drug. When tolbutamide is absorbed quickly, insulin secretion follows. It is responsible for the fall of blood sugar. When the tolbutamide absorption is slow, insulin secretion is small, but the blood sugar level is still falling. The three following hypotheses are proposed: either the insulin which appears in the pancreatic vein cannot be measured at the periphery and acts mostly in the liver, or the low concentration of tolbutamide in the serum causes only a slight secretion of insulin, but an important inhibition of the secretion of glucagon which is responsible for the observed hypoglycaemia. Extrapancreatic action of sulphonylurea compounds, particularly on muscle tissue, may too play an important role to explain the results.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Physical training ; glucose tolerance ; skeletal muscle glucose metabolism ; insulin sensitivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of physical training on glucose tolerance in vivo and skeletal muscle glucose metabolism in vitro was investigated in normal rats. Treadmill running for 10 days up to 240 min/day led to a decrease of basal and glucose-stimulated plasma insulin levels without major alterations of the IV glucose tolerance (1 g/kg body weight). Swim training of two weeks' duration, i. e. exercise up to 2×75 min/ day, which did not induce significant changes in body composition, skeletal muscle glycogen levels or citrate synthase activity, resulted in a significant improvement of IV glucose tolerance and substantial reductions of basal and glucose-stimulated plasma insulin levels. Associated with this apparent improvement of insulin sensitivity in vivo, significant increases of the insulin-stimulated glucose uptake (+ 55%) and lactate oxidation (+ 78%) in vitro were found on perfusion of the isolated hindquarter of swim-trained animals. It is suggested that mild physical training can improve glucose tolerance and insulin sensitivity in normal rats, at least in part, due to an increase of insulin sensitivity of skeletal muscle glucose metabolism.
    Type of Medium: Electronic Resource
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  • 5
    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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  • 6
    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.
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  • 7
    ISSN: 1432-1041
    Keywords: Sulfonylurea action ; glucose tolerance ; plasma insulin ; lipoproteins ; diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of a new sulfonylurea (Ro 6-4563) have been studied on glucose tolerance, plasma insulin, lipids, and lipoprotein pattern in 29 patients with maturity onset diabetes. After 4 weeks of treatment 3 different reactions have been distinguished and are discussed: I. No response, viz. same glucose tolerance and insulin levels before and after treatment. II. Improved glucose tolerance without increased insulin levels. III. Improved glucose tolerance with higher insulin levels. Sulfonylurea treatment had no effect on plasma lipids or lipoprotein pattern. Clinically “good blood sugar control” could not be correlated with good lipid control. Response II supports the view that sulfonylurea compounds do not necessarily act by increasing plasma insulin levels.
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  • 8
    ISSN: 1433-8580
    Keywords: Glucosidase inhibitor ; BAY g 5421 ; Blood glucose ; Serum insulin ; Serum triglycerides ; Acarbose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In blind studies the effects of a newα-glucosidase inhibitor (BAY g 5421) were tested in normal weight and overweight male volunteers after oral application of 75, 150, or 300 mg of BAY g 5421 or placebo per os before three standardized main meals of one day. Before and three hours after each meal blood glucose, serum insulin, and serum triglyceride levels were determined. In addition, safety studies were performed. BAY g 5421 induced a statistically significant, in part dose-dependent inhibition of the postprandial increase of blood glucose- and serum insulin levels. The reduction of the postprandial increase of serum triglyceride levels was variable. Routine blood chemistry and hematology tests have revealed no adverse side effects; but the application of the drug was frequently associated with intestinal effects, such as flatulence and diarrhea, which were substrate (carbohydrate) and, in part, dose-dependent.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1433-8580
    Keywords: Glucosidase inhibitor ; Blood glucose ; Serum insulin ; Serum triglycerides ; BAY g 5421 ; Acarbose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In a double-blind quadruple cross-over study the effect of a newα-glucosidase inhibitor (BAY g 5421) on postprandial blood glucose, serum insulin, and serum triglyceride increases was tested in 24 male healthy volunteers. They received before a standardized breakfast 50, 100, or 200 mg of BAY g 5421 or a placebo per os. The dose-time-response relationships were calculated and the drug tolerance was assessed. There was a statistically significant inhibition of the postprandial increases of the blood glucose, serum insulin, and triglyceride values. Further analysis showed no dose-dependent effect of the drug on the blood glucose values, whereas the serum insulin and triglyceride values were affected in a dosedependent fashion. The maximal inhibitory effect on the serum insulin levels occurred 69 min after breakfast and on the serum triglyceride levels 104 min after breakfast. One hundred and 200 mg of BAY g 5421 were equally inhibitory-effective on the serum insulin levels, whereas the highest dose used was markedly more effective on serum triglyceride values than lower doses. Based on these results, a dosage of 100–200 mg of BAY g 5421/meal is recommended for clinical trials in metabolic diseases.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Digestive diseases and sciences 30 (1985), S. 522-528 
    ISSN: 1573-2568
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The neutralizing capacity of two antacids (Alucol®=A, Syntrogel®=S), differing both in their composition and theoretical neutralizing capacity, was evaluatedin vitro andin vivo.In vitro at pH 3.5, 1 ml of A or S neutralizes 3.9 and 1.6 meq of acid, respectively, in an aqueous solution. When testedin vivo in the absence of food during near maximal acid secretion, induced by impromidine, 60 ml of either A or S reduced the 4-hr mean H+ activity by 83% and 65%, respectively. In contrast, the reduction of the 12-hr H+ activity observed after repeated administration of 30–60 ml of A or S at the end of the postprandial hour failed to reach significance with both preparations. This suggests that interaction with food produces a considerable loss ofin vivo antacid neutralizing capacity, not quantitatively predictable fromin vitro tests.
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