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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 67 (1989), S. 253-259 
    ISSN: 1432-1440
    Keywords: Platelet volume ; Thrombopoiesis ; Megakaryocytes ; Glycoprotein IB ; Flow-Cytometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Increased functional properties of diabetic platelets might be already conditionated during thrombopoiesis in the stem cell system. This hypothesis was studied by recording the distribution characteristics of the peripheral platelet pool in 218 diabetic patients versus 51 controls. Furthermore, platelet membrane coating with the stem cell marker glycoprotein IB was analyzed in 41 diabetic subjects and compared to 23 healthy volunteers. A consistant, significant shift of the volume distribution to larger platelets was found in diabetics: Mean platelet volume (MPV) — 7.9±0.9 versus 7.2±0.8 [fl]; Megathrombocyte index (MTI) — 20.4±2.8 versus 18.1±2.5 [fl]. These deviations were present in all patient subsets, however did not correlate to parameters of glucose metabolism. Whole blood platelet count was increased in the patient group: 195.0±59.5 versus 184.0±37.5×103 plts/ul. Coating with glycoprotein IB receptors correlated significantly to platelet size in platelets of both controls and diabetics (r normal=0.52±0.07;r diabetic=0.46±0.1). The quantitativ expression of glycoprotein IB was significantly enhanced in the diabetic group: 54500×1.28±1 versus 39100×1.3±1 molecules per platelet. In conclusion, these findings strongly support the assumption of diabetic stem cell dysfunction of the megakaryocytic series and progenitor cells resulting in platelets with primarily increased potency to adhere and aggregate in diabetes mellitus.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1440
    Keywords: Glycoproteins ; Prethrombotic State ; Monoclonal Antibodies ; Flow-Cytometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Formation of a hemostatic plug is trigered by platelets. Platelet function (e.g. adhesion, aggregation) depends essentially on membrane bound receptorproteins. Conventional chromatografic analysis of these glycoprotein macromolecules is difficult and not appropriate for diagnostic routine. In combination of cytoflowmetric single cell analysis with monoclonal staining we developed a bio-assay for qualitative and semi-quantitative analysis of glycoprotein IB and IIB/IIIA on vital fixed platelets. The expression of these molecules was evaluated in 20 healthy volunteers. The assay offers for the first time the possibility of screening the expression of receptor proteins on platelet membranes, which are related to indicate either a functional lack in bleeding disorders or a prethrombotic state due to an enhanced functional potential in high risk patients.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1440
    Keywords: Type 1 diabetes ; Hypoglycemia ; Glucose counterregulation ; Insulin pumps
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We were interested in studying whether impaired hypoglycemic awareness after intensified insulin treatment with insulin pumps is associated with impaired glucose counterregulation. Glucose counterregulatory hormones were measured in 7 type I diabetic patients with altered symptoms after 6 months of continuous subcutaneous insulin infusion (CSII) (group 1) and in 9 patients with unchanged symptoms of hypoglycemia under CSII (group 2). The groups did not differ in diabetic control, duration of diabetes, or prevalence of neuropathy. Counterregulatory hormone response to an insulin-induced episode of hypoglycemia was measured before (first test) and after 6 months (second test) of CSII. Glucose nadirs and glucose recovery were similar in both groups and both tests. The mean plasma glucagon values demonstrate a lack of glucagon response in both groups and both tests. Growth hormone and cortisol increased in both groups and both tests without any difference between the groups or first and second tests. Epinephrine response was similar in both tests of group 2 (first test: 50±5 to 416±73; second test; 45±5 to 456 pg/ml), while in group 1 the response was not increased significantly in the second test [first test: 32± 6 to 346± 63; second test: 44± 7 to 575± 91 pg/ml; areas under curve (AUC) 11977 and 16345 pg×ml−1×90 min−1 (p= 0.36)]. There was a norepinephrine response in both groups and both tests, with nonsignificantly higher plasma levels during the second test [AUC in pg×ml−1×90 min−1; group 1, first test: 20954, second test: 26675 (p=0.394); group 2, first test: 20745, second test: 27089 (p=0.302)]. The results demonstrate that impaired awareness of hypoglycemic symptoms after intensified insulin therapy is not associated with impaired glucose recovery of hypoglycemia or impaired response of glucose counterregulatory hormones. Further-more, we found that the frequency of glucopenic symptoms reported by the patients during everyday life increased after CSII, while adrenergic symptoms were less frequent.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1440
    Keywords: Type 1 diabetes ; Recent onset ; Glycemic control ; Nerve conduction ; Autonomic function ; Cutaneous sensation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Motor and sensory nerve conduction velocities (MNCV, SNCV), beat-to-beat variation (BBV) at rest, speed of pupillary dilation (SPD), and pupillary latency time (PLT) were measured in 32 patients aged 12–36 years after 19±2 (mean±SEM) days and again after 3, 12, and 24 months of insulin treatment. Moreover, BBV under deep respiration was determined after 12 and 24 months, and thermal discrimination thresholds (TDT) as well as pain and vibration perception thresholds (PPT, VPT) were evaluated after 24 months. Mean HbA1 levels during months 3–24 within the normal range (7.2±0.2%; mean±SEM) were observed in 20 patients (group 1), while in 12 patients (group 2) mean HbA1 of months 3–24 was elevated (10.1±0.4%). There were no significant differences between both groups with regard to the nerve function tests at baseline and after 3 months. After 12 months mean median MNCV and median, ulnar, and sural SNCV were significantly lower in group 2 than in group 1 (p〈0.05). After 24 months mean median MNCV, peroneal MNCV, median SNCV, and sural SNCV as well as both BBV tests and PLT were significantly impaired in group 2 as compared to group 1 (p〈0.05). In addition, mean malleolar VPT and PPT to heat and cold stimuli on the thenar and the foot were significantly elevated in group 2 as compared to group 1 (p〈0.05). These findings suggest that early deterioration of somatic nerve function after one year and of autonomic function after 2 years of diabetes may be prevented by effective glycemic control initiated immediately after diagnosis of the disease.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Weight reduction ; low-calorie-diet ; FFA ; esterified fatty acids ; glycerol ; glucose tolerance ; immunoreactive Insulin (IRI) ; insulinlike activity as measured on adipose tissue (FILA) ; on muscle tissue (MILA)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Pour voir jusqu'à quel degré les déviations métaboliques qu' on observe dans l'obésité sont réversibles par un régime de réduction, nous avons examiné 37 personnes obèses avec un excès de poids moyen de 71% d'aprèsBroca. D'abord nous avons exclu la présence d'un diabète sucré et d'une maladie endocrinienne. 20 personnes montraient des anomalies de la glycorégulation tandis que chez 17 les tests de l'hyperglycémie provoquée par voie intraveineuse et orale donnaient des résultats normaux. Un régime de 1000 cal. par jour a été institué pour les deux groupes et nous avons enregistré une perte de poids moyenne de 21.2kg pour la première et de 17.5kg pour la seconde, soit de 34 ou de 28% d'aprèsBroca, c'est à dire moins que la moitié de l'excès de poids. — Le groupe avec glycorégulation anormale montrait les changements suivants: — 1. Amélioration significative de la tolérance glucidique avec normalisation partielle du taux de glucose sanguin à jeun et 120 min après glucose par voie orale, ainsi que des coefficientsk pour les tests d'hyperglycémie provoquée par voie intraveineuse et orale. — 2. Une chute prononcée et significative des taux très élevés du glycérol libre dans le sang à jeun avec normalisation du quotient: acides gras libres/glycérol à jeun. — 3. Réduction significative des taux élevés de l'activité insulinosemblable et de l'insuline immunoréactive dans le sang. — Dans les mêmes conditions nous avons trouvé dans le groupe avec glycorégulation intacte seulement une augmentation légère des acides gras libres sanguins 90 et 120 min après glucose. Le groupe total des obèses montrait une réduction significative des acides gras estérifiés dans le sang à jeun. — Les résultats caractérisés sous 1–3 sont plus prononcés avec ce régime de réduction qu'après des cures de carence alimentaire totale et se trouvent surtout dans le groupe avec glycorégulation anormale. Ils indiquent que l'hyperinsulinisme accusé jusqu'ici comme pathogénique pour l'obésité est plutôt de nature adaptive.
    Abstract: Zusammenfassung Um Anhaltspunkte dafür zu gewinnen, welche der bei der Fettsucht beobachteten Stoffwechselanomalien durch eine Reduktionsdiät rückbildungsfähig sind, untersuchten wir unter ambulanten Bedingungen 37 adipöse Patienten mit einem mittleren Übergewicht von 71% nachBroca. Ein klinisch-manifester Diabetes und endokrine Erkrankungen wurden ausgeschlossen. 20 der Probanden zeigten Störungen der Kohlenhydrattoleranz. Bei 17 lagen der i.v. und der orale Glucosetoleranz-Test im Normbereich. Beide Teilkollektive behandelten wir mit einer 1000 Cal.-Mischkost und sahen darunter eine Gewichtsabnahme von 21.2 bzw. 17.5 kg, entsprechend 34 bzw. 28% nachBroca, d.h. im Durchschnitt etwas weniger als die Hälfte des bestehenden Übergewichtes. — Beim Teilkollektiv mit gestörter Kohlenhydrattoleranz traten dabei folgende Veränderungen ein: — 1. Signifikante Besserung der Glucosetoleranz mit weitgehender Normalisierung des Nüchternblutzuckers und des 120 Minuten-Wertes nach oraler Glucosegabe, sowie derk-Werte für die i.v. und oralen Glucosetoleranz-Teste. — 2. Ein hochsignifikanter Abfall der stark erhöhten Nüchternwerte für das freie Serumglycerin mit Normalisierung des Quotienten: Freie Fettsäuren/ Glycerin im Nüchternblut. — 3. Signifikanter Rückgang der überhöhten Werte für die insulinähnliche Aktivität und für das immunologisch reagierende Insulin. — Unter den gleichen Bedingungen fanden wir im Teilkollektiv mit normaler Kohlenhydrattoleranz lediglich einen mäßigen Anstieg der freien Fettsäuren 90′ und 120′ nach Glucose. — Im Gesamtkollektiv der Fettsüchtigen war unter der Reduktionsdiät ein signifikanter Rückgang der Esterfettsäuren festzustellen. — Die unter 1–3 geschilderten Veränderungen traten unter dieser Diätbehandlung deutlicher hervor als bei den bisher beschriebenen Fastenkuren und betreffen vorwiegend das Teilkollektiv mit gestörter Kohlenhydrattoleranz. Die Befunde deuten daraufhin, daß der Hyperinsulinismus, der von einigen Autoren als ursächlich für die Fettsucht angesehen wird, eher adaptiver Natur ist.
    Notes: Summary To find out which of the metabolic changes observed in obesity are reversible by a reducing diet, we examined 37 obese out-patients with a mean overweight of 71%Broca. A manifest diabetes mellitus and endocrine diseases were excluded by clinical means. 20 subjects showed disturbances of carbohydrate-tolerance. Oral and i.v. glucose-tolerance tests gave normal results in 17. Both subgroups were put on a 1000 cal. mixed diet and had mean weight-losses of 21.2, vs. 17.5 kg, corresponding to 34% vs. 28%Broca, i.e. less than half of their overweight. — The following changes were observed in the subgroup with impaired carbohydrate-tolerance: — 1. Significant improvement of glucose-tolerance with beginning normalization of fasting blood sugar, 120′ value after oral glucose and of thek-values for i.v. and oral glucose-tolerance tests. — 2. Highly significant reduction of the elevated fasting values for free serum glycerol with normalization of the quotient: free fatty acids/glycerol in fasting serum. — 3. Significant fall of the high levels for insulin-like activity and for immunologically reacting insulin. — Under identical conditions the subgroup with normal carbohydrate-tolerance showed only a moderate increase of free fatty acids 90′ and 120′ after glucose. In the obese group as a whole, we found a reduction of serum esterified fatty acids under low calorie diet. — The changes described under 1–3 were more pronounced with this dietary treatment than in fasting periods generally described until now, and occurred predominantly in the subgroup with impaired carbohydrate-tolerance. Our findings indicate that hyperinsulinism held responsible for obesity up to now by some authors is probably adaptive.
    Type of Medium: Electronic Resource
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  • 6
    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.
    Type of Medium: Electronic Resource
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