The enzyme glutamate decarboxylase (GAD) is considered one of the major Beta cell antigens in Type 1 diabetes mellitus. The GAD autoantibody (GAD-AAb) prevalence in newly diagnosed Type 1 diabetic patients has been described up to 80%, depending on the detection method used. The aim of this study was to evaluate a simple, specific, and sensitive radioimmunoassay (RIA) method for detection of AAb against both isoforms of the enzyme, GAD65 and GAD67, in a cross-sectional study using sera from newly diagnosed Type 1 diabetic patients and in a longitudinal study using sera from prediabetic patients and individuals at risk of developing the disease. The 125I-labelled full-length human recombinant proteins of GAD65 and GAD67 expressed in SF9 cells were used as the antigen source. The prevalence of GAD65-AAb in newly diagnosed Type 1 diabetic patients was found to be 73% (112/153), in contrast to 19% (14/72) of GAD67-AAb. Only one patient produced AAb restricted to GAD67. Furthermore, GAD65-AAb could also be detected in 73% (11/15) of prediabetic patients (up to 122 months before clinical manifestation of the disease), whereas only 27% (4/15) of them were positive for GAD67-AAb. In the group at risk of developing Type 1 diabetes, these prevalences were 77% (10/13) and 46% (6/13), respectively. In all GAD67-AAb-positive patients investigated in the longitudinal study, AAb to GAD65 were detectable. In 47% of patients positive for both GAD65-AAb and ICA, the GAD65-AAb appeared by up to 46 months before the occurrence of ICA was detected. The data illustrated that GAD65 is the main immunogenic isoform of the enzyme in the preclinical and clinical stages. The RIA detecting AAb against this isoform may facilitate the screening for individuals at risk of developing the disease.
In order to assess the validity of WHO criteria for the discrimination between Type I and Type II diabetes a cross-sectiona clinical study was performed in 84 normweight newly diagnosed diabetics with a mean age of 22 years. Taking into consideration clinical and biochemical characteristics of the carbohydrate and fat metabolism, the therapeutic requirement to maintain euglycemic metabolic control, the residual beta-cell function, the HLA phenotype and islet cell antibodies (ICA, ICSA) it could be shown that none of the tested criteria has the ability to distinguish between the types with absolute certainty. As shown by the frequency of the different markers in relation to the therapeutic requirements for euglycemic metabolic control as well as by the correlation analysis between the variables the discriminating validity of the markers decreased in the following sequence: diabetes associated HLA phenotype, residual beta-cell function, proneness to ketosis, age at onset, relative body weight. Neither the characteristics of the carbohydrate and fat metabolism nor the presence of islet cell antibodies contributed much to the differentiation between insulin-dependent and noninsulin-dependent diabetes.
Zusammenfassung Ziel: Es soll die Wertigkeit von 123l-mlBG-Szintigraphie, Knochenszintigraphie und Katecholaminmetaboliten bei der Verlaufskontrolle untersucht werden. Methode: Es wurden 19 Kinder mit Neuroblastom im Stadium IV retrospektiv mit 123l-mlBG- und 99mTc-MDP-Szintigraphie untersucht und deren Ergebnisse mit der Bestimmung von Homovanillinsäure, Vanillinmandelsäure, neuronenspezifische Enolase, Laktat-dehydrogenase und Ferritin über einen Beobachtungszeitraum von 7-132 (Median: 36) Monaten verglichen. Ergebnisse und Schlußfolgerung: Die Ergebnisse zeigen, daß die Wertigkeit der einzelnen Verfahren vom Zeitpunkt des diagnostischen Einsatzes abhängig ist. Prinzipiell ist die mlBG-Szintigraphie das Verfahren mit der höchsten diagnostischen Aussagekraft. Zum prätherapeutischen Staging und zur Diagnostik des Rezidivs ist die Kombination aller drei Methoden sinnvoll. Bei der Verlaufskontrolle unter Chemotherapie spiegelt die mlBG-Szintigraphie die Heterogenität des Therapieeffektes am besten wider. Die Laborparameter eignen sich zum Therapiemonitoring wenig; der diagnostische Zugewinn durch die Skelettszintigraphie ist umstritten.
Using the model of the in vitro non-recirculating perfused rat liver we studied kinetic aspects of the hepatic handling of glucagon. Under conditions of a 20 min glucagon infusion (glucagon mass flows of 0.05, 0.46 and 4.75 ng/g liver/min, respectively) according to a rectangular profile both total and individual glucagon extractions were dependent on mass flow and time. The time course of glucagon extraction started with an acute phase within the first minute of infusion with a maximum value of 70%, which decreased within the following 30 sec by more than 40%. Depending on concentration, there was a progressive decrease in the hepatic extraction of glucagon up to the end of perfusion. Hepatic glucagon degradation was found to take place only at a little extent. Immediately after terminating the hormone infusion, the liver changed over into a glucagon-releasing organ. Kinetics of glucagon infusion and glucagon-induced hepatic glycogenolysis did not distinguish by parallelism but rather by phase shifting.
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