Genetisches Risiko bei metabolischer Fettlebererkrankung

Die Diabetologie - Die nichtalkoholische Fettlebererkrankung (NAFLD) ist eng mit dem metabolischen Syndrom vergesellschaftet und soll laut Expertenempfehlung in metabolisch assoziierte...     

Neue Therapiemöglichkeiten bei nichtalkoholischer Fettleber

Insulin resistance is a major pathophysiological factor in the development of non-alcoholic fatty liver disease. Moderate weight reduction und exercise are therefore recommended as a standard treatment in obese patients. Based on the results of large prospective randomized clinical trials, there is currently no strong evidence to recommend the routine use of pharmacologic treatment for non-alcoholic fatty liver disease. Non-invasive markers for assessing staging and grading in patients with non-alcoholic fatty liver disease are not available. Metformin and the thiazolidinediones have shown promise in pilot trials, but further controlled studies are needed. Vitamin E and ursodeoxycholic acid cannot be recommend based on current evidence.     

Diabetestherapie mit oralen Antidiabetika bei chronischer Niereninsuffizienz

Due to a worldwide increase of type 2 diabetes a further increase in the number of patients with chronic kidney disease (CKD) and diabetes mellitus must be assumed although the individual risk for diabetic late complications is declining in some countries. The presence of CKD increases the risk for complicated hypoglycemia. Therefore, the HbA_1c target levels must be individually adjusted depending on comorbidities and treatment safety. This is complicated by the fact that in patients with advanced CKD the HbA_1c levels are falsely low. The role of the kidneys in glucose homeostasis is manifold. The inhibition of sodium glucose transporter (SGLT2) is a new and promising mechanism of action but the use is limited to patients with no or low grade CKD. In the clinical routine the type and dosage of antidiabetic drug treatment has to be adapted to the different stages of CKD. For kidney transplant recipients it is important to know that the occurrence of new onset diabetes after transplantation (NODAT) must be assumed. The implementation of appropriate screening programs is advisable.     

Orale Diabetestherapie

The prevalence of type 2 diabetes continues to show a clear upward trend in Germany. In earlier days it was considered the "harmless diabetes of old age," but has become increasingly recognized as a disease carrying a high risk of vascular sequelae as well as shortening the diabetic's remaining life expectancy if adequate therapy is not initiated. In addition to correcting hyperglycemia, treatment consists in effective management of concomitant risk factors such as hypertension, dyslipidemia, and adiposity resulting from faulty nutrition and lack of exercise. In the large majority of overweight type 2 diabetics, metformin is the oral antidiabetic agent of first choice provided the patient does not exhibit renal insufficiency, which represents the most important contraindication. This recommendation for monotherapy of overweight type 2 diabetics is supported by an endpoint study. In contrast, no equivalent evidence is available on any of the possible options for oral combination therapy.     

Genetik der Fettlebererkrankung

Alcoholic and non-alcoholic fatty liver diseases are the most common chronic liver disorders world-wide, especially in developed countries; however, the predominant risk factors, namely obesity, metabolic syndrome and chronic alcohol abuse, only lead to steatohepatitis and liver cirrhosis in the minority of patients. Thus, additional, possibly genetic risk factors may predispose to manifestation and progression of disease, a notion well supported by epidemiological data for both entities. Both phenotypes thus constitute complex diseases where environmental factors, behavior and genetic risk factors interact to determine disease risk and characteristics. As a result of initial genetic studies a robust susceptibility gene PNPLA3 (patatin-like phospholipase domain-containing 3) has been identified and confirmed for both disorders. Homozygous carriers of the risk variant PNPLA3-148M have an approximately ?4-fold increased risk of non-alcoholic steatohepatitis and a ?6-fold increased risk of alcoholic liver cirrhosis. Potentially, the relatively high risk conferred by this variant may be used for future prevention and risk stratification strategies.     

Diabetestherapie des akuten Koronarsyndroms

The early and differentiated optimization of the glucose level is essential for the improvement of cardiovascular disease. In all stages of such diseases, attaining a near-normal glucose range is the primary goal. The DIGAMI 1 and 2 studies as well as the Munich Myocardial Infarction Registry demonstrate that an intensification of treatment with insulin reduces mortality due to myocardial infarction. Giving insulin in the acute phase of cardiovascular complications is the therapy of choice to counter hyperglycemia quickly and over the long-term. Here, glucose-insulin infusion is advantageous as a controllable concept. In non-acute cardiac disease, insulin therapy and oral treatment strategies alone or in combination can be successful. Acarbose and metformin can successfully prevent cardiovascular disease. New evidence of the positive effects of glitazones in reducing the rate of restenosis and optimizing endothelial function is currently emerging.     

Diabetestherapie in besonderen Lebenssituationen

The hyperglycemic imbalance under the influence of cortisone therapy or during parenteral feeding is becoming increasingly more often a challenge in the daily practical hospital routine. Unfortunately there are no guidelines or relevant evidence-based data on optimal diabetes control. The quality of metabolic adjustment has to be even more individually well-defined than normal and must be arranged with the patient, relatives and all caregivers in the therapeutic team. In the often palliative situation the most important aspect is to avoid a hypoglycemic and a very high hyperglycemic status and not the avoidance of diabetic consequences, such as microangiopathy, macroangiopathy and neuropathic diseases. In the following it will be examined how a possible, mostly insulin-based therapy, can be initiated.     

Metformin in der Diabetestherapie

Ohne Zusammenfassung     

Endpunktstudien in der Diabetestherapie

The goal of this article is to provide a review of recently published cardiovascular endpoint studies and their consequences for diabetes treatment. Several recent cardiovascular outcomes studies have been published in recent years, demonstrating in patients with advanced disease duration and clinically manifest coronary artery disease that stringent glycemic control results in only a limited reduction of cardiovascular events. In addition, various safety studies have demonstrated the cardiovascular safety of various substances, e.g., DPP-4 inhibitors (DPP: dipeptidyl peptidase). At the same time, some substances, e.g., SGLT?2 inhibitors (SGLT?2: sodium-dependent glucose transporter 2) or certain GLP-1 analogs (GLP-1: glucagon-like peptide 1), were found to reduce the number of cardiovascular events in patients with diabetes and high cardiovascular risk, so that these drugs are increasingly included in the guideline for diabetes treatment. This review summarizes the current data and illustrates the clinical consequences of these findings.     

Relevanz von Fibraten in der Diabetestherapie

Die Diabetologie - Fibrate wirken auf die bei Typ-2-Diabetes (T2DM) typische Dyslipidämie besonders gut. Im Gegensatz zu der die Leitlinienempfehlungen begründenden Evidenz für...     

Bronchiektasien bei drei Geschwistern und bei deren Onkel

This report contains information about 4 cases of bronchiectasis found in two generations of the same family without direct transmission of the condition between parents and children. In one case the histological examination showed — aside from bronchiectasis — a cyst, which was thought to be of congenital origin.     

Dosis-Wirkungs-Beziehungen bei der Krebserzeugung durch 4-Dimethylamino-stilben bei Ratten

Zusammenfassung Die Dosis-Wirkungs-Beziehungen für die carcinogene Wirkung des 4-Dimethylamino-stilbens wurden in Fütterungsversuchen an Ratten des Stammes BD II in sieben verschiedenen Dosierungsgruppen untersucht. Praktisch alle genügend lange überlebenden Tiere entwickelten Gehörgangscarcinome. Die gefundenen Dosis-Wirkungs-Beziehungen ergaben in allen Gruppen lineare Regressionen über dem log der Gesamtdosis. Die carcinogene Wirkung erweist sich damit als Funktion der Summe aller Einzeldosen. Sie ist irreversibel und bleibt voll summationsfähig über die gesamte individuelle Lebenszeit der Versuchstiere erhalten. Ein Erholungsfaktor oder eine partielle Reversibilität der Wirkung waren nicht nachweisbar. Die zur Krebserzeugung erforderliche Gesamtdosis nimmt bei Verkleinerung der Tagesdosis in berechenbarer Weise ab.Die Größe der mittleren carcinogenen Gesamtdosis und der mittleren Induktionszeit zeigten im doppelt log Netz eine lineare Abhängigkeit von der Höhe der Tagesdosis. Die gefundenen Zusammenhänge zwischen den beiden maßgeblichen Einflußgrößen: Dosis und Zeit werden formuliert. Danach geht die carcinogene Wirkung über eine einfache Summationswirkung hinaus und entspricht einer Verstärkerwirkung. 4-Dimethylamino-stilben erzeugt an verschiedenen Rattenstämmen Krebs. Die dabei beobachteten Unterschiede betreffen lediglich die Höhe der zur Krebserzeugung benötigten Gesamtdosis, sind also nur quantitativer Natur.

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Summary The relations between the effects and the dosage of 4-dimethylaminostilbene in causing cancer were studied in feeding experiment in rats of the strain BD II in seven different dosage groups. Practically all of the animals surviving long enough developed carcinomas of the external auditory canal. In all dosage groups linear dose-response relationships have been observed, if the log of the total doses administered was plotted on the abscissa. Correspondingly the production of cancers is a function of the sum of all individual doses. The carciogenie effect was irreversible and remained completely additive over the entire individual life spans of the experimental animals. A recovery factor or a partial reversibility of the effect were not demonstrable. The total dose needed for carcinogenesis decreased with reduction of the daily dosage in a calculable way. The size of the average total carcinogenic dose and the average induction period showed in the double log net a linear dependence on the heighth of the daily dose. The relations found between the two standardizing factors, dose and time, were formulated. According to this, the carcinogenic effect goes beyond a simple summation effect, and corresponds to an amplified effect. 4-dimethylamino-stilbene caused cancer in different strains of rats. The differences in effect observed were related to the heighth of the total dose required to produce cancer; therefore, they were only of quantitative nature.

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Mit 6 Textabbildungen

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Herrn Prof. Dr. h. c. A. Butenandt zum 60. Geburtstag gewidmet. Die Untersuchungen wurden durch die Deutsche Forschungsgemeinschaft ermöglicht

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Dischler, W.: Quantitative Analyse der Krebserzeugung durch 4-Dimethylaminostilben. Inaug.-Diss. Freiburg 1959