P. Wahl

Peripheral blood mononuclear cells isolated from patients with diabetic nephropathy show increased activation of the oxidative-stress sensitive transcription factor NF-kB

Summary Increased oxidative stress and subsequent activation of the transcription factor NF-kB has been linked to the development of late diabetic complications. To determine whether oxidative stress dependent NF-kB activation is evident in patients with diabetic nephropathy we used an Electrophoretic Mobility Shift Assay based semiquantitative detection system which enabled us to determine NF-kB activation in ex vivo isolated peripheral blood mononuclear cells. We examined 33 patients with diabetes mellitus (Type I and Type II). Patients with diabetic nephropathy showed higher NF-kB binding activity in Electrophoretic Mobility Shift Assays and stronger immunohistological staining for activated NF-kBp65 than patients without renal complications. NF-kB binding activity correlated with the degree of albuminuria (r = 0.316) and with thrombomodulin plasma concentrations (r = 0.33), indicative for albuminuria associated endothelial dysfunction. In a 3 day intervention study in which 600 mg of the antioxidant thioctic acid (α-lipoic acid) per day were given to nine patients with diabetic nephropathy oxidative stress in plasma samples was decreased by 48 % and NF-kB binding activity in ex vivo isolated peripheral blood mononuclear cells by 38 %.

Blood pressure and metabolic control as risk factors for nephropathy in Type 1 (insulin-dependent) diabetes

SummaryThe respective rôles of arterial blood pressure and metabolic control in different stages of diabetic nephropathy were analyzed retrospectively in 52 sequentially-followed Type 1 (insulin-dependent) diabetic patients. A negative correlation was found between median post-prandial blood glucose and median duration of diabetes until onset of persistent proteinuria (p<0.01). Systolic blood pressure was higher in patients who subsequently developed persistent proteinuria than those who did not (140 versus 121 mmHg; p<0.05), but duration of the interval until onset of persistent proteinuria was not related to blood pressure. After onset of persistent proteinuria, hypertensive diabetic patients developed elevated serum creatinine concentrations more frequently than normotensive diabetic patients (67% versus 14%, p<0.05). In these patients, the delay until elevation of serum creatinine concentration was negatively correlated with blood glucose (p<0.01). Once serum creatinine was raised, decay of renal function occurred faster in patients with persistent than intermittent hypertension (p<0.05). No effect of metabolic control was demonstrable at this stage of nephropathy. It is concluded that metabolic control determines the early course of diabetic nephropathy, whereas blood pressure is more important in advanced stages of nephropathy.

Influence of diabetes control on synthesis of protein and basement membrane collagen in isolated glomeruli of diabetic rats

SummaryDiabetic rats were treated with insulin at various dosages and for various periods of time. The influence of metabolic control on the synthesis of protein and basement membrane collagen of isolated glomeruli was investigated. The protein and basement membrane collagen synthesis was increased in the untreated diabetic rats compared to non-diabetic controls. The synthesis was not affected by high doses of insulin with brief normalization of the blood sugar. Insulin treatment from the beginning of diabetes only led to a normalization of protein synthesis in moderate metabolic control. On the other hand, a rise of the basement membrane collagen synthesis could only be prevented by a strict metabolic control of the rats. The results show that basement membrane collagen synthesis reacts very sensitively to the diabetic metabolic situation. Insulin deficiency itself does not appear to be alone responsible for alterations of basement membrane synthesis in diabetes.

Neuere Behandlungskonzepte bei Diabetes und Schwangerschaft

Die Schwangerschaft der Diabetikerin war bis vor wenigen Jahren mit hohen Risiken, insbesondere fur den Feten, belastet. So lag die perinatale Mortalitat mit 5–15% 2-5fach hoher als bei stoffwechselgesunden Frauen. Der Prozentsatz an sog. Riesenkindern betrug 20–50% gegenuber 0, 1–2%, die Misbildungsrate 4–10% gegenuber 1–2,5% bei Nichtdiabetikerinnen. Auch andere Schwangerschaftskomplikationen wie Hydramnion und Gestosen kamen bei Diabetikerinnen in einem wesentlich hoheren Prozentsatz vor [1, 2, 3].

Antikörper gegen das HBs-Antigen bei Diabetikern

Die erhohte Hepatitismorbiditat der Diabetiker ist seit langem bekannt. Trotz mehrerer Mitteilungen uber die Haufigkeit des mit dem Hepatitis-B-Virus (HBV) assoziierten Hepatitis-B-Oberflachen-Antigens (HBsAg) [1, 2, 3] liegen Untersuchungen uber die Frequenz des korrespondierenden Antikorpers (anti-HBs) bei Diabetikern bisher nicht vor. Wir haben daher die anti-HBs-Frequenz bei Insulin- und nicht-Insulin-behandelten Diabetikern in zwei unterschiedlichen Zeitraumen mit unterschiedlichen Spritzgewohnheiten untersucht.