Decreased level of endogenous secretory receptor for advanced glycation end-products in diabetes with concomitant hyperlipidemia.

Endogenous secretory receptor (esRAGE) for advanced glycation end-product (AGE) acts as decoy for AGEs. The AGE-to-esRAGE ratio was hypothesized to be implicated in diabetic vasculopathy. We investigated an association of esRAGE and methylglyoxal-adducts serum level, as well as AGE-to-esRAGE ratio in subpopulation of diabetic patients with or without concomitant hyperlipidemia and macrovascular disease in history. In diabetes with concomitant hyperlipidemia esRAGE was significantly decreased compared to hyperlipidemia with normal glucose metabolism (0.306+/-0.2 vs. 0.367+/-0.1; p=0.019) or diabetes alone (0.306+/-0.2 vs. 0.404+/-0.1; p=0.004). High AGE/esRAGE ratio, found in diabetic patients with hyperlipidemia, pointed to increased production of AGEs and low expression of esRAGE. In multivariable analysis adjusted for several confounding factors, increased AGE/esRAGE ratio was recognized as a high risk for vascular disease outcomes.

Detection of autoantibodies against advanced glycation endproducts and AGE-immune complexes in serum of patients with diabetes mellitus.

Advanced glycation of protein causes their immunogenicity. The evidence that advanced glycation endproducts (AGEs) have antigenic properties has led to a hypothesis that the AGE structure found in vivo may exert an autoimmune response. In the present study, we showed the sera of diabetic patients as well as of nondiabetic individuals to contain autoantibodies to epitopes of AGE structures. Contrary to what might be expected, we observed lower AGE antibody titers in diabetic subjects, and postulated that the antibodies against AGEs form immune complexes in vivo, hampering their determination. The existence of immune complexes containing AGE moiety was established by two independent criteria: (a) serum AGE-immune complexes (AGE-IC) were detected by enzyme-linked immunosorbent assay (ELISA) using an immunochemical bridge; and (b) soluble AGE-IC were precipitated from serum by polyethylene glycol and analyzed. We demonstrated the presence of circulating AGE-IC in sera, predominantly in the sera of diabetic subjects. We also found an inverse correlation between serum AGE level and AGE-IC (r=-0.8, P<0.000), indicating the serum level of AGEs to decline with an increasing presence of AGE-IC. The content of AGE in soluble immune complexes was significantly higher in diabetic patients than in control subjects (3.51+/-1.9 vs. 1.89+/-1.0 microgEq/ml (P<0.00004), and correlated inversely with free antibodies (r=-0.26, P<0.01). Interactions of AGE autoantibodies with AGE as a continuously produced antigen result in the formation of AGE-immune complexes that may play a role in the atherogenic processes.

Reduction of diffusion capacity for carbon monoxide in diabetic patients.

Diabetes can cause the development of pulmonary complications due to collagen and elastin changes, as well as microangiopathy. This study demonstrates the relationship between pulmonary complications and other chronic complications in diabetes. Twenty-seven patients with diabetes, aged 21 to 62 years, who had had the disease from 3 to 32 years, were included in this study. The protein excretion rate (PER) and the diffusion capacity of the lung for carbon monoxide (DLCO) were included as parameters of the severity of complications. PER was determined by the Biuret method. DLCO was measured by the single-breath method and was corrected by the measurement of alveolar volume (VA). The values of DLCO as corrected by VA (DLCO/VA) were included in the statistical evaluation of the results. The variables of age, duration of diabetes, and complication parameters were included in a multiple regression model with forward, stepwise selection to assess their value in predicting DLCO/VA. The variables were found to be significant predictors of DLCO/VA (R2 = 0.46, adjusted R2 = 0.32, p < 0.022). However, proteinuria was the only significant independent predictor of DLCO/VA. This finding indicates that both renal and pulmonary complications of diabetes share a similar microangiopathic background.

Cigarette smoking and sarcoidosis.

The aim of the study was to analyze the effect of cigarette smoking on the occurrence of sarcoidosis. Sixty patients were examined (17 smokers had 43 nonsmokers). A control group consisted of 60 healthy subjects (33 smokers and 27 nonsmokers). The study showed sarcoidosis to more frequently occur in nonsmokers. Apart from the confirmation that sarcoidosis is predominantly a disease of nonsmokers, our aim was to determine whether smoking has an effect on the extent, course and outcome of the disease. Thus, at the beginning of the study the following examinations were performed in patients with sarcoidosis: chest X-ray, functional respiratory tests, determination of arterial blood acid-base status, blood cells, elastase and C-reactive protein in serum, and the cellular component of the bronchoalveolar lavage. Chest X-ray, functional respiratory tests and acid-base component of arterial blood were repeated after one year. In our patients, hilopulmonary sarcoidosis was most frequent (66.7%). No significant difference was found between smokers and nonsmokers according to radiographic extent of the disease. Analysis of the cellular component of the bronchoalveolar lavage showed significantly more macrophages and less lymphocytes in smokers. Analysis of serum indicators showed no differences between smokers and nonsmokers. Smokers and nonsmokers did not differ according to values of forced expiratory volume in the first second (FEV1). However significantly more nonsmokers had mild degrees of decreased FEV1 (75%-60%) at the beginning of the study, and significantly more smokers had a higher degree of respiratory pathway obstruction (60%-45% and less), both at the beginning and end of the study. At the beginning of the study, significantly higher values of residual volume (RV) and total lung capacity (TLC) were recorded in smokers. No statistically significant difference was found between smokers nad nonsmokers according to the extent of the disease, frequency of extrathoracic localization of disease and use of corticosteroids. Comparison of radiographic finding at the end of the study showed no significant difference between smokers and nonsmokers. There was no difference according to outcome, depending on the therapy used. Based on the results of this study the authors conclude that smoking plays a certain protective role in the occurrence of sarcoidosis, although smoking has no effect on the extent, course and outcome of the disease.

[Pulmonary changes in patients with type I neurofibromatosis and tuberous sclerosis]. / Plucne promjene u bolesnika s neurofibromatozom tip I i tuberoznom sklerozom.

Two patients with pulmonary affections in the course of neurofibromatosis and tuberous sclerosis are presented. We wanted to draw attention to the possibility of occurrence of diffuse interstitial pulmonary changes during congenital neurocutaneous syndromes, of which no data are reported in our literature. The affection of the lungs in 10-20% of the patients with neurofibromatosis and 1% with tuberous sclerosis is estimated, commonly in women. The most frequent changes in neurofibromatosis are fibrosing alveolitis and interstitial fibrosis, and in tuberous sclerosis cystic lung changes and lymphangiomyomatosis, what agrees with our findings. It is important to recognize such patients in order not to perform unnecessary diagnostic procedures, and not to draw wrong conclusions, thus being able to avoid an unnecessary therapy, ineffective in such cases. The patients should be followed up, and in the case of complaints symptomatic therapy has to be administered.