Insulin dependent diabetes mellitus (IDDM) is an autoimmune disease associated with the presence of different types of autoantibodies. The presence of these antibodies and the corresponding antigens in the circulation leads to the formation of circulating immune complexes (CIC). CIC are known to persist in the blood for long periods of time. Such CIC following deposition in the small blood vessels have the potential to lead to microangiopathy with debilitating clinical consequences. The aim of our pilot study was to investigate whether a correlation exists between CIC and the development of microvascular complications in diabetic children. Isolation of a new glycoprotein complement inhibition factor (CIF) from the parasitic plant Cuscuta europea seed, which appears to bind specifically to complement component C3 has provided an unique tool for the measurement of immune complexes by means of ELISA-type techniques (CIF-ELISA). We studied the levels of CIC (IgG, IgM and IgA) in 58 diabetic children (mean age 12.28±4.04 years, diabetes duration 5.3±3.7 years), 29 of them had vascular complications (group 1) and the other 29 were without vascular complications (group 2). As controls, we studied sera samples from 21 healthy children (mean age 13.54±4.03 years). Sera from the diabetic patients showed statistically significant higher levels of CIC IgG ( p=0.03) than sera from the control group. In sera from group 1 values of CIC IgG showed statistically significant higher levels than controls (0.720±0.31 vs. 0.46±0.045; p=0.011) Sera from 59% of the patients were positive for CIC IgG, 36% for CIC IgM and 9% for CIC IgA. Among 26 patients with microalbuminuria, sera from 17/26 (65%) were positive for CIC IgG, 8/26 (31%) for CIC IgM and 2/26 (8%) for CIC IgA. CIC IgG correlated with HbA1c (r=0.51; p=0.005) and microalbuminuria (r=0.42, p=0.033). CIC IgA correlated with age (r=0.44, p=0.03). CIC IgM correlated with the duration of diabetes (r=0.63, p=0.02). These findings suggest that elevated levels of CIC IgG are associated with the development of early diabetic nephropathy.
Endothelin-1 (ET-1) is one of the most potent vasoconstrictors known to date. While its plasma or serum concentrations are elevated in some forms of experimental and human hypertension, this is not a consistent finding in all forms of hypertension. Matrix metalloproteinases -2 and -9 (MMP-2 and MMP-9), which degrade collagen type IV of the vascular basement membrane, are responsible for vascular remodeling, inflammation, and atherosclerotic complications, including in type 2 diabetes (T2D). In our study, we compared concentrations of ET-1, MMP-2, and MMP-9 in pre-hypertensive (PHTN) and hypertensive (HTN) T2D patients with those of healthy normotensive controls (N). ET-1, MMP-2, and MMP-9 were measured by ELISA. Concentrations of ET-1 in PHTN and N were very similar, while those in HTN were significantly higher. Concentrations of MMP-2 and MMP-9 in PHTN and HTN were also significantly higher compared to N. An interesting result in our study is that concentrations of MMP-2 and MMP-9 in HTN were lower compared to PHTN. In conclusion, we showed that increased production of ET-1 in patients with T2D can lead to long-lasting increases in blood pressure (BP) and clinical manifestation of hypertension. We also demonstrated that increased levels of MMP-2 and MMP-9 in pre-hypertensive and hypertensive patients with T2D mainly reflect the early vascular changes in extracellular matrix (ECM) turnover.
Background and Aims: Proteins containing advanced glycation end products are highly immunogenic and anti-advanced glycation end products antibodies (anti-AGEs antibodies) are found in the sera of diabetics. Materials and methods: Enzyme-linked immunosorbent assay (ELISA) was used for measuring levels of anti-advanced glycation end products antibodies in sera of 93 patients with type 2 diabetes mellitus and arterial hypertension (mean age 61.4±11.3 years, diabetes duration 9.88±3.12 years; hypertension duration 9.28±4.98). These values were compared to serum anti-AGEs antibodies in 42 age and sex matched controls. Diabetics were divided in two groups according to presence or absence of microangiopathy, group 1 (n=67) and group 2 (n=26), respectively. Results: Serum levels of anti-AGEs antibodies in patients with type 2 diabetes mellitus and arterial hypertension were statistically significantly higher than those in the control group (1.39±0.39 vs. 1.05±0.32), (p<0.05). Group 1 showed significantly higher levels of anti-AGEs antibodies than those of healthy controls (1.53±0.14 vs. 1.05±0.32), (p<0.01). Anti-AGEs antibodies levels were higher in patients with microvascular complications than these in patients without complications. Anti-AGEs antibodies correlate with diastolic blood pressure (r=0.26, p=0.05) and body mass index (r=0.37, p=0.03). We found significantly higher percentage of positive patients for anti-AGEs antibodies (mean+2SD) in group 1 than in group 2. Conclusion: Determining the levels of serum anti-AGEs antibodies can help physicians make early diagnosis and prognosis of the severity of late diabetic complications in hypertensive patients.
Galectin-3 (gal-3) is lectin which is presumed to interact with extracellular matrix proteins and cell surface glycoproteins in normal and pathophysiological conditions. The expression of gal-3 at the fetal-maternal interface partially overlaps that of gal-1, suggesting that an interplay between them might be important for hypertensive disorders in pregnancy like preeclampsia. The aim of our study was to test the hypothesis whether galectin-3 could be used as a predictive marker for early-onset preeclampsia development. 32 patients with early-onset preeclampsia were examined, mean age 28.8 ± 5.5; and 22 age matched normal pregnancies mean age 28.5 ± 6.0. The enzyme-linked immunosorbent assay (ELISA) was used for measuring serum galectin-3 levels. There were no significant differences between serum levels of galectin-3 in sera of preeclampsia patients compared to normal pregnant women – 14.1 ± 4.77 vs. 15.7 ± 5.95 ng/ml (p>0.05). Serum galectin-3 levels correlated with maternal age (r=0.33; p=0.03) and BMI (body mass index) (r=0.52; p=0.01). Our data suggest that determination of serum galectin-3 levels may not be a useful method for prediction of early-onset preeclampsia. Studies should be aimed to other categories of biomarkers.
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