elastin and Diabetic-Retinopathy

Diabetes affects the microcirculation, the large arteries and occasionally the large and small veins, by inducing vessel wall sclerosis. The degree of stiffening produced is linked to its duration. The ability of the diabetic's circulation to distribute blood is affected, especially during increased blood flow. In most tissues this causes no serious burden, but three tissues are unusually susceptible to disturbance--the retina, renal cortex, and peripheral nerve. They develop serious problems in many longstanding diabetics. Damage to the kidney appears to be linked to its unique combination of high blood flow rate and precise control of intraglomerular filtration pressure. As renal arteriolar intima hyalinizes, the glomerular mesangium increases in volume. Diabetic renal changes appear to become irreversible when a critical stage, manifested be albuminuria and hypertension, is reached. The resulting renal failure is associated with clumpy deposits of type IV collagen in the cortex, suggesting that local microvascular autoregulation has been lost. The retinal circulation forms late in fetal life in a process in which local oxygen tension controls new vessel formation. In adult diabetics, local retinal oxygenation is disrupted by a condition called capillary closure, and intraretinal microaneurysms form. In advanced retinopathy, new microvessel systems grow into the vitreous through defects in the internal limiting membrane, producing hemorrhage and vitreous opacification. Macular degeneration is also seen in older diabetics, suggesting that the choroidal circulation may also be compromised. Evidence for a microcirculatory role in diabetic peripheral nerve damage is not as conclusive as for the kidney and retina. The longest peripheral nerves are typically the most affected. Recent studies suggest that nerve damage can be produced by a disturbance in local pressure-flow relationships combined with epineurial mechanical constraint. Hypotheses about the pathogenesis of diabetic vascular sclerosis are reviewed, including collagen-stiffening, elastin degeneration, hemorheologic burden, metabolic disruption, increased permeability, and auto-immune disturbance.

Topics: Capillary Permeability; Chronic Disease; Collagen; Diabetes Mellitus; Diabetic Angiopathies; Diabetic Neuropathies; Diabetic Retinopathy; Elastin; Glomerular Filtration Rate; Humans; Microcirculation; Regional Blood Flow; Renal Circulation; Retinal Vessels; Time Factors

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.. 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.. 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.. 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.

Topics: Aged; Albuminuria; Autoantibodies; Case-Control Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Neuropathies; Diabetic Retinopathy; Elastin; Female; Glycation End Products, Advanced; Humans; Hypertension; Male; Middle Aged

An important factor in the development of vascular wall alterations is degradation of the elastic fiber major protein-elastin. Elastin peptides derived from this degradation are present in the circulating blood and they are a stimulus for increased production of anti-elastin antibodies (AEAb). The aim of the present study was to examine the possible association between serum elastin AEAb and the development of diabetic vascular complications. Levels of AEAb (IgG, IgM and IgA) were determined by ELISA in sera of 28 children with Type 1 (insulin-dependent) diabetes mellitus (mean age 11.6+/-2.8 years, diabetes duration 5.1+/-2.5 years). None of the children had clinical or laboratory evidence of vascular complications. The children were followed over a period of 7 years, and 24 healthy children of similar age and sex served as a control group. During the study, four diabetics developed retinopathy, six microalbuminuria and two both retinopathy and microalbuminuria. Anti-elastin IgG showed correlation with diabetes duration (r=.48, P=.0007), HbA1c (r=.28, P=.05), triglycerides (r=.28, P=.05) and antibodies to advanced glycation endproducts (AGE) (r=.41, P=.005). Anti-elastin IgM correlated with HbA1c (r=.26, P=.038) and IgA with retinopathy (r=.32, P=.017). Our results suggest an association between the level of anti-elastin IgA antibodies and the development of diabetic retinopathy.

Topics: Adolescent; Antibodies; Child; Diabetes Mellitus, Type 1; Diabetic Retinopathy; Elastin; Female; Glycated Hemoglobin; Humans; Immunoglobulin A; Immunoglobulin M; Male