Serum anti-collagen type IV IgM antibodies and development of diabetic nephropathy in diabetics with essential hypertension.

INTRODUCTION AND AIMS: Arterial hypertension and diabetic vascular complications are connected with an elevated degradation of elastic tissue. This process leads to an increased production of antibodies to collagen type IV (ACIV Abs). In the present investigation we studied whether the serum levels of antibodies (IgG, IgM and IgA) to collagen are related with microvascular complications. MATERIAL AND METHODS: Serum levels of antibodies to collagen type IV (ACIV) IgG, IgM and IgA were measured using an ELISA method in 93 patients with type 2 diabetes mellitus and arterial hypertension (AH) (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 antibodies to CIV in 42 age and sex matched controls. RESULTS: ACIV IgM antibodies levels in patients with AH and T2DM were statisticaly significantly higher than controls 0.178 (0.145÷0.220) vs. 0.142 (0.118÷0.173) (KW = 6.31; p = 0.01). Group 1 (patients with microvascular complications) showed significantly higher levels of ACIV IgM than controls 0.180 (0.136÷0.223) vs. 0.142 (0.118÷0.173) (KW = 5.03; p = 0.02). Patients from Group 2 showed statistically significantly higher levels of ACIV IgM than controls 0.176 (0.151÷0.202) vs. 0.142 (0.118÷0.173) (KW = 6.15; p = 0.01). ACIV IgM antibodies showed correlation with microalbuminuria (r = 0.21); (p = 0.04), BMI (r = 0.19); (p = 0.04), creatinine clearance (r = -0.36); (p = 0.01) and GFR (r = -0.34); (p = 0.02). CONCLUSIONS: Our study showed an association between elevation of serum levels of ACIV IgM and development of diabetic nephropathy. We suggest that levels of ACIV IgM can be useful method for identfying a high risk for development of diabetic nephropathy.

Abnormal levels of age-elastin derived peptides in sera of diabetic patients with arterial hypertension.

INTRODUCTION: An important factor in vascular wall alterations is degradation of elastic fiber major protein - elastin. As a result, elastin derived peptides (EDP) are found in circulation. Advanced glycation might also involve elastin, because it is a protein with slow metabolism. The aim of our study was to measure serum levels of glycated elastin derived peptides (AGE-EDP) of elastin in patients with type 2 diabetes mellitus (T2DM) and arterial hypertension (AH). MATERIAL AND METHODS: We adapted an ELISA technique for the determination of AGE-EDP. Sera of 93 patients with T2DM and AH (mean age 61.4 ±11.3 years, diabetes duration 9.88 ±3.12 years; hypertension duration 9.28 ±4.98) were tested. These values were compared to 42 age- and sex-matched controls. Diabetics were divided in two groups according to presence - Group 1 (n = 67) or absence - Group 2 (n = 26) of microangiopathy. RESULTS: Patients with T2DM and AH showed statistically significantly higher levels of AGEEDP in comparison with healthy controls 0.060 (0.053÷0.065) vs. 0.039 (0.031÷0.044) (KW = 35.2; p < 0.0001). Group 1 showed significantly higher levels of AGE-EDP than the control group 0.069 (0.051÷0.070) vs. 0.039 (0.031÷0.044) (KW = 33.0; p < 0.0001). Group 2 also showed significantly higher levels of AGE-EDP than controls 0.058 (0.049÷0.064) vs. 0.039 (0.031÷0.044) (KW = 22.1; p < 0.0001). AGE-EDP showed a correlation with an insulin dose (r = -0.28; p = 0.05), systolic blood pressure (r = 0.25; p = 0.01), BMI (r = 0.39; p = 0.01) and retinopathy (r = 0.18; p = 0.05). CONCLUSIONS: The measurement of non-invasive markers of elastin glycation may be useful in monitoring development of vascular wall alterations and therapeutic interventions.

Abnormal levels of serum antielastin antibodies in children with diabetes mellitus type 1.

Antibodies to alpha-elastin (elastin breakdown product) and elastin sequences devoid of cross-linked regions (linear elastin) are found in the serum of all human subjects and correlate with their respective serum peptide levels. The aim of this study was to determine if the serum level of antielastin antibodies (AEAbs) differs between type 1 diabetic children and nondiabetic children. Enzyme-linked immunosorbent assay was used to measure the levels of immunoglobulin (Ig)G and IgM AEAbs in the sera of 45 diabetic children (mean age 12.8 +/- 3.2 years, diabetes duration 5.3 +/- 3.6 years). Twenty-two children presented with vascular complications (group 1), whereas 23 displayed no vascular complications (group 2). The controls were 18 healthy children (mean age 11.9 +/- 2.3 years). Diabetic patients showed statistically significant higher levels of IgM alpha-AEAbs (0.82 +/- 0.26 vs 0.61 +/- 0.14, p = .0013) than the control group. In group 1, alpha-AEAbs showed statistically significant higher level than controls: IgG (0.86 +/- 0.42 vs 0.59 +/- 0.12; p = .0109) and IgM (0.88 +/- 0.24 vs 0.61 +/- 0.14; p = .0001). IgM antilinear elastin antibodies (ALEAbs) in group 1 were significantly lower than in controls (0.462 +/- 0.191 vs 0.652 +/- 0.127; p = .0009). IgG alpha-AEAbs showed correlation with microalbuminuria (r = -.26; p = .05) and IgM ALEAbs correlated with microalbuminuria (r = -.32; p = .035). IgG alpha-AEAbs correlated with neuropathy (r = -.32; p = .035). Group 1 patients displayed a correlation between IgG ALEAbs and retinopathy (r = -.48; p = .023) and IgM ALEAbs and microalbuminuria (r = .52; p = .014). Levels of AEAbs and ALEAbs can serve as immunologic markers of the extent of elastin degradation. These markers may provide a tool to study elastin metabolism and a potential clinical role for AEAbs in the pathogenesis and development of vascular complications in diabetic children.

Detection of free antielastin antibodies among diabetic children.

Antibodies to elastin breakdown products are found in the serum of all human subjects and correlate with their respective serum peptide levels. The presence of these antielastin antibodies (AEAbs) and the corresponding antigens in circulation leads to the formation of circulating immune complexes (CICs). The aim of this study was to determine if the serum levels of free AEAbs (not bound in CICs) correlate with the development of vascular complications in diabetic children. To this end, we used a method for detecting immune complexes (complement inhibition factor [CIF]-enzyme-linked immunosorbent assay [ELISA]) in combination with an ELISA for detection of AEAbs. The levels of free immunoglobulin G (IgG) AEAbs were studied in the sera of 54 diabetic children (mean age 12.3+/-4 years; diabetes duration 5.2+/-3.7 years). Thirty-two of the children had vascular complications (group 1), and 22 were without vascular complications (group 2). Twenty healthy children (mean age 13.6+/-4.2 years) were used as controls. The diabetics showed statistically significant higher levels of free AEAbs (0.490 E492+/-0.244 E492 vs 0.307 E492+/-0.081 E492; p = .02) compared with the control group. In group 1, free AEAbs showed statistically significant higher levels than controls (0.523+/-0.269 vs 0.307+/-0.081; p = .016). Eighteen of 54 (33%) patients were positive for free AEAbs (13 of 32 [41%] in group 1 and 5 of 22 [22%] in group 2). Free AEAb levels in all diabetics showed a correlation with systolic blood pressure (r = .44; p = .01), diastolic blood pressure (r = .46; p = .009), total cholesterol (r = .33; p = .05), triglycerides (r= .38; p = .03), high-density lipoprotein (r= -.46; p = .009), serum fructose (r= .43; p = .001), and microalbuminuria (r= .41; p = .002). Patients who had vascular pathology showed a correlation of free AEAbs with microalbuminuria (r= .434; p= .026), serum fructose (r= .63; p = .0004), hemoglobin A1c (r= .392; p = .043), and triglycerides (r= .456; p = .025). These findings suggest that elevated levels of free IgG AEAbs are associated with the development of diabetic vascular complications in children.

Using Exercise to Ward Off Depression.

In brief For treatment of depression many physicians use exercise as an important adjunct to psychotherapy and antidepressant therapy. Low-intensity exercise and exercise that elicits an increase in [Formula: see text]o2max are equally effective in lessening depressive symptoms. Evidence has shown that exercise is as effective as psychotherapy and antidepressant therapy in treating mild-to-moderate depression, and even more effective when used in conjunction with the conventional therapies. When recommending exercise to their depressed patients, physicians should be aware of the pharmacology of various antidepressants to avoid unwanted interactions. Staying alert to the risks of overtraining and exercise addiction is also important.

Circulating immune complexes among diabetic children.

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 HbAlc (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.