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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 16 (1979), S. 165-171 
    ISSN: 1432-0428
    Keywords: Diabetes mellitus ; proteinuria ; nephropathy ; SDS-PAGE
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Renal damage is one of the most serious complications of diabetes mellitus. Most methods used to detect kidney malfunction show abnormalities only in the advanced stages. To find whether sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of the urinary proteins could give earlier indications of kidney malfunction, 68 patients with maturity-type diabetes and 22 with juvenile-type diabetes have been studied. Quantitative determination of proteinuria, urinary lysozyme, creatinine clearance and SDS-PAGE of urinary proteins were performed. Diabetics of both types with disease of more than 10 years duration showed significantly greater proteinuria and lysozymuria, higher serum creatinine values and lower creatinine clearances than their respective controls. Such differences were not seen in patients with diabetes of short duration. SDS-PAGE allowed detection of a higher proportion of patients with abnormalities. Thus, 3 out of 10 patients with juvenile diabetes of short duration showed predominant excretion of low molecular weight proteins, suggesting tubular dysfunction. This was not observed in the other groups of diabetics where increased elimination of high molecular weight proteins was noted, suggesting glomerular damage. SDS-PAGE revealed a higher frequency of abnormalities than other tests of renal function, with 67% abnormal in juvenile-type diabetes of greater than 10 years duration, 45% in maturity-type diabetes of less than 10 years duration and 76% abnormal in maturity-type diabetes of greater than 10 years duration.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Type 1 (insulin-dependent) diabetic patients ; low density lipoprotein ; pre-control LDL ; postcontrol LDL ; human fibroblasts ; LDL uptake ; LDL degradation ; cell culture ; LDL lipids ; LDL apolipoprotein B ; LDL-cell interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A previous study of low density lipoprotein metabolism by cultured cells focused on the metabolism of normal lipoproteins in vitro by fibroblasts isolated from diabetic patients. No abnormalities were found. We have followed the opposite approach. Using normal human fibroblasts as test cells we compared the metabolism in vitro of low density lipoproteins isolated from diabetic patients before and after metabolic control. We found a significant decrease (p〈0.02) in internalization and degradation of low density lipoproteins isolated from diabetic patients before metabolic control when compared with those isolated from normal control subjects or from the same patients after metabolic control. The observed changes were mainly apparent in intracellular degradation. To evaluate whether the observed differences in low density lipoprotein behaviour were correlated with lipid or apolipoprotein composition, we measured cholesterol, triglyceride, apolipoprotein B and total protein levels in the low density lipoproteins tested. A significant decrease (p〈0.05) of the triglyceride/protein ratio was found in post-control low density lipoproteins suggesting that a high triglyceride content may interfere with low density lipoprotein metabolism. The present study represents the first observation that metabolic control in diabetes mellitus can alter low density lipoprotein-cell interaction and suggests a possible mechanism for the enhanced incidence of atherosclerosis in diabetic patients.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 13 (1977), S. 285-291 
    ISSN: 1432-0428
    Keywords: High density lipoproteins (HDL) ; HDL-cholesterol ; apolipoprotein A ; serum glucose ; diabetes mellitus ; lipoproteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The purpose of the present investigation was the study of HDL lipoprotein changes in patients with diabetes mellitus. The comparison was made between 40 normal and 109 diabetic subjects and the following data was obtained: relative HDL concentration (polyacrylamide gel electrophoresis), HDL-cholesterol and apolipoprotein A concentrations. We found significant decreases in HDL (18–28%) and HDL-cholesterol (31–40 mg/ 100 ml) in most diabetics except in those with normalized serum levels of glucose and lipids (34% and 50 mg/100 ml respectively). There was a statistically significant difference in HDL and HDL-cholesterol concentrations between patients in the latter group and other diabetic patients. There was a negative correlation between HDL and HDL-cholesterol and serum glucose levels. No statistically significant difference was found when apolipoprotein A was compared in normal and diabetic subjects. Our results suggest that a deficient binding of cholesterol to apoprotein A might be present in diabetes.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Immune complexes ; anti-insulin antibodies ; diabetes mellitus ; nephropathy ; peripheral ; neuropathy ; diabetic complications
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A series of 148 diabetic patients were studied for the presence of soluble immune complexes using five different screening techniques. The percentage of positive results was 26% with direct nephelometry and PEG-C4, 27% with PEG-IgG, 33% with radiolabelled Clq binding and 57% with a specific technique for detection of insulin-anti-insulin immune complexes. The percentages of positivity in a group of 40 healthy donors were 2.5% for direct nephelometry and radiolabelled Clq binding, 5% for the PEG-C4 technique, and 10% for the PEG-IgG technique. Sixteen percent of the patients studied had positive results in three or more of the screening tests. When the results of the different screening tests in all patients and controls were compared among themselves, we found correlation coefficients between-0.01 (p = 0.854) when the direct nephelometry and the PEG-C4 tests were compared and 0.29 (p 〈 0.0003) when the direct nephelometry and PEG-IgG tests were compared. When the results of each test for the whole group of patients and the group of normal healthy donors were compared, significant differences were found for direct nephelometry (p = 0.004), PEG-IgG, PEG-C4, and insulin-anti-insulin immune complexes (p 〈 0.0001), as well as for anti-insulin antibodies (p 〈 0.001); no significant difference was observed when the results of radiolabelled Clq binding in diabetics and controls were compared (p = 0.2). Significant correlations were found between the results of several screening tests for soluble immune complexes, insulin dosage, and clinical or biochemical expressions of microangiopathy, nephropathy, or vasculopathy. These correlations were more consistent when we divided the patients into normal or abnormal groups for proteinuria, microangiopathy, and diabetic complications and considered the number of positive tests in each patient rather than the results of individual tests.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Type 2 (non-insulin-dependent) diabetes mellitus ; VLDL metabolism ; LDL metabolism ; human macrophages
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The very low- and low-density lipoprotein fractions were isolated from 16 normolipidaemic Type 2 (non-insulin-dependent) diabetic patients in good to fair glycaemic control and from corresponding age-, sex-, and race-matched, non-diabetic control subjects. Rates of cholesteryl ester synthesis averaged 268±31 vs 289±40 pmol 14C-cholesteryl oleate·-mg cell protein−1·20 h−1 for very low- and 506±34 vs 556±51 pmol 14C-cholesteryl oleate·mg cell protein−1·20 h−1 for low-density lipoproteins isolated from the Type 2 diabetic patients and control subjects, respectively, when they were incubated with human macrophages. A group of approximately one-third of the patients was selected for separate analyses because very low-density lipoproteins isolated from these patients did stimulate more cholesteryl ester synthesis when incubated with macrophages. There were no significant differences in the lipid composition of the lipoproteins isolated from the three groups of subjects. The relative proportion of apoprotein C to apoprotein E was significantly decreased (p〈0.002) in the very low-density lipoproteins from diabetic patients and was further decreased in samples from these selected diabetic patients. The apoprotein C-I content of very low-density lipoproteins isolated from diabetic patients was increased compared to control subjects and was further increased in samples from the selected diabetic patients (p〈0.02). There were no significant differences in the proportions of apoproteins C-III-0, C-III-1, or C-III-2 among the three groups. These studies suggest that in normolipidaemic Type 2 diabetic patients, the apoprotein composition of VLDL is abnormal and this may alter VLDL macrophage interactions and thus contribute to the increased prevalence of atherosclerosis in diabetic patients.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: Endothelial cells ; very low density lipoprotein subfractions ; diabetes mellitus ; atherosclerosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The very low density lipoprotein (VLDL) fraction was isolated from 11 normolipidaemic Type 1 (insulin-dependent) diabetic patients in good to fair glycaemic control and from 11 age-, sex- and race-matched, non-diabetic, control subjects. The rate of receptor-mediated degradation by human endothelial cells was significantly greater (p〈0.02) for the total VLDL fraction isolated from diabetic patients compared to control subjects and averaged 1008±300 and 717±150 ng·mg cell protein−1·16 h−1, respectively. The total VLDL fraction was separated into three subfractions: VLDL-I, Sf 100–400 (Sf = Svedberg units); VLDL-II, Sf 60–100; VLDL-III, Sf20–60. Rates of receptor-mediated degradation of VLDL-I and VLDL-II isolated from diabetic patients were significantly greater than the comparable subfraction isolated from control subjects and averaged 1023±279 vs 361±122 (p〈0.01) and 433±70 vs 294±70 ng·mg cell protein−1·16 h−1 (p〈0.03), respectively. Rates of receptor-mediated degradation of the V-III subfraction isolated from the two groups did not differ significantly. There were no significant differences in the chemical composition or in the plasma concentrations of the VLDL subfractions isolated from diabetic patients compared to control subjects. There was a significant increase in the apoprotein E content of VLDL-I (p〈0.01) and VLDL-II (p〈0.05) isolated from diabetic patients. There was a significant increase in the ratio of apoprotein C compared to apoprotein E (p〈0.03) in VLDL-I isolated from control subjects compared to the diabetic patients. There were no significant differences in the apoprotein composition of VLDL-III isolated from the two groups.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: Lipoproteins ; HDL ; LDL ; VLDL ; cholesterol ; triglycerides ; insulin-dependent diabetes ; control ; haemoglobin A1c
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Plasma and lipoprotein cholesterol and triglycerides, glucose and haemoglobin A1c concentrations were measured in 106 patients (56 males) with insulin-dependent diabetes mellitus (age range 2–22 years) and 36 normal volunteers (19 males) with similar age and sex distribution. The diabetic patients were further divided into three subgroups: “good”, fair and poor control, based on 24 h glycosuria and haemoglobin A1c concentrations. Total, low density lipoprotein and very low density lipoprotein cholesterol levels were significantly increased in male patients in poor control when compared with the group in “good” control and with normal subjects. Triglyceride and very low density lipoprotein triglyceride levels were also significantly increased in poorly controlled males. The most significant difference however was a decrease of high density lipoprotein cholesterol in male patients in poor control. There was a significant inverse correlation between haemoglobin A1c and high density lipoprotein cholesterol (r = -0.63) and a direct correlation between haemoglobin A1c and low density lipoprotein cholesterol (r = 0.35) and triglycerides (r = 0.62) in the male diabetics. The findings were similar in females. The most striking change was observed in low density lipoprotein cholesterol levels, which were more markedly increased in poorly controlled females than in poorly controlled males. No statistical singificant differences were found between the groups in good and fair control for any of the plasma and lipoprotein lipids studied. A significant difference however was found between the groups in poor and fair control. There was a significant correlation in females between haemoglobin A1c and low density lipoprotein cholesterol levels (r = 0.43), haemoglobin A1c and triglycerides levels (r = 0.54) and an inverse correlation between haemoglobin A1c and high density lipoprotein cholesterol (r = -0.59).
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0428
    Keywords: Diabetes ; low density lipoproteins ; glycosylation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Glycosylation of low density lipoproteins obtained from 16 patients with Type 1 (insulin-dependent) diabetes and from 16 age-, sex-, and race-matched controls, was determined. The diabetic patients were normolipaemic and were in good or fair glycaemic control. Eleven patients performed home blood glucose monitoring. Glycosylation of low density lipoproteins in the diabetic patients was significantly higher (p 〈 0.001) than in the control subjects, and was significantly correlated with haemoglobin A1c, (p 〈 0.01), glycosylation of plasma proteins, (p 〈 0.001), and mean home blood glucose, (p 〈 0.01). This study confirms that, in diabetic patients, increased glycosylation of low density lipoprotein occurs to an extent which correlates closely with other commonly used indices of glycaemic control.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0428
    Keywords: Diabetes ; LDL metabolism ; glycosylated LDL ; cholesteryl ester synthesis ; human macrophages
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Diabetes mellitus is an independent risk factor in the development of atherosclerosis. In this study we aimed to demonstrate whether there is an abnormal interaction between low-density lipoproteins from diabetic patients and human macrophages. We measured cholesteryl ester synthesis and cholesteryl ester accumulation in human monocytederived macrophages (obtained from non-diabetic donors) incubated with low density lipoproteins from Type 1 (insulin-dependent) diabetic patients in good or fair glycaemic control. Low density lipoproteins from the diabetic patients stimulated more cholesteryl ester synthesis than low density lipoproteins from non-diabetic control subjects (7.19±1.19 vs 6.11±0.94 nmol/mg cell protein/20 h, mean±SEM, p〈0.05). The stimulation of cholesteryl ester synthesis by low density lipoproteins isolated from diabetic patients was paralleled by a significant increase in intracellular cholesteryl ester accumulation (p〈0.02). There were no significant differences in the lipid composition of low density lipoproteins between the diabetic and control groups. Non-enzymatic glycosylation of low density lipoproteins was higher in the diabetic group (p〈0.01) and correlated significantly with cholesteryl ester synthesis (r=0.58). Similarly, low-density lipoproteins obtained from non-diabetic subjects and glycosylated in vitro stimulated more cholesteryl ester synthesis in macrophages than control low density lipoproteins. The increase in cholesteryl ester synthesis and accumulation by cells exposed to low density lipoproteins from diabetic patients seems to be mediated by an increased uptake of these lipoproteins by macrophages. This study suggests that glycosylation of low density lipoproteins to the extent occurring in diabetes may alter their interaction with human monocyte-derived macrophages and may lead to increased intracellular cholesteryl ester accumulation. The results suggest a possible mechanism by which hyperglycaemia may contribute to the acceleration of atherosclerosis in diabetes.
    Type of Medium: Electronic Resource
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