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  • 1
    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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  • 2
    ISSN: 1432-0428
    Keywords: Insulin-dependent diabetes ; diabetic retinopathy ; retinal photography ; grading scheme
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We present the methodology for 45
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Key words Insulin-dependent diabetes ; diabetic retinopathy ; retinal photography ; grading scheme.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We present the methodology for 45° retinal photography and detail the development, application and validation of a new system of 45° field grading standards for the assessment of diabetic retinopathy. The systems were developed for the EURODIAB IDDM Complications Study, part of a European Community funded Concerted Action Programme into the epidemiology and prevention of diabetes (EURODIAB). Assessment of diabetic retinopathy was carried out centrally by a trained reader of colour retinal photographs using the newly-developed system. The system proved to be acceptably accurate, repeatable and relatively simple to apply. It compared well with the recognised ’gold standard' 7-field 30° stereo photography (assessed using a modified Airlie House classification scheme), against which the new system was validated in a series of 48 eyes. Selection was as a stratified random sample based on clinical retinopathy status: 5, no retinopathy; 25, non-proliferative retinopathy; 16, proliferative or photocoagulated; plus 2, eyes with potentially confounding lesions (vein occlusion). Simple presence of retinal lesions was correctly detected by both systems in 43 of the 48 eyes, giving 100 % agreement on detection. Both systems correctly identified the two known cases of confounding vein occlusion. In eyes with diabetic retinopathy (n = 41), when severity was expressed in three groups: mild background, moderate/severe background and proliferative/photocoagulated, at least one grader (out of five) using the new system matched the verified results in 38 out of 41 (93 %) eyes and three or more graders matched in 31 (76 %) eyes. Individually the five graders' 2-field allocations agreed well with the verified levels (median number of agreements 37, range 28–43). Repeatability was assessed by measures of within and between observer variation using randomly selected samples of 10 % (n = 252 eyes) and 5 % (n = 123 eyes) of the main study, respectively, expressed as a resultant kappa value for chance-corrected proportional agreement. Within observer assessment yielded a kappa of 0.85 and between observers a value of 0.83; indicating very good agreement for both measures. The method is particularly useful for large epidemiological studies, in which participating centres have a limited experience in retinal photography. [Diabetologia (1995) 38: 437–444]
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Glycated haemoglobin A1 ; plasma glucose ; diabetic retinopathy ; risk factor ; receiver operating characteristic (ROC) analysis ; Pima Indians
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Among Pima Indians with Type 2 (non-insulin-dependent) diabetes mellitus the relationships between glycated haemoglobin (HbA1), fasting or 2-h post-load plasma glucose and diabetic retinopathy were examined by cross-sectional and prospective analyses, and the strengths of the associations were directly compared by receiver operating characteristic analysis. In the cross-sectional analysis, HbA1, fasting and 2-h plasma glucose were each significantly related to retinopathy among 789 diabetic subjects by separate logistic models. In a stepwise multiple logistic model in which HbA1, fasting and 2-h plasma glucose were included, HbA1 was selected as having the strongest association with retinopathy and neither fasting nor 2-h plasma glucose contributed significantly to the model once HbA1 was entered. Similarly, in the prospective analysis, HbA1, fasting and 2-h plasma glucose all predicted retinopathy in 227 diabetic subjects by separate proportional-hazards models. In a stepwise proportional-hazards model with HbA1, fasting and 2-h plasma glucose available to the model, HbA1 was again selected as having the strongest association with the incidence of retinopathy, and neither fasting nor 2-h plasma glucose significantly added to the prediction of retinopathy. A receiver operating characteristic analysis was used to determine if HbA1 was statistically significantly better than fasting or 2-h plasma glucose in assessing the risk for retinopathy. In neither the cross-sectional nor the prospective data did the area under the receiver operating characteristic curve for HbA1 differ significantly from that for fasting or 2-h plasma glucose (p〉0.05 for each). In conclusion, HbA1, an integrated measure of blood glucose concentration over a period of 2–3 months, is slightly more closely associated with the prevalence and incidence of diabetic retinopathy than a single blood glucose determination. However, the differences between HbA1 and fasting or 2-h plasma glucose in assessing the association with or the risk for retinopathy are not significant.
    Type of Medium: Electronic Resource
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  • 5
    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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