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  1. 1

    المصدر: Clinica Chimica Acta. 413:312-318

    الوصف: Background Patients with diabetes are recommended to self-monitor their blood glucose levels also at home. Accuracy of a hand-held glucometer and a Continuous Glucose Monitoring (CGM) device were comparatively evaluated. Methods Venous blood samples (for reference laboratory determinations; n = 428) were collected from 18 type 1 patients (35–65 years old), immediately followed by capillary measurement (Bayer ContourLink meter) and CGM readings (Medtronic Paradigm). Results Laboratory values did not differ statistically from ContourLink and CGM readings, mean difference (± SD) being − 0.05 ± 1.06 mmol/L and 0.10 ± 1.84 mmol/L glucose, respectively. A bias ((value − reference)/reference × 100) ≥ 15% was observed in 27.7% and 54.9% of cases, respectively. Notably, below 3.9 mmol/L glucose (hypoglycemic threshold), an absolute error > 0.8 mmol/L was found in 78.9% and 94.1% of cases. The absolute errors of the CGM device were inversely related to the rate of glucose change (r = 0.598, p Conclusions A very large error was observed at the extreme glycemic values, which may lead to erroneous therapy. Consequently, performance of future portable glucometers should be focused in particular under hypo- and hyper-glycemia. Moreover, integrated CGM devices should not disregard the effect of the rate of blood glucose change on the sensor readings.

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    المصدر: Clinica Chimica Acta. 367:103-107

    الوصف: Tissue expression pattern of matrix metalloproteinases (MMPs) and their inhibitors TIMPs indicate that microvascular complications of diabetes mellitus are associated with extracellular matrix remodelling. We investigated whether circulating levels of MMP-9 and TIMP-1 are altered in diabetic retinopathy and whether they might serve as biological markers of ocular complications in type 1 diabetes.We recruited 47 type 1 diabetic patients free of vascular complications (n=40) or with retinopathy (n=14). Patients with macroangiopathy, neuropathy and nephropathy were excluded. A group of nondiabetic control subjects (n=35) was also constituted for comparative purposes. Peripheral blood levels of MMP-9 and TIMP-1 were determined using immunoenzymatic assays.Type 1 diabetic subjects exhibited significantly higher circulating levels of both MMP-9 and MMP-9/TIMP-1 ratio, as well as a tendency to increased serum TIMP-1 levels relative to nondiabetic controls (p0.001). Diabetic patients with retinopathy also displayed elevated systemic values of MMP-9 and MMP-9/TIMP-1 ratio when compared to patients without retinopathy (p0.05). Logistic regression analysis identified diabetes duration firstly (P0.01), and MMP-9 serum levels secondly (P0.01) as significant and independent variables associated with the existence of retinopathy.Our data suggest that peripheral blood MMP-9 levels might serve as surrogate biomarkers of retinopathy in type 1 diabetic patients free of other vascular complications.

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    المصدر: Clinica Chimica Acta. 412:322-326

    الوصف: Objective Plasminogen activator inhibitor 1 (PAI-1) is thought to play a role in the pathogenesis of obesity and insulin resistance. A connection between gestational diabetes mellitus and the functional -675 PAI-1 genotype has been reported. Therefore, we examined the role of the PAI-1 gene polymorphism in kidney transplant recipients. Methods A total of 376 kidney transplant recipients were prospectively screened for posttransplant diabetes mellitus (PTDM). Eighty-one (21.5%) patients were diagnosed with PTDM and the other 295 patients were non-diabetic following kidney transplantation. DNA samples were isolated from the sera and analyzed for the functional − 675 4G/5G promoter polymorphisms of the PAI-1 gene. Results Kidney transplant recipients with PTDM were significantly associated with tacrolimus use (p = 0.03), older age (p = 0.036), and higher body mass index (p = 0.001). The genotype distribution was significantly different between the patients with PTDM (genotype 4G/4G:4G/5G:5G/5G = 33.3%:60.5%:6.2%) and those without PTDM (genotype 4G/4G:4G/5G:5G/5G = 36.9%:44.1%:19.0%) (p = 0.018). Patients with homozygosity for 5G had a significantly lower rate of PTDM (aOR, 0.286, p = 0.022) and higher cumulative event-free probability of time to PTDM (log rank test, p = 0.0058). Conclusion Homozygosity for the 5G allele of the PAI-1 gene constitutes a protecting factor for the development of PTDM. Our findings are similar to a previous study on gestational diabetes mellitus, and strongly support a possible genetic role of PAI-1 in the development of PTDM.

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    المصدر: Clinica Chimica Acta. 283:119-128

    الوصف: In order to assess the variability and possible causes of calcium and magnesium losses in diabetes mellitus, urinary calcium and magnesium excretion were monitored six monthly over a 3-year period in 108 stable, type 1 diabetic patients who were having assessment of their clinical status and glycaemic control over the same period. In the patients studied the ranges of excretion of both calcium and magnesium were considerably wider than our non-diabetic reference ranges but the within subject variation in excretion was high. However, using mean values obtained over the study period, a direct relationship was observed between the excretion of both calcium and magnesium and HbA1 in female patients (P < 0.01) but not in males who had similar HbA1 values. The urinary excretion of calcium and magnesium did not relate to any of the other clinical or biochemical indices measured, including body mass index, daily insulin dose, retinal status or albumin excretion. It is suggested that, in poorly controlled patients, females may have a greater risk than males of developing the complications associated with chronic calcium and magnesium loss.

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    المصدر: Clinica Chimica Acta. 229:5-14

    الوصف: Biochemical markers of early changes that are characteristic for diabetic microangiopathy are not completely understood. We investigated activities of serum N-acetyl-beta-glucosaminidase (NAG), tissue plasminogen activator and erythrocyte superoxide dismutase in well defined groups of type 1 diabetic patients. Patients were selected on the basis of 4 year follow-up observation. Forty-two type 1 diabetic patients were subdivided into those without retinopathy (n = 13) throughout the study, those with newly developed or worsened retinopathy (n = 12) during 4 years and those with retinopathy already established at the beginning of the study and without evidence of its progression (n = 17). All diabetic patients had albustix-negative urine. A significant increase of the mean serum NAG activity during 4 years was found only in patients without retinopathy (P < 0.01) whereas no changes of the altered enzyme activities were present in patients with developing and established retinopathy. The mean activity of tissue plasminogen activator was elevated in all groups of diabetic patients compared with healthy subjects (P < 0.001). A significant positive correlation was found between plasminogen activator and serum NAG (r = 0.51, P < 0.01). Erythrocyte superoxide dismutase was higher in diabetic patients than in healthy persons (P < 0.01) but no differences were observed between the patients with or without retinopathy. Superoxide dismutase positively correlated with NAG (r = 0.57, P < 0.01). We conclude that early functional changes precede a morphological development of diabetic retinopathy as was evident from the altered enzyme activities.

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    المصدر: Clinica Chimica Acta. 350:123-128

    الوصف: Background Beta-thalassemia minor (BTM) is a common benign condition that can be present in patients with diabetes mellitus. There are conflicting reports about the effect of BTM on glycated hemoglobin (gHb) measurements. We evaluated 6 gHb methods using samples from non-diabetic subjects with BTM. Methods Samples submitted for hemoglobin phenotype analysis were evaluated. A total of 57 samples (30 controls and 27 with BTM) from non-diabetic subjects were selected. GHb analysis was performed by Tosoh A1c 2.2+, Primus CLC 330, Bayer DCA 2000, Beckman Coulter, Synchron CX7 and LX20, and Roche Tina-quant II assays. Results The A1c 2.2+, CLC 330, DCA 2000 and Tina-quant II assays showed no statistically significant difference between the control and BTM groups. In contrast, BTM results were significantly higher than controls on the Synchron CX7 analyzer and borderline significant on the Synchron LX20 (p=0.051). Further investigation demonstrated an increase in Synchron %HbA1c results with decreasing hemoglobin concentrations. Conclusions In this study using samples from subjects with normal or near-normal gHb, BTM does not affect gHb measurements per se. However, the Synchron methods yielded higher results for samples with lower hemoglobin concentrations, like those that can be seen in BTM. The Synchron method was improved at the end of 2003, which minimized this problem.

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    المصدر: Clinica Chimica Acta. 219:131-138

    الوصف: Serum sialic acid is a risk factor for cardiovascular disease in the general population. Serum total sialic acid concentrations were therefore measured in 20 type 1 diabetic patients and in 20 age- and sex-matched non-diabetic subjects. Serum sialic acid were not significantly different in the type 1 diabetic patients and the normal subjects ( 2.00 ± 0.37 vs. 1.98 ± 0.67 mmol/l ), but was significantly correlated with serum total cholesterol ( r = 0.55, P ) and serum triglyceride concentration ( r = 0.63, P ) in the type 1 diabetic patients. There was no relationship of sialic acid levels to age, duration of diabetes, smoking, body mass index, systolic or diastolic blood pressure, plasma glucose, serum fructosamine, or daily insulin dosage. Six of the type 1 diabetic patients with retinopathy had higher total serum sialic acid concentrations than those patients without retinopathy ( 2.38 ± 0.33 vs. 1.85 ± 0.26 mmol/l , P ) A further study of 16 type 1 and 16 type 2 diabetic patients matched for serum fructosamine and blood glucose concentrations and without tissue complications showed that the serum total sialic acid concentration was significantly higher in the type 2 diabetic patients compared with the type 1 patients ( 2.32 ± 0.41 vs. 1.84 ± 0.24 mmol/l , P ). Although the serum concentrations of the non-sialylated acute phase protein, C-reactive protein, was higher in type 2 than type 1 diabetes, sialylated acute phase protein levels did not explain differences in serum total sialic acid in diabetes. We conclude that the serum sialic acid concentration is elevated in both type 2 diabetes and in patients with diabetic retinopathy, whether the retinopathy occurs in type 1 or type 2 diabetes.

  8. 8

    المصدر: Clinica Chimica Acta. 321:89-96

    الوصف: Background : Our aim was to evaluate oxidative stress parameters on three groups of diabetic patients, insulin-dependent diabetes mellitus (IDDM), non-insulin-dependent diabetes mellitus (NIDDM), and insulin-treated type 2 diabetes mellitus (ITDM2), with similar HbA1c value and to determine if insulin's impact on these parameters was the same for IDDM and ITDM2. Methods : This study has been conducted on 18 IDDM, 55 NIDDM, 27 ITDM2, compared to 12 healthy subjects. Plasmatic concentrations of thiobarbituric acid reactive substances (TBARS), fatty acids, total antioxidant status (TAS), α-tocopherol, and erythrocyte reduced glutathione (GSH) were measured as well as enzymatic activities of superoxide dismutase (SOD), and glutathione peroxidase/reductase. Results : Diabetic patients have significant increase of SOD activity, of TBARS concentration (concomitant with low levels of unsaturated fatty acids) and significant decrease of GSH and α-tocopherol. NIDDM have significantly lower levels of GSH and higher levels of TBARS compared to IDDM. ITDM2 values are intermediate between IDDM and NIDDM but are far from reaching those of IDDM. Conclusion : Diabetic patients undergo an important oxidative stress that is nearly corrected for IDDM, but only partially improved for ITDM2, although length of insulin treatment and HbA1c values are similar, suggesting metabolic differences between the two types of diabetes.

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    المصدر: Clinica Chimica Acta. 204:251-261

    الوصف: A raised content of arachidonic acid in platelets from diabetic patients with retinopathy was found without differences in platelet aggregation: platelet aggregability was not related to platelet fatty acid composition. In diabetes, platelet aggregation was inversely correlated to non-esterified fatty acids in plasma and may suggest an inhibiting effect. Mean platelet volume was raised in the diabetic patients, but without hyperaggregability. The findings do not exclude a relationship between platelet fatty acids and platelet aggregability, but suggest that variations in levels of nonesterified fatty acids in plasma might interfere with platelet aggregation.

  10. 10

    المؤلفون: Bojan Benko, Zdenka Turk, Ranko Mesić

    المصدر: Clinica Chimica Acta. 277:159-170

    الوصف: Glycation process in vivo results in two different products: early and advanced glycation endproducts (AGEs). The mechanism of early product formation has been well described, with HbA1c as the best-studied example. The finding that advanced glycation endproducts are also formed on haemoglobin suggests that HbA1c is a precursor for Hb-AGE formation. HbA1c has been well established as an important indicator for glycaemia monitoring, but the diagnostic role of Hb-AGE has not yet been clarified. A question is whether HbA1c and Hb-AGE are competitive or complementary parameters. In our study, Hb-AGE was quantified by the competitive ELISA technique using polyclonal anti-AGE-RNase antibodies to detect AGE immunoreactivities of proteins precipitated in red cell hemolysate. Results are expressed as AGE units/mg Hb. Hb-AGE was analysed in three groups of patients divided according to HbA1c values as follows: group I (n = 25) HbA1c7%, Hb-AGE = 6.93 (5.7-7.3) U/mg; group II (n = 25) HbA1c = 7-10%, Hb-AGE = 8.62 (7.7-10.2) U/mg; and group III (n = 25) HbA1c10%, Hb-AGE = 12.47 (10.8-13.9) U/mg (median (interquartile range)). A close relation between the amounts of red cell HbA1c and Hb-AGE was observed in all diabetic subjects (n = 75) r = 0.77, P0.001. Patients with HbA1c level8% were considered to be in poor glycaemic control and those with HbA1c8% in good control. In the well-controlled subgroup (n = 33), HbA1c and Hb-AGE were less tightly correlated (r = 0.37, P0.001). However, in those patients with a higher level of HbA1c = 12.55 (8.9-13.3)% (n = 42), the related Hb-AGE was 11.5 (10.3-12.8) U/mg Hb, yielding a more significant correlation (r = 0.51, P0.001). The content of Hb-AGE did not correlate with age (r = 0.09), diabetes duration (r = 0.05) or severity of retinopathy and/or nephropathy. The observed difference may reflect a different kinetic rate of HbA1c production and subsequently the rate of Hb-AGE formation. The discrepancy in the correlation between HbA1c and Hb-AGE suggests that they are complementary rather than opposed parameters. The amount of haemoglobin-linked AGEs does not correlate with the presence or absence of retinopathy and/or nephropathy. It seems that Hb-AGE represents only the metabolic status, equally in the subjects with and without diabetic microangiopathy.