Association between pollen exposure and nasal cytokines in grass pollen-allergic children

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Prognostic factors for survival in patients with metastatic renal cell carcinoma treated with targeted therapies.

BACKGROUND: The most important prognostic factors for survival in patients with metastatic renal cell carcinoma (mRCC) were evaluated in the era of cytokine therapy, and only recently were revalidating in patients receiving targeted therapies (TTs). METHODS: Clinical data for consecutive patients with mRCC who received TTs were retrieved from the database of Istituto Nazionale dei Tumori of Milan. Variables with a significant association with overall survival (OS) were estimated by proportional hazard regression, and a backward stepwise multivariate analysis identified the independent prognostic factors. RESULTS: Data for 336 consecutive patients treated with TTs for RCC during the period 2004-2011 were evaluated. According to the Motzer classification, 32% patients were low risk, 48% were intermediate risk and 20% were poor risk. One hundred and sixty-seven (49.7%) patients received one TT, 116 (34.5%) received a second-line TT, 42 (12.5%) a third-line TT and 11 (3.3%) patients received a fourth-line TT. The median OS was 24 months (95% CI 20.0, 27.0) and the 5-year OS rate was 24.6% (95% CI 18.7, 30.8%). In the uni- and multivariate analysis Motzer risk classification, Fuhrman grade and previous cytokine therapy were identified as independent prognostic factors (P<0.01). CONCLUSION: The Motzer classification was confirmed as an independent prognostic factor for OS in patients with mRCC receiving TTs. Additionally, Fuhrman grade and previous cytokine therapy were independent prognostic factors for clinical outcome.

Leukocyte telomere length is associated with complications of type 2 diabetes mellitus.

OBJECTIVE: The key goal of diabetes management is to prevent complications. While the patho-physiological mechanisms responsible for diabetes complications have been extensively studied, at present it is impossible to predict which patient with diabetes could develop complications. In recent years, the role of leukocyte telomere length in the pathogenesis of cardiovascular disease and Type 2 diabetes has been investigated. However, studies aiming to investigate the role of telomeres in the development and progression of Type 2 diabetes, as well as diabetic complications, are still lacking. As a consequence, this study aimed to verify whether leukocyte telomere length is associated with the presence and the number of diabetic complications in a sample of patients with Type 2 diabetes. METHODS: This is a cross-sectional study. Nine hundred and one subjects were enrolled, including 501 patients with Type 2 diabetes, of whom 284 had at least one complication and 217 were without complications, and 400 control subjects. Leukocyte telomere length was measured by quantitative real-time PCR. RESULTS: Patients with diabetes complications had significantly shorter leukocyte telomere length than both patients without diabetes complications and healthy control subjects. Moreover, among patients with diabetes complications, leukocyte telomere length became significantly and gradually shorter with the increasing number of diabetes complications. The magnitude of the effect of the decrease of the abundance of telomeric template vs. a single-copy gene length (T/S ratio) on complications is described by the estimated odds ratio OR=5.44 (95%CI 3.52-8.42). CONCLUSIONS: The results of the study support the hypothesis that telomere attrition may be a marker associated with the presence and the number of diabetic complications.

Understanding biological dynamics: following cells and molecules to track functions and mechanisms.

The dissection of the molecular circuitries at the base of cell life and the identification of their abnormal transformation during carcinogenesis rely on the characterization of biological phenotypes generated by targeted overexpression or deletion of gene products through genetic manipulation. Fluorescence microscopy provides a wide variety of tools to monitor cell life with minimal perturbations. The observation of living cells requires the selection of a correct balance between temporal, spatial and "statistical" resolution according to the process to be analyzed. In the following paper ad hoc developed optical tools for dynamical tracking from cellular to molecular resolution will be presented. Particular emphasis will be devoted to discuss how to exploit light-matter interaction to selectively target specific molecular species, understanding the relationships between their intracellular compartmentalization and function.

Spatial control of pa-GFP photoactivation in living cells.

Photoactivatable green fluorescent protein (paGFP) exhibits peculiar photo-physical properties making it an invaluable tool for protein/cell tracking in living cells/organisms. paGFP is normally excited in the violet range (405 nm), with an emission peak centred at 520 nm. Absorption cross-section at 488 nm is low in the not-activated form. However, when irradiated with high-energy fluxes at 405 nm, the protein shows a dramatic change in its absorption spectra becoming efficiently excitable at 488 nm. Confocal microscopes allow to control activation in the focal plane. Unfortunately, irradiation extends to the entire illumination volume, making impracticable to limit the process in the 3D (three-dimensional) space. In order to confine the process, we used two advanced intrinsically 3D confined optical methods, namely: total internal reflection fluorescence (TIRF) and two-photon excitation fluorescence (2PE) microscopy. TIRF allows for spatially selected excitation of fluorescent molecules within a thin region at interfaces, i.e. cellular membranes. Optimization of the TIRF optical set-up allowed us to demonstrate photoactivation of paGFP fused to different membrane localizing proteins. Exploitation of the penetration depth showed that activation is efficiently 3D confined even if limited at the interface. 2PE microscopy overcomes both the extended excitation volume of the confocal case and the TIRF constraint of operating at interfaces, providing optical confinement at any focal plane in the specimen within subfemtoliter volumes. The presented results emphasize how photoactivation by non-linear excitation can provide a tool to increase contrast in widefield and confocal cellular imaging.

Photoactivation of pa-GFP in 3D: optical tools for spatial confinement.

Photoactivatable fluorescent proteins represent an innovative tool for the direct observation of time dependent macromolecular events in living systems. The possibility of switching on a selected and confined subset of the expressed target proteins allows to follow biological processes reaching high signal to noise ratios. In particular, use of non-linear interactions to bring the molecules in the activated fluorescent form make it possible to extend the advantages of photoactivation to events that requires 3D spatial localization. In this work, we show the possibility to realize confined activated volumes in living cells, by employing photoactivatable green fluorescent protein (paGFP) in two-photon microscopy. The analysis of the kinetics of two-photon paGFP activation in dependence of the wavelength, the laser intensity and the exposure time is provided. This study allowed to assess the optimal conditions to induce photoactivation in living samples and to track the behaviour of tagged histone H2B during cellular division. Furthermore we investigate paGFP photoactivation under evanescent wave illumination. Total internal reflection set-up has been used to selectively activate subresolved distribution of proteins localized in the basal membrane surroundings. These two photoactivation methods provide a suitable tool for many biological applications, combining subresolved surface and in-depth three-dimensionally confined investigations.

Effect of 4G/5G PAI-1 polymorphism on the response of PAI-1 activity to vitamin E supplementation in Type 2 diabetic patients.

Plasminogen activator inhibitor type 1 (PAI-1) is an independent cardiovascular risk factor and increases in patients with Type 2 diabetes mellitus. The 4G/5G polymorphism of PAI-1 has been reported to be involved in the incidence of cardiovascular disease by regulation of PAI-1 levels, but this relation is still under debate. The aim of the study was to test the effect of 4G/5G polymorphism on the lowering of PAI-1 levels in Type 2 diabetic patients during vitamin E supplementation. Ninety-three Type 2 diabetic subjects (age +/- SD, 62.1 +/- 6.1 yr) were enrolled and treated with vitamin E (500 IU/die) for 10 weeks. We determined the 4G/5G polymorphism and PAI-1 activity at baseline, during (5th and 10th week) and after (30th week) vitamin E supplementation. No significant differences were found in PAI-1 and its determinants among the three genotypic groups at baseline. Decrements were detected in the whole group in PAI-1 at the 5th and the 10th week from baseline followed by an increase at the 30th week (p<0.001). Patients with 4G/4G and 4G/5G genotypes showed a different trend with respect to those with 5G/5G in PAI-1. In particular, there was a decrease in 4G/4G and 4G/5G PAI-1 levels from the 10th week, while a decrease in 5G/5G PAI-1 was observed from the 5th week (p<0.01). The delayed decrease, found in patients with at least one 4G allele with respect to those with 5G/5G genotype, demonstrates that 4G/5G polymorphism mainly influences the rate of decrease of PAI-1 after supplementation with vitamin E in Type 2 diabetic subjects.

Helicobacter pylori masks differences in homocysteine plasma levels between controls and type 2 diabetic patients.

BACKGROUND: Data in the literature have not clarified whether type 2 diabetes mellitus affects homocysteine plasma levels. Different variables able to influence homocysteine could be the cause of these controversial findings. An important but neglected confounding factor is Helicobacter pylori, which has been demonstrated to be a cause of elevated levels of homocysteine and which is prevalent in the Caucasian population, ranging from 30 to 40% incidence. Starting from these findings we wanted to verify whether differences in homocysteine levels exist between a type 2 diabetic population and a control group, taking into account the presence/absence of Helicobacter pylori. DESIGN: The study was carried out on a group of uncomplicated and normotensive type 2 diabetic patients (n = 30, 55.7 +/- 9.7 years) and on a control group (n = 43, 51.2 +/- 11.3 years). On these subjects we evaluated: main parameters of glyco- and lipo-metabolic balance, presence of Helicobacter pylori by 13C Urea Breath Test, plasma homocysteine, vitamin B12, folate and genetic polymorphism of methylenetetrahydrofolate reductase. RESULTS: Evaluating the two groups as a whole, significant differences in homocysteine were found when considering Helicobacter pylori presence/absence (14.0 +/- 6.5 vs. 10.6 +/- 4.7 micromol L-1, respectively, P < 0.01) without differences of vitamins and the genetic polymorphism of methylenetetrahydrofolate reductase. The positive interaction found among Helicobacter pylori, diabetes and homocysteine (P = 0.03) taking into account all the other evaluated confounding factors, demonstrates that a significant difference in homocysteine plasma levels exists between diabetics and controls (Helicobacter pylori-negative: diabetics 12.5 +/- 5.6 micromol L-1, controls 9.4 +/- 3.8 micromol L-1; Helicobacter pylori-positive: diabetics 13.6 +/- 5.8 micromol L-1, controls 14.3 +/- 7.0 micromol L-1). CONCLUSIONS: Type 2 diabetes seems to induce per se higher levels of homocysteine, which appears to be one of the factors responsible for the increased risk of vascular damage.

Vitamin E intake reduces plasminogen activator inhibitor type 1 in T2DM patients.

Previous studies hypothesised that vitamin E could protect against coronary heart disease and vascular complications in diabetes, but no studies have been performed regarding its eventual effects on fibrinolysis. Nevertheless, in Type 2 diabetes mellitus (T2DM) a profound reduction in the fibrinolytic activity has been demonstrated to be involved in vascular complications, probably due to plasminogen activator inhibitor type 1 (PAI-1) overproduction. On this basis we aimed to verify whether an antioxidant treatment with vitamin E is able to lower PAI-1 plasma levels in T2DM. Thirteen T2DM patients (9 males and 4 females; mean age+/-SD, 64.4+/-3.3 yr) were selected through strict admission criteria. These patients were treated with vitamin E (500 IU/die) for 10 weeks. Glyco-lipometabolic, oxidative and haemocoagulative parameters were evaluated at baseline and after 5, 10, 30 and 60 weeks. Vitamin E levels at different times were [median (interquartile range)] 6.1 (5.3-7.7), 8.5 (7.3-9.9), 9.7 (8.9-12.9), 5.6 (4.4-6.8), 5.7 (4.5-7.1) microg/ml, respectively. Significant differences were found for PAI-1 antigen (p=0.006), PAI-1 activity (p=0.028), apolipoprotein B (p=0.015) and antioxidant defence, evaluated as ferric reducing ability of plasma (FRAP) values (p=0.005). Particularly, decrements were detected for PAI-1 antigen between baseline and the 10th week (p<0.05), followed by an increase back to basal at the 30th week. Similar behaviour was found for PAI-1 activity. Regarding the antioxidant defence, FRAP values increased until the 30th week (p<0.05) with a decrease at the 60th week. These results demonstrate that vitamin E is able to lower PAI-1 levels in diabetic patients but this effect does not seem related to improvements of glycometabolic data or to the increase in FRAP values, suggesting that PAI-1 overproduction can be decreased by other effects of vitamin E on endothelial cells.

Diagnosis of MODY in the offspring of parents with insulin-dependent and non-insulin-dependent diabetes mellitus.

Maturity Onset Diabetes of the Young (MODY) is an autosomal dominant monogenic form of type 2 diabetes mellitus (DM) representing 5% of youth-onset DM in the Caucasian population. In young adults the disease can be present as either non-insulin dependent or insulin-dependent DM. The diagnosis of this genetic disorder in children and adolescents is rare because of the mild glucose metabolism disorder at this time. We performed a metabolic, autoimmune and genetic study in 40 offspring of young parents affected by insulin-dependent DM (Group A) and in 35 offspring of young parents affected by early-onset non-insulin-dependent DM (Group B). Two children of Group A (5%) were found to be affected by fasting hyperglycemia and carry a GCK gene mutation that in one case was present also in the diabetic father. Eighteen offspring of Group B (51%) were positive for GCK or HNF-1alpha gene mutations present in the affected parents. All but two of these young patients had impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). Eleven of them were younger than 16 years. We conclude that screening for DM in youth should be extended to MODY in young families with both non-insulin-dependent and insulin-dependent DM. The sensitivity of the metabolic tests will precede the genetic diagnosis.

Age-dependent changes of serum oxygen radical scavenger capacity and haemoglobin glycosylation in non-insulin-dependent diabetic patients.

BACKGROUND: Contradictory results have been reported in the literature concerning the correlation between glycosylated haemoglobin (HbA1c) and peroxidation level in serum of diabetic patients. OBJECTIVE: To evaluate this correlation in type 2 diabetic patients by comparing the level of HbA1c with the oxygen radical absorbance capacity (ORAC(OH)) of serum. METHODS: One hundred and five type 2 diabetic patients were enrolled for the study. After having obtained informed consent, venous blood samples were drawn after overnight fast at the time of routine diabetic check-ups. The blood was collected in plain and EDTA (1 mg/ml) tubes. Glycosylated haemoglobin (HbA1c) was determined by cation-exchange chromatography (HPLC), and spectrophotometric detection (Diamat Analyzer, BioRad). Serum was used for biochemical determinations performed by standard laboratory procedures and for ORAC(OH) analysis. This last parameter was determined measuring the loss of beta-phycoerytrin fluorescence due to oxidation by hydroxyl radicals generated by Cu(2+) and H(2)O(2), in the presence and absence of serum. Seventy-eight control age-matched subjects were obtained from the personnel staff of our Research Department and old healthy subjects, selected on the basis of Senieur Protocol, were relatives of the above mentioned personnel. RESULTS: When the population of diabetic patients was taken as a whole, a decrease of ORAC(OH) has been observed compared to the controls. Moreover, negative correlations were found comparing ORAC(OH) either with HbA1c (r = -0.213; p = 0.029) and with the age of patients (r = -0.27; p = 0.005). To better understand the effect of age, the data were re-examined dividing the diabetics into two populations, i.e. under and over 65 years of age. An age-dependent decrease of ORAC(OH) and an increase in HbA1c levels has been observed comparing these two populations; however, the correlation between the two parameters remained statistically significant only in the oldest group (r = -0.31; p = 0.026). CONCLUSIONS: Present data point to an involvement of oxidative stress in the glycation of haemoglobin especially in old diabetic patients, and provide support for the potential use of an antioxidant therapy in these patients, irrespective of their glycaemic control.

Fast, simple and cost-effective determination of thiopental in human plasma by a new HPLC technique.

BACKGROUND: Thiopental is an anaesthetic drug that is largely used in both short-term and long-term infusion. After long-term infusion of thiopental, non-linear and inter-individual-dependent pharmacokinetics occur because of the saturation and/or induction of the metabolism. Clinical monitoring is important so that therapeutic adjustments can be made in many of the different pharmacological treatments, especially when long-term infusion is required. We describe a new, rapid HPLC method for the determination of plasma thiopental. METHODS: Sample preparation involved precipitation of plasma proteins using a mixture of methanol, zinc sulfate and ethylene glycol, and containing the internal standard 5-ethyl-5-p-tolyl-barbituric acid. After adding trichloroacetic acid, the sample was centrifuged and the supernatant was injected into a C(18) reversed-phase column. The mobile phase used was water-methanol-acetonitrile (50:40:10, v/v). The eluent was monitored at 290 nm. RESULTS: The calibration curve was linear from 0.2 to 100 microg/mL. Precision, calculated as the coefficient of variation (%), was in the range of 3.62-0.70% for the within-day assay and 5.77-1.51% for the between-day assay. The absolute recoveries obtained from supplemented samples were never less than 100%. CONCLUSIONS: This technique shows good reliability and seems to be suitable for a very fast and simple therapeutic monitoring of plasma thiopental.

Fibronectin and lipoprotein(a) are inversely related to plasminogen activator inhibitor type-1 levels in Type 2 diabetic patients without complications.

Plasminogen activator inhibitor type-1 (PAI-1), the most important physiological fibrinolysis inhibitor, is considered an independent factor of cardiovascular risk in Type 2 diabetes mellitus (T2DM). In previous papers we demonstrated that a T2DM population without complications presents: 1) PAI-1 not increased with respect to a control group; and 2) a negative correlation between PAI-1 and lipoprotein(a) [Lp(a)], suggesting that in these subjects PAI-1 levels could be modulated by the "endothelial stress" induced by Lp(a) and diabetes. This work has been performed in order to better verify this intriguing hypothesis, and the endothelial stress has been evaluated through a marker of endothelial damage, fibronectin (FNC). For this purpose we chose a T2DM population without complications (n=73) and a control group (n=46). Plasma concentrations of FNC, Lp(a), PAI-1 antigen and activity, and the main parameters of lipo- and glycometabolic balance were determined. Fibronectin was significantly higher in diabetics with respect to controls (p<0.01). As expected, significant correlation between PAI-1 antigen, PAI-1 activity and Lp(a) (r=-0.54,p<0.01 and r=-0.39,p<0.01, respectively) was found only in diabetic patients. In the same group FNC showed a significant correlation with PAI-1 antigen and activity (r=-0.49,p<0.01 and r=-0.47; p<0.01, respectively), while no relationship was found between Lp(a) and FNC. Multiple regression analysis showed statistically significant correlation between PAI-1 antigen and PAI-1 activity with FNC and Lp(a) in diabetic patients without complications (p<0.05). These data suggest that in absence of complications, the endothelium is able to modulate PAI-1 levels, favouring in that way the fibrinolytic pathway and, subsequently, the recovery of the endothelial integrity. This modulation seems to be related to parameters such as Lp(a) and FNC, although the mechanisms of the endothelial stress of these two molecules seem to be different.

Autoimmune thyroid diseases in patients with undifferentiated connective tissue disease.

Previous data have indicated that organ-specific and non-organ-specific autoimmune diseases may occur in the same patient. We report here our study on the type and prevalence of endocrine autoimmune diseases in undifferentiated connective tissue disease (UCTD). A retrospective analysis revealed five out of 75 UCTD cases (6.6%) with cytology-verified autoimmune thyroiditis (associated with insulin-dependent diabetes mellitus in one case). Other UCTD patients had Graves' disease (one case), non-toxic multinodular goitre (two cases) and central hypothyroidism (one case). In a prospective study, thyroid function was evaluated in 15 consecutive UCTD patients with neither clinical nor laboratory signs of thyroid involvement. Basal and post-TRH stimulation TSH levels were significantly higher in UCTD patients than in healthy subjects.

One- and two-compartment minimal models detect similar alterations of glucose metabolism indexes in hypertension.

A standard intravenous glucose tolerance test (IVGTT) was performed in 10 nondiabetic patients with essential hypertension (H group) and 9 normotensive control subjects (N group). A 2-compartment minimal model (2CMM) of glucose kinetics was applied to estimate indexes of glucose effectiveness, S2G and insulin sensitivity, S2I, by means of a maximum a posteriori (MAP) bayesian estimation technique. These estimates were contrasted to the S1G and S1I indexes provided by the classic minimal model (1CMM). In both the N group and the H group, the 2CMM underestimated the glucose effectiveness and overestimated the insulin sensitivity. In the H group, S2G was, on average, 63% of S1G (P > .05) and S2I was 137% of S1I (P > .05). In the N group S2G was 67% of S1G (P > .05) and S2I was 134% of S1I (P > .05). The 2CMM detected a reduction of approximately 40% (P > .05) and approximately 48% (P > .05) in S2G and S2I estimates, respectively, from the N group to the H group. Despite its reduced complexity, the 1CMM also detected a reduction of approximately 35% (P < .05) and approximately 49% (P < .05) in the S1G and in S1I indexes, respectively. Thus, the 1CMM and 2CMM showed a substantial equivalence in detecting a severe reduction in insulin sensitivity and impaired glucose effectiveness in hypertensive patients compared with normal.

Determination of plasma metformin by a new cation-exchange HPLC technique.

Metformin is an oral antihyperglycemic agent used in the therapy of noninsulin-dependent diabetic patients. This biguanide can induce dangerous complications such as lactic acidosis when its plasma concentration is too high. For this reason, the determination of plasma metformin should always be done during treatment. We developed a new HPLC method, for the routine determination of plasma metformin, with good reliability, rapid execution, and low costs. Sample preparation involved precipitation of the plasma proteins containing the internal standard buformin with a mixture of methanol, zinc sulfate, and ethylene glycol; the diluted supernatant was injected into a cation-exchange column. The mobile phase was potassium dihydrogenphosphate buffer-containing acetonitrile. The eluent was monitored at 236 nm. The calibration curve is linear within the range of 20-4000 ng/mL; the within-day coefficients of variation were less than 2.2% for metformin and 1.5% for buformin; the day-to-day coefficients of variation were less than 2.5% for metformin and 1.9% for buformin. The mean recoveries obtained from supplemented samples were included between 99.4 and 104.2% for metformin. Many characteristics make this method useful and easily accessible to all clinical laboratories equipped with HPLC instrumentation.

A strong inverse relationship between PAI-1 and Lp(a) in hypertensive Type 2 diabetic patients.

Thrombophilia with a contemporary reduction of fibrinolytic activity has been observed both in diabetes mellitus and hypertension. Previously, we found a relationship between plasminogen activator inhibitor Type 1 (PAI-1) and lipoprotein(a) [Lp(a)] in Type 2 diabetes mellitus patients without complications. We hypothesised that this relationship could be due to a compensatory mechanism able to lower the risk of hypofibrinolysis as found in Type 2 diabetes mellitus. The present work was aimed at investigating the influence of concurrent hypertension and diabetes mellitus on the plasma levels of these two fibrinolytic inhibitors. In addition, other risk factors, known to influence the fibrinolytic parameters, were taken into account. Forty-nine Type 2 nonhypertensive diabetic patients without complications, 47 Type 2 hypertensive diabetic patients without complications, 54 non-diabetic hypertensive subjects without complications as well as 87 control subjects were studied. Plasma concentrations of Lp(a), PAI-1 antigen and activity, and the main parameters of oxidative, lipo- and glycometabolic balance were determined. Significant statistical differences between diabetic and non-diabetic subjects were found concerning triglycerides and antioxidant defence (p<0.01). Analysis of variance showed the F test statistically significant in evaluating the Log PAI-1/Lp(a) (p = 0.02). Correlation analysis between Log PAI-1 antigen and Lp(a) was significant in non-hypertensive diabetic patients, as expected (r = -0.38, p<0.01), and even stronger in hypertensive diabetic patients (r = -O.72,p<0.01). These results allow to hypothesise that the relationship between PAI-1/Lp(a) could be determinant in avoiding vascular complications due to diabetes mellitus and hypertension.

A significant relationship between plasminogen activator inhibitor type-1 and lipoprotein(a) in non-insulin-dependent diabetes mellitus without complications.

We previously found a relationship between plasminogen activator inhibitor type-1 and lipoprotein(a) in non-insulin-dependent diabetes mellitus and hypothesized that this could be due to a compensatory mechanism able to lower the risk of hypofibrinolysis found in type II diabetes mellitus. The aims of the present study were: (1) to confirm the association between plasminogen activator inhibitor type-1 and lipoprotein(a) in a different group of non-insulin-dependent diabetes mellitus patients and (2) to investigate whether the association could be related to diabetic complications. Other vascular risk factors able to influence fibrinolytic parameters such as glycemia, obesity, hypertension, dyslipidemia, and oxidative stress were also considered. Sixty-six non-insulin-dependent diabetes mellitus patients without diabetic complications (48 men, 18 women), 45 non-insulin-dependent diabetes mellitus patients with complications (21 men, 24 women), and 31 control subjects (17 men, 14 women) were studied. Plasma concentrations of lipoprotein(a), plasminogen activator inhibitor type-1 antigen and activity, and the main parameters of lipo- and glycometabolic balance were determined. Antioxidant defense was assayed as oxygen radical absorbance capacity of serum. Statistically significant differences among controls and the two diabetic groups were found for fasting glucose, cholesterol, triglycerides, and oxygen radical absorbance capacity of serum, while no statistically significant differences were evident for plasminogen activator inhibitor type-1 antigen and activity and lipoprotein(a). Regression analysis of log plasminogen activator inhibitor type-1/lipoprotein(a) showed a significant correlation only in diabetic patients without complications (r = -0.57, P < 0.001). These results show that a relationship between plasminogen activator inhibitor type-1 and lipoprotein(a) is characteristic of a diabetic population without complications, supporting the suggestion that this relationship could be a compensatory mechanism of the fibrinolytic system to limit the risks of hypofibrinolysis. A lack or a loss of capacity to balance lipoprotein(a) and plasminogen activator inhibitor type-1 could contribute to the pathogenesis of the diabetic complications.