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.

+647 A/C and +1245 MT1A polymorphisms in the susceptibility of diabetes mellitus and cardiovascular complications.

Diabetes mellitus is a chronic disease characterized by an overproduction of reactive oxygen species, which perturbs zinc metabolism and promotes the onset of cardiovascular disease (CVD) in diabetic patients. Metallothioneins (MT) are cysteine-rich metal-binding proteins which, by means of their antioxidant and zinc-buffering properties, might prevent the development of diabetic cardiovascular complications. A recent investigation shows that a polymorphism (+647 A/C) in the human MT-1A gene, affects the intracellular zinc ion release (iZnR) from the proteins and is associated with longevity in Italian population. The aim of the present study is to assess the involvement of +647 A/C and +1245 A/G MT1A polymorphisms with the susceptibility to type 2 diabetes (DM2) and cardiovascular complications. The study included 694 old individuals: 242 old healthy controls, 217 DM2 patients without clinical evidence of CVD (DNC) and 235 diabetic patients with diagnosis of CVD (DCVD). +647 A/C MT1A polymorphism, but not the second SNP, was associated with DM2. C allele carriers were more prevalent in DNC and DCVD patients than in control group (OR=1.37, p=0.034; OR=1.54, p=0.002, respectively). C+ carriers was associated with higher glycemia and glycosylated hemoglobin in DCVD patients, but not in DNC or control subjects. No differences in plasma zinc, but a modulation of MT levels and iZnR in PBMCs were observed in DCVD cohort when related to +647 A/C MT1A polymorphism. In summary, this work provides novel evidence on the association of the +647 A/C MT1A polymorphism with DM2. Moreover, C+ carriers in DCVD patients presented a worse glycemic control, a reduced iZnR and a higher MT levels, suggesting a possible role of MT in diabetic cardiovascular complications.

C-reactive protein is directly related to plasminogen activator inhibitor type 1 (PAI-1) levels in diabetic subjects with the 4G allele at position -675 of the PAI-1 gene.

BACKGROUND AND AIMS: C-reactive protein (CRP) has been identified as a possible factor able to promote atherosclerosis. "In vitro" studies have demonstrated that CRP induces plasminogen activator inhibitor type 1 (PAI-1) expression, suggesting a hypofibrinolytic role for CRP. As CRP and PAI-1 levels increase in type 2 diabetic subjects, we decided to study the relationship between CRP and PAI-1, and the role of the 4G/5G polymorphism of the PAI-1 gene on this relationship in a diabetic population without complications. METHODS AND RESULTS: Two hundred and ninety-five type 2 diabetic patients (age 60.9+/-10.5 years) and 290 healthy controls (age 59.2+/-11.5 years) were enrolled. A significant correlation between PAI-1 and CRP in diabetic subjects was found (r=0.45, p<0.001), whereas no relationship was evident in the control subjects between these inflammatory markers. Multiple regression analysis highlighted that CRP is the only one significant variable of PAI-1 antigen in diabetic subjects (partial r=0.31, p<0.01). Stratifying by genotype, a positive correlation between PAI-1 and CRP in 4G/4G (partial r=0.64 p<0.001) and 4G/5G (partial r=0.47, p<0.001) subjects was found, whereas no correlation in 5G/5G was present. Multiple regression analysis confirmed the presence of this correlation in 4G/4G (partial r=0.45, p<0.001) and in 4G/5G (partial r=0.34, p=0.007) diabetic patients. CONCLUSIONS: These findings demonstrate that CRP plays an important role in the complex mechanism regulating PAI-1 antigen in 4G diabetic carriers.

Effect of etanercept on insulin sensitivity in nine patients with psoriasis.

Metabolic syndrome is associated to chronic low grade inflammation, characterized by increased levels of inflammatory cytokines, such as Tumor Necrosis Factor-alpha (TNF-alpha) and Interleukin-6 (IL-6). In particular, TNF-alpha causes a decrease in the insulin-stimulated kinases related to the early phases of the insulin cascade, thereby leading to insulin resistance. Etanercept is a human fusion protein used in the treatment of psoriasis and inflammatory arthritis. It blocks inflammatory response by interfering in the binding of TNF-alpha to its receptors. The aim of this case report study is to verify the effect of Etanercept on insulin sensitivity, lipid profile and inflammatory status in psoriatic patients. Nine psoriatic patients with stable, active, plaque type psoriasis were enrolled and treated with Etanercept for 24 weeks. We found an improvement in the metabolic assessment with a significant reduction of insulin plasma levels. In particular, this treatment allows to maintain their euglycemic state with lower insulin plasma levels, as confirmed by the improved Homeostasis Model Assessment (HOMA) index. We conclude that Etanercept, probably acting on inflammation, improves insulin sensitivity in psoriatic subjects.

Interleukin-6-174 G > C polymorphism affects the association between IL-6 plasma levels and insulin resistance in type 2 diabetic patients.

Interleukin-6 (IL-6), a powerful inflammatory mediator, plays a pivotal role in the pathogenesis of insulin resistance and type 2 diabetes. Recently, the IL-6 promoter polymorphism, at position -174 (G > C), has been associated to insulin sensitivity although contrasting data have been reported. The aim of this study was to evaluate the effect of the IL-6-174 G > C polymorphism on insulin resistance. In 238 type 2 diabetic patients without diabetic complications and in 255 control subjects, age and gender-matched, we evaluated the IL-6 -174 G > C genotype, the IL-6 plasma levels and the insulin resistance by the homeostasis model assessment (HOMA). The levels of IL-6 and HOMA were not genotype-dependent and were higher in diabetic patients (p < 0.01). Control subjects, both C+ (CG + CC genotypes) and C- (GG genotype) carriers, showed IL-6 plasma levels significantly related to BMI, fasting insulin and HOMA. The same relationships were found in C+ diabetic carriers. Differently, diabetic C- carriers did not show any relationship between IL-6 levels and all the evaluated variables. Interestingly, all the correlations were dependent on BMI. These findings highlight that IL-6-174 G > C polymorphism affects insulin resistance in type 2 diabetes, where C+ carriers have an insulin resistance "IL-6-sensitive", while C- carriers do not. The identification of two categories of diabetic patients may, therefore, lead to different therapeutic strategies in the management of insulin resistance.

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.

Smoking is associated with reduced serum levels of the antioxidant enzyme, paraoxonase, in Type 2 diabetic patients.

AIMS: To analyse the association of smoking with paraoxonase (PON1) in Type 2 diabetic patients. METHODS: Type 2 diabetic patients were recruited independently in two centres (Ancona, Italy and Geneva, Switzerland) and serum PON1 mass and activities were assayed. Current smoking status was established and its association with serum PON1 analysed. RESULTS: Type 2 diabetic patients who smoked had significantly lower serum PON1 mass and activity. This was evident in both groups of patients, even though Swiss patients were composed of coronary patients. Multivariate analyses established that smoking was an independent determinant of serum PON1 status. CONCLUSIONS: Smoking is associated with reduced serum levels of the antioxidant enzyme, PON1, even against an already unfavourable background of diabetes and coronary disease. It suggests that a combination of smoking and diabetes may be particularly deleterious for PON1 and consequently for the anti-oxidant capacity of high-density lipoproteins.

Apolipoprotein E polymorphisms and mortality in Italian type 2 diabetic patients.

AIMS: To determine if apolipoprotein E polymorphism is associated with cardiovascular or all-cause mortality in Italian Type 2 diabetic patients. METHODS: A prospective study of mortality in Type 2 diabetic patients (n = 433) as a function of apolipoprotein E phenotype, which was assessed at entry into the study. During follow up (10 years), 110 (25.4%) patients died of which 66 (15.2%) were the result of cardiovascular causes. Cause of death was established from death certificates and clinical records. The clinical status of the survivors was determined at the end of the study. RESULTS: Apolipoprotein E polymorphisms were not associated with excess cardiovascular or all-cause mortality in the Italian Type 2 diabetic patients either in univariate or multivariate analyses. Age, duration of diabetes and glycated haemoglobin levels at entry were the primary determinants of premature mortality in the diabetic population. CONCLUSIONS: Apolipoprotein E polymorphisms are not markers for premature mortality in Italian Type 2 diabetic patients. The impact of apolipoprotein E mutations may be attenuated by environmental factors, notably a healthier diet, in Italian patients.

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.

Serum paraoxonase is reduced in type 1 diabetic patients compared to non-diabetic, first degree relatives; influence on the ability of HDL to protect LDL from oxidation.

Paraoxonase is a serum enzyme with an anti-oxidant function, protecting low density lipoproteins (LDL) from oxidative modifications. Diabetic patients are suggested to be at greater risk of oxidative stress, which may contribute to the significantly higher incidence of vascular disease in this population. Less efficient protection mechanisms may be one feature of the greater susceptibility to oxidation in diabetes. In this context, the present study examined the hypothesis that serum paraoxonase is reduced in type 1 (insulin-dependent) diabetic patients and that the reduction can affect the anti-oxidant capacity of HDL. Serum paraoxonase concentrations and activities were compared in type 1 patients and first degree, non-diabetic relatives with particular attention paid to the confounding effects of paraoxonase gene polymorphisms. In addition, the ability of HDL-paraoxonase to protect low density lipoproteins from oxidation was analysed in an in vitro system. Serum concentrations and enzyme activities of paraoxonase were significantly lower in type 1 patients compared to non-diabetic, first degree relatives. The differences were independent of promoter and coding region polymorphisms, which influence serum concentrations and activities of the enzyme. Overall, paraoxonase concentrations were a mean 13.3+/-4.5% lower (P<0.02) in type 1 patients. Specific activities did not differ between diabetic and non-diabetic groups. The concentration ratios of LDL cholesterol:paraoxonase (1.37+/-0.51 vs. 1.18+/-0.37, P=0.003) and apolipoprotein B:paraoxonase (0.84+/-0.33 vs. 0.71+/-0.40; P=0.012) were significantly higher in diabetic patients, consistent with a reduced capacity to protect LDL from oxidation. In vitro oxidation studies showed that a significantly higher level of lipid hydroperoxides was generated in LDL in the presence of HDL, containing paraoxonase levels equivalent to those of type 1 patients, compared to HDL containing paraoxonase levels equivalent to those of control subjects (mean difference 8.1%, P<0.05). The study demonstrates that serum concentrations of the antioxidant enzyme paraoxonase are significantly lower in type 1 (insulin-dependent) diabetic patients compared to non-diabetic, first-degree relatives, independently of known gene polymorphisms. Concentrations are reduced to an extent that can affect its anti-oxidant capacity. The results are consistent with the contention that modifications to serum paraoxonase in type 1 patients can increase risk of lipoprotein oxidation and, consequently, risk of vascular disease.

Relationship between lipoprotein(a) levels, oxidative stress, and blood pressure levels in patients with essential hypertension.

High plasma levels of lipoprotein(a) [Lp(a)] are considered a risk factor for the development of coronary artery disease. In vitro experiments have shown that oxidized Lp(a) is able to impair the arterial endothelium-dependent dilation, thus suggesting a possible role of Lp(a) in the genesis of essential hypertension. The aim of our work was to investigate the correlation of blood pressure levels with plasma Lp(a) concentration, apo(a) isoform size, and peroxidative stress in patients with essential hypertension. The study was performed in 54 untreated hypertensive patients whose blood pressure was monitored for 24 h by ambulatory blood pressure monitoring. Lp(a) concentration was measured by a double monoclonal antibody-based enzyme immunoassay demonstrated to be insensitive to apo(a) size heterogeneity. Apo(a) isoforms were determined by a high-resolution SDS-agarose gel electrophoresis followed by immunoblotting. A significant correlation was found between Lp(a) levels and the night-time systolic and diastolic pressures (r=0.32, P<0.05 and r=0.30, P<0.05, respectively), as well as with the mean night-time fall in systolic and diastolic blood pressures (r=-0.28, P<0.05 and r=-0.29, P<0.05, respectively). These relationships were further potentiated when peroxidative stress data were taken into consideration (r=0.37 and r=0.40, P<0.01 for the night-time systolic and diastolic pressures, respectively and r=-0.34 and r=-0.38, P<0.01 for the night-time fall in systolic and diastolic blood pressures, respectively). Apo(a) isoform size did not affect these relationships. Our data suggest that Lp(a) and peroxidative stress may be involved as cofactors in essential hypertension, with a mechanism that remains to be elucidated.

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.

Renal disease as a determinant of increased lipoprotein(a) concentrations in diabetic patients.

OBJECTIVE: This study examined the hypothesis that kidney function is an independent determinant of lipoprotein(a) [Lp(a)] concentrations in people with diabetes. RESEARCH DESIGN AND METHODS: Lp(a) concentrations were measured in plasma samples from 273 type 2 and 223 type 1 diabetic patients recruited from a diabetes clinic. Kidney function was categorized as normal or pathological according to plasma creatinine levels and creatinine clearance rates. RESULTS: Macroalbuminuria was uniformly associated with significantly raised plasma concentrations of Lp(a) regardless of the marker used to identify kidney dysfunction. In contrast, in patients with microalbuminuria, significantly raised plasma Lp(a) levels were observed only when creatinine clearance rates or plasma creatinine levels indicated pathological kidney function. These conclusions were independent of diabetes type. CONCLUSIONS: In microalbuminuria and apparently in normoalbuminuria, altered kidney function determined by creatinine clearance rates or creatinine levels appears to be a major determinant of raised Lp(a) levels in both type 1 and type 2 diabetic patients. In contrast, Lp(a) concentrations were uniformly raised in patients with macroalbuminuria.

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.

Reproducibility of normal facial motor nerve conduction studies and their relevance in the electrophysiological assessment of peripheral facial paralysis.

To determine the intra-examiner intertrial reproducibility of normal facial motor nerve conduction studies (FNCS) and their relevance in electrophysiological assessments of peripheral facial paralysis, 52 patients with acute unilateral Bell's palsy were examined on two separate occasions 1 months apart. Three electroneurographic methods were assessed. On the unaffected side of the face, FNCS are reliable when performed by a single examiner over time. Nevertheless, compound muscle action potential (CMAP) baseline-to-peak and peak-to-peak amplitude showed a rather high intertrial variability. Reproducibility of the assessed surface electrode recording procedures was similar. Regarding the affected side, in patients with mild axonotmesis of the facial nerve variations of electroneurographic parameters 1 months apart fell within the range of normal intertrial variability. In patients with severe or moderate axonotmesis, the distal latency and the M wave amplitude variations showed significant intertrial variations. Reproducibility of FNCS appears to be similar to that found in limb motor nerves. Normal variability curtails the sensitivity of FNCS in detecting mild facial nerve axonotmesis, although this technique remains useful in severe cases.

Lipoprotein (a) and vascular disease in diabetic patients.

In order to assess the potential role of lipoprotein (a) as a risk factor for cardiovascular disease in diabetes mellitus, plasma concentrations were measured in a large group (n = 500) of non-insulin-dependent (NIDDM, n = 355) and insulin-dependent (IDDM, n = 145) patients. Concentrations of lipoprotein (a) were compared in diabetic patients with (n = 153) or without (347) documented vascular disease (ischaemic heart disease, peripheral vascular disease or macroangiopathy). They were significantly higher (p < 0.05) in patients with ischaemic heart disease (mean [interquartile range] 15.5 (5.0-38.0) vs 9.0 (4.5-26.0) mg/dl) or macroangiopathy (13.0 (5.0-38.0) vs 9.0 (4.0-25.0) mg/dl) compared to patients without manifestations of vascular disease. In addition, stepwise logistic regression analysis identified lipoprotein (a) levels > or = 30 mg/dl as being independently associated with the presence of cardiovascular disease. Lipoprotein (a) was an independent risk factor for ischaemic heart disease and macroangiopathy in this group of IDDM and NIDDM patients.