Plasma levels of soluble urokinase plasminogen activator receptor (suPAR) and high-sensitivity C-reactive protein after Roux-en-Y gastric bypass or sleeve gastrectomy: a 1-year prospective observational study.

PURPOSE: Low-grade inflammation in obesity contributes to the development of cardiovascular disease, diabetes mellitus and cancer, and is associated with increased mortality. The purpose of this 1-year prospective observational study was to examine the weight loss effect of bariatric surgery on plasma concentrations of two inflammatory markers, namely high-sensitivity C-reactive protein (hsCRP) and soluble urokinase-type plasminogen activator receptor (suPAR), in patients with obesity. METHODS: Sixteen subjects without obesity and 32 patients with obesity class III, who had already settled upon Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) were included in the study. Subjects without obesity were examined once, at baseline; patients with obesity were examined preoperatively (baseline) and 3, 6 and 12 months postoperatively. RESULTS: Plasma suPAR and hsCRP concentrations at baseline were higher in patients with obesity than in lean participants (2.68 ± 0.86 vs 1.86 ± 0.34 ng/mL, p < 0.001 and 9.83 ± 9.55 vs 1.36 ± 1.95 mg/dL, p < 0.001). Levels of suPAR following bariatric surgery increased significantly 3 months after either RYGB or SG (3.58 ± 1.58 vs 3.26 ± 0.7 ng/mL, respectively) and declined at 6 (3.19 ± 1.75 vs 2.8 ± 0.84 ng/mL, respectively) and 12 months (2.6 ± 1.5 vs 2.22 ± 0.49 ng/mL, respectively; p < 0.05 for the effect of time on suPAR levels during the study), whereas those of hsCRP declined consistently after bariatric surgery (3 months: 5.44 ± 3.99 vs 9.47 ± 11.98 mg/dL, respectively; 6 months; 5.39 ± 5.6 vs 10.25 ± 17.22 mg/dL, respectively; and 12 months: 2.23 ± 2.5 vs 3.07 ± 3.63 mg/dL, respectively; p < 0.001 for the effect of time on hsCRP levels during the study). 1-year change in BMI was negatively associated with suPAR levels at 12 months. CONCLUSION: Our findings support an association between obesity and low-grade inflammation. Weight loss following bariatric surgery is associated with a consistent decline in plasma hsCRP, while plasma suPAR levels increase at 3 months and decline by 12 months.

Baseline osteocalcin levels and incident diabetes in a 3-year prospective study of high-risk individuals.

AIM: Experimental evidence suggests that osteocalcin is a key messenger that affects both adipocytes and insulin-producing ß cells. Epidemiological cross-sectional studies have shown a negative association between plasma levels of osteocalcin and glucose. For this reason, the hypothesis that lower baseline osteocalcin plasma levels are associated with diabetes was prospectively tested. METHODS: The study population consisted of individuals at high risk for type 2 diabetes who were screened for participation in the Greek arm of a European type 2 diabetes prevention study (the DE-PLAN study). All participants were free of diabetes at baseline and underwent a second evaluation 3 years later. Diabetes status was defined according to an oral glucose tolerance test. RESULTS: A total of 307 subjects were included in the present analysis. The population, including 154 men (50.3%), was middle-aged (54.4 ± 10.2 years) and overweight (BMI: 29.5 ± 4.9 kg/m(2)). At baseline, mean total plasma osteocalcin was lower in those with impaired fasting glucose and/or impaired glucose tolerance compared with those with normal glucose tolerance (6.0 ± 3.1 ng/mL vs. 7.3 ± 4.0 ng/mL, respectively; P = 0.01). After 3 years, 36 subjects had developed diabetes. In the prospective evaluation, there was no association between baseline osteocalcin levels and diabetes (OR: 1.04 per 1 ng/mL, 95% CI: 0.93-1.15; P = 0.49) on multivariable logistic regression analysis, nor was there any correlation with changes in plasma glucose after 3 years (r = 0.09, P = 0.38). CONCLUSION: Our prospective results show that lower levels of circulating osteocalcin do not predict future diabetes development and, in contrast to most cross-sectional published data so far, suggest that this molecule may not be playing a major role in glucose homoeostasis in humans.

Cardiac autonomic function correlates with arterial stiffness in the early stage of type 1 diabetes.

Arterial stiffness is increased in type 1 diabetes (T1D), before any clinical complications of the disease are evident. The aim of the present paper was to investigate the association between cardiac autonomic function and arterial stiffness in a cohort of young T1D patients, without history of hypertension and any evidence of macrovascular and/or renal disease. Large artery stiffness was assessed by measurement of carotid-femoral pulse wave velocity (PWV). Cardiac autonomic function was assessed by the cardiovascular tests proposed by Ewing and Clarke. Patients with a high cardiac autonomic neuropathy score (≥4) had significantly higher PWV than those with a low score (0-1). A negative, heart rate-independent, correlation between PWV and heart rate variation during respiration was observed (r = -0.533, P < 0.001). In multivariable analysis, E/I index was the strongest correlate of PWV (ß-coefficient = -0.326, P = 0.002). Cardiac parasympathetic function is a strong predictor of large arterial stiffness, in young T1D patients free of macrovascular and renal complications.

Validation of the Finnish diabetes risk score (FINDRISC) questionnaire for screening for undiagnosed type 2 diabetes, dysglycaemia and the metabolic syndrome in Greece.

AIM: The present study aimed to validate the Finnish Type 2 Diabetes Risk Score (FINDRISC) questionnaire for its ability to predict the presence of any glucose homoeostasis abnormalities and the metabolic syndrome (MetS) in the Greek population. METHODS: Validation was performed on a sample of individuals who had agreed to participate in a screening program for type 2 diabetes (T2D) prevention (the Greek part of the DE-PLAN study), using both FINDRISC and oral glucose tolerance tests (OGTT). Impaired fasting glucose (IFG) was defined as a fasting plasma glucose level of 6.1-6.9 mmol/L, and impaired glucose tolerance (IGT) as a 2-h plasma glucose of 7.8-11.0 mmol/L. The predictive value of the FINDRISC was cross-sectionally evaluated using the area under the receiver operating characteristic (AUROC) curve method. RESULTS: A total of 869 individuals (379 men, aged 56.2 ± 10.8 years) were screened from the general population living in the city and suburbs of Athens. OGTT revealed the presence of unknown diabetes in 94 cases (10.8%), IFG in 85 (9.8%) and IGT in 109 (12.6%). The sensitivity of a FINDRISC score greater or equal to 15 (45% of the population) to predict unknown diabetes was 81.9% and its specificity was 59.7%. The AUROC curve for detecting unknown diabetes was 0.724 (95% CI: 0.677-0.770). For any dysglycaemia, the AUROC curve was 0.716 (0.680-0.752) while, for detection of the MetS, it was 0.733 (0.699-0.767). CONCLUSION: The FINDRISC questionnaire performed well as a screening tool for the cross-sectional detection of unknown diabetes, IFG, IGT and the MetS in the Greek population.

The association between the spatial QRS-T angle with cardiac autonomic neuropathy in subjects with Type 2 diabetes mellitus.

AIMS: To examine differences in the spatial QRS-T angle in patients with Type 2 diabetes mellitus with and without cardiac autonomic neuropathy. METHODS: Two hundred and thirty-two patients with diabetes mellitus (105 with cardiac autonomic neuropathy and 127 without cardiac autonomic neuropathy) and 232 control subjects, matched by gender and age, were studied. Diagnosis of cardiac autonomic neuropathy was based on the classic autonomic function tests. All subjects underwent a digital electrocardiographic recording. Electrocardiographic parameters were measured using the Modular Electrocardiographic Analysis (MEANS) program. Left ventricular mass index (LVMi) and global myocardial performance index (Tei index) of the left ventricle were assessed by ultrasonography. RESULTS: The spatial QRS-T angle was higher in the patients with diabetes in comparison with the control subjects (24.5 ± 10.7 vs. 9.7 ± 4.5°, P < 0.001) and in the patients with diabetes and cardiac autonomic neuropathy than in those without cardiac autonomic neuropathy (30.1 ± 11.3 vs. 19.5 ± 7.1, P < 0.001). No differences were found in the QT interval between the studied groups. Multivariate linear regression analysis in subjects with diabetes after controlling for age, gender, BMI, blood pressure, diabetes duration, HbA(1c) , lipids, microalbuminuria and insulin resistance, demonstrated significant and independent associations between the spatial QRS-T angle with presence and severity of cardiac autonomic neuropathy, all parameters of heart rate variability, LVMi and Tei index. CONCLUSIONS: The spatial QRS-T angle is increased in patients with Type 2 diabetes who have cardiac autonomic neuropathy, suggesting increased ventricular arrhythmogenicity, and is associated with the structural and functional properties of the myocardium. Further research is warranted to evaluate its role in cardiovascular risk stratification of patients with diabetes.

Implementation and effectiveness of the first community lifestyle intervention programme to prevent Type 2 diabetes in Greece. The DE-PLAN study.

AIMS: To report our experience of implementing the first community-based lifestyle intervention programme to detect high-risk individuals and prevent the development of Type 2 diabetes mellitus (T2DM) in a general population sample in Athens, Greece (the DE-PLAN Study). METHODS: The Finnish Type 2 Diabetes Risk Score (FINDRISC) questionnaire was distributed to 7900 people at workplaces and primary-care centres. High-risk individuals were invited to receive an oral glucose tolerance test (OGTT) and, after excluding persons with diabetes, to participate in a 1-year intervention programme, based on bimonthly sessions with a dietitian. RESULTS: Three thousand, two hundred and forty questionnaires were returned; 620 high-risk individuals were identified and 191 agreed to participate. Recruitment from workplaces was the most successful strategy for identifying high-risk persons, enrolling and maintaining them throughout the study. The 125 participants who fully completed the programme (66 did not return for a second OGTT) lost on average 1.0+/-4.7 kg (P=0.022). Higher adherence to the intervention sessions resulted in more significant weight loss (1.1+/-4.8 vs. 0.6+/-4.6 kg for low adherence). Persons with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) at baseline lost more weight than those with normal glucose tolerance (1.5+/-4.8 vs. -0.2+/-4.5 kg). The percentage of people with any type of dysglycaemia (IFG/IGT) was lower after the intervention (68.0% at baseline vs. 53.6% 1 year later, P=0.009); 5.6% developed diabetes. CONCLUSIONS: The implementation of a lifestyle intervention programme to prevent T2DM in the community is practical and feasible, accompanied by favourable lifestyle changes. Recruitment from workplaces was the most successful strategy.

Vinegar reduces postprandial hyperglycaemia in patients with type II diabetes when added to a high, but not to a low, glycaemic index meal.

BACKGROUND/OBJECTIVES: Earlier studies have shown that the addition of vinegar in a carbohydrate-rich meal lowers glucose and insulin response in healthy individuals. The mechanism of how this is accomplished, however, remains unclear. The aim of this study is to examine the effect of vinegar on glucose and insulin response in patients with type II diabetes (T2D) in relation to the type of carbohydrates consumed in a meal. SUBJECTS/METHODS: Sixteen patients with T2D were divided into two groups, matched for age, gender and HbA(1c). Patients in the first group (group A) were given a high-glycaemic index (GI) meal (mashed potatoes and low-fat milk) on two different days, with and without the addition of vinegar, respectively. In the second group (group B), patients were given an isocaloric meal with the same nutrient composition, but low GI (whole grain bread, lettuce and low-fat cheese). Postprandial plasma glucose and insulin values were measured every 30 min for 2 h. RESULTS: In group A, the incremental area under the curve of glucose (GiAUC(120)) was lower after the addition of vinegar (181+/-78 mmol min/l vs 311+/-124 mmol min/l, P=0.04). The iAUC of insulin (IiAUC(120)) was also reduced, but the difference was of marginal statistical significance (2368+/-1061 microU min/ml vs 3545+/-2586 microU min/ml, P=0.056). In group B, the addition of vinegar did not affect either the GiAUC(120) (229+/-38 mmol min/l vs 238+/-25 mmol min/l, P=0.56) or the IiAUC(120) (2996+/-1302 microU min/ml vs 3007+/-1255 microU min/ml, P=0.98). CONCLUSIONS: We conclude that the addition of vinegar reduces postprandial glycaemia in patients with T2D only when it is added to a high-GI meal.

A European evidence-based guideline for the prevention of type 2 diabetes.

BACKGROUND: The prevalence and socioeconomic burden of type 2 diabetes (T2DM) and associated co-morbidities are rising worldwide. AIMS: This guideline provides evidence-based recommendations for preventing T2DM. METHODS: A European multidisciplinary consortium systematically reviewed the evidence on the effectiveness of screening and interventions for T2DM prevention using SIGN criteria. RESULTS: Obesity and sedentary lifestyle are the main modifiable risk factors. Age and ethnicity are non-modifiable risk factors. Case-finding should follow a step-wise procedure using risk questionnaires and oral glucose tolerance testing. Persons with impaired glucose tolerance and/or fasting glucose are at high-risk and should be prioritized for intensive intervention. Interventions supporting lifestyle changes delay the onset of T2DM in high-risk adults (number-needed-to-treat: 6.4 over 1.8-4.6 years). These should be supported by inter-sectoral strategies that create health promoting environments. Sustained body weight reduction by >or= 5 % lowers risk. Currently metformin, acarbose and orlistat can be considered as second-line prevention options. The population approach should use organized measures to raise awareness and change lifestyle with specific approaches for adolescents, minorities and disadvantaged people. Interventions promoting lifestyle changes are more effective if they target both diet and physical activity, mobilize social support, involve the planned use of established behaviour change techniques, and provide frequent contacts. Cost-effectiveness analysis should take a societal perspective. CONCLUSIONS: Prevention using lifestyle modifications in high-risk individuals is cost-effective and should be embedded in evaluated models of care. Effective prevention plans are predicated upon sustained government initiatives comprising advocacy, community support, fiscal and legislative changes, private sector engagement and continuous media communication.

Quality indicators for the prevention of type 2 diabetes in Europe--IMAGE.

BACKGROUND: The marked increase of type 2 diabetes necessitates active development and implementation of efficient prevention programs. A European level action has been taken by launching the IMAGE project to unify and improve the various prevention management concepts, which currently exist within the EU. This report describes the background and the methods used in the development of the IMAGE project quality indicators for diabetes primary prevention programs. It is targeted to the persons responsible for diabetes prevention at different levels of the health care systems. METHODS: Development of the quality indicators was conducted by a group of specialists representing different professional groups from several European countries. Indicators and measurement recommendations were produced by the expert group in consensus meetings and further developed by combining evidence and expert opinion. RESULTS: The quality indicators were developed for different prevention strategies: population level prevention strategy, screening for high risk, and high risk prevention strategy. Totally, 22 quality indicators were generated. They constitute the minimum level of quality assurance recommended for diabetes prevention programs. In addition, 20 scientific evaluation indicators with measurement standards were produced. These micro level indicators describe measurements, which should be used if evaluation, reporting, and scientific analysis are planned. CONCLUSIONS: We hope that these quality tools together with the IMAGE guidelines will provide a useful tool for improving the quality of diabetes prevention in Europe and make different prevention approaches comparable.

Acute hyperhomocysteinemia impairs endothelium function in subjects with type 2 diabetes mellitus.

The objective of the present study was to examine the effect of acute, methionine-induced hyperhomocysteinemia (HHCY) on endothelial function and indices of arterial stiffness in subjects with type 2 diabetes mellitus (T2DM). A total of 30 subjects with T2DM, free of macrovascular disease were examined in a crossover study. L-methionine (M) (0.1 g/kg) and water (W) load were given in random order with an interval of about 1 week in between. Endothelial function was assessed by flow-mediated vasodilation (FMD). Arterial stiffness was assessed by determination of augmentation index (AI). Measurements were performed in the fasting state, 1, 2 and 3 h after the M or the W load. Total plasma homocysteine (HCY) levels did not change after W administration, while M administration resulted in a significant increase in HCY concentrations at 3 h. FMD throughout the experiment expressed as area under the curve (AUC) was significantly lower after the M than after the W load. Consistent with impairment in endothelial function, the AUC of AI was significantly higher after the M than after the W administration. Acute HHCY impairs endothelial function and increases arterial stiffness in patients with T2DM. This effect is probably mediated by a reduction of nitric oxide bioavailability in endothelium.

Rates of lipid fluxes in adipose tissue in vivo after a mixed meal in morbid obesity.

OBJECTIVE: Although insulin resistance in obesity is established, information on insulin action on lipid fluxes, in morbid obesity, is limited. This study was undertaken in morbidly obese women to investigate insulin action on triacylglycerol fluxes and lipolysis across adipose tissue. SUBJECTS AND DESIGN: A meal was given to 26 obese (age 35+/-1 years, body mass index 46+/-1 kg m(-2)) and 11 non-obese women (age 38+/-2 years, body mass index 24+/-1 kg m(-2)). Plasma samples for glucose, insulin, triglycerides and non-esterified fatty acids (NEFAs) were taken for 360 min from a vein draining the abdominal subcutaneous adipose tissue and from the radial artery. Adipose tissue blood flow was measured with (133)Xe. RESULTS: In obese vs non-obese: (1) Arterial glucose was similar, but insulin was increased (P=0.0001). (2) Adipose tissue blood flow was decreased (P=0.0001). (3) Arterial triglycerides (P=0.0001) and NEFAs (P=0.01) were increased. (4) Lipoprotein lipase was decreased (P=0.0009), although the arteriovenous triglyceride differences were similar. (5) Veno-arterial NEFA differences across the adipose tissue were similar. (6) NEFA fluxes and hormone-sensitive lipase-derived glycerol output from 100 g adipose tissue were not different. (7) Total adipose tissue NEFA release was increased (P=0.02). CONCLUSIONS: In morbid obesity: (a) hypertriglycerinemia could be attributed to a defect in the postprandial dynamic adjustment of triglyceride clearance across the adipose tissue, partly caused by blunted BF; and (b) postprandially, there is an impairment of adipose tissue to buffer NEFA excess, despite hyperinsulinemia.

Trends in the management of type 2 diabetes and its prescription drug costs in Greece (1998 & 2006).

AIMS Aim of the present study is to compare control of hyperglycaemia and other diabetes-related cardiovascular risk factors during the years 1998 and 2006 and to estimate the change in the cost of medications prescribed for this purpose. METHODS We compared the medical records of all patients who were regularly followed in three major diabetes centers located in Athens and Piraeus, Greece, during 1998, with those who were examined at the same centers during 2006. The cost of medications was calculated in Euros per patient-year (euroPY), using the 2006 official Greek market prices. RESULTS A total of 1 743 eligible files were included in the study (805 files from 1998 and 938 from 2006). HbA (1c), LDL-cholesterol and blood pressure improved significantly in 2006 as compared to 1998 (7.0% vs. 8.1%, 2.9 mmol/l vs. 3.9 mmol/l and 134.9/77.6 mmHg vs. 139.3/80.9 mmHg respectively, p<0.001 for all comparisons). Treatment of hyperglycaemia was more intense and had a different pattern in 2006. The proportion of patients receiving antihypertensive, hypolipidaemic and antiplatelet drugs increased from 48.8% to 74.4%, from 15.2% to 61.2% and from 17.6% to 51.1% respectively (p<0.001 for all comparisons). A highly significant increase in the cost per patient-year was observed for all classes of medications in 2006. The total cost of all diabetes-related medications increased in 2006 by 221.1% (from 341.3+/-276.0 euroPY to 1095.8+/-634.1 euroPY). CONCLUSIONS Control of cardiovascular risk factors of patients with T2D, regularly followed by diabetes specialists, improved significantly in 2006 as compared to 1998. This improvement, however, was associated with a considerable increase in the cost of medications prescribed for treatment of these parameters.

Sudomotor dysfunction is associated with foot ulceration in diabetes.

AIM: To examine the relationship between sudomotor dysfunction and foot ulceration (FU) in patients with diabetes. METHODS: Ninety patients with either Type 1 or Type 2 diabetes [30 without peripheral sensorimotor neuropathy (PN), 30 with PN but without FU and 30 with FU] were recruited in this cross-sectional study. Assessment of PN was based on neuropathy symptom score (NSS), neuropathy disability score (NDS) and vibration perception threshold (VPT). Sudomotor dysfunction was assessed using the sympathetic skin response (SSR). Cardiac autonomic nervous system activity was assessed by the battery of the classical autonomic function tests. RESULTS: Patients with foot ulcers had longer duration of diabetes, higher values of VPT and NDS and lower values of the autonomic functions tests in comparison with the other study groups. Sudomotor dysfunction and cardiac autonomic neuropathy were significantly more common in the FU group. Multivariate logistic regression analysis after adjustment for gender, body mass index, duration of diabetes and glycated haemoglobin (HbA(1c)) demonstrated that the odds ratio (95% confidence intervals) of FU increased with measures of neuropathy such as NDS >or= 6 (10.2, 6.2-17.3) and VPT >or= 25 volts (19.8, 9.9-47.5), but was also significantly increased with absent SSR (15.3, 5.3-38.4). CONCLUSIONS: Sudomotor dysfunction is associated with increased risk of FU and should be included in the screening tests for identification of diabetic patients at risk of ulceration.

The consumption of bread enriched with betaglucan reduces LDL-cholesterol and improves insulin resistance in patients with type 2 diabetes.

AIM: Previous studies have shown that the water-soluble dietary fibre betaglucan, a natural component of oats, reduces cholesterol and postprandial hyperglycaemia. The aim of the present study was to investigate the effect of betaglucan-enriched bread consumption on the lipid profile and glucose homoeostasis of patients with type 2 diabetes (T2D). METHODS: We conducted a randomized, double-blind study in which 46 patients with T2D and LDL-C greater than 3.37 mmol/l (130 mg/dl) were randomized to incorporate into their diet, for 3 weeks, either bread enriched with betaglucan (providing 3g/day of betaglucan) or white bread without betaglucan. RESULTS: The consumption of bread containing betaglucan led to significant reductions (vs the control group) in LDL-C of 0.66 mmol/l (15.79%) versus 0.11 mmol/l (2.71%) (P=0.009), in total cholesterol of 0.80 mmol/l (12.80%) versus 0.12 mmol/l (1.88%) (P=0.006), in Fasting plasma insulin (FPI) of 3.23 microU/ml versus an increase of 3.77 microU/ml (P=0.03) and in Homa-IR (Homoeostasis model assessment-insulin resistance) by 2.08 versus an increase of 1.33 (P=0.04). CONCLUSIONS: Betaglucan enriched bread may contribute to the improvement of the lipid profile and insulin resistance in patients with T2D.

The effects of medications used for the management of dyslipidemia on postprandial lipemia.

Postprandial lipemia has emerged as an independent risk factor for coronary artery disease. In this systematic review we examined the effect of the medications used for the management of dyslipidemia on postprandial lipemia. Statins, beyond their effects on fasting lipid levels, reduce also postprandial lipemia mainly by inhibiting the production of apoB containing lipoproteins from the liver and thus increasing the clearance of triglyceride-rich lipoproteins of either liver or intestinal origin. Fibrates decrease fasting triglyceride and increase high density lipoprotein cholesterol levels. Besides, fibrates are particularly potent drugs in the reduction of postprandial lipemia; they decrease the production or triglyceride-rich lipoproteins and increase their clearance by enhancing the activity of lipoprotein lipase.

Comparative topoisomerase IIa and ki 67 protein expression in papillary thyroid carcinoma based on tissue microarrays and image analysis.

PURPOSE: Topoisomerase II alpha (Topo IIa gene location 17q21) is a nucleic enzyme involved in the DNA replication, transcription and chromosome topological formation. Topo IIa inhibition strategies include specific chemotherapeutic agents such as anthracyclines. Our aim was to investigate potential protein alterations of the enzyme comparing them to ki 67 proliferation marker expression in papillary thyroid carcinoma (PTC). MATERIALS AND METHODS: Using tissue microarray (TMA) technology, 50 specimens consisting of histologically confirmed PTCs (n=20), multi-nodular goiters (n=20) and also normal thyroid epithelia (n=10) were cored and re-embedded in the final paraffin block. Immunohistochemical analysis was performed using monoclonal anti-Topo IIa and anti-ki 67 (MIB-1) antibodies. Digital image analysis assay was also applied for the evaluation of the protein expression results (Nuclear Labeling Index-NLI). RESULTS: Topo IIa and ki 67 proteins were overexpressed in 4/20 (20%) and 14/20 (70%) cases, respectively. Concerning multi-nodular goiters, overexpression was observed in 2/20 and 4/20 specimens, respectively. Statistical association was assessed correlating ki 67 expression to pathology type, capsular invasion and also to vascular infiltration (p=0.001, p=0.008, and p=0.012, respectively). Topo IIa protein expression was strongly correlated only to capsular invasion (p=0.004). Overall expression of the examined markers demonstrated a medium concordance (kappa=0.27), but a strong association (p=0.001). CONCLUSION: Topo IIa and also ki 67 overexpression are correlated to an aggressive phenotype in PTC. Topo IIa overexpression maybe is a reliable marker for a rational application of targeted chemotherapeutic strategies in some subgroups of patients.

Usefulness of a new indicator test for the diagnosis of peripheral and autonomic neuropathy in patients with diabetes mellitus.

AIMS: The aim of the present study was to assess the performance of a new indicator test (NIT), based on the measurement of sweat production after exposure to dermal foot perspiration, in the diagnosis of both peripheral sensorimotor polyneuropathy (PSN) and autonomic neuropathy in patients with diabetes. METHODS: One hundred and seventeen diabetic patients were examined. PSN was assessed using the neuropathy symptoms score, the neuropathy disability score and the vibration perception threshold. Cardiac autonomic neuropathy (CAN) was assessed using the battery of the four classical standardized tests proposed by Ewing et al., Diabetes Care 1985; 8: 491-498. Sudomotor dysfunction was assessed using the NIT. RESULTS: Fifty patients (42.7%) had PSN and 44 patients (37.6%) had CAN. Of the 50 patients with PSN, 43 had a positive NIT (sensitivity 86%) and, out of the 67 patients without PSN, a negative NIT was obtained in 45 patients (specificity 67%). The positive and the negative predictive value of the NIT in detecting PSN were 66.2 and 86.5%, respectively. The sensitivity and specificity of NIT in detecting CAN was 59.1 and 46.5%, respectively. In the case of severe CAN, the sensitivity was increased to 80.9% and the specificity to 50%. CONCLUSIONS: The NIT has good sensitivity and negative predictive value for diagnosis of PSN and can be used as a screening method for detection of this complication in patients with diabetes. In addition, the test has a low sensitivity for detection of autonomic neuropathy in patients with milder forms of CAN.