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Eur J Clin Invest 2011; 41 (6): 652–658 Abstract Background Insulin-resistant states, such as metabolic syndrome and diabetes mellitus type 2 (DM2), have been associated with chronic low-grade systemic inflammation. Elevated levels of interleukin-6 (IL-6), monocyte chemoattractant protein (MCP-1) and C-reactive protein (hs-CRP), are found in patients with type 2 diabetes with and without complications. Angiotensin II (Ang II), a potent vasopressor, seems to regulate also the expression of the above inflammatory mediators acting as proinflammatory cytokine. In this study, we examined the effects of candesartan, an angiotensin receptror blocker, in the chronic low-grade inflammation observed in DM 2. Materials and methods Seventeen patients with DM2 of

Diabet. Med. 27, 1420–1429 (2010) Abstract 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

Executive SummaryWhen we ask people what they value most, health is usually top of the list. While effective care is available for many chronic diseases, the fact remains that for the patient, the tax payer and the whole of society: Prevention is Better Than Cure.Diabetes and its complications are a serious threat to the survival and well-being of an increasing number of people. It is predicted that one in ten Europeans aged 20–79 will have developed diabetes by 2030. Once a disease of old age, diabetes is now common among adults of all ages and is beginning to affect adolescents and even children. Diabetes accounts for up to 18 % of total healthcare expenditure in Europe.The Good News is That Diabetes is Preventable. Compelling evidence shows that the onset of diabetes can be prevented or delayed greatly in individuals at high risk (people with impaired glucose regulation). Clinical research has shown a reduction in risk of developing diabetes of over 50 % following relatively modest changes in lifestyle that include adopting a healthy diet, increasing physical activity, and maintaining a healthy body weight. These results have since been reproduced in real-world prevention programmes. Even a delay of a few years in the progression to diabetes is expected to reduce diabetes-related complications, such as heart, kidney and eye disease and, consequently, to reduce the cost to society.A comprehensive approach to diabetes prevention should combine population based primary prevention with programmes targeted at those who are at high risk. This approach should take account of the local circumstances and diversity within modern society (e.g. social inequalities). The challenge goes beyond the healthcare system. We need to encourage collaboration across many different sectors: education providers, non-governmental organisations, the food industry, the media, urban planners and politicians all have a very important role to play.Small Changes in Lifestyle Will Bring Big Changes in Health.Through Joint Efforts, More People Will be Reached.The Time to Act is Now. When we ask people what they value most, health is usually top of the list. While effective care is available for many chronic diseases, the fact remains that for the patient, the tax payer and the whole of society: prevention is better than cure. Diabetes and its complications are a serious threat to the survival and well-being of an increasing number of people. It is predicted that one in ten Europeans aged 20-79 will have developed diabetes by 2030. Once a disease of old age, diabetes is now common among adults of all ages and is beginning to affect adolescents and even children. Diabetes accounts for up to 18 % of total healthcare expenditure in Europe. The good news is that diabetes is preventable. Compelling evidence shows that the onset of diabetes can be prevented or delayed greatly in individuals at high risk (people with impaired glucose regulation). Clinical research has shown a reduction in risk of developing diabetes of over 50 % following relatively modest changes in lifestyle that include adopting a healthy diet, increasing physical activity, and maintaining a healthy body weight. These results have since been reproduced in real-world prevention programmes. Even a delay of a few years in the progression to diabetes is expected to reduce diabetes-related complications, such as heart, kidney and eye disease and, consequently, to reduce the cost to society. A comprehensive approach to diabetes prevention should combine population based primary prevention with programmes targeted at those who are at high risk. This approach should take account of the local circumstances and diversity within modern society (e.g. social inequalities). The challenge goes beyond the healthcare system. We need to encourage collaboration across many different sectors: education providers, non-governmental organisations, the food industry, the media, urban planners and politicians all have a very important role to play. Small changes in lifestyle will bring big changes in health. Through joint efforts, more people will be reached. The time to act is now.

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 (HbA1c) demonstrated that the odds ratio (95% confidence intervals) of FU increased with measures of neuropathy such as NDS ≥ 6 (10.2, 6.2–17.3) and VPT ≥ 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.

Diabetic muscle infarction (DMI) is a rare, long-term complication of poorly controlled diabetes (typically of type I). DMI was first described in 1965 and more than 100 cases have been reported thereafter in the English literature. Usually, there is a coexistence with concomitant nephropathy, neuropathy, and retinopathy. The etiology remains uncertain, but appears to be attributable to diabetic microangiopathy and hypercoagulability and is believed that hypoxia-reperfusion injury is involved. DMI presents with sudden onset of pain associated with a tender mass in the thigh in most instances. The diagnosis is based on magnetic resonance imaging, which is not specific but highly indicative. Treatment is conservative with relapses occurring in 50% of the patients, but not necessarily in the same muscle group. We describe a case of DMI that occurred 4 months after simultaneous kidney and pancreas transplantation in one patient with type I diabetes mellitus and end-stage renal disease.

Summary Background and Aim Hyperhomocysteinemia is a major and independent risk factor for atherothrombotic vascular disease. It may be promoted by genetic factors, nutritional deficiencies of the vitamin cofactors required for homocysteine metabolism, and other modifiable factors. This cross-sectional study investigated the effect of dietary habits and lifestyle on plasma total homocysteine (tHcy) levels in patients with type 2 diabetes in a Mediterranean population. Methods and results A total of 126 diabetic and 76 healthy subjects were interviewed using a food-frequency questionnaire. Information consisted of dietary and smoking habits, coffee and alcohol consumption and physical activity recording, during the month prior to enrolment. Measurements included blood pressure, body mass index (BMI), waist-to-hip ratio (WHR), plasma tHcy, folate, vitamin B12, lipids, HbA 1c , creatinine, uric acid, and glomerular filtration rate (GFR). Plasma tHcy levels were not different between diabetic and control subjects (11.49±3.68 vs 12.67±3.79 μmol/l respectively, P =0.40). Diabetic subjects had significantly higher plasma folate levels and consumed more fish, fruit and vegetables, in comparison with controls. Controls consumed more red meat, coffee, and alcohol. Multivariate analysis in diabetic subjects, after controlling for age, sex, systolic blood pressure, duration of diabetes, GFR, plasma uric acid levels, and the amount of the weekly consumption of fruit and vegetables, demonstrated that age, GFR and the weekly amount of fruit and vegetable consumption were independently associated with plasma tHcy concentrations [regression coefficient (B)=0.11, SE (B)=0.03, P =0.001, B=−0.07, SE (B)=0.01, P P =0.04, respectively]. The weekly amount of coffee, alcohol and red meat consumption, and physical activity level were not related with plasma tHcy levels in either study group. Conclusions 1) Plasma tHcy levels were not different in the diabetic group as compared to the control group. 2) In patients with type 2 diabetes age, GFR and the consumption of fruit and vegetables were strong and independent determinants of plasma tHcy levels.

Background and aim: Postprandial glycaemia and lipaemia are known risk factors for atherosclerosis in type 2 diabetes. Coagulation activation in the postprandial. state also contributes to acceleration of atherosclerosis. Nateglinide is effective in reducing postprandial glycaemia. Its effect on glycaemia may also be beneficial in postprandial lipaemia and coagulation. The aim of this study was to examine the potential effect of a single dose of nateglinide on postprandial triglyceridaemia, coagulation, and fibrinolysis in patients with type 2 diabetes. Methods and results: Ten subjects with type 2 diabetes, treated with diet alone were recruited in a crossover randomized study. In the morning, after a 12- to 14-h fast, each subject received a standard mixed meat (total energy 783 kcal), preceded by one tablet of 120 mg nateglinide or placebo. Venous blood samples were drawn prior to meat consumption and 6 h afterwards for the measurement of plasma glucose, insulin, and C-peptide, lipids, coagulation, and fibrinolysis factors. As expected, there was a significant reduction in postprandial glycaemia after nateglinide administration compared to placebo (P < 0.001). Plasma insulin levels were significantly higher after nateglinide than after placebo (P = 0.002). Nateglinide administration resulted in a lower overall postprandial reduction of tissue-plasminogen activator than placebo (-2.9 ± 1.3 vs. -8.3 ± 3.7 ng/ml h, P = 0.003). In addition, a significant reduction of postprandial plasminogen activator inhibitor-1 was observed in comparison with the baseline values after nateglinide (P = 0.001), although the overall response was not significantly different after nateglinide and placebo (P = 0.31). Plasma concentrations of C-peptide, lipids and the remaining coagulation parameters studied were not different between nateglinide and placebo. Conclusions: Acute nateglinide administration improves postprandial glycaemia and fibrinolytic activity in patients with type 2 diabetes. This combined effect, if confirmed by a long-treatment study, might reduce cardiovascular risk in type 2 diabetes. © 2005 Published by Elsevier Ltd. Nutrition Metabolism and Cardiovascular Diseases

AIMS To compare plasma adiponectin levels between healthy controls and patients with chronic renal failure and to examine for a relationship between plasma adiponectin levels and ischemic heart disease as well as aortic distensibility which is an early marker of atherosclerosis. METHODS We included 89 patients with CRF (45 on and 44 not on hemodialysis) and 70 controls in a cross-sectional study. Plasma adiponectin levels were measured by radioimmunoassay. Aortic distensibility was assessed by high-resolution ultrasonography. RESULTS Plasma adiponectin levels were significantly almost twice as high in patients with renal failure compared to controls (9.7 +/- 1.1 vs. 5.4 +/- 0.6 microg/ml, p < 0.0001). No significant differences were found between renal patients on hemodialysis and not on hemodialysis (p = 0.71). Multivariate linear regression analysis in the renal patient group demonstrated a significant negative relationship between plasma adiponectin levels and ischemic heart disease (p = 0.02). The same analysis in the control subjects group showed a significant, negative relationship between plasma adiponectin levels and body mass index (p = 0.02) and a highly significant positive relationship with the high density lipoprotein cholesterol (p < 0.0001). In the total study population, glomerular filtration rate was the only independent predictor of plasma adiponectin concentrations. Aortic distensibility was lower in renal patients than in controls at a high level of significance (p < 0.0001). However, no significant relationship could be found between plasma adiponectin and aortic distensibility in either the controls or the renal patients. CONCLUSIONS Plasma adiponectin levels are almost twice as high in patients with chronic renal failure in comparison with healthy controls, but not different between renal patients on and those not on hemodialysis. In addition, low plasma adiponectin levels are strongly associated with ischemic heart disease, but not with aortic distensibility in chronic renal failure.

Objective: To compare the nutritional habits among six Mediterranean countries and also with the various official recommendations and the ‘Mediterranean diet’ as originally described. Design: Cross-sectional study. Settings: Three centres in Greece, two in Italy and one in Algeria, Bulgaria, Egypt and Yugoslavia. Subjects: Randomly selected non-diabetic subjects from the general population, of age 35–60, not on diet for at least 3 months before the study. Interventions: A dietary questionnaire validated against the 3-Day Diet Diary was used. Demographic data were collected and anthropometrical measurements done. Results: All results were age adjusted. Energy intake varied in men, from 1825 kcal/day in Italy–Rome to 3322 kcal/day in Bulgaria and in women, from 1561 kcal/day in Italy–Rome to 2550 kcal/day in Algeria. Protein contribution (%) to the energy intake varied little, ranging from 13.4% in Greece to 18.5% in Italy–Rome, while fat ranged from 25.3% in Egypt to 40.2% in Bulgaria and carbohydrates from 41.5% in Bulgaria to 58.6% in Egypt. Fibre intake, g/1000 kcal, ranged from 6.8 in Bulgaria to 13.3 in Egypt and the ratio of plant to animal fat from 1.2 in Bulgaria to 2.8 in Greece. The proportion of subjects following the WHO and the Diabetes and Nutrition Study Group (DNSG) of the EASD recommendations for carbohydrates, fat and protein ranged from 4.2% in Bulgaria to 75.7% in Egypt. Comparison with the Mediterranean diet, as defined in the seven Country Study, showed significant differences especially for fruit, 123–377 vs 464 g/day of the Mediterranean diet, meat, 72–193 vs 35 g/day, cheese, 15–79 vs 13 g/day, bread, 126–367 vs 380 g/day. Conclusions: (a) Dietary habits of the ‘normal’ population vary greatly among the Mediterranean countries studied. (b) Egypt is closest to the DNSG recommendations. (c) Significant differences from the originally described Mediterranean diet are documented in most Mediterranean countries, showing a Westernization of the dietary habits.

Aim Experimental evidence suggests that osteocalcin is a key messenger that affects both adipocytes and insulin-producing β 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±4.9kg/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±3.1ng/mL vs. 7.3±4.0ng/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 1ng/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.

Purpose: To assess the frequency of retinopathy and vision loss in patients with insulin-dependent diabetes mellitus and their relations to potentially modifiable risk factors. Methods: The authors conducted a multicenter cross-sectional study of diabetic complications and their risk factors using standardized methods of assessment. The sample was comprised of 3250 insulin-dependent diabetic patients (1668 men, 1582 women) aged 15 to 60 years with mean (standard deviation) duration of diabetes of 14.7 (9.3) years from 31 European diabetes centers; 2991 of the patients were eligible for retinal photography. Visual acuity was measured using the Snellen chart. Retinopathy was evaluated by retinal photographs (two fields per eye) graded at a central facility. Glycated hemoglobin (HbA,c), cholesterol, triglyceride, fibrinogen, von Willebrand factor, and urinary albumin excretion rate were assessed at a single location. Results: Corrected visual acuity was greater than or equal to 1.0 in both eyes in 69.7% of patients and less than or equal to 0.1 in the best eye in 2.3%. Factors significantly related to vision loss were age, duration of diabetes, glycated hemoglobin (HbA 1c ), and level of retinopathy. Mild nonproliferative retinopathy was found in 25.8% of the patients, moderate-severe nonproliferative retinopathy in 9.8% of the patients, and proliferative retinopathy in 10.6% of the patients. After adjustment for age, duration of diabetes, HbA 1c , and albumin excretion rate, significant risk factors for moderate-severe nonproliferative retinopathy were blood pressure and triglyceride, and risk factors for proliferative retinopathy were triglyceride and fibrinogen. Conclusion: Vision loss is a common complication of patients with insulin-dependent diabetes, with diabetic retinopathy an important cause. Apart from poor glycemic control, several other potentially modifiable risk factors for retinopathy may be important, including elevated blood pressure, plasma triglyceride, and fibrinogen. In view of the possible barriers to the full implementation of strict glycemic control in this type of diabetes, additional strategies for the prevention and slowing of progression of retinopathy should be investigated, such as blood pressure and lipid lowering therapies.

The regulation of bcl-2 and fas (Apo-1/ CD95) gene product expression plays a significant role in lymphocyte proliferation, survival, and apoptosis. Dexamethasone (Dex) and the immunosuppressive agent cyclosporin-A (CsA) inhibit primary activation of lymphocytes by distinct, though overlapping mechanisms that trigger undefined signals and can induce or prevent apoptosis in lymphoid cells in vitro . Here we demonstrate that Dex and CsA, at concentrations that markedly inhibit phytohemagglutinin (PHA)-induced proliferation of normal human peripheral blood lymphocytes, suppress the activation-dependent expression of interleukin 2 (IL-2) and the α-chain IL-2 receptor in a dose-dependent fashion without affecting the inducible accumulation and kinetics of either bcl-2 or fas mRNAs. Similar results were obtained when PHA-stimulated lymphocytes were cultured in the presence of the CsA analogue FK-506 or rapamycin. Moreover, the inducible maximal expression of either bcl-2 or fas protein levels on 48-h PHA-activated lymphocytes was not changed in the presence of either Dex or CsA. These findings show that the cell activationinduced biosynthesis of bcl-2 and fas proteins is not affected by immunosuppressive agents, suggesting that the expression of IL-2 and both bcl-2 and fas genes is regulated through independent mechanisms.

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 . 5 3 3 , 𝑃 < 0 . 0 0 1 ). In multivariable analysis, 𝐸 / 𝐼 index was the strongest correlate of PWV (β-coefficient = −0.326, 𝑃 = 0 . 0 0 2 ). Cardiac parasympathetic function is a strong predictor of large arterial stiffness, in young T1D patients free of macrovascular and renal complications.

To examine differences in the spatial QRS-T angle in patients with Type 2 diabetes mellitus with and without cardiac autonomic neuropathy.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.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°, P0.001) 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, P0.001). 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.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.

Diabet. Med. 27, 459–465 (2010) Abstract 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.

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. 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.

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 ≥ 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. 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.

Background. Previous studies in different clinical settings have established heart rate variability (HRV) as a significant independent risk factor for higher mortality and cardiac death. The aim of this study was to examine the effect of chronic haemodialysis therapy on time- and frequencydomain parameters of HRV in diabetic and non-diabetic patients with chronic kidney disease (CKD). Methods. We studied 25 patients with stage 4 CKD and type 2 diabetes mellitus (CKD4+DM), 25 patients with stage 4 CKD without diabetes (CKD4), 25 patients with type 2 diabetes mellitus (DM) and 25 healthy subjects (HS). The study was performed in two phases. In the first phase, a 24-h Holter electrocardiographic (ECG) monitoring was performed in all subjects. The patients with stage 4 CKD were followed up until they progressed to stage 5, and in the second phase of the study, they underwent a 24-h Holter ECG monitoring after completion of 3months of conventional haemodialysis treatment. Results. In the first phase of the study, a reduction in cardiac sympathetic activity in CKD4 patients (significantly lower SDNN, SDANN/5 min, SD and VLF vs. HS) and worse autonomic function in CKD4+DMpatients (significantly lower SDNN, SDANN/5 min, SD, VLFand LF/HF) vs. HS,DM and CKD4 was observed. After 3 months of dialysis therapy, the patients with CKD+DM showed a significant improvement only in the time-domain parameter SDANN/5 min, while the time-domain parameters SDNN, SDANN/5 min and SD were improved in CKD patients without diabetes. Frequency-domain parameters of HRV remained unchanged in both groups. Conclusions. CKD is associated with worse cardiac autonomic function. Haemodialysis therapy for 3 months improves some indices of HRV, and this effect is more pronounced in non-diabetic subjects. Our findings suggest that the improvement of HRVafter the initiation of chronic dialysis therapy can ameliorate clinical outcomes and survival in patients with end-stage renal disease. © The Author 2010.

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.

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).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).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).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.

Background and Aims: Although whole-body insulin resistance in obesity is established, information on insulin action in peripheral tissues, especially adipose tissue (AD), is limited. This study was undertaken in morbid obesity to investigate insulin action on glucose disposal in AD and muscle (M). Subjects and Methods: A meal was given to 30 obese (age 34 ± 1 yr, body mass index 47 ± 1 kg/m2) and 10 nonobese women (age 39 ± 4 yr, body mass index 23 ± 1 kg/m2). Samples for glucose and insulin were taken for 360 min from veins draining the abdominal subcutaneous AD and forearm muscles and from the radial artery. Blood flow (BF) was measured in AD (133Xe) and M (plethysmography). Results: The area under the curve divided by time (AUC0-360min/360min) in obese vs. nonobese was as follows: 1) arterial glucose was similar 6.04 ± 0.2 vs. 5.67 ± 0.1 mM), but insulin was increased (65.5 ± 6.6 vs. 28.7 ± 1.7 mU/liter, P = 0.0004); 2) BF was decreased (3 ± 0.2 vs. 4.4 ± 0.3 ml/min per 100 ml tissue in M, P = 0.002 and 1.8 ± 0.1 vs. 3.7 ± 0.3 ml/min per 100 ml tissue in AD, P < 0.0001); 3) glucose uptake was decreased (0.9 ± 0.1 vs. 2.3 ± 0.4 μmol/min per 100 ml tissue in M, P = 0.002 and 0.45 ± 0.1 vs. 1.1 ± 0.17 μmol/min per 100 ml tissue in AD, P = 0.01); 4) fractional glucose extraction was decreased in M (5 ± 1 vs. 9 ± 1%, P = 0.03), but was similar in AD (3 ± 1 vs. 3.6 ± 1.4%); 5) glucose uptake (per total fat mass) was increased (0.275 ± 0.04 vs. 0.12 ± 0.02 mmol/min, P = 0.027). Conclusion: In morbid obesity, the sensitivity of glucose metabolism to insulin is impaired in M, due to defects in insulin-stimulated glucose use and decreased BF, and in AD, at least in part, due to decreased BF. However, increased total fat mass provides a sink for the excess of glucose and compensates for insulin resistance. Copyright © 2009 by The Endocrine Society.

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 3 g/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 3.23U/ml versus an increase of 3.77U/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. © 2009 Elsevier Masson SAS. All rights reserved.

Hintergrund und Fragestellung: Die Dyslipidamie ist bei Patienten mit Typ-2-Diabetes mellitus (T2DM) als einer von den wichstigsten Faktoren kardiovaskulares Risikos anerkannt und ist besonders eng mit Endothelysfunktion and vermehrten Steifheit der Arterienwand assoziert. Die Behandlung mit Statinen stellt einen wichtigen Baustein in der Therapie der Dyslipidamie in Patienten mit T2DM zur Reduzierung der kardiovaskularen Ereignisse. Pulswellengeschwindigkeit (pulse wave velocity, PWV), deren Zunahme bei Patienten mit T2DM zu beobachten ist, wiederspiegelt der Verlust der Elastizitatseigenschaften der Arterien und dient als Prognosefaktor fur Kardiovaskulare Erkrankungen. Bislang ist wenig bekannt uber die Wirkungen einer Behandlung mit Atorvastatin auf die Arterienwandelastizitat. Daher haben wir in der vorliegenden Arbeit den Einfluss einer Behandlung mit Atorvastatin auf die PWV bei Patienten mit T2DM untersucht. Patienten und Methodik: Insgesamt wurden 33 Patienten (9Manner und 24 Frauen) mit T2DM und Dyslipidamie untersucht (durchschnittliches Alter 60.2±8.9 Jahre; Diabetesdauer 6.8±6.0 Jahre). Alle Patienten unterlagen einer vollstandigen klinischen und laboratorischen Untersuchung. Eingeschlossen wurden Patienten 40–75 Jahre alt, mit LDL-C ≥100mg/dl und ohne offensichtliche makrovaskulare Erkrankungen. Patienten wurden mit Atorvastatin fur 12 Monate behandelt (10mg taglich). Zur Eingangsuntersuchung, nach 3, nach 6 und nach 12 Monate wurde die Karotis-Femoralis PWV (cfPWV) und die Karotis-Radialis PWV (crPWV) gemessen. Alle Analysen wurden mit dem statistischen Packet SPSS durchgefuhrt. Ergebnisse: Es gab eine Verbesserung der Dyslipidamie im Sinne einer statistisch signifikant Senkung von LDL-C 3, 6 und 12 Monate nach Atorvastatin Behandlung (35%, 38.3% und 39.26% Senkung des LDL-C 3, 6 und 12 Monate nach Atorvastatin entsprechend, p