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Hyperglycemia significantly contributes to complications in patients with diabetes mellitus. While lifestyle interventions remain cornerstones of disease prevention and treatment, most patients with type 2 diabetes will eventually require pharmacotherapy for glycemic control. The definition of individual targets regarding optimal therapeutic efficacy and safety as well as cardiovascular effects is of great importance. In this guideline we present the most current evidence-based best clinical practice data for healthcare professionals., (© 2023. The Author(s).)

Hyper- and dyslipidemia contribute to cardiovascular morbidity and mortality in diabetic patients. Pharmacological therapy to lower LDL cholesterol has convincingly shown to reduce cardiovascular risk in diabetic patients. The present article represents the recommendations of the Austrian Diabetes Association for the use of lipid-lowering drugs in diabetic patients according to current scientific evidence., (© 2023. The Author(s).)

Background: Obesity and its health consequences will dominate health care systems in many countries during the next decades. However, the body mass index (BMI) optimum in relation to all-cause mortality is still a matter of debate., Material and Methods: Data of the Vorarlberg Health Monitoring & Prevention Program (VHM&PP, 1985-2005) and data provided by the Main Association of Austrian Social Security Institutions (MAASSI, 2005-2015) were analyzed. Information was available on age, sex, smoking status, measured height and weight, and mortality. Generalized additive models were used to model mortality as a function of BMI, calendar time, age, and follow-up., Results: In MAASSI (N = 282,216, 46.0% men), men and women were on average 2.7 years older than in VHM&PP (N = 185,361, 46.1% men). Average BMI was slightly higher in men (26.1 vs 25.7 kg/m 2 ) but not in women (24.6 vs 24.7 kg/m 2 ). We found an interactive effect of age and follow-up on the BMI optimum. Over age 35 years in men and 55 years in women, the BMI optimum decreased with length of follow-up. While keeping covariates fixed, BMI optimum increased slightly between 1985 and 2015 in men and women, 24.9 (95% CI, 23.9-25.9) to 26.4 (95% CI, 25.3-27.3), and 22.4 (95% CI, 21.7-23.1) to 23.3 (95% CI, 22.6-24.5) kg/m 2 , respectively., Conclusion: Age and length of follow-up have a pronounced effect on the BMI associated with the lowest all-cause mortality. After controlling for age and length of follow-up, the BMI optimum increased slightly over 30 years in this large study sample.

The availability of efficient lipid-lowering drugs has substantially reduced the incidence and mortality for cardiovascular disease (CVD). Despite that, CVD still represents a major cause of death and disability; efforts are thus required to prevent this disease, since reducing the established CV risk factors may slow or prevent the onset of cardiovascular events. Current guidelines recommend a healthier lifestyle for all CV risk categories, as it may have a beneficial impact on several risk factors; in individuals with a low-to-moderate hypercholesterolemia, which are not eligible for a pharmacological approach and are not far from the cholesterol target recommended for their risk category, functional foods or nutraceuticals may be considered as supplement to reduce their CV risk status. Of note, counseling and lifestyle intervention in people at moderate CV risk represents a major issue for both preventing a further risk increase and reducing the need for drugs. Studies on general populations have clearly indicated that lifestyle interventions translate into a clinical benefit, with reduction of the incidence of myocardial infarction and the risk of developing type 2 diabetes., Competing Interests: Declaration of competing interest B.F. has received lecture fees from MEDA pharmaceuticals; C.J. and A.P. report no conflicts of interest; L.T. is Company consultant for Abbott, Amgen, Bayer, MSD, Mylan, Sanofi, and has received honorarium as speaker from Abbott, Actelion, Amgen, Astra, Bayer, Daiichi Sankyo MSD, Mylan, Novartis, Novo Nordisk, Sanofi, Servier, Pfizer, Recordati; M.P. reports no conflicts of interest; ALC reports grants from Amgen, Sanofi, Regeneron personal fees from Merck, Sanofi, Regeneron, AstraZeneca, Amgen, Novartis, outside the submitted work., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Elevated blood pressure remains a major cause of cardiovascular disease, disability, and premature death in Austria, with suboptimal rates of detection, treatment and control also in recent years. Management of hypertension is a common challenge for physicians with different spezializations. In an attempt to standardize diagnostic and therapeutic strategies and, ultimately, to increase the rate of patients with controlled blood pressure and to decrease the burden of cardiovascular disease, 13 Austrian medical societies reviewed the evidence regarding prevention, detection, workup, treatment and consequences of high blood pressure in general and in various clinical scenarios. The result is presented as the first national consensus on blood pressure. The authors and societies involved are convinced that a joint national effort is needed to decrease hypertension-related morbidity and mortality in our country.

In critical illness hyperglycemia is associated with increased mortality. Based on the currently available evidence, an intravenous insulin therapy should be initiated when blood glucose is above 180 mg/dl. After initiation of insulin therapy blood glucose should be maintained between 140 and 180 mg/dl.

Hyper- and dyslipidemia contribute to cardiovascular morbidity and mortality in diabetic patients. Pharmacological therapy to lower LDL cholesterol has convincingly shown to reduce cardiovascular risk in diabetic patients. The present article represents the recommendations of the Austrian Diabetes Association for the use of lipid-lowering drugs in diabetic patients according to current scientific evidence.

Hyperglycemia significantly contributes to complications in patients with diabetes mellitus. While lifestyle interventions remain cornerstones of disease prevention and treatment, most patients with type 2 diabetes will eventually require pharmacotherapy for glycemic control. The definition of individual targets regarding optimal therapeutic efficacy and safety as well as cardiovascular effects is of great importance. In this guideline we present the most current evidence-based best clinical practice data for healthcare professionals.

The present article is a recommendation of the Austrian Diabetes Association for the practical use of insulin in type 2 diabetes, including the various insulin regimens.

Background: The wearable cardioverter-defibrillator is a treatment option for patients at temporarily high risk of sudden cardiac death or in whom implantation of a cardioverter-defibrillator is temporarily not possible., Objectives: The aim of this study was to provide real-world data on patients receiving this therapy in a nurse-based wearable cardioverter-defibrillator training programme., Methods: A registry including all patients prescribed with a wearable cardioverter-defibrillator in Austria between 2010 and 2016. Overall, 448 patients received a wearable cardioverter-defibrillator in 48 centres. Patients received structured nurse-based wearable cardioverter-defibrillator educational initial training followed by remote monitoring., Results: Main indications were: severe non-ischaemic cardiomyopathy (21%); recent myocardial infarction and percutaneous coronary intervention (20%); and stable coronary artery disease with percutaneous coronary intervention/coronary artery bypass grafting (14%). Eleven patients (2.5%) received 22 appropriate wearable cardioverter-defibrillator shocks. Two patients (0.4%) received three inappropriate shocks. The risk of sudden cardiac death varied between different aetiologies. Eight out of 11 (73%) patients received their first wearable cardioverter-defibrillator shock within 30 days. The main reasons for termination of the wearable cardioverter-defibrillator therapy were implantable cardioverter-defibrillator implantation (55.5%) and improvement of left ventricular ejection fraction to more than 35% (33%)., Conclusion: The wearable cardioverter-defibrillator is an effective and safe treatment option in patients at either transiently elevated risk of ventricular tachycardia/ventricular fibrillation or mandated postponed implantable cardioverter-defibrillator implantation, with a 2.5% shock rate over a median 54 days wearable cardioverter-defibrillator treatment period. However, both the wearable cardioverter-defibrillator shock rate and implantable cardioverter-defibrillator implantation rate vary widely depending on the wearable cardioverter-defibrillator indication. Nurse-based wearable cardioverter-defibrillator training is associated with high patient adherence, with a median wearing duration per day of 23.5 (1-24) hours.

Background: Obesity is suggested to underlie development of other metabolic aberrations, but longitudinal relationships between metabolic factors at various ages has not been studied in detail., Methods: Data from 27,379 men and 32,275 women with in total 122,940 health examinations in the Västerbotten Intervention Project, Sweden and the Vorarlberg Health Monitoring and Prevention Programme, Austria were used to investigate body mass index (BMI), mid-blood pressure, and fasting levels of glucose, triglycerides, and total cholesterol at baseline in relation to 10-year changes of these factors and weight. We included paired examinations performed 10±2 years apart and used them for longitudinal analysis with linear regression of changes between the ages 30 and 40, 40 and 50, or 50 and 60 years., Results: Higher levels of BMI were associated with increases in glucose and mid-blood pressure as well as triglycerides levels, and, to a lesser extent, decreases in cholesterol levels. For instance, per 5 kg/m2 higher BMI at age 40, glucose at age 50 increased by 0.24 mmol/l (95%CI: 0.22-0.26) and mid-blood pressure increased by 1.54 mm Hg (95%CI: 1.35-1.74). The strongest association observed was between BMI at age 30 and mid-blood pressure, which was 2.12 mm Hg (95% CI: 1.79-2.45) increase over ten years per 5 kg/m2 higher BMI level. This association was observed at an age when blood pressure levels on average remained stable. Other associations than those with BMI at baseline were much weaker. However, triglyceride levels were associated with future glucose changes among individuals with elevated BMI, particularly in the two older age groups., Conclusion: BMI was most indicative of long-term changes in metabolic factors, and the strongest impact was observed for increases in blood pressure between 30 and 40 years of age. Our study supports that lifestyle interventions preventing metabolic aberrations should focus on avoiding weight increases., Competing Interests: The authors have declared that no competing interests exist.

Previous literature indicates that pre-diagnostic diabetes and blood glucose levels are inversely related to glioma risk. To replicate these findings and determine whether they could be attributed to excess glucose consumption by the preclinical tumour, we used data from the Apolipoprotein MOrtality RISk (AMORIS) (n = 528,580) and the Metabolic syndrome and Cancer project (Me-Can) cohorts (n = 269,365). We identified individuals who were followed for a maximum of 15 years after their first blood glucose test until glioma diagnosis, death, emigration or the end of follow-up. Hazard ratios (HRs), 95% confidence intervals (CIs) and their interactions with time were estimated using Cox time-dependent regression. As expected, pre-diagnostic blood glucose levels were inversely related to glioma risk (AMORIS, P trend  = 0.002; Me-Can, P trend  = 0.04) and pre-diagnostic diabetes (AMORIS, HR = 0.30, 95% CI 0.17 to 0.53). During the year before diagnosis, blood glucose was inversely associated with glioma in the AMORIS (HR = 0.78, 95% CI 0.66 to 0.93) but not the Me-Can cohort (HR = 0.99, 95% CI 0.63 to 1.56). This AMORIS result is consistent with our hypothesis that excess glucose consumption by the preclinical tumour accounts for the inverse association between blood glucose and glioma. We discuss additional hypothetical mechanisms that may explain our paradoxical findings.

Several studies have indicated weakly increased risk for kidney cancer among occupational groups exposed to gasoline vapors, engine exhaust, polycyclic aromatic hydrocarbons and other air pollutants, although not consistently. It was the aim to investigate possible associations between outdoor air pollution at the residence and the incidence of kidney parenchyma cancer in the general population. We used data from 14 European cohorts from the ESCAPE study. We geocoded and assessed air pollution concentrations at baseline addresses by land-use regression models for particulate matter (PM 10 , PM 2.5 , PM coarse , PM 2.5 absorbance (soot)) and nitrogen oxides (NO 2 , NO x ), and collected data on traffic. We used Cox regression models with adjustment for potential confounders for cohort-specific analyses and random effects models for meta-analyses to calculate summary hazard ratios (HRs). The 289,002 cohort members contributed 4,111,908 person-years at risk. During follow-up (mean 14.2 years) 697 incident cancers of the kidney parenchyma were diagnosed. The meta-analyses showed higher HRs in association with higher PM concentration, e.g. HR = 1.57 (95%CI: 0.81-3.01) per 5 μg/m 3 PM 2.5 and HR = 1.36 (95%CI: 0.84-2.19) per 10 -5 m -1 PM 2.5 absorbance, albeit never statistically significant. The HRs in association with nitrogen oxides and traffic density on the nearest street were slightly above one. Sensitivity analyses among participants who did not change residence during follow-up showed stronger associations, but none were statistically significant. Our study provides suggestive evidence that exposure to outdoor PM at the residence may be associated with higher risk for kidney parenchyma cancer; the results should be interpreted cautiously as associations may be due to chance., (© 2016 UICC.)

Hyperglycemia significantly contributes to micro- and macrovascular complications in patients with diabetes mellitus. While lifestyle interventions remain cornerstones of disease prevention and treatment, most patients with type 2 diabetes will eventually require pharmacotherapy for glycemic control. The definition of individual targets regarding optimal therapeutic efficacy and safety is of great importance. In this guideline we present the most current evidence-based best clinical practice data for healthcare professionals.

In 2010, eight Austrian medical societies proposed a joint position statement on the management of metabolic lipid disorders for the prevention of vascular complications. An updated and extended version of these recommendations according to the current literature is presented, referring to the primary and secondary prevention of vascular complications in adults, taking into consideration the guidelines of other societies. The "Austrian Lipid Consensus - 2016 update" provides guidance for individualized risk stratification and respective therapeutic targets, and discusses the evidence for reducing vascular endpoints with available lipid-lowering therapies. Furthermore, specific management in key patient groups is outlined, including subjects presenting with coronary, cerebrovascular, and/or peripheral atherosclerosis; diabetes mellitus and/or metabolic syndrome; nephropathy; and familial hypercholesterolemia.

In critical illness hyperglycemia is associated with increased mortality. Based on the currently available evidence, an intravenous insulin therapy should be initiated when blood glucose is above 180 mg/dl. After initiation of insulin therapy blood glucose should be maintained between 140 and 180 mg/dl.

Hyper- and dyslipidemia contribute to cardiovascular morbidity and mortality in diabetic patients. Pharmacological therapy to lower LDL cholesterol has convincingly shown to reduce cardiovascular risk in diabetic patients. The present article represents the recommendations of the Austrian Diabetes Association for the use of lipid-lowering drugs in diabetic patients according to current scientific evidence.

After the publication of the new guidelines of the European Society of Cardiology and the European Atherosclerosis Society for the prevention and treatment of dyslipidemias (Eur Heart J 32:1769-1818, 2011; Eur Heart J 33:1635-1701, 2012), a group of authors has recently published on behalf of the American Heart Association and the American College of Cardiology guidelines on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk (Circulation 2013). These new guidelines are supposed to replace the until now widely accepted, at least in the USA, recommendations of the National Cholesterol Education Program Adult Treatment Panel III from the years 2002 (Circulation 106:3143-3421, 2002) and 2004 (Circulation 110:227-39, 2004). Furthermore, they claim to be based mainly on hard evidence derived from the interpretation of results of prospective randomized controlled trials. This Joint Position Statement of the Society for the Prevention of Cardiovascular Diseases e.V. (D.A.CH), the Austrian Atherosclerosis Society and the Working Group on Lipids and Atherosclerosis (AGLA) of the Swiss Society of Cardiology concludes that the use of individualized prevention strategies based on specific indications and LDL cholesterol target concentrations, a strategy whose worth has been widely proven and accepted for more than a decade in Europe, should not be given up.

Unlabelled: Low density lipoprotein (LDL-C) levels determine the cardiovascular risk. Previous studies indicated an LDL-C target attainment of around 50%, but no Austrian wide analysis on results for the federal states was available. We therefore sought to detect potential differences., Design: Open-label, non-interventional, longitudinal study, registered: www.clinicaltrials.gov NCT 01381679. In all, 746 statin treated patients not at LDL-C goal received intensified therapy for 12 months. The sample was split into nine subgroups, representing the federal states of Austria.We detected an east-west gradient for baseline LDL-C. Individual target values were achieved by 37.2% (range: 26.1-57.7%). After 12 months, LDL-C < 70 mg/l was achieved by 13.5% (5.9-38.5%). Univariate ANCOVA retrieved significant differences within the states (Upper Austria and Salzburg, p = 0.001 and p = 0.0015, respectively). Furthermore, the capacity of intensified lipid lowering therapy applied in practice was as high as -42% as compared to previous standard therapy (additional LDL-C reduction after switch from baseline therapy in Vorarlberg).

Hyperglycemia frequently occurs in critically ill patients resulting in major complications like an increased cardiovascular event rate or an increased incidence of infections. Based on the currently available evidence insulin therapy should be initiated in patients with blood glucose levels above 180 mg/dl. Blood glucose values should be maintained between 180 and 140 mg/dl. In surgical patients lower target values ranging from 140 to 110 mg/dl should be applied. After transition to the general ward a complete workup of diabetes mellitus should be performed.

The primary defect underlying abnormalities in lipoprotein transport in type 2 diabetes is insulin resistance, which leads to increased triglycerides in the fasting and postprandial states, preponderance of small, dense LDL and low concentrations of dysfunctional HDL. Concentrations of LDL-cholesterol (LDL-C) are most often not remarkably abnormal. Based on this lipoprotein profile, it seems somewhat counterintuitive to prioritize LDL-C lowering in type 2 diabetes. Nevertheless, ≈20 years of statins trials in >18,000 diabetic patients have unequivocally established this priority. Patients with type 2 diabetes without manifest atherosclerosis should reach an LDL-C goal <100 mg/dl or a Non-HDLcholesterol (NHDL-C) goal <130 mg/dl. If their baseline LDL-C is already between 70 and 100 mg/dl LDL-C should be lowered by 30 to 40%. Thus, the majority of these patients can be managed successfully with monotherapy using standard-intensity statins (e.g. simvastatin 40 mg/d). Patients with type 2 diabetes with manifest CHD should reach an LDL-C goal <70 mg/dl or an NHDL-C goal <100 mg/dl. A sizable fraction of these patients will require high-intensity statins (e.g. atorvastatin 80 mg/d or rosuvastatin 20-40 mg/d). If LDL-C goals are still not reached or high-intensity statins are not tolerated, combination of statins with ezetimibe is advisable. In patients with persistent pronounced dyslipidemic features, i.e. high TG/low HDL-C despite maximal lifestyle intervention and optimized statin dosage, pioglitazone should be incorporated in the antidiabetic management and combinations of statins with either niacin or fenofibrate should be considered. However, it has to be recognized that evidence supporting HDL-raising therapy is currently still much weaker than evidence supporting LDL lowering with statins.

Background: A hospital-based screening project (HSP) in Austria found 47% of high-risk patients (LDL-C < 100 mg/dl) and 24% of very high-risk patients (LDL-C < 70 mg/dl) at goal. Separate data for the sexes were not reported. We analyze whether LDL-C goal attainment in patients with manifest atherosclerosis and/or diabetes on stable lipid-lowering treatment differs between private practice and hospital and between men and women., Patients and Methods: From September to November 2007, 49 Austrian centers (36 private practice, 13 hospitals) documented vascular morbidity, lipid levels, and lipid lowering treatment in patients with high risk (atherosclerosis or diabetes, n = 978) and very high risk (coronary heart disease and diabetes or acute coronary syndrome, n = 322)., Results: 75% and 25% of the 1300 patients were high and very high risk, respectively. LDL-C goals of < 100 and < 70 mg/dl, respectively, were attained by 45.4% and 26.4% of patients (p < 0.001). A similar percentage of patients with very high risk was found in men and women (26.4% vs. 22.9%, NS) and goal attainment was not influenced by sex (high risk: 47.2% (m) vs. 43.8% (w), NS and very high risk: 29.1% (m) vs. 22.4% (w), NS). In patients with high risk, 41.6% treated in private practice vs. 57.9% treated in the hospital were at goal (p < 0.001). In patients with very high risk, 15.9% treated in private practice vs. 45.2% treated in the hospital were at goal (p < 0.001). Lower goal-attainment in private practice occurred despite significantly more intensive lipid intervention and probably reflects higher baseline LDL-C. LDL-C > 100 mg/dl leads to a more aggressive lipid lowering in approx. 70% of patients, irrespective of whether they are treated in private practice or in the hospital. LDL-C between 70 and 100 mg/dl, however, leads to a more aggressive lipid lowering in < 5% of patients, irrespective of whether they are high or very high risk., Conclusion: As observed in EUROASPIRE III for other European countries, there is substantial potential for improvement in lipid control in Austrian cardiovascular high-risk patients, irrespective of whether they are treated in private practice or in the hospital.

BACKGROUND: The purpose of the investigation presented here was to study the effects of insulin therapy in type 2 diabetes mellitus (type 2 DM) not only on glycemic control but also on other components of the metabolic syndrome, including lipid metabolism, blood pressure, and body weight. METHODS: Twelve patients with type 2 DM were studied before and after replacement of sulphonylurea treatment with insulin for 4 months. RESULTS: Insulin therapy resulted in a significant decrease in fasting glucose levels by 26%; glycated hemoglobin decreased by 17% and fructosamine values by 19%. With insulin treatment, fasting plasma triglyceride levels decreased by 28% and total HDL cholesterol and HDL(3) cholesterol increased by 17 and 11%, respectively. Low-density lipoprotein (LDL) cholesterol showed no significant change. The magnitude of postprandial lipemia after ingestion of a standard fatty meal decreased by 38%. Insulin treatment was also accompanied by a 21% increase in lipoprotein lipase (LPL) activity in postheparin plasma and by a 20% increase in cholesteryl ester transfer protein (CETP) activity. Hepatic lipase activity was not changed significantly with insulin. Mean BMI decreased from 28.5+/-4.2 to 28.0+/-3.1 kg/m(2) (P=0.02), which is in keeping with the finding that peripheral insulin levels did not increase and which can be explained by the fact that the insulin regimen was combined with dietary counseling. Accordingly, blood pressure showed no significant change. CONCLUSION: Our study demonstrates that judicious replacement of sulfonylurea treatment with insulin therapy, together with dietary counseling, can result in a simultaneous improvement in the major stigmata of the metabolic syndrome, i.e. a significant improvement in glycemic control and lipid metabolism without unfavorable effects on body weight and blood pressure.

To study possible mechanisms for the suggested protective effect of hormone-replacement therapy (HRT) with respect to cardiovascular disease we investigated lipoprotein parameters, mass and activity of lipoprotein-metabolizing enzymes, magnitude of postprandial lipemia, and vascular endothelial function in 13 postmenopausal women. All patients were examined before and 3 months after implementation of HRT with estrogen alone (group A, n = 6) or estrogen plus gestagen (group B, n = 7). HRT (groups A and B) resulted in enhanced total transfer of cholesteryl ester (CE) from high-density lipoprotein (HDL) to apolipoprotein B (apoB)-containing lipoproteins (56% +/- 11.45% v 50.82% +/- 13.68%, P <.05) and increased apoA-I plasma concentration (171 +/- 30 v 147 +/- 22 mg/dL, P <.05). Fasting triglycerides (TG) were increased (134 +/- 40 v 115 +/- 39 mg/dL, P <.05). In group A patients the magnitude of postprandial lipemia increased significantly (1,737 +/- 756 v 1,475 +/- 930 mg TG/dL plasma/8 h, P <.05) without any change in lipoprotein lipase (LPL) activity, but with a concomitant decrease in low-density lipoprotein (LDL) size. In both groups flow-mediated dilation (FMD) reflecting vascular endothelial function was not influenced, suggesting that HRT may not directly affect vascular function but rather alters lipoprotein metabolism. The increase of apoA-I was not accompanied by an equivalent rise of HDL cholesterol. Based on the present data this finding can be readily explained by an increase in CE transfer from HDL to TG-rich lipoproteins, which is not due to increased cholesteryl ester transfer protein (CETP) plasma levels, but rather reflects an increase in fasting and postprandial TG. In conclusion, the net effect of accelerated CE transfer due to HRT depends on the balance of proatherogenic aspects, like the generation of small dense LDL, and antiatherogenic aspects, like the stimulation of reverse cholesterol transport., (Copyright 2002, Elsevier Science (USA). All rights reserved.)

Phospholipid transfer protein (PLTP) plays an important role in plasma lipoprotein metabolism. However, PLTP is expressed in a wide range of tissues suggesting additional local functions. To analyze the tissue distribution of PLTP in an animal with high-level expression of the structurally and functionally related CETP, we have cloned the full-length cDNA of rabbit PLTP (1,796 bp). Rabbit PLTP cDNA shows high homology to human, murine, and porcine PLTP cDNA, averaging 86.1%, 80.4%, and 86.1%, respectively. Interestingly, the C-terminus contains a unique seven amino acid insertion not found in previously characterized mammalian PLTPs. In clear contradistinction to human PLTP, rabbit PLTP mRNA was prominent in brain. In situ hybridization studies revealed specific, high-level synthesis of PLTP mRNA in choroid plexus and ependyma, the organs responsible for production of cerebrospinal fluid. Consistent with these findings, PLTP activity in cerebrospinal fluid amounted to 23% +/- 3% of that in rabbit plasma. In contrast, neither CETP mRNA nor CETP activity were detectable in rabbit brain.A role of PLTP in the central nervous system could involve some of its actions previously established in vitro, like proteolysis of apolipoproteins, and be physiologically relevant for neurodegenerative disorders such as Alzheimer's disease.

Endothelial dysfunction is an early marker of atherosclerosis occurring in patients with type 2 diabetes mellitus. Endothelium-dependent dilation (EDD) has been shown to improve by combined therapy of insulin and metformin. Studies on endothelium-independent vasodilatory capacity, however, have had controversial results. We sought to investigate the vascular reactivity--EDD and endothelium-independent dilation--and their changes induced by the addition of insulin therapy to patients with type 2 diabetes mellitus pretreated with diet and oral hypoglycemic drugs. We therefore performed vascular studies in 21 poorly controlled type 2 diabetic patients and 11 nondiabetic control subjects by using high resolution ultrasound of the brachial artery. After 3 months of additional insulin therapy, vascular and laboratory measurements including C-reactive protein and parameters of glucose and lipoprotein metabolism were repeated. At baseline, EDD was significantly impaired in diabetic patients compared with controls (2.7 +/- 2.2% vs 7.0 +/- 1.8%, p <0.001), whereas endothelium-independent dilation was normal in both groups. After insulin therapy, EDD increased from 2.7 +/- 2.2% to 5.0 +/- 2.8% (p <0.001) in diabetic patients. All other vascular parameters did not change over the treatment period. The absolute change in EDD showed a significant negative correlation with the change in hemoglobin A(1c) (r = -0.67, p <0.001) and with fasting blood glucose (r = -0.84, p <0.001) levels. In contrast, there was no correlation between EDD and the observed changes in lipid and C-reactive protein levels. Our findings demonstrate that insulin therapy has beneficial effects on vascular function, resulting in enhanced EDD, most probably due to an improved glycemic control as the underlying mechanism.