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HEART2D was a multinational, randomized, controlled trial designed to compare the effects of prandial insulin versus basal insulin on risk for subsequent cardiovascular (CV) outcomes in patients with type 2 diabetes (T2D) after acute myocardial infarction (MI). Trial design was based on the hypothesis that 2.5 mmol/L postprandial blood glucose (BG) difference between groups would result in risk reduction of 19 to 23% over the planned follow up period (18-36 mo) in the group with lower postprandial BG. One thousand one hundred and fifteen (1115) patients were randomized [prandial strategy (N = 557), basal strategy (N = 558)]. HEART2D was stopped after futility rule implementation at the fourth interim analysis. The risk of a first combined adjudicated CV events in the prandial group (N = 174, 31.2%) and basal (N = 181, 32.4%) groups was similar (HR = 0.98; 95% CI [0.8, 1.21]). The results of HEART2D left the question of the role of postprandial hyperglycemia in diabetic CV disease unanswered. Here, we discuss possible reasons for this outcome, including characteristics of daily BG profiles in the two treatment groups, event rate, risk factors other than standard CV risk factors and glycemic variables. The main reasons for this outcome of HEART2D study could be smaller than expected on-study differences between the study groups in postprandial hyperglycemia, and low event rate. Further trials with larger patient populations and improved designs, focusing also on diabetic patients with lower cardiovascular risk and lower baseline HbA(1c) levels are needed in order to shed more light on this important clinical problem.

It is well known that cardiovascular alterations are the principal causes of mortality in patients with diabetes. Premature and accelerated atherosclerosis cannot be the sole cause of diabetic heart disease because functional disorders develop both in experimental and in clinical diabetes before the onset of the detectable morphological changes of the vessel wall. Namely, altered adrenergic responses and prostaglandin metabolism and diminished vasodilatory ability can be seen in diabetic vessels. This leads to enhanced vasoconstriction, which – combined with increased sympathetic activity – may induce myocardial edema and an increase in myocardial stiffness, resulting in diminished heart function. Increased myocardial stiffness due to myocardial dehydration caused by hyperglycemic hyperosmolality can also result in impaired heart function. Thus, myocardial water content plays a key role in the development of diabetic heart dysfunction. Disturbances in the myocardial energy metabolism may also contribute to the diminished cardiac performance in the diabetic state. Some antidiabetic agents may also have deleterious cardiovascular effects. Whether the functional abnormalities observed in the reviewed studies lead to clinically manifest heart disease in diabetes may depend on the superimposition of the classical cardiovascular risk factors. Thus, adequate control of carbohydrate and lipid metabolism and the possible concomitant hypertension may prevent the further impairment of heart function and the development of overt heart disease.

Aim The objective of this observational study was to assess the status of glycemic control and associated patient-reported outcomes in ambulatory Hungarian patients with type 2 diabetes mellitus (T2DM) who were prescribed either a sulfonylurea (SU) or a thiazolidinedione (TZD) in addition to the prior metformin (MF) monotherapy. Methods Type 2 diabetics aged ≥ 30 years and who had added an SU or TZD to previous MF monotherapy at least 1 year prior to the visit date were identified during January 2006 to March 2007. Information on HbA1c (A1C), medication use and co-morbid conditions was extracted from the medical record up to 6 months prior to the addition of SU or TZD to MF (baseline), and a minimum of one year after the initiation of either SU or TZD. Glycemic control (A1C < 6.5%) was assessed using the last available A1C value in the medical record. Self-reported hypoglycemia, health-related quality of life (HRQoL) and treatment satisfaction were also assessed. Results A total of 414 patients (82% SU+MF and 18% TZD+MF) with a mean age of 60.5 years (SD = 9.4 years) participated in the study. About 27% of patients reported hypoglycemic episodes, with about one-third reporting episodes that resulted into interruption of activities or required medical/non-medical assistance. Three quarters of patients were not at glycemic goal and BMI was the only factor significantly associated with failure to have an A1C level < 6.5%. Patients' HRQoL was significantly associated with self-reported hypoglycemic episodes (p = 0.017), and duration of diabetes (p = 0.045). Conclusion Nearly 75% of patients were not at A1C goal of < 6.5% despite using two oral anti-hyperglycemic medications. Approximately 9% of patients reporting hypoglycemia required some kind of medical/non-medical assistance. Greater BMI at baseline was associated with an A1C level ≥ 6.5%. Finally, self- reports of hypoglycemia and duration of diabetes were associated with low HRQoL.

QT interval alterations were measured in 41 non-insulin-dependent (type 2) diabetic patients and 14 age- and sex-matched control subjects. Cardiac autonomic neuropathy (CAN) was assessed by noninvasive tests (deep breathing, Valsalva maneuver and lying-to-standing) and diabetics were divided into three groups according to the results of these tests: diabetics with definitive (n = 14), early (n = 13) and without (n = 14) CAN. The corrected values of QT intervals (QTc) at rest were significantly longer in diabetics with definitive (447 +/- 5 ms; p less than 0.001), early (426 +/- 5 ms; p less than 0.05) and without (424 +/- 5 ms; p less than 0.05) CAN than in controls (407 +/- 5 ms). Moreover, QTc intervals at rest were significantly (p less than 0.01) longer in diabetics with definitive CAN than in diabetics with early and without CAN. QTc intervals at maximum tachycardia, induced by Valsalva maneuver, were considerably longer in diabetics with definitive CAN (451 +/- 6 ms) than in controls (407 +/- 6 ms; p less than 0.001) and in diabetics with early (434 +/- 6 ms; p less than 0.05) or without (422 +/- 6 ms; p less than 0.01) CAN. Furthermore, QTc intervals at maximum tachycardia were significantly (p less than 0.01) longer in diabetics with early CAN than in controls.(ABSTRACT TRUNCATED AT 250 WORDS)

The measurement of waist circumference for assessing abdominal obesity has become widely accepted.To evaluate the reliability of measuring waist circumference, anthropometric parameters were measured in 150 adult patients by two diabetes educators on two consecutive days. The intraobserver difference was defined as the difference in the measurements made by the same educator on different days and the interobserver difference as the difference in the measurements made by the two educators on the same days.The correlation coefficients (r values) of the measurements were0.99 for the educators and days. The interobserver difference was statistically significant for waist circumference (96.23 cm vs. 97.08 cm, p0.0001). Although the %Delta values (percent difference in the two means) for waist circumference proved to be 2.5-6.3 times higher and the% absolute Delta values (percent average difference) 1.5-2.8 times higher than those for body mass index, the absolute values of the differences (Delta, the difference of the two means, and absolute delta, the average difference) were small (waist circumference Delta: 0.17 cm and 0.85 cm, absolute Delta: 1.51 cm and 2.15 cm; body mass index Delta: 0.02 kg/m(2) and 0.04 kg/m(2), absolute Delta: 0.292 kg/m(2) and 0.226 kg/m(2); intraobserver and interobserver differences, respectively).The intraobserver and interobserver variability for waist circumference were higher than those for body mass index. Nevertheless, the differences in repeated measurements of waist circumference were small when expressed in absolute values. The reliability of waist circumference should be considered in the clinical practice.

The use of insulin pump treatment (CSII: continuous subcutaneous insulin infusion) became widely accepted in the last couple of years. A growing body of experiences accumulated in paediatric practice because CSII is preferable for treating young patients with type 1 diabetes. Nevertheless, CSII can be used, if indicated, for treating type 2 diabetic patients as well. Recently, fast acting insulin analogues are exclusively used for CSII. At moment, clinical observations with insulin lispro and insulin aspart are available but experiences with glulisine are still limited. Although some inconsistencies could be observed in the literature, it is widely accepted, that higher reduction in HbA(1c) values could be achieved by CSII as compared to intensive conservative insulin treatment; this could be more pronounced in cases with high initial HbA(1c) values. CSII with short acting insulin analogues could lead to a higher reduction of HbA(1c) values than CSII with human regular insulin. Moreover, the decrease of hypoglycaemic events could be expected in some cases.

Objective:Arterial stiffness, an independent predictor of cardiovascular disease has been associated with the presence and extent of coronary artery calcification (CAC). We sought to assess the relationship between various hemodynamic parameters and presence of coronary atherosclerotic plaques.Desig

Femoral atherosclerosis, a major cause of peripheral artery disease, has been associated with higher cardiovascular risk in lower extremity peripheral arterial disease patients. The purpose of our study was to assess the effects of the heritable components of atherosclerotic plaque formation in the femoral artery. 161 Hungarian and Italian twin pairs (n = 322, 75 Hungarian and 86 Italian pairs from Padua, Perugia and Terni; 83 monozygotic /MZ/, 78 dizygotic /DZ/; mean age 50 ± 13 years) recruited from the Hungarian and Italian Twin Registries underwent B-mode sonography of bilateral common and superficial femoral arteries (CFA, SFA). Concordance rates between members of the MZ and DZ pairs were calculated, and compared by Chi-square test. Rough heritability was analysed by Falconer formula. Plaques were identified in 24% and 6% of patients in CFA and SFA, respectively. Significantly higher concordance rate was found in MZ twins compared to DZ pairs regarding the presence of plaques in CFA (rMZ = 0.869 vs. rDZ = 0.696) and SFA (rMZ = 0.622 vs. rDZ = 0.403) on left or right side, which indicated a 34% and 44% rough heritability, respectively. Femoral atherosclerotic plaque formation in CFA and SFA is moderately genetically determined. Further studies should elucidate whether offsprings of families at high risk for femoral atherosclerosis may benefit from early ultrasound screening.

The third generation beta-blocker (carvedilol) is effective in reduction of hypertension, and of mortality and morbidity as a supplement to conventional drugs of heart failure therapies (diuretics, ACE inhibitors), based on randomized controlled trials and retrospective analysis.To analyse the efficacy of carvedilol in the treatment of heart failure with special focused on morbidity, mortality endpoints.We assessed the multicenter, randomised, double-blind studies involving more than 150 patients (1995-2005) from MEDLINE database, in which carvedilol was used in the case of moderate to severe heart failure. We also present the results of health-economic publications (2000-2005).In U.S. Carvedilol Heart Failure Study (n 1096) the mortality declined by 65% (3.2% vs. 7.8%; p0.001) with carvedilol vs. placebo, while the cardiovascular hospitalization decline was 27% (14.1% vs. 19.6%; p = 0.036) in heart failure (LVEFor = 5%) applied together with the basic therapy (diuretic and ACE-inhibitor). In the COPERNICUS trial the efficacy of carvedilol was compared to placebo in the case of severe HF patients (LVEF25%, n = 2889). The annual mortality risk declined by 35% (19.7% vs. 12.8%, 95% CI 19-48%, p = 0.00013) while the risk of mortality or any risk of hospitalisation by 24% (p = 0.00004) in the active group. The CAPRICORN study (LVEFor = 0%, n=1959) showed that carvedilol is efficacious in reduction of total (HR: 0.77; 95% CI 0.60-0.98; p = 0.031) and cardiovascular mortality (HR: 0.75; 95% CI 0.58-0.96; p = 0.024) as far as high-risk patients are concerned.The effectiveness of carvedilol is certified in reduction of mortality and hospitalization in the treatment of moderate-severe heart-failure as part of the combination therapy. The benefits of use of the drug are well measurable not only on the level of patients but on the suppliers and the financer as well, thanks to the decline of resource utilization.

Background Aim of this trial was to test whether heat shock protein peptide DiaPep277 treatment in adult and paediatric patients with recent-onset type 1 diabetes (T1D) is safe and whether it can preserve endogenous insulin production. Methods Two studies were performed in a prospective, multicentre, double-blind, placebo-controlled trial. Fifty adult (study p520, aged 16–44 years) and 49 paediatric patients (study p521, 4–15 years) with recent-onset T1D were treated subcutaneously at four different time points with 0.2 mg or 1.0 mg DiaPep277 versus placebo and followed for 18 months. Adult patients were treated with 0.2 mg, 1.0 mg or 2.5 mg DiaPep277 versus placebo. Stimulated C-peptide served as readout for functional s-cell-mass. Results DiaPep277-treatment was not associated with severe side effects. No differences were found in placebo and DiaPep277 treated groups. In adults, a modest trend towards better maintenance of s-cell function was observed in the 0.2 mg and 1.0 mg group, while there was significant loss of stimulated C-peptide in the placebo and 2.5 mg group. Paediatric patients with low HLA risk showed stable C-peptide levels until 13 months upon treatment with 1 mg DiaPep277. Despite similar stimulated C-peptide levels at baseline, children exhibited a more pronounced loss of s-cell function over 18 months than adults (p = 0.0003). Conclusion Administration of DiaPep277 seems safe and may have beneficial effects on C-peptide levels over time in some patients with T1D, but this finding was not accompanied by reduced HbA1c or insulin requirement. Studies with more patients and longer follow-up are needed to further study the effect of DiaPep277. Copyright © 2007 John Wiley & Sons, Ltd.

The public health burden of type 2 diabetes mellitus has been dramatically increasing world-wide. The chronic complications of type 2 diabetes play an important role in decreasing life expectancy and adversely affecting quality of life. Diabetic nephropathy, which is originally microvascular in nature, is widely considered an important complication of diabetes. In prospective clinical investigations, increased urinary albumin excretion proved to be associated not only with subsequent renal outcomes but also with cardiovascular morbidity/mortality independently of other risk factors. Therefore, microalbuminuria as an early sign of increased urinary albumin excretion should be considered important for both treatment and even for prevention. Preventing microalbuminuria might diminish progression to overt nephropathy and, hopefully, might limit cardiovascular events. Regarding primary prevention of diabetic nephropathy, therapeutic intervention should optimally be initiated at the stage of normoalbuminuria. Although additional factors such as smoking cessation, reduction of protein intake, and treatment of lipid abnormalities are important, providing optimal diabetic control as well as targeting optimal blood pressure are the key elements of a prevention strategy in diabetic patients. Recently, the Bergamo Nephrologic Diabetes Complications Trial (BENEDICT) documented that a significant decrease of the development of persistent microalbuminuria could be achieved by using an ACE-inhibitor, trandolapril alone or in combination with verapamil SR, a non-dihydropyridine calcium-channel blocker in hypertensive type 2 diabetic patients with normoalbuminuria. The results of this primary-prevention strategy should be corroborated by further investigations to determine whether these beneficial changes could later result in improvement of renal clinical outcomes, macrovascular complications, or both.

The First Hungarian Therapeutic Consensus Conference took place on 3rd Nov. 2003 with the participation of 9 medical societies. Over the past 2 years the results of new major studies have been published and the American ATP III has also updated its guidelines issued in 2004. Based on the above proposals, the Second Hungarian Therapeutic Consensus Conference held on 3rd Nov. 2005 partly confirmed its earlier suggestions, but made some changes as well. Within the high risk category the Conference optionally created a very high risk group from those patients who - in addition to their cardiovascular disease--have either diabetes or metabolic syndrome or acut coronaria syndrome or who are chain smokers. We have included - as a complement - into the asymptomatic high risk category such newly emerging risk factors, one of which already in itself means high risk: ankle/arm indexor = 0.9, GFR60 ml/min, microalbuminuria (30-300 mg), preclinical atherosclerosis (plaque). Besides, 4 other risk factors were also categorised such as Lp/a (or = 30 mg/dl), CRP (or = 3mg/l), homocysteine (or = 12 micromol), familiarity--atherogenic gene constellation, but only the presence of at least two of these verify high risk. In very high risk group the goals of 3.5 mmol/l and 1.8 mmol/l were determined as therapeutic option. The goal in obese patients--expressed earlier only in BMI--can now be equally determined by the abdominal circumference (94 cm for men, 80 cm for women respectively). ACE inhibitors were recommended earlier as a preventive therapy in case of dysfunction of the left ventricle, while at present they are suggested for all patients with cardiovascular disease. In the recent recommendations guidelines related to nutrition, smoking, exercise have also been included.

The primary prevention of type 2 diabetes mellitus (T2DM) is of great importance. There is now substantial evidence that T2DM can be prevented or delayed by lifestyle modification. A statistically significant reduction of relative risk of newly diagnosed T2DM was observed in large clinical trials with metformin, acarbose or orlistat in subjects with impaired glucose tolerance as well as with troglitazone in women with previous gestational diabetes. A relative risk reduction of newly diagnosed diabetes was observed in prospective, double blind clinical studies evaluating the effect of different antihypertensive drugs (ACE-inhibitors, angiotensin repector blockers, calcium channel blockers) or that of lipid-lowering agents (pravastatin) on the cardiovascular morbidity and mortality in high risk patients. In studies with postmenopausal hormone replacement therapy a relative risk reduction of newly developed T2DM was also observed. Thus, T2DM should be considered as a preventable disease. Nevertheless, it is noteworthy that oral antidiabetic drugs with an indication of preventing T2DM are not registered in several countries at present, so that drug therapy should not be used as a routine for preventing diabetes. On the other hand, patients with pre-diabetes (impaired fasting glycaemia, impaired glucose tolerance) should be given counseling on weight loss as well as instruction for increasing physical activity in order to prevent T2DM.

A fast development in therapy with insulin was observed after its discovery. Besides the widely used human regular insulin preparations, nowadays ultrashort and long-acting insulin analogues are also available for the patients. At present, the results of large clinical trials enable an evidence based diabetes care. It is well documented, that near-normoglycemia should be achieved by intensive conservative insulin treatment or pump therapy in type 1 diabetic patients. The beneficial effects of the good metabolic control could also be observed years later concerning late specific complications of diabetes. Similarly, as good as possible metabolic control should be aimed with antidiabetic treatment including insulin, if necessary, in type 2 diabetic patients. It is documented that the risk of cardiovascular complications is not increased in type 2 diabetic patients treated with insulin. Hypoglycemia and weight gain are the most important side effects of the insulin treatment. Recently, evidence based recommendations for treatment with ultrashort (insulin lispro, insulin aspart) and long-acting insulin analogues (glargine) can also be determined.

The medical history of a 43-year-old non-insulin-dependent diabetic patient with severe and repetitive hypoglycemic episodes is reported. The exact diagnosis proved to be difficult. Finally, surreptitious insulin administration was documented by high serum insulin and low C-peptide values with an elevated molar ratio of insulin to C-peptide in peripheral venous blood during hypoglycemia. Confronting the patient with evidences of surreptitious insulin administration, hypoglycemic episodes abruptly stopped. Hypoglycemia factitia was assessed as a manifestation of Munchhausen syndrome in diabetes mellitus.

Decreased first-phase secretion of insulin may play a role in the development of insulin resistance. In the development of type 2 diabetes an abnormal function of the beta-cells and insulin resistance of liver, fat cells and muscle play the main role. An early sign of beta-cell damage can be the loss of first-phase insulin response. This is supposed to precede the development of insulin resistance. Decrease of first-phase secretion of insulin can induce early postprandial hyperglycaemia and hypertriglyceridaemia damaging endothelium of precapillary arterioles of the nutritive capillaries. Insulin-induced endothelium-dependent dilation of these arterioles is inhibited by high glucose and triglyceride levels preventing metabolic effect of insulin on the parenchymal cells surrounded by nutritive capillaries and leading this way to insulin resistance. Second-phase hyperinsulinaemia develops in the impaired glucose tolerance. With the progression of the disease into the type 2 diabetes, insulin secretion decreases in the second-phase, as well. Because of decrease of first-phase insulin secretion in type 2 diabetic patients, early insulin therapy could be a choice of treatment in type 2 diabetes. Results of the UKPDS suggest that insulin-treated type 2 diabetic patients are longer in the near-euglycaemic state compared to those treated by oral hypoglycaemic agents. Recent data support that early insulin therapy of type 2 diabetic patients retains their own insulin secretion capacity and results in lower haemoglobin A1c. A comparison of before-meal rapid-acting insulin analogue and bedtime NPH insulin regimens verified that rapid-acting insulin analogue decreased haemoglobin A1c compared to NPH insulin treatment in type 2 diabetes. On the basis of these data arises the possibility of the change of the attitude "Oh no, not insulin in type 2 diabetes" to the "early rapid-acting insulin analogue treatment" of these patients.

The treatment of hypertension in diabetic patients due to its high prevalence rate belongs to the everyday clinical practice of internists, diabetologists and general practitioners. The main points of the initiation on of antihypertensive treatment in diabetic patients are reviewed. In order to decrease the target organ damages the treatment of early recognized cardiovascular risk factors are of great importance. The target value of antihypertensive treatment in diabetic patients is130/80 mmHg (in case of proteinuria1 g daily:125/75 mmHg). The global cardiovascular risk is high or very high in diabetic patients both with grade I-III hypertension and with high normal blood pressure, therefore, treatment with antihypertensive drug (besides life style optimalisation) should be initiated promptly in these cases. In case of micro- or macroalbuminuria antihypertensive drug (mainly with characteristics of blocking the renin-angiotensin-system) should be given to each diabetic subject irrespective of actual blood pressure values. Success of antihypertensive treatment in diabetic patients could be achieved mainly with combination therapy only. It is reasonable to initiate antihypertensive therapy primarily with a low dose combination of two agents in diabetic patients with hypertension.

To test whether microalbuminuria in patients with type 2 diabetes and hypertension is primarily dependent on the severity of hypertension, and to compare the effectiveness of two antihypertensive drugs with opposite effects on the renin-angiotensin system [the diuretic, indapamide sustained release (SR), and an angiotensin-converting enzyme inhibitor, enalapril] in reducing microalbuminuria.A multinational, multicentre, controlled, double-blind, double-dummy, randomized, two-parallel-groups study over 1 year.After a 4-week placebo run-in period, 570 patients (ages 60.0 +/- 9.9 years, 64% men) with type 2 diabetes, essential hypertension [systolic blood pressure (SBP) 140-180 mmHg, and diastolic blood pressure (DBP)110 mmHg], and persistent microalbuminuria (20-200 microg/min) were allocated randomly to groups to receive indapamide SR 1.5 mg (n = 284) or enalapril 10 mg (n = 286) once a day. Amlodipine, atenolol, or both were added, if necessary, to achieve the target blood pressure of 140/85 mmHg.There was a significant reduction in the urinary albumin : creatinine ratio. Mean reductions were 35% [95% confidence interval (CI) 24 to 43] and 39% (95% CI 30 to 47%) in the indapamide SR and enalapril groups, respectively. Equivalence was demonstrated between the two groups [1.08 (95% CI 0.89 to 1.31%); P = 0.01]. The reductions in mean arterial pressure (MAP) were 16.6 +/- 9.0 mmHg for the indapamide SR group and 15.0 +/- 9.1 mmHg for the enalapril group (NS); the reduction in SBP was significantly greater (P = 0.0245 ) with indapamide SR. More than 50% of patients in each group required additional antihypertensive therapy, with no differences between groups. Both treatments were well tolerated.Indapamide-SR-based therapy is equivalent to enalapril-based therapy in reducing microalbuminuria with effective blood pressure reduction in patients with hypertension and type 2 diabetes.

The public health burden of type 2 diabetes mellitus has been dramatically increased worldwide. Not only its prevalence rate at present but the increase of its incidence in the near future can create a global health problem. The rapid increase of the total number of newly diagnosed diabetic patients proved to be associated with the increasing prevalence rate of obesity. The metabolic syndrome and type 2 diabetes can contribute to accelerated atherosclerosis and, therefore, the target organ damages can carry a serious problem for the individuals and also for the whole society. It is obvious, that the primary prevention of type 2 diabetes mellitus is of great importance. There is now substantial evidence that type 2 diabetes can be prevented or delayed by lifestyle interventions, i.e. diet and exercise should be the first choice in order to avoid weight gain when preventing diabetes. Pharmacological intervention should not be routinely used to prevent diabetes although results of large clinical trials with metformin and acarbose in subjects with impaired glucose tolerance are available. It is noteworthy that a decrease in the number of newly diagnosed diabetes was observed in prospective, double blind clinical studies evaluating the effect of new antihypertensive drugs (captopril, ramipril, lisinopril, nifedipine GITS, amlodipine, losartan) or lipid-lowering agents (pravastatin) on the cardiovascular morbidity and mortality in high risk patients. In these studies the relative risk reduction of newly diagnosed diabetes was evaluated in comparison to placebo or other drugs in a subgroup of non-diabetic patients at baseline. In addition, the incidence of newly diagnosed type 2 diabetes decreased parallel with weight loss in clinical trials with orlistat, an anti-obesity drug. Although new results were provided by evidence based clinical trials a lot of questions remained to be solved. Further research is necessary to understand better how to facilitate effective primary prevention of type 2 diabetes. Further data are needed to evaluate the clinical significance of currently used antidiabetic drugs and, in addition, the possible role of other drugs (antihypertensives, lipid lowering agents, anti-obesity drugs) should also be investigated in order to identify the optimal primary prevention policy of type 2 diabetes.

Authors based on studies fullfiling the principles of evidence based medicine review the efficiency and benefits of angiotensin receptor blocking agents in congestive heart failure and hypertension. Special attention is focused on their application in diabetes mellitus. The data support efficacy, good tolerability, beneficial side effect profile as well as cardio- and renoprotective properties of these drugs. Their safety in diabetic as well as and in non-diabetic persons can be underlined.

The angiotensin (II) receptor (1) blockers are known first of all as antihypertensive drugs, however, due to the role of the tissue renin-angiotensin system (RAS) in different pathological conditions, their clinical importance became more pronounced and are at present more widely used. The article gives an overview of the recent knowledge in this field. Beside of summarizing physiological and the most important pathophysiological aspects of the RAS, as well as pharmacokinetic properties of the different angiotensin receptor blocker drugs used at present in Hungary, the potential differences in blocking of the converting enzyme and the angiotensin II receptors are also reviewed.

The screening of subjects at risk for metabolic syndrome is of considerable importance in order to prevent atherosclerosis.In order to assess the clinical-laboratory characteristics of metabolic syndrome,a screening procedure was performed in subjects (age 20 -65)who exhibited hypertension and/or abnormal body mass index (BMI)and/or elevated waist-hip ratio,excluding patients with known diabetes. An oral glucose tolerance test with 75 g glucose was performed. Plasma glucose and insulin values were measured,as well as plasma lipids.In subjects available for complete statistical analysis (n=944;women/men ratio 1.37:1),hyperinsulinemia was detected in 52.9%. Hyperinsulinemia with normal glucose tolerance was more often detected (33.2%),hyperinsulinemia with impaired glucose tolerance [IGT ]or diabetes less frequently (13.0%and 6.7%,respectively). When abnormal clinical signs were separately analysed,hyperinsulinemia was found in 56.8%of subjects with abnormal BMI,in 43.8% of subjects with abnormal waist-hip ratio,and in 27.1% of subjects with hypertension. Metabolic syndrome (WHO criteria,modified)was diagnosed in 35.2%of subjects,with male predominance (men:40.6%;women:31.2%;p0.01).Obesity (abnormal BMI;abnormal waist-hip ratio)is of greater importance than hypertension alone for detecting subjects with hyperinsulinemia.Routine clinical and laboratory investigations (anthropometric data,measuring blood pressure,oral glucose tolerance test)are simple but useful for identifying subjects with metabolic syndrome,enabling the implementation of a primary strategy to prevent cardiovascular morbidity.

Pioglitazone, a thiazolidinedione, improves glycemic control primarily by increasing peripheral insulin sensitivity in patients with type 2 diabetes, whereas metformin, a biguanide, exerts its effect primarily by decreasing hepatic glucose output. In the first head-to-head, double-blind clinical trial comparing these two oral antihyperglycemic medications (OAMs), we studied the effect of 32-wk monotherapy on glycemic control and insulin sensitivity in 205 patients with recently diagnosed type 2 diabetes who were naive to OAM therapy. Subjects were randomized to either 30 mg pioglitazone or 850 mg metformin daily with titrations upward to 45 mg (77% of pioglitazone patients) and 2550 mg (73% of metformin patients), as indicated, to achieve fasting plasma glucose levels of less than 7.0 mmol/liter (126 mg/dl). Pioglitazone was comparable to metformin in improving glycemic control as measured by hemoglobin A1C and fasting plasma glucose. At endpoint, pioglitazone was significantly more effective than metformin in improving indicators of insulin sensitivity, as determined by reduction of fasting serum insulin (P = 0.003) and by analysis of homeostasis model assessment for insulin sensitivity (HOMA-S; P = 0.002). Both OAM therapies were well tolerated. Therefore, pioglitazone and metformin are equally efficacious in regard to glycemic control, but they exert significantly different effects on insulin sensitivity due to differing mechanisms of action. The more pronounced improvement in indicators of insulin sensitivity by pioglitazone, as compared with metformin monotherapy in patients recently diagnosed with type 2 diabetes who are OAM-naive, may be of interest for further clinical evaluation.

Microalbuminuria in diabetes is a risk factor for early death and an indicator for aggressive blood pressure (BP) lowering. We compared a combination of 2 mg perindopril/0.625 mg indapamide with enalapril monotherapy on albumin excretion rate (AER) in patients with type 2 diabetes, albuminuria, and hypertension in a 12-month, randomized, double-blind, parallel-group international multicenter study. Four hundred eighty-one patients with type 2 diabetes and hypertension (systolic BP ≥140 mm Hg, 20 and P =0.012; systolic BP −1.5 [95% CI −3.0, −0.1] diastolic BP P =0.019) and AER −42% (95% CI −50%, −33%) versus −27% (95% CI −37%, −16%) with enalapril. The greater AER reduction remained significant after adjustment for mean BP. Adverse events were similar in the 2 groups. Thus, first-line treatment with low-dose combination perindopril/indapamide induces a greater decrease in albuminuria than enalapril, partially independent of BP reduction. A BP-independent effect of the combination may increase renal protection.

The normal-pathological threshold of fasting blood glucose values was modified by the new WHO diagnostic criteria (1999) and, in addition, impaired fasting glucose (IFG) was introduced as a new clinical entity. Nevertheless, the 2-h post-glucose challenge criteria and the concept of the impaired glucose tolerance (IGT) remained unchanged. There is no unequivocal agreement whether new fasting or unchanged post-challenge blood glucose criteria should be used for classification of glucose intolerance.To assess the clinical-laboratory characteristics of metabolic syndrome a screening procedure was performed in hypertensive or obese subjects registered within primary health care and the reliability of the new fasting blood glucose criteria was analysed.For inclusion, subjects of both sexes aged from 20 to 65 years exhibited at least one of the following clinical characteristics: hypertension (ongoing antihypertensive treatment or raised (or = 140/90 mmHg) actual blood pressure), abnormal (30.0 kg/m2) body mass index [BMI] or elevated waist-hip ratio (0.85 in women,0.90 in men). Subjects with known diabetes were not involved. An oral glucose tolerance test (OGTT) with 75 g glucose was performed in each subject. Subjects with complete clinical and laboratory findings were statistically analysed (n = 944; women/men: 545/399; age: 46.1 +/- 7.3 years; BMI 32.2 +/- 5.4 kg/m2; waist-hip ratio 0.90 +/- 0.09; x +/- SD).In the total cohort newly diagnosed diabetes mellitus (based on the 120 min post-challenge glucose values) was found in 87 subjects (9.2%), IGT was detected in 136 cases (14.4%) while normal glucose tolerance was documented in 721 subjects (76.4%). Using fasting blood glucose values for classification, diabetes mellitus was detected in 79 subjects (8.4%), IFG was found in 124 cases (13.1%) while 741 subjects (78.5%) had normal glucose tolerance. Impaired glucoregulation (IGT + IFG) was found in 223 subjects (IGT alone 99 cases [44.4%], IFG alone 87 cases [39.0%], IGT and IFG in combination 37 cases [16.6%]). The sensitivity and specificity of fasting blood glucose criteria for detecting diabetes were 63.2% and 97.1%, respectively, while those for detecting glucose intolerance (IFG and diabetes as well as IGT and diabetes) were 52.9% and 88.2%, respectively. Clinical characteristics of subjects with abnormal post-challenge but normal fasting blood glucose values (n = 105) did not differ significantly from those of subjects with normal post-challenge but abnormal fasting blood glucose values (n = 85) (age: 46.7 +/- 6.9 years vs 46.7 +/- 6.1 years; BMI: 33.1 +/- 5.4 kg/m2 vs 32.3 +/- 4.5 kg/m2; waist-hip ratio: 0.91 +/- 0.09 vs 0.92 +/- 0.07; p0.05).OGTT and 2-h post-glucose challenge criteria should be used for the diagnosis of different categories of glucose intolerance in screening for metabolic syndrome.

Aim Shift workers may be at risk of different diseases. In order to assess cardiometabolic risk in shift workers, a cross-sectional study was performed among active workers. Methods A total of 481 workers (121 men, 360 women) were investigated; most of them were employees in light industry (58.2%) or in public services (23.9%). Past medical history was recorded and physical examination was performed. Questionnaires were used to characterize daily activity. Fasting venous blood sample was collected for measuring laboratory parameters. Data from shift workers (n = 234, age: 43.9 ± 8.1 years) were compared to those of daytime workers (n = 247, age: 42.8 ± 8.5 years), men and women were analyzed separately. Results In men, systolic blood pressure was higher in shift workers compared to daytime workers (133 ± 8 vs 126 ± 17 mmHg; p < 0.05). In women, weight (73.6 ± 15.5 vs 67.7 ± 13.2 kg; p < 0.001), body mass index (27.5 ± 5.7 vs 25.0 ± 4.3 kg/m2; pvs 13.4%; p < 0.01) were higher in shift workers compared to daytime workers. In addition, the proportion of current smokers was higher (37.7 vs 21.7%; p < 0.001) and HDL-cholesterol level was lower (1.56 ± 0.32 vs 1.68 ± 0.36 mmol/l; p < 0.01) in female shift workers than in female daytime workers. Both in men and in women, rotating shift workers spent less time sleeping both on working days and on non-working days, spent less time with sport activity, drank more coffee and they spent less time working per day, especially in light physical work, compared to daytime workers. In addition, low and middle educational levels were most frequently found among rotating shift workers as opposed to the daytime workers where high educational level was more common. Conclusion Middle-aged active shift workers, especially women, have a less healthy lifestyle and are at higher cardiometabolic risk as compared to daytime workers. Our study highlights the importance of measures for identifying and preventing cardiometabolic risk factors in shift workers.

Signs of autonomic cardiac neuropathy and its association with distal somatic neuropathy were investigated in 36 type 1 and 28 type 2 diabetic patients free from clinical symptoms of autonomic neuropathy. Using bedside tests (deep-breathing, Valsalva manoeuvre and lying-to-standing) definitive cardiac autonomic neuropathy was found in 28 patients (44%), early cardiac autonomic neuropathy was observed in 19 patients (30%) while 17 patients (26%) showed no alterations. The values of motor nerve conduction velocity in peroneal nerves (41.8 +/- 0.7 m/s, mean +/- SEM) were significantly (p less than 0.01) lower in patients with definitive cardiac autonomic neuropathy than those (45.8 +/- 1.1 m/s) of patients without any signs of cardiac autonomic neuropathy. These latter values were, however, significantly (p less than 0.001) lower than those (53.7 +/- 0.7 m/s) of control subjects (n = 50). Signs of early or definitive cardiac autonomic neuropathy were recorded in 31 of 35 diabetic patients with distal somatic neuropathy assessed by measurement of motor nerve conduction velocity in peroneal nerves. It was concluded that abnormal results of noninvasive tests for autonomic neuropathy, i.e. alterations in cardiorespiratory reflexes indicating parasympathetic impairment of cardiac innervation could be often found in diabetic patients without clinical signs of autonomic neuropathy. These alterations could be frequently observed in diabetic patients with distal symmetrical somatic neuropathy.

The left ventricular systolic function of 32 patients with insulin-dependent diabetes mellitus was investigated by measurement of systolic time intervals. Patients with clinical signs of sclerosis in the coronary arteries were excluded. Twenty-nine sex- and age-matched healthy people served as controls. Resting values of PEP/LVET ratio and of the corrected pre-ejection period were significantly higher in diabetics than in controls. The alterations of systolic time intervals during volume-loading induced by passive leg-raising as well as by isometric handgrip test indicated an increase in left ventricular performance in healthy people. The unchanged systolic time intervals observed in diabetics during the same loadings indicated a decrease in the functional reserve of the diabetic left ventricle. The systolic time intervals observed in patients with type-1 diabetes could be evaluated as a preclinical abnormality of left ventricular performance and as early signs of diabetic cardiomyopathy.