[CROATIAN GUIDELINES FOR THE PHARMACOTHERAPY OF TYPE 2 DIABETES]. / HRVATSKE SMJERNICE ZA FARMAKOLOSKO LIJECENJE SECERNE BOLESTI TIPA 2.

INTRODUCTION: The Croatian Association for Diabetes and Metabolic Disorders of the Croatian Medical Association has issued in 2011 the first national guidelines for the nutrition, education, self-control, and pharmacotherapy of diabetes type 2. According to the increased number of available medicines and new evidence related to the effectiveness and safety of medicines already involved in the therapy there was a need for update of the existing guidelines for the pharmacotherapy of type 2 diabetes in the Republic of Croatia. PARTICIPANTS: as co-authors of the Guidelines there are listed all members of the Croatian Association for Diabetes and Metabolic Diseases, as well as other representatives of professional societies within the Croatian Medical Association, who have contributed with comments and suggestions to the development of the Guidelines. EVIDENCE: These guidelines are evidence-based, according to the GRADE system (eng. Grading of Recommendations, Assessment, Development and Evaluation), which describes the level of evidence and strength of recommendations. CONCLUSIONS: An individual patient approach based on physiological principles in blood glucose control is essential for diabetes' patients management. Glycemic targets and selection of the pharmacological agents should be tailored to the patient, taking into account the age, duration of disease, life expectancy, risk of hypoglyce- mia, comorbidities, developed vascular and other complications as well as other factors. Because of all this, is of national interest to have a practical, rational and applicable guidelines for the pharmacotherapy of type 2 diabetes.

A case of transient constrictive pericarditis in a 42-year-old patient.

We report a case of 42 year old patient with acute idiopathic pericarditis in whom we describe transient cardiac constriction, consisting of the temporary development of features of constrictive pericarditis with subsequent return to normality after medical therapy alone. After a mean of 6 months, there have been no recurrences of constrictive physiology or clinical symptoms. The results of our study suggest that patients who have constrictive features early in the course of their illness and are hemodynamically stable should be considered for a trial of conservative therapy before pericardiectomy is pursued.

The metabolic syndrome is associated with high-normal urinary albumin excretion and retinopathy in normoalbuminuric type 1 diabetic patients.

Although metabolic syndrome was not extensively studied in type 1 diabetes, higher insulin resistance, the core feature of the syndrome was found to be associated with increased risk of developing microvascular complications. As diabetic nephropathy may progress to advanced lesion before microalbuminuria appears, we investigated the association of the metabolic syndrome and estimated glucose disposal rate (eGDR) with urinary albumin excretion (UAE), retinopathy and neuropathy in normoalbuminuric type 1 diabetic patients. Two hundred and 98 patients (UAE < 30 mg / 24 h at three occasions) were divided according to the IDF metabolic syndrome; eGDR (mg kg(-1) min(-1)) was calculated: 24.31-(12.22 x WHR) - (3.29 x HT) - (0.57 x HbA1c), (WHR = waist-to-hip ratio, HT = hypertension). Patients with (n = 99) compared to those without metabolic syndrome (N = 199) showed higher UAE (15.96 +/- 9.10; 13.48 +/- 8.36 mg /24 h), C-reactive protein (2.39 +/- 4.09;1.12 +/- 2.03 mg/L), prevalence of retinopathy (70.7; 55.27%) and polyneuropathy (80.8; 68.3%), and lower eGDR (5.75 +/- 1.74; 8.96 +/- 1.9), (p > 0.05). In patients with high-normal UAE, retinopathy and polyneuropathy eGDR was significantly lower compared with patients with low-normal UAE, and without retinopathy and polyneuropathy. In multiple regression analysis UAE and retinopathy were associated with diabetes duration (beta = -0.20, beta = -0.62), eGDR (beta = - 0.106; beta = -0.041), metabolic syndrome (beta = 0.49, beta = 0.28), (p > 0.05). In type 1 diabetic patients insulin resistance and IDF defined metabolic syndrome are associated with high-normal UAE, retinopathy and polyneuropathy. The predictive value of the metabolic syndrome for development of microalbuminuria and retinopathy needs to be assessed in further follow-up studies.

Glycemic index in diabetes.

The Glycemic Index (GI) is a rating system that ranks carbohydrate-containing foods according to their postprandial blood glucose response relative to the same quantity of available carbohydrate of a standard such as white bread or glucose. The concept of GI was first introduced in the early 80's by Jenkins and coworkers. Since then, numerous trials have been undertaken, many indicating benefits of a low GI diet on glycemic control, as well as lipid profiles, insulin and C-peptide levels, inflammatory and thrombolytic factors, endothelial function and regulation of body weight. As a result, a low-GI diet may prevent or delay the vascular complications of diabetes. However, despite many studies supporting the benefits of the Glycemic Index as part of the treatment of diabetes mellitus, several areas of controversy have been raised in the literature and are addressed here. Clinicians treating diabetic patients should be aware of the potential benefits of low-GI foods in the prevention and treatment of diabetes and its complications.

Urinary obstruction depresses erythropoiesis which recovers after parenchyma-saving surgery but not SWL.

We tested the hypotheses that chronic human urinary obstruction impairs the renal regulation of the red blood cell (RBC) production and compared the chronic outcome of relief of obstruction between parenchyma-saving surgery and extracorporeal lithotripsy (SWL). We measured RBC count and serum erythropoietin (Epo) concentration before and 3 months after relief of urinary obstruction in 60 patients treated with pyelolithotomy, ureterolithotomy or ureteroscopy and in 62 patients treated with SWL. Compared with 333 healthy controls, at baseline, patients scheduled for parenchyma-saving surgery had lowered RBC count [9.9% (6.9-13.1); 95% confidence interval] in case of males and 17.7% (14.2-21.4) in case of females; minor depression in RBC count was also observed in female patients scheduled for SWL. Epo serum levels were mildly reduced in SWL patients and halved in parenchyma-saving surgery group. At 3 months following relief of obstruction in 50 operated patients without recurrent or residual stone, Epo levels almost doubled, becoming normal, while RBC count and haemoglobin concentration increased for 6.1% (3.8-8.8) and 8.8% (6.1-10.6). In contrast, in 49 SWL patients only minor, bidirectional responses to treatment were observed. We conclude that obstructive uropathy is associated with clinically relevant effects on erythropoiesis, which is reversed after relief of obstruction by parenchyma-saving surgery that saves the renal parenchyma.

New paradigm in training of undergraduate clinical skills: the NEPTUNE-CS project at the Split University School of Medicine.

Clinical skills' training is arguably the weakest point in medical schools' curriculum. This study briefly describes how we at the Split University School of Medicine cope with this problem. We consider that, over the last decades, a considerable advancement in teaching methodologies, tools, and assessment of students has been made. However, there are many unresolved issues, most notably: (i) the institutional value system, impeding the motivation of the teaching staff; (ii) lack of a strong mentoring system; (iii) organization, timing, and placement of training in the curriculum; (iv) lack of publications pertinent to training; and (v) unwillingness of patients to participate in student training. To improve the existing training models we suggest increased institutional awareness of obstacles, as well as willingness to develop mechanisms for increasing the motivation of faculty. It is necessary to introduce changes in the structure and timing of training and to complement it with a catalog, practicum, and portfolio of clinical skills. At Split University School of Medicine, we developed a new paradigm aimed to improve the teaching of clinical skills called "Neptune-CSS," which stands for New Paradigm in Training of Undergraduate Clinical Skills in Split.

Comparison between continuous ambulatory arterial blood pressure monitoring and standard blood pressure measurements among patients of younger and older age group.

The purpose of the study was to evaluate whether there is a difference between blood pressure measured in a physician's office and the average 24 hr continuous blood pressure monitored by hypertensive patients at home. If there is a difference between these two situations then is it possibly the result of a blood pressure response by the patient to the physician which is known as "white coat effect" or "white coat hypertension". We studied 80 hypertensive outpatients which were divided into two groups of 40 patients each--a younger patient group, with a mean age of 22.8 +/- 1.8 years, and an older patient group with a mean age of 50.3 +/- 5.7 years. They were selected because they had been diagnosed as essentially hypertension grade 1, according to 2007 ESH/ESC Guidelines, or the USA Joint National Committee Guidelines (JNC 7) (i.e., arterial blood pressure > 140/90 mm Hg and < 160/100 mmHg) and 35 were not having any antihypertensive treatment. All participants in the study went through a two-week "wash-out" period without medication. At the beginning of the study blood pressure was measured using the Riva-Rocci-Korotkoff method (mercury sphygmomanometer) after 5 minutes of rest and with the patient in the sitting position. The average of the two last measurements by sphygmomanometer was used in the analysis. The subsequent measurement was made by continuous ambulatory blood pressure monitoring (SpaceLabs 90207 device). Continuous ambulatory blood pressure monitoring revealed that 17 patients of the younger age group (42.5%) who were diagnosed hypertonic, according to mercury sphygmomanometeric measurement, were in fact normotonic. In the older age group only 7 (17.5%) of participants were normotonic during 24 hr blood pressure monitoring. The proportion of miss-diagnosed normotonic younger patients was directly related to elevated clinic blood pressure, which could be referred to as office hypertension or isolated clinic hypertension (white coat hypertension). This was statistically significant (chi2 = 5.95; p = 0.015). Hypertension diagnosed in younger patients based only on occasional doctor's office mesurements, using a mercury sphygmomanometer, could be miss-interpreted and treated as the start of arterial hypertension. This could sometimes have unwanted results due to the side effects of precipitate antihypertensive medication as well as the unnecessary cost of testing, cost of treatment, prevalence of white-coat hypertension at baseline, and the varying incidence of new hypertension after the initial screening. The results indicate a potential savings of 3-14% in the cost of care for hypertension, and a 10-23% reduction in treatment days when ambulatory blood pressure monitoring is incorporated into the diagnostic process. Therefore CABPM should be used as a legitimate method in the diagnosing of "white coat hypertension", particularly in young patients. The identification of white coat hypertensive"' patients should be followed by a search for metabolic risk or organ damage using the latest guidelines, and medication should start after an organ damage or cardiovascular risk assesement.

Effects of obesity reduction on cardiovascular risk factors: comparison of individual and group treatment--substudy of the Croatian Healthy Weight Loss Programme.

Prevention of obesity may help reduce the morbidity and mortality from cardiovascular diseases. In Croatia, over half of adult population is overweight. Aldo the basic medical principles of healthy weight-loss programmes are well known, it is believed that mainly because of the leak of successful therapeutic approach obesity remains the most challenging changeable cardiovascular risk factor in nowadays clinical practice. Objective of this Croatian Healthy Weight Loss Programme substudy was to determine effects and differences between the intensive group and intensive individual weight-loss program on weight loss and cardiovascular risk factor. A clinical trial included 476 adults whose body mass index (BMI) was > 30 or > 28 accompanied by increased blood pressure, glucose, and cholesterol. The study participants completed either a group (n = 243) or individually-based (n = 233) 6-month weight-loss program consisting of education, low-fat diet, pharmacological treatment with orlistat, psychological counselling, and exercise. Body weight, body mass index, blood pressure, blood sugar, and blood cholesterol were measured in all participants after 3 and 6 months. The average weight loss was 12.2 (13%) kg and 7.6 (9%) kg in the group and individual program, respectively. Beside the weight reduction, the levels of blood cholesterol, glucose, and blood pressure were also significantly reduced in comparison with baseline, decreasing to normal values in all participants (P < 0.001 for all). Decrease in the monitored parameters was greater in participants in the group program. The weight loss program provided a healthy loss of extra weight in the period of 6 months. The group program produced greater decrease in body weight, body mass index, blood pressure, glucose, and cholesterol than the individual program.

[Recommendations of Croatian societies on treatment of macrovascular and microvascular complications in patients with metabolic syndrome and diabetes type 2--treatment of residual risk]. / Preporuke Hrvatskih strucnih drustava o lijecenju makrovaskularnih i mikrovaskularnih komplikacija u bolesnika s metabolickim sindromom i secernom bolesti tipa 2--lijecenje preostalog kardiovaskularno [corrected] rizika.

Quite a number of studies have shown that despite achieving targets for total and LDL cholesterol, blood pressure and glycemia according to the guidelines, many patients remain at high residual risk for cardiovascular diseases (CVD), both macrovascular and microvascular. This is particularly true for patients with established CVD, type 2 diabetes, obesity and/or metabolic syndrome who have very often atherogenic dyslipidemia characterized by decreased plasma concentrations of HDL cholesterol and increased triglycerides. To address this issue a working group of experts has been established to produce this document in order to recommend therapeutic interventions for reducing this residual risk. This document has been endorsed by relevant Croatian scientific and professional societies (Croatian atherosclerosis socitey, Croatian hypertension society, Croatian cardiac society, Croatian diabetes society, Croatian endocrinology society, Croatian obesity society, Croatian internal medicine society and Croatian society for clinical pharmacology).

Specific and gender differences between hospitalized and out of hospital mortality due to myocardial infarction.

In this paper, the authors evaluate gender related differences of myocardial infarction mortality before and after hospital admittance. Myocardial infarction mortality in the Clinical Hospital Split in the seven years period between 2000 and 2006, have been analyzed together with out of hospital sudden death patients with acute myocardial infarction established during autopsy. During the seven year period between 2000 and 2006, 3434 patients were treated for myocardial infarction in the Split Clinical Hospital, 2336 (68%) males and 1098 (32%) females with a 12% total mortality (427 patients). The annual number of hospitalized persons has been increasing during that period (474 in yr. 2000 us. 547 in yr. 2006), while mortality decreased from 15% in 2000 to 9.6% in 2006. Female patients had significantly higher hospital mortality than male patients, (228 or 21% vs. 202 or 9%, p<0.05). Women also had significantly higher total AMI mortality (23.7% vs. 15,7%, p <0.05). Anterior myocardial infarction with ST elevation in precordial leads had significantly higher mortality (19%) compared to patients with lateral (11%), inferior (10%) myocardial infarction with ST elevation and also NSTEMI (4%) mortality p<0.05. Female patients more frequently die in hospital, 84% (230) than out of hospital 16% (43). From the total number of AMI deaths (388) in male patients, 56% (217) were in hospital and 44% (171) out of hospital (p<0.001). Men had significantly higher prehospital mortality rate than women (81% vs. 19%, p<0.05). Men also more frequently died from ventricular fibrillation (22% vs. 10%, p<0.05), while women died more frequently of heart failure, cardiogenic shock, and myocardial rupture (33% vs. 15% p<0.05). Regarding the total number of deaths from myocardial infarction men had significantly higher prehospital mortality compared to women (178 or 7.3% vs. 43 or 3.7%, p<0.05). Anterior myocardial infarction had a significantly higher rate in patients dying pre-hospital (58%), in contrast to inferior (36%) and lateral myocardial infarction with ST elevation (6%) p<0.05. We have concluded that male patients die more frequently within the first few hours of AMI mostly due to malignant arrhythmias, while female patients died in sub acute stage due to heart failure while being hospitalized. Nevertheless total mortality of AMI remains significantly higher in women.

Prediabetes awareness among Southeastern European physicians.

AIMS/INTRODUCTION: Prediabetes (PD) represents a transitional state where the glucose levels are higher than normal, but not enough for diabetes mellitus diagnosis. As there is a growing number of the population with PD, its early detection and treatment could prevent the development of diabetes mellitus and its complications. We aimed to assess the overall knowledge of PD among medical professionals of different varieties. MATERIALS AND METHODS: A questionnaire-based study addressing PD and type 2 diabetes mellitus knowledge among Southeastern European general practitioners, postgraduates, physicians and superior specialists was carried out. RESULTS: A total of 397 physicians completed the questionnaire. The total rate of correct answers from diabetologists, non-diabetologist internists, residents and general practitioners was 69, 56.1, 54 and 53%, respectively. Questions related to the PD definition achieved a total of 46.6% correct answers. Correct responses considering the numerical definition of impaired fasting glucose and impaired glucose tolerance were 46.3 and 46.8%, respectively. Younger physicians had better knowledge of numerical values regarding PD and type 2 diabetes mellitus criteria (P < 0.001). CONCLUSIONS: The present results show that overall knowledge of PD is poor among Southeastern European physicians, which necessitates adequate educational programs on PD in this region.

Relevant sonographic parameters of a painful shoulder in symptomatic dialyzed patients versus asymptomatic dialyzed and healthy volunteers.

The aim of this study is to find dialysis relevant sonographic parameters of painful shoulder of the symptomatic dialyzed patients comparing them with parameters in asymptomatic dialyzed patients and healthy volunteers. Significant difference in all metric parameters (thickness of supraspinatus tendon, diameter of biceps tendon sheet and capsula-bone distance) were noticed between all groups and the symptomatic had the highest values. Asymptomatic had the higher values then volunteers. Inhomogenicity of the tendon and biceps tendon sheet effusion in the symptomatic patients were the most often occurred. Subdeltoid effusion, deposits and tendon rupture were found only in symptomatic patients. No difference in presence of calcifications between symptomatic and asymptomatic was found. Metric parameters are relevant and associated with dialysis, as well as biceps tendon effusion tendon inhomogenicity, deposits and subdeltoid effusion. Tendon ruptures are relatively rare and nonspecific.

Transcranial Doppler ultrasound assessment of intracranial hemodynamics in patients with type 2 diabetes mellitus.

BACKGROUND: Diabetics have a 3-fold risk for cardiovascular diseases compared with non-diabetics. This study was designed to evaluate cerebral hemodynamic changes related to type 2 diabetes mellitus (DM) with transcranial Doppler ultrasonography (TCD). TCD is a highly sensitive and specific method of quick bedside assessment of cerebrovascular circulation hemodynamics. PATIENTS AND METHODS: In a prospective study, we compared a group of 100 patients with the diagnosis of type 2 diabetes mellitus (aged 48 to 67 years) and an age- and sex-matched control group of 100 healthy subjects without diabetes mellitus. We measured flow velocities (Vm) and the Gosling pulsatility index (PI) of the middle cerebral artery (MCA). RESULTS: The rate of TCD abnormalities was significantly higher in diabetic patients than in healthy control subjects (55% vs. 11%, P < 0.05). The PI was significantly higher in diabetic patients than in healthy controls (P < 0.001). Atherosclerotic changes were found in 34.0% and 71.4% of patients suffering from diabetes for <5 and > or =5 years, respectively. CONCLUSION: This study suggests that TCD is a useful marker for the detection of diabetic cerebrovascular changes. The duration and type of diabetes were found to have an impact on the development of pathologic cerebrovascular changes.

Lispro insulin and metformin versus other combination in the diabetes mellitus type 2 management after secondary oral antidiabetic drug failure.

The purpose of the study was to find out differences between treatments of diabetes type 2 after secondary oral antidiabetic drug failure. Three different methods of treatment were compared: lispro insulin in combination with metformin, glimepiride and metformin combination or two daily doses of biphasic insulin 30/70 together with bed-time NPH insulin. The study included 87 patients with diabetes mellitus type 2 randomly distributed into 3 different treatment groups. Fasting and postprandial glucose were analyzed by enzymatic colorimetric method and HbA1c was measured by ion exchange chromatography. HbA1c significantly decreased in all three study groups. The decrease was mostly expressed among patients treated with lispro and metformin. When focused on postprandial glucose control, antihyperglycemic metformin and insulin lispro therapy has greater impact on the overall metabolic control (decrease in level of HbA1c) in comparison with the above mentioned more traditional approaches.

Comparative assessment of the treatment of type 2 diabetes mellitus.

BACKGROUND: The objective of the study was to estimate the most successful way of treating patients with type 2 diabetes mellitus. PATIENTS AND METHODS: A total of 87 patients with type 2 diabetes mellitus were selected for a three-month study. The patients were divided into three groups comprising 29 patients in each group, based upon the treatment regimen. Group 1 (BMI 32.3+/-3.6 kg/m(2)) was treated with glimepiride and metformin; group 2 (BMI 27.9+/-3.9) was treated with daily doses of insulin mixture 30/70 and bed-time NPH insulin; and group 3 (BMI 30.2+/-4.8) was treated with a combination of three daily doses of lispro and metformin. The groups did not differ significantly in terms of sex and age. RESULTS: Initially, there were significant statistical differences in HbA1c (P=0.035) between the three groups (9.21%+/-1.72%; 9.21%+/-1.54%; and 10,0%+/-1.73%, respectively). After three months, there were no statistically significant differences in HbA1c (P=0.66) between the groups (8.52%+/-1.7%; 8.03%+/-1.05%; and 8.0%+/-0.63%, respectively). Decreases in HbA(1c) were significant in all groups, but most pronounced in patients treated with lispro and metformin (17% on average). CONCLUSION: The study results suggest the need for establishing guidelines on how to treat type 2 diabetics.

Impact of a guide dog on glycemia regulation in blind/visually impaired persons due to diabetes mellitus.

The aim was to assess glycemia regulation in a blind diabetic patient after getting a guide dog. Glycosylated hemoglobin (HbA1c) results of a blind patient before and after getting the guide dog were retrospectively collected. The paired t-test results yielded a two-tailed P value of 0.0925, a difference considered not statistically significant; the 95% confidence interval of this difference varied from -0.2494 to 1.889. An improvement of glycemia regulation was observed with the guide dog compared to previous glycemia regulation, however, the difference was not statistically significant. The moderate improvement could probably be attributed to the mobility of the blind person having a guide dog. Standard quality of life tests should be included in the evaluation of diabetic blind persons, especially the impact of a guide dog on glycemic control or other chronic complications of diabetes.

The impact of hormone replacement therapy on metabolic syndrome components in perimenopausal women.

Hormone replacement therapy (HRT) is in use for more than a half of century, but the question of indications and ideal candidates for HRT remains unclear. Postmenopausal women are a population with the increasing risks for cardiovascular diseases which are the main cause of death in this group. Decline in oestrogen concentrations is linked to a number of changes in peri and postmenopause: increased total cholesterol, triglycerides, and low density lipoprotein, increased insulin resistance and impaired fibrinolysis. These changes are the main components of metabolic syndrome, the epidemic of the modern age. HRT is currently recommended as the gold standard for the management of vasomotor symptoms, but the benefit of HRT on components of metabolic syndrome and risk for cardiovascular events is still uncertain. In the initial reports from the Women's Health Initiative trial (WHI), overall health risks exceeded benefits in the cohort taking combined estrogen-progestin trial. Observational study in postmenopausal women, some meta-analyses and subsequent analyses of WHI had suggested that the timing of exposure to postmenopausal estrogen therapy may be an important factor in determining subsequent cardiovascular risk. It seems that the early therapy onset is a key factor in accomplishing positive results, but there are almost no surveys regarding the effects on the metabolic syndrome components in perimenopausal women. We hypothesized that the early, low dosage HRT in healthy perimenopausal women would have beneficial effects on the compounds of metabolic syndrome and could decrease the risk of cardiovascular events. Beneficial effect of HRT on cardiovascular diseases is due to the maintained integrity and functional status of the endothelium in younger women. We are aware of the fact that further studies are necessary to test the effects of different doses and routes of administration of HRT on cardiovascular outcomes.