Croatian guidelines for the pharmacotherapy of type 2 diabetes

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.

Factors predictive of drop-out and weight loss success in weight management of obese patients.

BACKGROUND: The prevention and treatment of overweight and obese individuals on a population-wide basis is challenging because patients have difficulties with adhering to weight loss programmes. The present study aimed to evaluate patients' adherence to the weight reduction programme by identifying factors predictive of both drop-out rate and weight loss success. METHODS: One-hundred and twenty-four obese patients participated in a 12-month weight reduction programme, involving group therapy during an intensive 5-day educational intervention, followed by five, 2-h follow-up visits. The primary outcome measures included drop-out rate and percentage weight loss. Sociodemographic and clinical characteristics, as well as type of diet, were explored as potential predictive factors. Type of diet was assigned based on randomisation. Regression analyses were conducted to identify predictive variables of drop-out and weight loss success. RESULTS: In total, 33.1% of all recruited participants were deemed successful because they reduced the initial weight by more than 5% after the 12-month intervention. The overall attrition rate was 32.3%. In a multiple regression model, initial weight loss and marital status were the strongest predictors of weight loss success after 1-year period (r(2) = 0.481, P < 0.001). In a separate analysis, subjects more likely to drop-out were those with a lower educational level [odds ratio (OR) = 3.26, 95% confidence interval (CI) = 1.22-8.70, P = 0.018] and a higher level of obesity (OR = 0.974, 95% CI = 0.95-0.99, P = 0.010). CONCLUSIONS: The present study demonstrates that initial weight loss at 1 month made the strongest unique contribution to the prediction of percentage weight loss after 12 months, whereas being married was a negative predictor. Those with a lower educational level and a higher level of obesity were more likely to drop-out.

[How much do we know about human brucellosis?]. / Wie viel wissen wir über die humane Brucellose?

Human brucellosis manifests as an acute or persistent febrile disease with a wide variety of symptoms. To our knowledge this is the first case report of brucellar monoarthritis of the hip in Croatia, with difficulties regarding its diagnosis and protracted clinical course.

Treatment of autonomous and toxic thyroid adenomas by percutaneous ultrasound-guided ethanol injection.

PURPOSE: To evaluate the feasibility and efficacy of US-guided percutaneous ethanol injection (PEI) in the treatment of autonomous and toxic thyroid adenomas. MATERIAL AND METHODS: PEI was performed in 42 patients with solitary, scintigraphically "hot" nodules (n=37) or toxic nodular goiter (n=5). The nodular volume ranged from 2.5 to 38 cm3 (mean volume, 20.7+/-14.1 cm3). Ethanol was injected using a free-hand technique, usually in multiple sessions, using color and power Doppler US guidance. Treatment success was evaluated following 3-4 months after PEI by scintigraphy, hormonal status, and US findings. RESULTS: The procedure was technically successful in 39 patients (93%). Three patients were lost to follow-up. Minor complications were pain (all patients), subcutaneous hematoma (n=6), and transitory dysphonia (n=1). A complete cure was achieved in 22 patients (52%), and a partial cure in 10 patients (24%). In 4 cases (9%), the result was unsatisfactory since only moderate hormonal remission was observed. A satisfactory results was thus achieved in 32/42 patients (76%). Significant nodular volume reduction was observed in all cases. Better results were observed in smaller nodules and in cases of autonomous adenomas. There were no cases of recurrent hyperthyreosis. CONCLUSION: US-guided PEI is an efficient and safe method in the treatment of autonomous thyroid nodules and it enables inactivation of nodules with minimal or transitory complications.

[The effect of implementation of a unit dose drug distribution system on drug consumption]. / Utjecaj primjene sustava raspodjele jedinicne terapije na potrosnju lijekova.

As an important drug consumer in Dubrava University Hospital, Department of Cardiac Surgery has been chosen for testing a new model of drug distribution system known as unit dose drug distribution system. During the first 39 weeks in 1996--comparative period, drugs were delivered from the Pharmacy to the Department of Cardiac Surgery in traditional way, known as floor stock system. Next 65 weeks, until the end of 1997--pilot study period, drugs were delivered directly from the Pharmacy to the patients, using unit dose drug distribution system. Consumption of drugs was measured every week by statistical unit DDD/100 hospital days (Defined Daily Dose) according to Anatomic-Therapeutic-Chemistry (ATC) classification of drugs. For statistical measurements, beside common arithmetic means, geometric means were used which are less sensitive to extreme values of drug consumption. During comparative period drug consumption was chaotic with great oscillations around mean value, while in pilot study period that process was without great oscillations around lower mean value and did not exceed the limits of process. Drug consumption was completely under control, so it was a predictable process. In the pilot study period total drug consumption was 39% less, while consumption of drugs from group C was 30% less. During comparative period group C makes 34%, while in the pilot study period it makes 38% of the total drug consumption. This model of drug distribution in hospital leads to a rationalization of drug consumption and great savings. The pharmacist-physician interactive role began to emerge as a direct result of these changes in the drug distribution system. Hospital pharmacist has become a visible member of health care team who is responsible for Quality of all medication-related activities and thus has taken opportunity for clinical pharmacy practice.

Renal vascular resistance in essential hypertension: duplex-Doppler ultrasonographic evaluation.

Duplex Doppler ultrasonography has been validated as a noninvasive method to evaluate hemodynamic features of renal blood flow in renal and intrarenal arteries in patients with various renal diseases. The significance of duplex Doppler sonography in the evaluation of renal vascular resistance in essential hypertension has not yet been clearly determined. The aim of the present study was to evaluate the renal vascular resistance in patients with essential hypertension by measuring intrarenal arterial resistance (RI) and to correlate RI with renal functional tests and other clinical and laboratory data. Duplex Doppler ultrasonography was used to measure RIs in intrarenal arteries in 128 patients with essential hypertension and 61 age-matched normotensive control examinees. The renal vascular resistance index (RI) was determined by use of Doppler ultrasound. Hypertension was classified according to the 1997 Joint National Committee Guidelines (JNC-VI). Mean RI in hypertensive patients was 0.66 +/- 0.05 (+/- sd) and in healthy controls 0.60 +/- 0.03 (+/- sd) (p = 0.0001). RI correlated significantly with patient's age (r = 0.577, p = 0.001), duration of hypertension (r = 0.335, p= 0.001), stage of hypertension according to the JNC-VI classification (r = 0.315, p = 0.006), creatinine clearance (r = -0.383, p = 0.001), systolic blood pressure (SBP, r = 0.41, p = 0.001) and mean blood pressure (MBP, r = 0.30, p = 0.002). RI values did not correlate significantly with plasma renin concentration (r = -0.198 NS), diastolic blood pressure (DBP, r = 0.17, p = 0.06), and cardiac pulse (r = -0.10, p = 0.16). Multiple regression analysis showed that independent variables for RI were the patient's age (multiple R = 0.53, signif. F = 0.001) and systolic blood pressure (multiple R = 0.57, signif. F = 0.03). The renal Doppler resistance index (RI) is increased in essential hypertension and it correlates with renal functional tests as well as with patient's age, duration of hypertension, with a stage of hypertension according to the JNC-VI classification, and with systolic and mean blood pressure. The increased renal vascular resistance (RI) in hypertensive patients could be a sign of developing hypertensive nephrosclerosis and consequently renal failure. The utilization of the renal vascular resistance index (RI), provides a new noninvasive parameter in the followup of patients with essential hypertension.

Pleural mesothelioma and membranous nephropathy.

Underlying malignancy has been thought to be responsible for 5-10% of the cases of membranous nephropathy in adults, with the risk being highest in patients over the age of 60 years. Solid tumors such as carcinomas of lung or colon, are most often involved. It is presumed that tumor antigens are deposited in the glomeruli; this is followed by antibody deposition and complement activation, leading to epithelial cell and basement membrane injury and proteinuria due to the associated increase in glomerular permeability. We describe a patient with a resistant nephrotic syndrome and massive proteinuria due to membranous nephropathy associated with pleural mesothelioma.

[The diabetic foot. The Croatian model--national consensus (clinical recommendations for diagnosis, prevention and therapy)]. / Dijabeticko stopalo. Hrvatski model--nacionalno usuglaseno misljenje (klinicke preporuke za dijagnostiku, prevenciju i lijecenje).

Diabetic foot occurs due to the loss of protective sense and circulation disorder and a marked proneness to infections. Mechanical stress of bone growths frequently leads to ulcerations. The prevention and timely treatment of diabetic foot requires the participation of both patients and all health care levels. This consensus is given for the purpose of procedure standardization. Education is the basis of prevention and should be carried out with every patient suffering from diabetes mellitus and those with a sensory defect in particular. Appropriate footwear significantly contributes to prevention and treatment of ulcers. As regards the treatment, the necessity of surgical approach with a long term and often manifold antibiotic therapy should be pointed out. Infections are usually mixed. The deeper the ulceration, the more likely the infection with anaerobes and Gram-negative bacteria occurs in addition to Gram-positive ones which are normally present in surface lesions. Strict metabolic control is a precondition for successful treatment. In conclusion, diabetic foot is a major health problem which requires multidisciplinary approach with permanent patient education as its essential part, and a specific cooperation of all levels and different health care specialties.

Effect of feeding olive by-products on certain blood parameters and serum enzyme activities of fattening rabbits.

The effect of feeding different levels (10 and 20%) of dehydrated olive cake pulp on certain blood parameters and on the catalytic activity of serum enzymes was studied in fattening rabbits. A total of 60 rabbits were divided into a control group (C) and two experimental groups (E1, E2), each comprising 10 males and 10 females. Rabbits of Group C received no dehydrated olive cake pulp in their diet, while rabbits of Group E1 and Group E2 were fed 10% and 20% dehydrated olive cake pulp, respectively. After Day 56 of the experiment, blood samples were obtained by cardiac puncture and certain blood parameters as well as the catalytic activity of serum enzymes were determined. Following the experimental feeding period no significant differences were found between Group C and Groups E1 and E2 in red blood cell (RBC) and white blood cell (WBC) count, haemoglobin concentration and haematocrit value. Similarly, after 56 days of experimental fattening no significant differences were found between the control group and the experimental groups in the catalytic activity of the serum enzymes alkaline phosphatase (AP), aspartate amino-transferase (AST), gamma-glutamyltransferase (GGT), and lactate dehydrogenase (LDH). However, Group E2 rabbits manifested a significantly higher alanine amino-transferase (ALT) activity in the serum than did rabbits of Group E1. The results indicate that the inclusion of dehydrated olive cake pulp in the diet at the rate of 10% or 20% caused no changes in the investigated blood parameters and serum enzyme activities of fattening rabbits.

Lipoprotein (a) levels in thyroid dysfunction before and after treatment.

AIM: To investigate the possible effects of thyroid hormones on the lipoprotein (a) (Lp(a)) serum concentration. METHODS: Eleven patients with hyperthyroidism (Grave's disease), 18 patients with hypothyroidism and low Lp(a) (Hashimoto's disease), and 13 patients with hypothyroidism (Hashimoto's disease) and elevated Lp(a) were examined before and after thyroid hormone normalization. The measurements included total cholesterol, HDL cholesterol (including HDL2 and HDL3 subfractions), LDL cholesterol, VLDL cholesterol, triglycerides, apoproteins A1 and B, and Lp(a), thyrotropin (TSH) and thyroid hormones/total thyroxine (T4), triiodothyronine (T3), free thyroxine (FT4), and free triiodothyronine (FT3). RESULTS: In patients with hyperthyroidism, serum concentrations of total cholesterol, LDL cholesterol, and apo B significantly increased (p<0.05) after the treatment, whereas a moderate increase in HDL (HDL2 subfraction), triglyceride, and Lp(a) concentrations did not reach statistical significance. In both groups of patients with hypothyroidism, concentrations of total cholesterol, LDL cholesterol, apo B, and triglycerides significantly decreased after the treatment, whereas the changes in HDL (HDL2 and HDL3 subfractions), VLDL cholesterol, apo A1, and Lp(a) were not significant. CONCLUSION: Thyroid hormones had only a moderate effect on the metabolism of Lp(a).

Superoxide dismutase activity in lymphocytes and polymorphonuclear cells of diabetic patients.

Copper-zinc superoxide dismutase (Cu,Zn-superoxide dismutase) activity was evaluated in lymphocytes and polymorphonuclear cells of insulin-dependent (n = 33) and non-insulin-dependent (n = 34) diabetic patients. A commercial method for the measurement of superoxide dismutase activity was adapted for use on a discrete analyser and evaluated for interference by other antioxidants with superoxide anion-scavenging properties. In comparison to healthy control subjects (n = 32), a significantly lower Cu,Zn-superoxide dismutase activity was found in both lymphocytes and polymorphonuclear cells of insulin-dependent (2.08 +/- 0.58 vs. 1.70 +/- 0.46 U/mg protein, p < 0.05, and 1.06 +/- 0.46 vs. 0.64 +/- 0.40 U/mg protein, p < 0.001, respectively) and non-insulin-dependent diabetic patients (2.08 +/- 0.58 vs. 1.61 +/- 0.48 U/mg protein, p < 0.01, and 1.06 +/- 0.46 vs. 0.53 +/- 0.24 U/mg protein, p < 0.001, respectively). There was a week, but significant negative correlation between age and Cu,Zn-superoxide dismutase activity in lymphocytes and polymorphonuclear cells (r = -0.22 and r = -0.28, p < 0.05, respectively), whereas no influence of gender, diabetes duration and glycaemic control was observed. The results indicate that diabetes mellitus could elicit a significant disturbance in superoxide anion-scavenging potential of lymphocytes and polymorphonuclear cells.

The use of visual evoked potentials to follow-up prisoners of war after release from detention camps.

Visual evoked potentials were examined in released prisoners of war (POWs) in order to evaluate the extent of neurological impairment after imprisonment in Serbian detention camps. On two occasions visual evoked potentials were determined in a group of 11 released prisoners of war (POWs): 157 days and 379 days after release from detention camp. During the first examination no significant differences were found in VEP parameters between the right and left eye. However, during the second examination significant differences were found in the latencies of waves P100 and N145, statistically significantly prolonged latencies of the P100 wave and significantly greater amplitudes of waves P50 and N75. The results can be regarded as progression of the VEP changes in the released POWs. It is hypothesized that these changes are a result of a demyelination process, caused by the altered immunological status of the POWs during posttraumatic stress syndrome.

Diabetic nephropathy. Comparison of conventional and duplex Doppler ultrasonographic findings.

BACKGROUND: The purposes of this study were: to compare conventional and duplex Doppler ultrasonography in the detection of renal changes in diabetes mellitus; to investigate whether a correlation was found with various clinical stages; and to assess whether increased renal vascular resistance in asymptomatic patients correlated with mild renal functional impairment. MATERIAL AND METHODS: In 190 diabetic patients and 85 controls, conventional ultrasonography was used to assess renal length, parenchymal thickness, and cortical echogenicity. Renal vascular resistance was estimated by duplex Doppler measurements of intrarenal arterial resistive indices. According to clinical stage, the patients were classified into 3 groups. Resistive indices were compared between controls and patient groups and correlated with age and renal function. RESULTS: In asymptomatic diabetic nephropathy, renal length and parenchymal thickness were significantly increased compared to that of controls, reflecting hyperfiltration-induced nephromegaly. Differences between controls and patients with clinically manifest nephropathy were insignificant; only in advanced renal disease were both values significantly decreased. Cortical hyperechogenicity was noted only in very advanced disease. Resistive indices correlated well with renal function, and pathologic values (i.e. > or = 0.70) were observed in 15% in the asymptomatic group and in 87% in the group with advanced nephropathy. CONCLUSION: Renal changes in diabetic patients are detectable by conventional ultrasound only in very advanced stages of the disease. Pathologic resistive indices, however, may be detected in the earlier stages. Resistive indices correlate with serum creatinine levels and creatinine clearance rates. However, it remains unclear as to whether a diagnostic or prognostic benefit can be expected as compared to standard laboratory examinations.

Brain stem evoked potentials and visual evoked potentials in relation to the length of occupational exposure to low levels of toluene.

In 49 printing-press workers occupationally exposed to toluene for approximately 21.6 years, the values of BEAP and VEP parameters were examined in relation to the length of exposure. With the exception of P2 wave, there was a significant increase in the latencies of all the BEAP waves examined as well as in the interpeak latency (IPL) P3-P4, whereas IPL P4-P5 decreased significantly with the length of exposure. The amplitude of all the VEP examined decreased significantly with the length of exposure. Toluene exposure was evaluated by measuring the concentration of toluene in peripheral blood and of hippuric acid in urine on Wednesday morning prior to the workshift, and of hippuric acid in urine after the workshift on the same day. According to the average concentration of hippuric acid in urine after the workshift, the levels of toluene exposure were estimated to range from 40-60 ppm. Evoked potentials were determined on Mondays 10-12 hours after a nonworking weekend.

Serum total, LDL, HDL cholesterol and triglycerides related to age, gender and cigarette smoking in patients with first acute myocardial infarction.

The aim of this study was to examine relationships between total cholesterol, LDL, HDL cholesterol, triglycerides and age, gender, and cigarette smoking in 190 patients (132 men and 58 women) aged 34-87 years with first AMI. The control group included 103 patients (57 men and 46 women) aged 29-90 years without a history of angina pectoris or AMI. High total cholesterol (over 5.2 mmol/L) was observed in 75% of patients with AMI vs. 48% of patients in the control group (p < 0.001). Patients with AMI had significantly higher total cholesterol and LDL cholesterol levels than controls (p < 0.0001). HDL cholesterol levels were significantly lower among patients with AMI than among the control group patients (p < 0.0001). Serum total cholesterol and LDL cholesterol is higher in patients with AMI up to 60 years old, but lower in patients older than 60 years. Women aged less than 50 years had significantly higher HDL cholesterol (p < 0.001), lower LDL cholesterol (p < 0.001), and lower total cholesterol (p < 0.05) than those over 50 years. Smokers with AMI who smoked over 20 cigarettes per day had significantly higher total cholesterol, LDL cholesterol and triglycerides levels than the non-smokers (p < 0.05). These findings suggest important influences of hyperlipoproteinemia and cigarette smoking upon development of myocardial infarction, especially in younger patients.

Brainstem auditory evoked potentials in individuals exposed to long-term low concentrations of toluene.

Brainstem auditory evoked potentials (BAEPs) were examined in 49 workers employed in a printing press, who were occupationally exposed to low concentrations of toluene for an average of 20.3 years, and in 59 subjects in a control group. In the group of exposed workers, a significant decrease was found in all wave amplitudes examined, a significant prolongation of P1 wave latency, and an increased interval of interpeak latencies (P3-P5), indicating that the extramedullary and high medullary part of the auditory pathway are biologically most frequently affected by chronic exposure to low concentrations of toluene. The level of exposure to toluene in both groups was evaluated by defining the concentration of toluene in peripheral blood and the concentration of hippuric acid and ortho-cresol in urine.

[Fatal "overwhelming" strongyloidiasis in an immunosuppressed patient]. / Smrtonosna "preplavljujuca" strongiloidoza u bolesnika sa suprimiranim imunitetom.

The increased use of immunosuppressants in the treatment of malignant and non-malignant diseases in today's medicine has significantly contributed to the increased interest in infections caused by opportunistic microorganisms and rare parasites. A fifty-eight-year old male patient, professor, born in Bosnia, was admitted to the Institute due to poor general condition and decompensated steroid diabetes. He had been under immunosuppressant therapy for the previous 5 weeks. Six months before, he noticed squamous and crusted changes on capilli, and afterwards on his body too. As these changes did not respond to local therapy he was admitted to the Department of Dermatovenereology, Zagreb University School of Medicine. Histologic analysis indicated pemphigus erythematosus. He was treated with immunosuppressants (methylprednisolone + azathioprine). Endoscopic examinations revealed duodenal ulcer, in addition to diabetes which could not be regulated by oral hypoglycemics. He received antiulcerative therapy for ulcer treatment. Several hours upon admission the patient became highly febrile, and vomited a sanguinolent content. In spite of intensive therapy, he became comatose and died 20 hours later. On autopsy, generalized strongyloidosis of the lungs, liver, duodenum and small intestine, and a bleeding duodenal ulcer due to strongyloidosis were found. This review should remind us that hyperinfestation with strongyloides is a rare and severe complication, and could be expected in immunocompromised patients.