Lege Artis Medicinae


DURA Eszter

JULY 20, 2006

Lege Artis Medicinae - 2006;16(07)

[Recent data suggest that the copper-containing semicarbazide-sensitive amine oxidase enzyme (SSAO) may play a role in vascular endothelial damage through conversion of certain endogenous monoamines, such as methylamine, into cytotoxic aldehydes, hydrogen peroxide and ammonia. SSAO is present in various human tissues and in the serum. Elevated SSAO activities have been reported in patients with both types of diabetes mellitus. We have demonstrated that the activity of serum SSAO is significantly higher in type 2 diabetic patients with high-risk proliferative diabetic retinopathy compared to those without retinopathy. Our clinical results support the hypothesis that elevated SSAO activity may be involved in the pathogenesis of microvascular diabetic late complications, such as retinopathy. The enzymatic conversion of the endogenous monoamines (e.g. methylamine, aminoacetone) into toxic aldehydes and hydrogenperoxide may be one of the possible mechanisms of the development of microangiopathy. Also, the vascular adhesion protein-1 (VAP-1) function of the molecule can cause leukostasis and leukocyte activation through increased leukocyte adhesion, resulting in worsening of the capillary circulation and hypoxia. Further prospective, larger studies are needed to elucidate the role of the possible association between serum SSAO activity and highrisk proliferative retinopathy in patients with type 2 diabetes. The pharmacological manipulation of SSAO activity might be an interesting new concept for prevention and treatment of diabetic retinopathy.]



Further articles in this publication

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[In the focus: periferal vascular diseases - Readers’ questions answered by dr. Éva Meskó]


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[Sustained oral anticoagulant therapy]


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LAKATOS László, LAKATOS Péter László

[Antibiotic treatment is complicated by diarrhea in 5 to 25% of the cases. Its prevalence depends on the antibiotic used, the patient’s age, the concomittant diseases and the immune response. The severity of the diarrhoea is variable ranging from a mild self-limiting disease lasting for 1 or 2 days to a severe condition with high mortality. The diarrhea may result from a direct effect on the gut, but more commonly it is the consequence of changes in resident gut flora. Clostridium difficile is responsible for 10 to 20% of all antibiotic-associated diarrhea cases. The clinical presentation varies from asymptomatic carriage to fulminant pseudomembranous colitis. This latter typically develops as a nosocomial infection, mainly in patients treated with cephalosporins, amoxicillin-clavulanic acid combination or clindamycin. Risk factors are advanced age, severe underlying disease, treatment in an intensive care unit, long hospitalization and invasive medical procedures. The clinical picture is characterized by frequent, watery (occasionally bloody) diarrhea, abdominal pain, tenesmus, fever, weakness. Fulminant colitis develops in 3-5% of cases. The diagnosis is based on testing for C. difficile toxins, but in selected cases rapid diagnosis can be made by flexible sigmoidoscopy. The treatment consists of the withdrawal of the implicated antibiotic along with administration of oral metronidazole or vancomycin which target C. difficile itself. Most patients respond to this treatment; however, the mortality of fulminant cases or those with severe underlying disease is high. Fifteen to 20% of the patients relapse and management of the recurrent cases is difficult. Combination treatment, probiotics and/or passive immunization may be used. Preventive measures include judicious use of antibiotics and aggressive control of the spread of C. difficile infection.]

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[Night Swim The Collages of Zsolt Sándor]

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NAGY Pál, Z.SZABÓ László, DOMJÁN Gyula, GADÓ Klára, BALOGH Károly

[INTRODUCTION - Wegener's granulomatosis has an uncertain pathomechanism, but is probably autoimmune in origin. In typical cases the mucosa of the nose, paranasal sinuses and of the lower respiratory tract, as well as the lungs and the kidneys are affected. Patients present with sinusitis, recurrent pneumonia or renal disease associated with microhaematuria, pyuria or azotaemia. Fever, polyarthralgia or polyarthritis may also occur. The underlying pathologic changes are necrotizing vasculitis, granulomas and parenchymal necrosis. The diagnosis is based on a combination of the clinical picture, microscopic findings and immunofluorescent demonstration of cANCA. CASE REPORT - A 27-year-old woman presented with symptoms of unilateral mastoiditis. In the following 7 months she underwent 7 operations in 4 hospitals for a locally progressive, destructive process of uncertain etiology showing a septic course. The clinical picture was not specific, the cANCA test was not definitive, and the histologic findings were initially interpreted as nonspecific inflammation. Repeated biopsies, multiple reviews of the microscopic specimens, consultations, differential diagnostic considerations, and, finally, the success of the treatment with corticosteroids and cyclophosphamide led to the diagnosis of Wegener’s granulomatosis. Currently the patient has been in remission for 32 months. CONCLUSION - The definitive diagnosis of Wegener’s granulomatosis, particularly of its localized or limited form, may be problematic despite well-defined diagnostic criteria. Setting up the correct diagnosis may take months or years. In case of unusual respiratory or otological symptoms, and in view of ineffective medical or surgical treatment, Wegener’s granulomatosis has to be considered. An atypical clinical picture, inconclusive histologic, radiologic and laboratory findings warrant the need for close collaboration of various specialists. This is particularly important since state-of-the-art therapy of Wegener’s granulomatosis promises a favourable prognosis.]

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[Cost minimization analysis of basal insulin analogues in the treatment of type 2 diabetes]

MERÉSZ Gergő, TABÁK Gy. Ádám, KALÓ Zoltán

[INTRODUCTION - Basal insulin analogues are essential drugs for the treatment of type 2 diabetes mellitus. Basal insulin analogues have been shown to reduce the frequency of hypoglycaemia versus NPH insulin, and thus may be beneficial in the treatment of type 2 diabetes. Here we present a cost-minimisation analysis of basal insulin analogues, comparing insulin glargine and insulin detemir available in Hungary. METHODS - A literature review was conducted to identify randomized, controlled clinical trials with a duration of 12 weeks or more in which a direct comparison of insulin glargine and insulin detemir was made in patients with type 2 diabetes. In a meta-analysis of the eligible trials, the following endpoints were investigated: metabolic status, body weight, frequency of hypoglycaemia, insulin doses administered and the number of insulin injections required. If a high heterogeneity (I2>75%) was found, meta-regression was performed to identify the underlying reasons. The funder’s perspective was applied in the cost-minimization analysis by taking into account the cost of the drug and of medical devices necessary for its administration, based on the daily number of insulin injections. RESULTS - No further studies were found in addition to those included in a metaanalysis published by The Cochrane Library. On the basis of three eligible studies, insulin detemir was injected more frequently compared with glargine (weighted mean difference: 0.42 95% CI 0.14-0.69 injections/day). High heterogeneity was present in case of two endpoints: the incidence of overall hypoglycaemia per patient-year (I2=83%), and daily basal insulin dose in units per body weight (I2=94%). The reason for the high heterogeneity in hypoglycaemia rates was not identified by meta-regression; however, the difference in insulin doses per body weight was negatively associated with body weight (-0.027 IU/kg per 1 kg, 95%CI: -0.051; -0.004). On the basis of the present meta-analysis and meta-regression, our calculations suggest that treating an average weight (90 kg) patient with type 2 diabetes with insulin glargine would result in an annual cost reduction of 93 452 HUF compared with insulin detemir by employing gross public drug prices. CONCLUSION - On the basis of the available clinical evidence, insulin glargine might be a cost-saving alternative of insulin detemir in an average-weight patient with type 2 diabetes. In an era of scarce resources, the role of therapeutic alternatives offering cost savings with the same efficacy become more important. The generalisability of our conclusions might be influenced by potential differences in the manufacturers’ claw-back rate of detemir vs glargine insulin.]

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TABÁK Gy. Ádám

[Type 2 diabetes mellitus and metabolic syndrome are important risk factors of cardiovascular morbidity and mortality. Both diseases present with a similar set of metabolic disturbances including hyperglycaemia, hyperlipidaemia, hypertension and obesity. Therefore, their nonpharmacological treatment is based on similar principles. Medical nutritional therapy aims to promote moderate weight loss through decreased energy intake, and to correct metabolic disturbances by ensuring appropriate composition of micro- and macronutrients. In a healthy diet, carbohydrates and cis-fatty acids make up approximately 60 to 70% of total energy intake. It is important to reduce the intake of saturated fatty acids and trans-fatty acids. The consumption of foods with low glycaemic index may be beneficial for diabetic patients. The increase of physical activity (both aerob and resistance exercise) is useful in maintaining weight loss, and it also improves blood lipid levels and blood pressure. Abandonment of smoking results in significant cardiovascular risk reduction. Lifestyle changes should include all of the above factors in order to achieve most reduction in morbidity and mortality associated with type 2 diabetes mellitus and the metabolic syndrome.]

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[Titration of insulin glargin in type 2 diabetic patients treated with oral agents and with necessity of basal insulin in everyday medical practice ]


[INTRODUCTION - Early insulin treatment is a widely accepted option for combination glucose-lowering therapy, and its most common form is basal insulin supported oral therapy (BOT). Due to its 24-hour action and lack of peaks in plasma insulin concentrations, insulin glargine is an ideal choice for BOT. METHODS - We conducted a prospective, non-interventional study to evaluate the efficiency and safety of dose titration, the period of time necessary to reach the target fasting blood glucose level, and the changes in glargine insulin dose. The study group included patients with type 2 diabetes who had been treated with insulin glargine in BOT regimen for no longer than four weeks. The follow-up period was six months. RESULTS - During the study period, the mean fasting plasma glucose was decreased from 9.8 mmol/L to 6.7 mmol/L, the mean HbA1c level decreased from 8.8% to 7.3%, and the mean postprandial glucose level decreased from 11.5 mmol/L to 8.2 mmol/L. Mild hypoglycaemic episodes occurred in 6.5% of patients in the first 3 months and in 6.9% of patients between months 3 and 6. During the same periods, severe hypoglycaemic episodes occurred in 0.08% and 0.17% of patients, respectively. Both mean body weight and mean BMI decreased during the study period. The average daily dose of glargine continuously increased during the observation period from baseline 10.42 IU to 17.69 IU. DISCUSSION - In the study population, glargine therapy in BOT regimen significantly improved glycaemic control, while a slight but statistically significant reduction was observed in the patients’ body weight. The daily dose of insulin glargine increased during titration, and the therapy proved to be safe.]

Lege Artis Medicinae

[Antidiabetic therapy of patients with type 2 diabetes - The place of administration of acarbose]


[Administration of the alpha-glucosidase enzyme inhibitor acarbose leads to a prolonged absorption of carbohydrates, which has a smoothing effect on blood glucose excursions, and results in a more even daily blood glucose profile. The glucose lowering effect is mainly due to the reduction of postprandial blood glucose levels. Non-glycaemic effects of acarbose, including those on blood pressure, lipids and the coagulation system are also clearly beneficial. According to the available data, the preparation also reduces cardiovascular risk. If used as a monotherapy, acarbose does not cause hypoglycaemia. Flatulence and diaorrhea represent the main side effects. From a professional point of view, acarbose should be given if postprandial blood glucose excursions exceed 2.2 mmol/l.]

Image challenge

What do you see on the feet of the diabetic patient?