LAM Extra for General Practicioners



MARCH 20, 2013

LAM Extra for General Practicioners - 2013;5(01)



Further articles in this publication

LAM Extra for General Practicioners


KANCZ Sándor

[In this article, we summarise the available information on dabigatran, focusing on clinical practice, in particular on the prevention of stroke and systemic embolism, the critical aspects of anticoagulant treatment with dabigatran, potential drug-drug interactions and adverse reactions in nonvalvular atrial fibrillation. The most important molecular characteristics of dabigatran are also described. We highlight the implications of safety issues that have emerged during everyday clinical practice.]

LAM Extra for General Practicioners


KOHUT László

[INTRODUCTION - The protein complex coenzyme Q10 (CoQ10) has a role in ATP production as a mitochondrial electron transport molecule, and it also has a strong antioxidant effect. Several studies have proved the correlation between the decrease in CoQ10 level and the severity of heart failure. Heart failure is a multifactorial syndrome, the development of which is greatly influenced by an abnormal energy metabolism. CASE REPORT - The 61-year-old woman developed heart failure after a myocardial infarction. She complained of fatigue, dyspnoea and reduced physical endurance even with optimal treatment. When her therapy was completed by CoQ10, her endurance and life quality significantly improved and her symptoms ameliorated. CONCLUSIONS - Medical treatment of chronic heart failure is an evidence-based, complex therapy. Despite the complex management, morbidity and mortality of this condition remain high. A number of studies have shown that CoQ10 substitution can improve the clinical and haemodynamical parameters of patients with heart failure. On the basis of these results, the use of CoQ10 as an adjuvant therapy to complex treatment has an increasing role.]

LAM Extra for General Practicioners



[The role of LDL-cholesterol in cardiovascular risk has been established in a number of studies. According to current recommendations, therefore, the primary goal of lipidlowering therapy is reducing the level of LDL-cholesterol. Of lipid-lowering drugs, statins are the most efficient in reducing cardiovascular risk. According to large studies on statins, however, there is a significant residual risk even in patients receiving aggressive treatment. It is well known that many patients continue to have dyslipidaemia despite statin therapy, and not all patients with cardiovascular disease have elevated LDL-cholesterol levels. These observations indicate that lipids other than LDL-cholesterol also have a role in the development of atherosclerosis. A growing attention is paid to non-HDL-cholesterol as a cardiovascular risk factor. Calculating non-HDL-cholesterol target is easy: LDL-cholesterol measurement plus 0,8. Non-HDL-cholesterol incorporates a number of atherogenic lipoprotein particles [VLDL-cholesterol, IDL-cholesterol, LDL-cholesterol, and lipoprotein(a)]. As the atherogenic effect of apoB-containing lipoproteins (LDL, IDL-C és VLDL) is significant, they may be stronger predictors of coronary heart disease (CHD) risk than LDL-cholesterol is. Considering the strong correlation between apoB and non-HDLcholesterol and the limitations of apoB measurement (standardisation, cost), non- HDL-cholesterol is a more useful parameter and therapeutic target, especially if triglyceride levels are greater than 2.26 mmol/l.]

LAM Extra for General Practicioners



[The development of malignous tumours is a prolonged, multistage process. The onset of clinical symptoms and subjective complaints is preceded by the preclinical detectable phase, during which the tumour does not cause any symptoms but it has some signs and can be detected by screening. Information on the tumour’s natural history is of practical importance for choosing the screening strategy. When evaluating screening results, the various biases related to biological reasons need to be taken into consideration.]

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Lege Artis Medicinae



[The number of diabetic patients will be doubled in the coming decades reaching 300 million for year 2025. The number of type 1 diabetics will also be increased but the majority of it will result from the increased number of type 2 diabetics. All types of diabetes are the consequence of a combination of genetic susceptibility and environmental factors, meaning that the prevention of diabetes epidemic cannot be done without the clarification of the genetic background. Significant progression has happened in the discovery of the genetic background of type 1 diabetes mellitus. It was helped by the etiologic classification of the disease: with the new classification the patient groups became more homogeneous. The HLA system is responsible for about 50-70% of the genetic risk while the effects of other genetic factors contribute 1-2% of the genetic susceptibility, respectively. Presently 25 gene regions are known as the different genetic factors of type 1 diabetes mellitus. Regarding the HLA system, the genes and pathomechanism causing the disease are not known. The classification of diabetes mellitus can be based on the HLA type while the predictability of type 1 diabetes mellitus is helped by the HLA type and the INS-VNTR. Much less is known about the genetic background of the polygenic type 2 diabetes mellitus. Its manifestation is now happening at younger age before. The best-fit genetic model consists of only a few genes with moderate effect superimposed on a polygenic background. Several „candidate” genes participating in the impaired insulin secretion and insulin action have already been investigated as the genes responsible for type 2 diabetes. These data showed the specificity in the population and most showed mild or modest association with the disease. Genomewide scans have resulted a number of significant diabetes susceptibility genes specific for a variety of populations, but these investigations have only resulted in the isolation of one gene (calpain 10) that is thought to contribute to type 2 diabetes. Most recent genomewide scans found loci on chromosome 20 in two different populations with significant segregation of type 2 diabetes. These loci are near to the region harboring the transcription factor hepatocyte nuclear factor genes. The transcription regulator HNF family is responsible for the regulation of the expression of several genes participating in the function of liver and pancreatic islet becoming a strong candidate for being a diabetes gene.]

Lege Artis Medicinae

[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.]

Lege Artis Medicinae

[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

[Type 2 diabetes in children and adolescents: early complications]


[INTRODUCTION - The prevalence of type 2 diabetes mellitus in children and adolescents is increasing worldwide. PATIENTS AND METHODS - Authors have investigated the prevalence of type 2 diabetes mellitus and of impaired glucose tolerance among the patients of the 1st Department of Pediatrics at the Semmelweis University between January 1989 and September 1998. RESULTS - During this period, 161 children with impaired glucose tolerance and 34 patients with type 2 diabetes mellitus were diagnosed. There was a female predominance. 53% of the patients were already in puberty. The majority of the patients were obese. Serum triglyceride and cholesterine levels exceeded normal values as compared to age matched healthy children. Ambulatory blood pressure monitoring revealed relative nocturnal hypertension. 35% of the patients also had microalbuminuria. CONCLUSION - In type 2 diabetes mellitus the early signs of late complications can be detected in the young. It reveals the importance of establishing the diagnosis of this disease as soon as possible.]

Image challenge

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