Lege Artis Medicinae

[THE GENETICS OF DIABETES MELLITUS]

KORÁNYI LÁSZLÓ, PÁNCZÉL Pál

JULY 20, 2004

Lege Artis Medicinae - 2004;14(07)

[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.]

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[INTRODUCTION - In Hungary the number of induced abortions is three times higher than in European Union countries. The exploration of the bio-psycho-social factors in the background of abortions may serve as an instrument to develop effective prevention. METHODS - The Hungarostudy 2002 national representative study included 12,634 interviewed subjects. The sample represents the Hungarian population above the age of 18, according to gender, age and geographical location. The aim of the health survey was to analyse the physical and psychological status of the Hungarian population as well as the psychosocial risk factors. The prevalence of abortion in the female sub-sample was 22%. We analysed the background factors of abortion with the help of a statistical analysis. RESULTS - The risk factors behind abortions can be grouped as: physical abuse on behalf of partners and/or parents, attachment disorder and early traumatisation, lack of social support, low financial status and inadequate social environment. These factors have all shown significant connection to abortions. Suicide attempts and suicidal thoughts, high Beck Depression (BDI) scores, smoking and alcohol consumption are also significant among those who had abortions. CONCLUSION - An important aim of the Hungarostudy 2002 survey and the follow-ups is to serve a more extensive and effective prevention by exploring the background factors of induced abortions.]

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[INTRODUCTION - In recent years a number of clinical trials have been proved that infliximab, a monoclonal chimeric antibody against tumour necrosis factor (one of the proinflammatory cytokines) is an effective induction and maintenance therapy in severe and fistulizing Crohn’s disease. The authors summarize the results of the first Hungarian, open, multicenter clinical trial with biological treatment of Crohn’s disease. PATIENTS AND METHODS - Overall 74 patients in 9 study-centers were enrolled and allocated into the following two groups: 29 patients (31%) with severe, active, therapy-resistent clinical picture of Crohn’s disease and 45 individuals (61%) showing fistulizing forms of the disease. Infliximab was administered iv. in a dose of 5 mg/kg body mass one single occasion in patients formed the first group and altogether three times in cases suffering of fistulizing form of the disease. RESULTS - In active Crohn cases infliximab exerted its beneficial effect within 4 weeks (58% of patients improved) which was most pronounced at week 8th (79% of the patients was in better condition). However, in cases of fistulizing form longer period is neccessary for developing the effect. In 76% of treated patients proved to be efficacious within 14 weeks but later on flare-ups were observed. Concomittantly administered immunsuppressive agents did not altered the beneficial effect of infliximab. CONCLUSIONS - The results are proving the benefit of infliximab induction therapy both in cases of severe, active or in fistulizing forms of the disease. The article reviews the indication of infliximab treatment and provides a „user’s guide” for practizing clinicians.]

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