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ABSTRACT: Type 2 diabetes is a complex disease and genetic as well as environmental factors play a role in its pathogenesis. Six different genes have been identified so far to be responsible for rare forms of autosomal dominant, early onset type 2 diabetes mellitus. All but one are transcription factors which influence expression of the other genes through the regulation of mRNA synthesis. These are hepatocyte nuclear factor (HNF)-4 alpha, HNF-1 alpha, insulin promoter factor (IPF)-1 and HNF-1 beta, which are associated with MODY1, 3, 4, 5 respectively. MODY1 is a relatively rare and usually severe form of diabetes. It is associated with progressive hyperglycemia and frequent chronic complications. The HNF-4 alpha gene is localized on chromosome 20q. Similar clinical characteristics apply to the MODY3 form, however the latter is much more frequent among early onset, autosomal dominant type 2 diabetes (20-40%). HNF-1 alpha gene is localized on chromosome 12q. HNF-1 beta (MODY5 locus on chromosome 17q) is a protein which forms heterodimers with HNF-1 alpha. This rare form of diabetes has a clinical picture similar to MODY1 and MODY3. It is sometimes accompanied by symptoms of early kidney damage which are independent from diabetes. The other two transcription factors responsible for the development of autosomal dominant type 2 diabetes are proteins which bind directly to the insulin promoter. MODY4 (IPF-1, chromosome 13q) is a rare form and of a typical middle and late onset type 2 diabetes. BETA 2/Neurod1 has been recently associated with MODY by Dr Krolewski's group from Joslin Diabetes Center, Boston, MA, USA. BETA 2 is responsible for about 2% of autosomal dominant type 2 diabetes. The clinical characteristics depend on the localization of the mutations in the specific functional domains of the protein. Mutations identified in the glucokinase gene are associated with the MODY2 form. Glucokinase is an enzyme involved in the first level of glucose metabolism in b-cells-enzymatic phosphorylation. MODY2 is a modest form of diabetes. It is characterized by mild hyper-glycemia, mainly fasting, and the chronic complications are very rare. Glucokinase gene is localized on chromosome 7p. It is expected that in the nearest future more type 2 susceptibility genes will be identified.
Przegla̧d lekarski 02/2000; 57 Suppl 3:13-8.
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ABSTRACT: The aim of the study was to find out which model of insulin therapy in patients with noninsulin-dependent diabetes mellitus with secondary inefficacy of sulphonylurea is most effective for glycemia normalization, inhibition of late complications, prevention of atherosclerosis and better quality of life. In 27 patients aged 40-70 years with a history of diabetes over 3 years, BMI < 30, treated with maximal doses of Euclamine we applied 4 therapeutic models: 1) intensive insulin therapy (M1), 2) two injections of three insulins (M2), 3) Euclamin 20 mg + intermediate insulin (M3), 4) Euclamine 20 mg + intermediate insulin (M4). The study lasted 3 months whereas education was carried out within the first two weeks. The following parameters were evaluated: beta cell reserve (glibenclamide test), peptide C level, HbA1C concentration, glycemia profile, lipids, creatinine level. Foci of infection were eradicated. It was found out that: 1) all models of insulin therapy, produced near normoglycemia, 2) the model of intensive insulin therapy does not generate hyperinsulinism in face of body weight loss and improved lipid profile, 3) the model of intensive insulin therapy shows long-term efficacy in the absence of effects when assessing fasting glycemia state (HbA1C, Schilchtkrull's index, lipid indices), 4) the model combining Euclamine with intermediate insulin is on intermediate step leading to another form of insulin therapy.
Przegla̧d lekarski 01/1997; 54(5):308-13.
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M Małecki
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ABSTRACT: The structure and effect of glipizide, the second generation derivates of sulfonylurea were described. The special role in the treatment of polymetabolic syndrome of this drug was stressed.
Przegla̧d lekarski 02/1996; 53(9):663-5.
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ABSTRACT: A case of Werner's syndrome has been reported. The patient presented with insulin resistance, non insulin dependent diabetes mellitus and muscular atrophy.
Przegla̧d lekarski 02/1996; 53(9):676-9.
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ABSTRACT: There is very few data on the prevalence of reactive gastritis (RG) in diabetes mellitus (DM). The typical histological findings in RG are foveolar hyperplasia, oedema with apparent diminution in glands, telangiectasia of lamina propria, a paucity of inflammatory cells. RG has been connected so far with a long term use of non-steroidal anti-inflammatory drugs (NSAIDs) or bile reflux, which is particularly frequent after cholecystectomy. RG is regarded as less frequently associated with the Helicobacter pylori (Hp) infection. The aim of the study was to define: 1. The prevalence of RG in diabetics with dyspeptic symptoms as compared with the non-diabetic group. 2. The prevalence of Hp infection in RG as compared with chronic active gastritis (CAG) in DM. 3. The association of these types of gastritis with autonomic neuropathy (AN). Study design: Gastroscopy was performed in 152 patients with symptoms related to upper alimentary tract disorders-52 with DM (13 with IDDM and 39 with NIDDM) and 100 without DM. The presence of RG, CAG and Hp infection was analysed in 3 biopsies. AN was evaluated in 35 diabetics in 4 cardiovascular tests using ProSciCard. Results: RG was significantly more frequent in DM than in control group (10/52, 19.2% vs. 3/100, 3%, respectively, p < 0.01). This difference was preserved after excluding all patients with NSAIDs use or being after cholecystectomy (8/36, 22.2% vs. 2/81, 2.5%, respectively, p < 0.001). Hp infection in diabetics with RG was significantly lower than diabetics with CAG (2/10, 20% vs. 16/23, 69.5%, respectively, p < 0.05). AN was more frequent in diabetics with RG than with CAG (7/10, 70% vs. 6/15, 40%, respectively, p < 0.001). Hp infection in diabetics with RG was significantly lower than diabetics with CAG (2/10, 20% vs. 16/23, 69.5%, respectively, p < 0.05). AN was more frequent in diabetics with RG than with CAG (7/10, 70% vs. 6/15, 40%, respectively), the difference was not significant with this sample size. Conclusions: 1. RG seems to be more frequent in DM than in general population. 2. Hp infection is less frequent in RG than in CAG in DM. 3. The higher prevalence of RG in DM may result from impaired motility and reflux of bile caused by AN.
Przegla̧d lekarski 01/1996; 53(7):540-3.
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ABSTRACT: The influences of genetic and environmental factors form a clinical picture of type 2 diabetes mellitus. Genetic studies of type 2 diabetes mellitus become increasingly important. The knowledge of the molecular background of type 2 diabetes has been growing rapidly over recent years. One of the forms of the disease defined on the molecular level is maternally inherited type 2 diabetes mellitus. This diabetes, which is frequently accompanied by hearing impairment of deafness (maternally inherited diabetes with deafness-MIDD), was linked with sequence differences in mitochondrial DNA. The most frequent cause of MIDD is A3243G substitution in a mitochondrial tRNA(Leu) gene. While this mutation was identified in different races in several populations, it is still important and valuable to evaluate its prevalence in various ethnic groups. The aim of the project was to determine the prevalence of A3243G substitution in a mitochondrial tRNA(Leu) gene among Polish diabetic subjects.
In total 129 individuals, with type 2 diabetes and 12 with gestational diabetes were selected for this study. Two techniques based on restriction fragment length polymorphism (RFLP) method were used to screen for A3243G mutation. In the first approach, non-radioactive PCR reactions of mitochondrial DNA region of interest were performed using DNA of the study participants. This was followed by Apa I restriction enzyme digestion of the PCR product. Subsequently an electrophoretic separation was done on 2% agarose gel with ethidium bromide staining. In the second, more sensitive, modification of RFLP, [alpha 32P]dCTP was used for internal primer labeling and the electrophoresis was done on acrylamide gel. A positive sample was used to control the quality of the genotyping.
In both approaches none of the samples, except for the positive control, showed the evidence of the G variant.
In summary, the A3243G mutation in mitochondrial tRNA(Leu) gene is not a frequent cause of diabetes in the Polish population. Further screening of enlarging study group is necessary to fully determine the prevalence of this mutation in our population. This, together with the search for other mitochondrial mutations, should allow to fully determine the prevalence of MIDD and its specific molecular background in the Polish population.
Medical science monitor: international medical journal of experimental and clinical research 7(2):246-50. · 1.70 Impact Factor
