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Biomedical subjects

J Sieradzki

Publications and source records attributed to J Sieradzki.

At least 19 recordsLinked to original sources
PubMed2006

Clinical risk factors and the role of VDR gene polymorphisms in diabetic retinopathy in Polish type 2 diabetes patients.

Evidence exists that some clinical, metabolic and genetic risk factors are associated with the development of diabetic retinopathy (DR). The aim of the study was: (1) to define the prevalence of DR in the examined group of 267 patients with type 2 diabetes mellitus (T2DM) from a Polish population; (2) to identify in cross-sectional analysis, the clinical features associated with DR in the study group; and (3) to search for the association of 4 markers of vitamin D receptor (VDR), a candidate gene for vascular complications in diabetes, with DR. The examined group consisted of 146 female and 121 male T2DM patients (mean age at examination: 61.3+/-9.4 years; age at T2DM diagnosis: 50.0+/-9.2; T2DM duration: 11.3+/-7.8 years; body mass index (BMI): 30.5+/-5.5 kg/m(2); HbA1c: 7.8+/-1.5%). In all patients, the clinical and metabolic profile was determined. Diagnosis of DR was determined by a trained ophthalmologist by ophthalmoscopy after pupillary dilatation. Colour photographic documentation was made. The examined T2DM patients were genotyped for FokI, ApaI, BsmI and TaqI frequent VDR polymorphisms based on the restriction fragment length polymorphism method. The statistical analysis was performed using univariate and multivariate logistic regression (SAS) and haplotype analysis (Haplostat). DR was detected in 85 (31.8%) patients with T2DM. The multivariate analysis revealed that significant predictors of this complication were: never-smoking status (odds ratio 2.2, 95% confidence interval 1.2-4), urea serum level (1.3, 1.1-1.5), HbA1c level (1.4, 1.1-1.8) and insulin treatment (2.7, 1.4-5.1). Other features such as age of T2DM diagnosis, T2DM duration prior to ophthalmic exam, obesity (BMI>30), serum creatinine level, albumin/creatinine ratio and arterial hypertension were univariate predictors of DR, however they lost significance as independent predictors in multivariate analysis. Similarly, the alleles, genotypes, haplotype and haplotype combination of VDR were not associated with the examined complication. However, there was a suggestion of a possible slight association between the fbaT haplotype and DR (p=0.11). In conclusion, our study showed that DR in T2DM patients remains a frequent complication in Polish T2DM patients. We were able to confirm the role of some clinical risk factors, surprisingly including not-smoking status, as was previously shown in the UK Prospective Diabetes Study (UKPDS). VDR gene polymorphisms did not constitute a risk factor for this size of study group.

Body Mass Index↗
PubMed2006

Polymorphisms in the gene encoding hepatocyte nuclear factor-4alpha and susceptibility to type 2 diabetes in a Polish population.

Recently, several association studies of type 2 diabetes mellitus (T2DM) and the hepatocyte nuclear factor (HNF)-4alpha gene were reported with conflicting results. Our aim was to search for association between two polymorphisms of HNF-4alpha and T2DM in Polish Caucasians. The study groups comprised of 461 T2DM cases and 366 controls. Genotype-quantitative trait analyses were based on the oral glucose tolerance test (OGTT), glucose and insulin results, and comprised 310 glucose-tolerant subjects. All individuals were genotyped for two HNF-4alpha polymorphisms. The frequencies of the minor alleles were as follows: 19.2% in T2DM vs. 17.6% in controls for rs2144908; and 20.6% vs. 20.1% for rs4810424, respectively. The distributions of alleles, genotypes, and haplotypes of the HNF-4alpha polymorphisms did not differ between the study groups (lowest P = 0.41). None of the examined SNPs showed an association in control subjects with quantitative traits of fasting plasma glucose, fasting insulin, as well as plasma glucose and insulin 2 hours after glucose load in OGTT. We conclude that both examined polymorphisms in HNF-4alpha are not associated with T2DM and prediabetic phenotypes in Polish Caucasian study groups of this size.

Blood Glucose↗
PubMed2003

The Ala45Thr polymorphism of BETA2/NeuroD1 gene and susceptibility to type 2 diabetes mellitus in a Polish population.

The BETA2/NeuroD1 gene product is a transcription factor, a member of a helix-loop-helix (HLH) family that is specifically expressed in the endocrine pancreas. HLH and homeobox proteins are involved in the development and function of pancreatic islets cells. Mice homozygous for a targeted disruption of BETA2/NeuroD1 showed abnormal pancreatic islet morphogenesis and developed overt diabetes. Mutations in the NeuroD/BETA2 gene were linked to the development of type 2 diabetes (T2DM). The aims of the study were to determine the allele and genotype frequency of Ala45Thr polymorphism of BETA2/NeuroD1 in a Polish population and to examine the role of this amino acid variant in the genetic susceptibility to T2DM. We included 394 individuals into this study: 223 T2DM patients with the age at diagnosis above 35 years and 171 controls without a family history of T2DM. The fragment of the gene, corresponding to the Ala45Thr amino acid variant, was amplified by polymerase chain reaction. Alleles and genotypes were determined based on electrophoresis of the specific restriction enzyme EcoI57 DNA digestion products. Differences in distribution between the groups were examined by chi(2) test. The frequencies of the Ala and Thr alleles in T2DM patients (62% and 37.9%) were similar to those in the controls (65.5% and 34.5%; p=0.32). Similarly, there was no difference between the groups when we analyzed the genotype distribution (p=0.24). The stratification analysis based on family history of T2DM, obesity, and age of diagnosis did not show any difference between the groups. In conclusion, the frequency of Ala45Thr polymorphism in this studied Polish population is similar to its frequency in other Caucasians. We did not find evidence that the Ala45Thr polymorphism of BETA2/NeuroD1 played a role in the risk of T2DM in the examined Polish population.

Adult↗
PubMed2003

Association study of the vitamin D: 1alpha-hydroxylase (CYP1alpha) gene and type 2 diabetes mellitus in a Polish population.

OBJECTIVES: Type 2 diabetes mellitus (T2DM) is a complex disease. Genetic and environmental factors cooperate together to form its clinical picture. Polymorphisms in genes involved in the metabolism of vitamin D may influence susceptibility to T2DM. One of them is the vitamin D 1alpha-hydroxylase (CYP1alpha) gene. In this study we searched for the association of two markers, one in its intron 6 and the another one located upstream from the 5' end of CYP1alpha gene, with T2DM in a Polish population. METHODS: Overall 522 individuals were included in this study: 291 T2DM patients and 231 controls. The sequences, which contain both examined variants, were amplified by polymerase chain reaction (PCR). The T-->C polymorphism in intron 6 was assessed by the dot-blotting method using P(32). Genotyping of the other variant in the 5' end of CYP1alpha gene was carried out by restriction fragment length polymorphism (RFLP) method. Since variants of both SNPs were in very strong linkage disequilibrium, haplotypes could be assigned to phase-unknown individuals. The distribution of alleles, genotypes, haplotypes and haplotype combinations was compared between the groups by chi(2) test. RESULTS: The frequency of T/C alleles of the 5'end variant was 81.7%/18.3% in T2DM patients and 82.8%/17.2% in the controls (chi(2)=0.2, 1.d.f., p=0.65). For a T-->C polymorphism in intron 6 the frequency of alleles was 65.1%/34.9% and 67.5%/32.5% in T2DM patients and controls, respectively (chi(2)=0.413, 1.d.f., p=0.669). Distribution of genotypes, haplotypes and haplotype combinations were similar in both groups. In stratified analysis, we observed that the T-C/T-T heterozygous haplotype combination was more prevalent in the subgroup of obese T2DM patients (BMI >=30) than in the controls (41.5% vs 28.6%, p=0.01). CONCLUSIONS: Vitamin D 1alpha-hydroxylase is not a major gene for T2DM in a Polish population. However, this gene may be associated with T2DM in subjects with obesity. Thus, to definitely determine the role of this gene in T2DM further studies are necessary in other populations using larger sample size.

Cytosine↗
PubMed2003

Vitamin D receptor gene polymorphisms and association with type 2 diabetes mellitus in a Polish population.

Vitamin D plays an important role in insulin secretion. There is also evidence that this steroid may influence the insulin sensitivity. Thus genes involved in its metabolic pathway have been regarded as good candidates for type 2 diabetes mellitus (T2DM). One of them is vitamin D receptor gene (VDR). Its multiple polymorphisms have been examined for the association with T2DM in several populations. Those studies did not provide clear answers about the role of VDR in this disease. The aim of the study was to search for the association of FokI, ApaI, BsmI, and TaqI polymorphisms of VDR gene with T2DM in a Polish population using a case-control study design. Overall, 548 individuals were examined: 308 T2DM patients and 240 control individuals. The study groups were genotyped for VDR FokI, ApaI, BsmI, and TaqI variants using the restriction fragment length polymorphism (RFLP) method. Since variants of ApaI, BsmI, and TaqI polymorphisms were in very strong linkage disequilibrium, three loci haplotypes could be assigned to phase-unknown individuals with a high degree of confidence. Differences in allele, genotype, haplotype, and haplotype combination distribution between the groups were examined by chi2 test. The VDR allele frequencies for T2DM patients and controls were as follows: FokI-F/f - 53.4 %/46.6 % vs. 55.2 %/44.8 %, BsmI-B/b - 34.4 %/65.6 % vs. 37.5 %/62.5 %, ApaI-A/a - 47.9 %/52.1 % vs 50.9 %/49.1 %, TaqI-T/t - 67.6 %/32.4 % vs. 62.7 %/37.3 %, respectively. There was no difference between the groups in allele frequency. Similarly, distribution of genotypes, three locus BsmI/ApaI/TaqI haplotypes and their combinations were similar in the groups. In conclusion, our study did not provide evidence for the association of four examined VDR polymorphisms with T2DM in a Polish population. We postulate that to fully determine whether the sequence differences in VDR gene are susceptibility variants for T2DM, additional studies in different populations are required in a large study group.

Adult↗
PubMed2001

The evaluation of analytical performance of the Precision G point-of-care glucometer.

In this study analytical and functional performance of the Precision G "point-of-care" glucometer (MediSense Inc.) was evaluated. Studies were carried-out using capillary blood collected for routine monitoring of glycemia in diabetic patients. Each glucose test measurement with the glucometer was paralleled by the laboratory measurement of glucose on the same blood sample, using the GOD/PAP method. Mean accuracy error in the glucose concentration range of 1.1-33.3 mmol/l calculated for the glucometer vs. the laboratory method amounted to only 0.2%. However, for glucose concentrations below 4.4 mmol/l the mean accuracy error was 3.9%, and for the concentrations above 10.0 mmol/l it was 4.6%. Within-run CV for three concentration levels was 2.76%, 2.89%, and 4.22%, respectively. Linearity of the meter response in samples with glucose concentration ranging from 1.7 mmol/l to 16.7 mmol/l, expressed as the correlation coefficient r, yielded r=0.996 and linear regression equation [y1 = 0.996 y2 - 0.005], where y1 is the measured glucose concentration and y2 is the target glucose concentration calculated in diluted samples. Correlation studies on a set of 114 blood samples collected from patients and assayed by glucometer and by the laboratory method yielded a relationship expressed by the equation: y = 0.84x + 1.13 where y is glucometer read-out and x is glucose concentration obtained by the laboratory method. Passing-Bablok test showed a significant agreement between the glucometer measurements and the reference laboratory results in the studied glucose concentration range. The error grid analysis of series of the paired patient's samples showed that 95% of results were in the clinically acceptable zone A and 1% of results in zone D.

Blood Glucose↗
PubMed2001

Identification of a new mutation in the hepatocyte nuclear factor-1alpha gene in a Polish family with early-onset type 2 diabetes mellitus.

Recently, several genes associated with early-onset, autosomal dominant Type 2 diabetes (MODY) have been identified. Mutations in the hepatocyte nuclear factor (HNF)-1alpha gene seem to account for a substantial proportion of this type of diabetes in several populations. However, it is still of interest to estimate the frequency of HNF-1alpha mutations in various ethnic groups. The aim of our study was to determine the contribution of the HNF-1alpha gene to the development of MODY in a Polish population. We selected 15 families with MODY for this project. The 10 exons and promoter region of the gene were screened for sequence differences by direct sequencing of probands DNA. We detected 7 previously described polymorphisms that were not associated with diabetes. However, one sequence difference, a deletion of a cytosine in codon 225 in exon 3 (designated S225fdelC), was a new mutation resulting in a frame shift and synthesis of a nonsense peptide from amino acid 225 to 232 followed by the stop codon. Thus, the S225fdelC mutation effectively caused the loss of a part of the DNA binding domain and the entire transactivation domain. This mutation was present in 4 affected members of the family. They developed diabetes at an early age (mean age at diagnosis 23 yr) and were characterized by severely impaired insulin secretion. In addition, one family member who was not a carrier of the S225fdelC mutation was diagnosed with diabetes. Thus, he represents an example of phenocopy. In conclusion, we have identified a new HNF-1alpha variant that represents the first MODY mutation described in a Polish population. MODY3 mutations, including those in the exon 4 "hot spot", do not appear to be a very common cause of MODY in the Polish population.

Adolescent↗
PubMed2001

[Bone metabolism as assessed with selected markers of bone turnover as well as densitometry analysis in patients after successful kidney transplantation].

The degree of advancement as well as symptoms of renal osteodystrophy improve significantly in patients after successful kidney transplantation; however bone pathology is still present even after many post-transplant years. The aim of this study was to analyze the bone densitometry in patients during different periods after kidney transplantation and to assess bone metabolism using selected biochemical markers of bone turnover in comparison to healthy controls. Study population consisted of 73 patients of mean age 41.7 +/- 12.6 years (27F, 46M) mean 34 +/- 42 months after kidney transplantation. Mean period of maintenance dialysis prior to surgery was 28.6 +/- 20.3 months. We also analyzed age- and sex-matched control group of 24 subjects. Three-point densitometry was performed with DEXA technique. Serum levels/activity of osteocalcin, C-terminal propeptide of procollagen type I (PCTP), alkaline phosphatase (AP) and its bone-specific isoform (BAP) as well as desoxypiridine (DPD) urine level were analyzed as markers of bone turnover. Serum levels/activity of all mentioned parameters were significantly increased (p < 0.001) and urine DPD--significantly decreased (p < 0.05) in patients as compared to controls. Based on DEXA technique 26% of patients were categorized as having osteoporosis, 32.9%--osteopenia and 41.1% as normal in bone densitometry. Patients with diagnosed osteoporosis spent significantly longer time with functioning graft as compared to those with normal densitometry. In addition, subjects with osteoporosis were characterized by significantly higher serum level of osteocalcin as compared to those with osteopenia and normal DEXA (42.5 +/- 19.9 vs 26.6 +/- 15 ng/ml and 42.5 +/- 19.9 vs 30.2 +/- 104 ng/ml, respectively; p < 0.05). Identical relationship was also observed for serum PTH (128 +/- 42 vs 77.2 +/- 30.4 pg/ml and 128 +/- 42 vs 81.2 +/- 232 pg/ml, respectively; p < 0.001). There was also significant difference in PCTP level in all analyzed groups (203 +/- 85, 171 +/- 69 and 137 +/- 40 ng/ml in subjects with osteoporosis, osteopenia and normal; p < 0.05 for all differences). BAP activity reduction was observed only in the latter group of patients. Results of our study led us to conclude that the prevalence of osteoporosis and osteopenia in three-point densitometry among patients with functioning graft is high. Increased serum levels/activity of osteocalcin, PCTP, AP and BAP with concomitant decrease of urine DPD elimination suggest the predominance of bone formation over the bone resorption process.

Absorptiometry, Photon↗
PubMed2001

[Deep breathing test type I diabetic patients and parameters of spectral analysis].

UNLABELLED: Nervous system injury, affecting also its autonomic part, occurs in the natural course of chronic complications in patients with type 1 and 2 diabetes. The aim of the study was to compare heart rate frequency analysis parameters at rest and after deep breathing test in healthy persons and in the group of type 1 diabetes patients without complications. The study was performed in 34 patients with type 1 diabetes without chronic complications (N0), hospitalized in the Chair and Department of Metabolic Diseases in 1993-1996. The control group (K) consisted of 23 healthy persons. All diabetic patients underwent examinations to identify chronic complications of the disease. Aiming at answering the question how simple physiological tests influence frequency parameters of heart rate variability, assessment of VLF, LF and HF parameters was performed at rest and after the deep breathing test. In both groups K and N0 no changes were observed in the spectrum power within VLF values after deep breathing compared to the initial values. In the group K the deep breathing test significantly (p < 0.001) increased spectrum power within LF values, whereas in the group N0 the test did not produce statistically significant changes of this parameter compared to the initial values. In the control group K as well as in diabetic patients N0 the test caused significant (p < 0.01 and p < 0.001, respectively) decrease in the HF spectrum power in comparison to the values at rest. VLF/LF ratio after the deep breathing test as well as LF/HF ratio at rest were significantly lower in the group K compared to the group N0. CONCLUSION: Analysis of the autonomic nervous system imbalance may be an indispensable tool in the early diagnostics of patients with type 1 diabetes. Results of spectrum analysis may be useful in cases when classical Ewing battery tests do not identify autonomic dysfunction.

Adult↗
PubMed2000

Effects of comicronised fenofibrate on lipid and insulin sensitivity in patients with polymetabolic syndrome X.

BACKGROUND: This study investigated the effects of comicronised fenofibrate in patients with dyslipidemia and polymetabolic syndrome X. DESIGN: After a 6-week dietary run-in phase, 37 male patients eligible on lipid criteria entered a 12-week treatment phase consisting of diet plus one capsule daily containing 200 mg of comicronised fenofibrate (Lipanthyl(R)). RESULTS: A significant reduction in plasma concentrations of total cholesterol, LDL cholesterol and triglyceride was observed after 4, 8 and 12 weeks of treatment with fenofibrate. The improvement in the atherogenic index LDL/HDL cholesterol from a pretreatment 3.8 to 3.0 after treatment was highly statistically significant and may be judged as satisfactory. Significant changes were also observed in haemostatic factors (fibrinogen reduced by 19%, factor VII activity reduced by 18%). Fasting serum insulin levels and insulin response (area under the curve) after oral glucose load were significantly reduced by 26.8% and 18.7%, respectively, indicating an improvement of insulin sensitivity. Systolic and diastolic blood pressure were significantly reduced. Uric acid was significantly reduced by 21.6%. CONCLUSION: These favourable effects of comicronised fenofibrate both on lipid and non lipid parameters, including insulin sensitivity, may confer to this product a particular interest in the treatment of patients with polymetabolic syndrome X.

Adult↗
PubMed2000

[Drugs stimulating insulin release. Importance of their use for improving glycemia, safety and quality of life in diabetes mellitus type 2].

Etiopathogenesis of diabetes mellitus is bipolar. On one hand there occurs impairment in beta-cell function caused by genetic factors or abnormal development during fetal period. On the other hand defects of peripheral insulin action are also of significant importance. The bipolarity is also expressed by changing relationship between genetic and environmental factors. Insulin release is connected with closing ATP-dependent kalium channel, a structure closely connected with sulfonylurea receptors. Several receptors may be distinguished: SUR1 in Langerhans isles and SUR2 in heart (SUR2A) and vessel smoot muscles (SUR2B). In the treatment of insulin release disorders sulfonylureas are still of significant importance though repaglinid and phenyloalanine derivates also have some clinical importance. Within sulfonylurea derivates there have been developed some preparations of slow drug release (Glibenese GITS, Diaprel MR). One daily dose of Glibenese GITS and lower tendency to hypoglycaemia favour acceptation of the therapy by the patients what is also important for their quality of life. Quality of life is now regarded as important as obtaining good indices of diabetes control.

ATP-Binding Cassette Transporters↗
PubMed2000

[Uprighting test, deep respiration test and Valsalva test in patients with diabetes type 1].

Autonomic diabetic neuropathy of cardiovascular system is one of the late diabetic complications. The aim of the study was to compare heart rate time domain analysis in 23 healthy controls and in diabetic patients without (N0; n = 34) and with complications (N1, n = 55) such as retinopathy, peripheral neuropathy as well as autonomic neuropathy. The study was performed in a group of 89 patients with diabetes mellitus type 1. Classical tests of Ewing battery (upright test, Valsalva test, deep breathing test) were performed using the ProSciCard machine as well as parameters of time domain analysis were observed during prolonged to 15 minutes standing in upright body position. Comparing group N1 to group N0 significantly higher heart rate, lower standard deviation of RR interval as well as lower value of rMSSD both at rest and during prolonged stay in upright position were demonstrated.

Adult↗
PubMed2000

[Risk factors for occurrence of ophthalmopathy in the course of Graves-Basedow disease].

Ophthalmopathy is a serious complication of Graves-Basedow disease. It is a common and the most significant symptom of this illness and usually persists even when other symptoms associated with abnormal thyroid function disappear. Despite of well-known auto-immunologic patho-genesis of ophthalmopathy it is still hard to predict when this severe complication will occur. This condition is thought to be associated with diagnosis and treatment errors. We studied the patients suffering from Graves-Basedow disease with and without ophthalmopathy. We concluded that the risk factors for ophthalmopathy were: many non-treated episodes of hyperthyroidism, delayed diagnosis and initiation of therapy, no thyroxine supplementation, improper preparation to strumectomy.

Adult↗
PubMed2000

[The role of sulphonylurea derivatives in treatment of diabetes type 2. The role of glimepiride].

Type 2 diabetes is characterised by some kind of duality. In its pathogenesis an important role have as well genetic as environmental factors. Both of them influence the insulin secretion at the one side and the insulin resistance at the other one. Very important group of antidiabetic drugs are sulphonylureas. They bind to the sulphonylurea receptor localized at the potassium channel in the cellular membrane. Contemporary sulphonylurea derivatives should be characterised by rather weak binding with the receptor, action during mealtime only (prandial regulation of glycemia), not to strong insulin secretion and for the quality of life reason once daily application. This criteria are fulfilled by e.g. slow-releasing preparations of glipizide and glikiazide and also by glimepiride.

ATP-Binding Cassette Transporters↗
PubMed2000

[The role of genetic studies in finding the etiopathogenesis of diabetes mellitus].

The role of genetic investigations in diabetes one can describe in aspect of their role in the pathogenesis of type 1 and type 2 as well as in pathogenesis of chronic complications and gene therapy of diabetes. There is not only one gene responsible for type 1 diabetes. Similarly there are many gene-candidates in type 2 diabetes. Only in 6 types of MODY the genes responsible for beta-cell dysfunction were described. In diabetic complications some role e.g. in retinopathy may be played by genes of growth factors, heparan sulfate synthesis as well as genes of adrenergic receptor beta 3. In diabetic nephropathy the genes of renin synthesis, converting enzyme, aldose reductase or angiotensin receptor can be of importance. It should be emphasized that identification of human genome and genes responsible for diabetes can contribute to introduction of gene therapy in diabetes.

Diabetes Mellitus, Type 1↗
PubMed2000

[Familial LCAT deficiency--clinical picture. Case report].

We report a case of familial LCAT deficiency, diagnosed in a 35 year old women. The disease manifested itself by a presence of proteinuria, corneal opacities and haemolytic anaemia with target cells. Suspecion of familial LCAT deficiency was based on renal biopsy, which revealed characteristic serpiginous fibrillar deposits in electron microscopy. The diagnosis was confirmed by a marked decrease of estrified cholesterol, low HDL-cholesterol concentration, decrease of LCAT activity in serum, typical "stacked coins" picture of HDL lipoproteins in electron microscopy examination and positive familial history--diagnosis of LCAT deficiency in dialysed brother of patient.

Adult↗