Distinct Cardiac Connexin-43 Expression in Hypertrophied and Atrophied Myocardium May Impact the Vulnerability of the Heart to Malignant Arrhythmias. A Pilot Study.

Our and other studies suggest that myocardial hypertrophy in response to hypertension and hyperthyroidism increases propensity of the heart to malignant arrhythmias, while these are rare in conditions of hypothyroidism or type-1 diabetes mellitus associated with myocardial atrophy. One of the crucial factors impacting the susceptibility of the heart to life-threatening arrhythmias is gap junction channel protein connexin-43 (Cx43), which ensure cell-to-cell coupling for electrical signal propagation. Therefore, we aimed to explore Cx43 protein abundance and its topology in hypertrophic and hypotrophic cardiac phenotype. Analysis were performed in left ventricular tissue of adult male spontaneously hypertensive rat (SHR), Wistar Kyoto rats treated for 8-weeks with L-thyroxine, methimazol or strepotozotocin to induce hyperthyroid, hypothyroid and type-1 diabetic status as well as non-treated animals. Results showed that comparing to healthy rats there was a decrease of total myocardial Cx43 and its variant phosphorylated at serine368 in SHR and hyperthyroid rats. Besides, enhanced localization of Cx43 was demonstrated on lateral sides of hypertrophied cardiomyocytes. In contrast, total Cx43 protein and its serine368 variant were increased in atrophied left ventricle of hypothyroid and type-1 diabetic rats. It was associated with less pronounced alterations in Cx43 topology. In parallel, the abundance of PKCepsilon, which phosphorylates Cx43 at serine368 that stabilize Cx43 function and distribution was reduced in hypertrophied heart while enhanced in atrophied once. Findings suggest that differences in the abundance of cardiac Cx43, its variant phosphorylated at serine368 and Cx43 topology may explain, in part, distinct propensity of hypertrophied and atrophied heart to malignant arrhythmias.

Gestational diabetes - metabolic risks of adult women with respect to birth weight.

Metabolic disorders such as obesity, insulin resistance and other components of metabolic syndrome (MetS) are connected with birth weight. Low and high birth weight is associated with a higher risk of developing type 2 diabetes mellitus, the mechanism is not clear. In this study, we evaluated the association between birth weight and anthropometric as well as biochemical components of MetS in women with a history of gestational diabetes mellitus (GDM) in comparison with control women. In part of the GDM group, we re-evaluated metabolic changes over 5-8 years. Anthropometry, blood pressure, glucose metabolism during the 3-h oGTT, lipid profile, uric acid, thyroid hormones, and liver enzymes were assessed. From the analyzed components of MetS in adult women we proved the association of low birth weight (birth weight <25th percentile) with glucose processing, in particular among women with a history of GDM. Low birth weight GDM women revealed significantly higher postchallenge insulin secretion and lower peripheral insulin sensitivity. Re-examinations indicate this association persists long after delivery.

T2D risk haplotypes of the TCF7L2 gene in the Czech population sample: the association with free fatty acids composition.

The association of transcription factor 7-like 2 (TCF7L2) gene variants with the pathogenesis of T2D, gestational diabetes and polycystic ovary syndrome (PCOS) was examined. The study involved 1460 individuals: 347 T2D patients (D); 261 gestational diabetics (G); 147 offspring of T2D (O); 329 women with PCOS, and 376 controls (C). The SNPs: rs7901695; rs7903146; rs12255372 in the TCF7L2 gene were genotyped. Anthropometric and biochemical parameters, oGTT derived indices were assessed. In addition, free fatty acids (FFAs) were evaluated in 183 non-diabetic women. The CTT haplotype showed the strongest association with T2D with OR 1.57, p=0.0003. The frequency of the CTT/CTT haplotype was decreasing in following order: D 10.6, O 9.5, G 6.1, C 5.3 and PCOS 4.9 [%]. Among CTT carriers, significantly decreased levels of oGTT-stimulated insulin and C-peptide as well as proportions of fasting PUFAs were observed. The carriership of CTG/TCG was associated with gestational diabetes, OR 2.59, p=0.036. The association of TCF7L2 haplotypes with T2D and gestational diabetes but not with PCOS was confirmed. Novel association of TCF7L2 with FFAs composition was found.

Screening of mutations and polymorphisms in the glucokinase gene in Czech diabetic and healthy control populations.

Glucokinase (GCK) plays a key role in glucose metabolism. GCK mutations are known as a pathogenic cause of maturity-onset diabetes of the young type 2 (MODY2). These mutations are also found in gestational diabetics. The aim of our study was to assess the variability of the GCK gene in the Czech diabetic and control populations. We screened all 10 exons specific for the pancreatic isoform of glucokinase (1a and 2-10) including the intron flanking regions in 722 subjects (in 12 patients with an unrecognised type of MODY and their 10 family members, 313 patients with diabetes mellitus type 2 (DM2), 141 gestational diabetics (GDM), 130 healthy offspring of diabetic parents, and 116 healthy controls without family history of DM2). In two MODY families we identified two mutations in exon 2 of the GCK gene: a novel mutation Val33Ala and the previously described mutation Glu40Lys. In other subgroups (excluding MODY families) we detected only intronic variants and previously described polymorphisms in exons 6 (Tyr215Tyr) and 7 (Ser263Ser), we did not find any known GCK pathogenic mutation. We observed no difference in the frequencies of GCK polymorphisms between Czech diabetic (DM2, GDM) and non-diabetic populations.

[Views of a diabetologist on pregnancy in diabetic patients]. / Pohled diabetologa na tehotenství pacientky s diabetem.

In recent years a very marked drop of complications in mothers with type 1 diabetes (DM 1) and type 2 diabetes (DM 2) was achieved. Nevertheless this group of patients is still considered at risk. The most serious possible complications are congenital malformations of the foetus and possible deterioration of long-term diabetic complications of the mother. The subsequent text is a brief review of contemporary views on pregnancy of diabetic patients.

[Prediction of pregnancy-induced hypertension in women with risk factors]. / Moznosti predikce tehotenstvím indukované hypertenze u zen s rizikovými faktory.

UNLABELLED: The objective of the presented work was to find possible predictive factors of pregnancy-induced hypertension (PIH) in women with the risk of gestational diabetes (GDM) during pregnancy. A group of women with the risk of development of gestational diabetes was selected because it is known that in women with GDM a hypertension is encountered 2-4 times more frequently than in women without disorders of glucose tolerance during pregnancy. The patients were divided into four groups with regard to the risk of development of hypertension. The examinations were made once during the 20th week of gestation. PIH is manifested in the great majority of patients only after the 20th week of pregnancy. All patients were normotensive at the time of examination. During the subsequent course of pregnancy in all patients the diagnosis of gestational diabetes and pregnancy-induced hypertension was investigated. The investigated parameters were fasting insulin levels during the 20th week of gestation, coagulation factors--antithrombin III (AT III), D-dimer, number of thrombocytes. The authors investigated also anamnestic data on the presence of type II diabetes and hypertension in close relatives of the patients. RESULTS: No differences were found in the insulin, antithrombin III and D-dimer levels nor in the number of thrombocytes. A significant relationship was revealed between the incidence of hypertension during pregnancy and the family history of the patient. In women where there was diabetes type 2 and hypertension in the family, there was a markedly more frequent incidence of pregnancy-induced hypertension after the 20th week of pregnancy (p > 0.0002) than in the other investigated groups.

[Importance of anticardiolipin antibody screening in pregnancy]. / Význam screeningového vysetrení antikardiolipinových protilátek v tehotenství.

We performed 1698 examinations of anticardiolipin antibodies (ACLA) among pregnant women with gestational age from 16 to 37 weeks of pregnancy during eleven months of 1996. The ACLA levels above normal range were found in patients with pregnancy induced hypertension, preeclampsia, gestational diabetes, diabetes mellitus type I, venous thrombosis, thrombocytopenia and rheumatological diseases. The following results show the possible relations between high ACLA levels and pregnancy induced hypertension and gestational diabetes. The screening test for ACLA is recommended as a supportive method for prenatal follow-up of pregnant patients.

[Practical results of monitoring pregnancy in women with systemic lupus erythematosus]. / Praktické výsledky sledování tehotenství u zen se systémovým lupus erythematodes.

BACKGROUND: The authors dealt with the urgent problem under what conditions it is possible to achieve in a woman with systemic lupus erythematosus (SLE) or another collagenosis, or secondary antiphospholipid syndrome (APS) a favourable outcome of pregnancy and the delivery of a healthy infant. METHODS AND RESULTS: The investigation comprised 23 women incl. 20 with SLE, two with the mixed form of a diffuse connective tissue disease (MCTD) and one with Sjögren's syndrome of the primary type. From the total number of 20 pregnancies six were consulted in advance with a doctor (group I-s-called planned pregnancies) and all terminated by a successful delivery. Of 11 pregnancies which were not consulted with a doctor in advance (group II-so-called unplanned pregnancies) 9 were terminated in term, however, only 5 with a successful delivery (55.5%), two women are still pregnant. Exacerbation of the basic disease during pregnancy was recorded only once and did not lead to discontinuation of the pregnancy. CONCLUSIONS: The authors provide evidence that desired pregnancy of informed women suffering from SLE or another collagenosis when assisted by a specialized medical team can lead to a successful delivery of an infant.