A synonymous variant in GCK gene as a cause of gestational diabetes mellitus

The diagnosis of MODY as a subtype of gestational diabetes mellitus (GDM) is important for an adequate management during pregnancy and the postnatal period. The present report describes a case of GDM caused by a synonymous с.666C>G р.V222V substitution in the GCK gene. The variant, which was initially ranked as ‘likely benign’, was later proven to be pathogenic by in vitro studies. The с.666C>G substitution led to the use of a new donor splice site and synthesis of the aberrant mRNA with deletion of 16 base pairs. The case illustrates that additional clinical and experimental data may be required for the correct interpretation of sequence variants pathogenicity

Erratum: a synonymous variant in GCK gene as a cause of gestational diabetes mellitus (diabetes mellitus. 2019;22(2). Doi: 10.14341/dm9938)

An erratum on «A synonymous variant in GCK gene as a cause of gestational diabetes mellitus» by Natalya A. Zubkova, Petr M. Rubtsov, Liudmila I. Ibragimova, Nina A. Makretskaya, Evgeny V. Vasiliev, Vasily M. Petrov, Anatoly N. Tiulpakov (2019). Diabetes mellitus. 22(2). doi: 10.14341/DM9938An error was made in the list of authors: Fatima F. Burumkulova was not indicated as author of this article. The correct list of authors: Natalya A. Zubkova, Petr M. Rubtsov, Fatima F. Burumkulova, Liudmila I. Ibragimova, Nina A. Makretskaya, Evgeny V. Vasiliev, Vasily M. Petrov, Anatoly N. Tiulpakov.The editorial board apologize for this error and state that this does not change the scientific conclusions of the article in any way.The original article has been updated

Birth weight and length in offsprings of mothers with gestational diabetes mellitus due to mutations in GCK gene

Background. Gestational diabetes (GDM) due to GCK gene mutations is the most frequent form of monogenic diabetes mellitus (DM) presenting during pregnancy. It has been suggested that the use of insulin in pregnancies with fetuses carrying GCK mutations may lead to intrauterine growth retardation. In the present study we evaluated the effect of insulin therapy during pregnancy on birth weight and length in the offsprings of mothers with GDM due to GCK mutations. Aims. The aim was to study birth weight and length in offsprings of mothers with gestational diabetes mellitus due to mutations in GCK, depending on the therapy during pregnancy. Materials and methods. The study included 38 patients with GDM caused by GCK gene mutations (18.7%) and the 45 offsprings. To define molecular basis of GDM in pregnant women we used a targeted NGS. Diabetes panel genes were sequenced using a custom Ion Ampliseq gene panel and PGM semiconductor sequencer (Ion Torrent). To found the same mutations in their offsprings was used Sanger sequencing. All children were divided into 3 groups depending of their genotype and therapy received by the mothers during pregnancy. Results. We found statistically significant differences in birth length (p=0.04) and weight (p=0,031) depending on the genotype of the child and therapy in the mother. The risk of macrosomia was shown in non-mutation-carrying offsprings only. The birth weight in children with GCK gene mutations whose mothers received insulin during pregnancy was significantly lower. However, the birth weight remained in the normal range. Conclusions. Since prenatal diagnostics in the mothers with GCK gene mutations is not always justified, we recommend insulin therapy in order to prevent fetal macrosomia, which, however, should be less aggressive than in GDM due to other causes

Mutations in transcription factor as rare causes of diabetes in pregnancy

MODY1 and MODY3 represent rare causes of diabetes in pregnancy. Establishing a molecular diagnosis of MODY1 or MODY3 during pregnancy may be important for minimizing risk of perinatal complications and for improving glycemic control after pregnancy. The objective of the study was to evaluate the contribution of mutations in HNF4A and HNF1A genes in development of diabetes in pregnancy and to describe clinical characteristics of diabetes in pregnancy associated with these mutations. 230 pregnant women (20-43 years) with different type of glucose intolerance complicated during their current pregnancy were included in the study. A custom NGS panel targeting 28 diabetes causative genes was used for sequencing. Heterozygous mutations in HNF4A and HNF1A genes were detected in 3% of cases. Mutations p.I271T in HNF4A gene and p.L148F, p.Y265C, p.G288W in HNF1A gene were novel. This study includes a description of patients with pregnancy diabetes due to mutations in hepatocyte nuclear factors

Анализ сродства гемоглобина к кислороду и потребление кислорода тканями

The tissue and blood oxygenation estimation with taking into consideration the hemoglobin affinity for oxygen with new parameter pO2-effective use was studied. The calculation algorithm and its program realization for paeO2 and estimation of the dissociation oxyhemoglobin curve (ODC) were produced.28 patients were examined with the measurement of next parameters of arterial blood: pH, gas composition (paO2 and paCO2), and blood oxygenation (SO2, ctO2). The calculation of paeO2 value and the shift of ODC was carried out. The estimation of oxygen consumption (VO2) was carried out in 11 patients.The analysis of the obtained data allowed to conclude that paeO2 reflects changes of the hemoglobin affinity for oxygen in such a way, that when affinity is decreased then ODC shift is greater than zero and when the affinity is increased then ODC shift is less than zero. The parameter paeO2 allows to estimate more correctly the blood oxygenation than paO2 in mmHG terms. The correlation with the coefficient 0.8 was found between the value of the DOC shift and oxygen consumption. In the case of the negative ODC shift, the oxygen consumption is decreased, in the case of the positive ODC shift oxygen consumption is increased.Thus, on the basis of ODC, it is possible to estimate the blood and tissue oxygenation with taking into consideration the hemoglobin affinity for oxygen and, therefore, the respiration of organism in general.Исследована возможность оценки оксигенации крови и тканей с учетом сродства гемоглобина к кислороду с использованием нового параметра рО2 эффективное. Разработаны алгоритм расчета параметра рaeО2 и определения положения кривой диссоциации оксигемоглобина (КДО) и его программная реализация.Проведенное у 28 пациентов обследование включало измерение параметров артериальной крови: КЩС (pH), газового состава (рaО2, рСО2) и оксигенации крови (SO2, сtO2); расчет величины раеO2 и сдвига КДО. У 11 пациентов проведено определение значения потребления кислорода (VO2).Анализ полученных результатов позволил сделать следующие выводы: раеО2 отражает изменение сродства гемоглобина к кислороду, при снижении сродства сдвиг КДО>0, при увеличении сродства сдвиг КДО<0; раеО2 дает более точную оценку оксигенации крови, чем раО2 в терминах мм рт.ст.; между величиной сдвига КДО и значением потребления кислорода тканями существует линейная зависимость с коэффициентом корреляции 0,8; при отрицательном значении сдвига КДО потребление О2 а снижено, а при положительном — увеличено.Таким образом, на основе анализа КДО можно оценить оксигенацию крови и тканей с учетом сродства гемоглобина к кислороду, а, значит, и эффективность дыхания организма в целом

Патогенетические основы назначения кислородотерапии у больных с дыхательной недостаточностью при РаО2>55 мм рт. ст

The aim of this study was to elaborate indication criteria for oxygen therapy and its modes for the treatment of hypoxemia with РаО2 above 55 mm Hg, on the basis of assessment of separate links of respiratory chain. We studied 18 consecutive patients (age of 41 to 80 years) with respiratory insufficiency (stage 2–3). Minute ventilation (MV), tidal volume (Vt), breathing frequency (BF), forced expiratory volume in one second (FEV1), single-breath lung diffusing capacity (TLCOsb), arterial partial carbon dioxide tension (РаCО2), arterial partial oxygen tension (РаО2), arterial oxygen saturation (SaCb), arterial oxygen content (СО2), anion gap (AG) were measured while breathing room air (baseline) and after 2 hours of oxygen therapy. Reactions of patients to oxygen-enriched air and to carbon dioxide-enriched air were compared.Analisis of obtained data showed that respiratory assessment during tentative oxygen treatment is very important before indication of oxygen. Some patients during oxygen therapy produced alterations in breathing pattern with reduction of Vt and increase in BF (rapid, shallow breathing). Oxygen therapy may be of little benefit in the cases of redused diffusing capacity and high hemoglobin concentration.Целью настоящей работы является разработка критериев назначения кислородотерапии при РаО2 >55 мм рт. ст. и режимов е е проведения на основании исследования состояния отдельных звеньев дыхательной цепи. Проведен анализ обследования 18 больных в возрасте от 41 до 80 лет с дыхательной недостаточностью II и III степени до и после 2-часового сеанса кислородотерапии. Для исследования реакции пациентов были выбраны следующие параметры: минутная вентиляция легких (MV), дыхательный объем (Vt), частота дыхания (BF), объем форсированного выдоха за 1 сек. (FEV1), диффузионная способность легких, измеренная по методу единичного вдоха (TLCOsb), РаО2, парциальное напряжение углекислого газа в артериальной крови (РаСО2), насыщение гемоглобина кислородом (SaО2), содержание кислорода в крови (СО2), “анионный разрыв“ (AG). Проведено сравнение реакции пациента на вдыхание воздушной смеси с повышенным содержанием кислорода и смеси с повышенным содер анием углекислого газа.Анализ полученных данных показал, что при назначении кислородотерапии важным становится оценка дыхания в процессе проведения пробного сеанса. У некоторых пациентов на фоне проведения кислородотерапии наблюдается неадекватная реакция – повышение частоты дыхания при снижении дыхательного объема. При снижении диффузионной способности легких и высоком значении гемоглобина кислородотерапия будет малоэффективной