Viimeaikaiset trendit tyypin 1 diabeetikkojen raskauksissa

BACKGROUND: Although great advances in diabetes care and obstetrics have been made in the past decades, adverse outcomes remain increased in the pregnancies of women with type 1 diabetes (DM) compared with background populations. AIMS: To analyze the trends in pre-pregnancy body mass index (BMI), glycemic control and blood pressure (BP) levels and their relations to obstetric and perinatal outcomes in women with type 1 DM during 1988-2011. SUBJECTS AND METHODS. A retrospective review of the obstetric records of a population-based cohort of 1094 consecutive type 1 DM patients with a singleton childbirth during 1988-2011 at Helsinki University Hospital (HUH) was carried out. RESULTS: During 1988-2011, the frequencies of BMI 25-29.9 kg/m2 and ≥30 kg/m2 increased from 19% and 2%, respectively, in 1988-1991 to 37% and 10% in 2008-2011. Glycemic control was suboptimal in early pregnancy and deteriorated in late pregnancy. The proportion of women with BP > 130/80 mmHg during pregnancy increased and the preeclampsia rate remained high (19-34%). In the total cohort, the elective and the total caesarean section (CS) rates decreased from 58% and 74%, respectively, in 1988-1991 to 27% and 66% in 2008-2011. The emergency CS rate increased from 16% in 1988-1991 to 39% in 2008-2011. Deliveries before 37 weeks of gestation increased from 29% in 1988-1991 to 49% in 2008-2011, and deliveries before 32 weeks decreased from 4% in 1988-1991 to 2% in 2008-2011. Among the newborn infants, the rates of fetal macrosomia remained high (27-39%) during 1988-2011. The frequencies of umbilical artery pH <7.15 and <7.05 increased from 4% and 1%, respectively, in 1988-1991 to 18% and 4% in 2008-2011. The frequency of neonatal hypoglycaemia decreased from 66% in 1988-1991 to 55% in 2008-2011. Neonatal intensive care unit (NICU) admissions persisted above 15%. The perinatal mortality rate was 1.8% in the total cohort In the analyses of risk factors, poor glycemic control in early and late pregnancy was associated with delivery before 37 weeks, preeclampsia, fetal macrosomia, and NICU admission. Poor glycemic control in late pregnancy was also associated with fetal acidemia at birth and neonatal hypoglycemia. Early-pregnancy BP >130/80 mmHg predicted delivery before 37 weeks, small-for-gestational age infant, NICU admission, and decreased risk of fetal macrosomia. Early-pregnancy BP ≥140/90 mmHg predicted preeclampsia. Maternal overweight was associated with fetal macrosomia. Proliferative retinopathy predicted preeclampsia and delivery before 37 weeks. Diabetic nephropathy predicted preeclampsia, delivery before 37 weeks, reduced risk of fetal macrosomia and NICU admission. CONCLUSIONS: Pre-pregnancy BMI increased, glycemic control before pregnancy and during the second half of pregnancy deteriorated, and BP levels during pregnancy increased in type 1 DM parturients during 1988-2011. The frequencies of most adverse obstetric and perinatal outcomes either persisted at high levels or increased. The results call for an intensified therapeutic approach in type 1 DM women, both before and during pregnancy.Tyypin 1 diabeteksen ilmaantuvuus on Suomessa maailman korkeimpia. Tautiin liittyy vakavia raskaus- ja synnytyskomplikaatioita, kuten sikiön epämuodostumia ja liikakasvua, pre-eklampsiaa, ennenaikaisia synnytyksiä ja sikiökuolemia. Äidin huono verensokeritasapaino ja korkea verenpaine altistavat raskaushäiriöille. Synnyttäjillä lisääntynyt ylipaino voi vaikeuttaa ihanteellisen sokeritasapainon ja verenpaineen saavuttamista. Laajaa väestöpohjaista tutkimusta suomalaisten tyypin 1 diabeetikoiden raskauksien ja synnytysten hoitotuloksista ei ole aikaisemmin julkaistu. Tutkimuksen tavoitteena oli analysoida raskautta edeltävän painoindeksin, raskautta edeltävän ja raskaudenaikaisen sokeritasapainon (”pitkäsokeri”, HbA1c) sekä verenpaineiden trendejä tyypin 1 diabeetikoilla sekä näiden yhteyksiä raskaus- ja synnytystuloksiin sekä sikiön ja vastasyntyneen vointiin. Väestöpohjaisessa tutkimuksessa analysoitiin 1094 Helsingin Naistenklinikalla vuosina 1988-2011 synnyttäneen tyypin 1 diabeetikon raskaus- ja synnytystiedot. Analyysiin sisällytettiin jokaisen naisen viimeisin yksisikiöinen synnytys. Tutkimuksessa todettiin, että tyypin 1 diabetesta sairastavien synnyttäjien raskautta edeltävä painoindeksi nousi vuosina 1988-2011. Samalla ajanjaksolla raskautta edeltävä sekä keski- ja loppuraskauden sokeritasapaino huononi. Alkuraskauden sokeritasapaino ei vastannut suosituksia. Naisten osuus, joilla verenpaine ylitti 130/80 mmHg raskauden aikana lisääntyi ja 19-34%:lle kehittyi pre-eklampsia. Suunnitellut keisarileikkaukset vähenivät ja kiireelliset lisääntyivät. Vastasyntyneillä napa-valtimon pH laski alatiesynnytyksissä ja liikakasvuisten (27-39%) sekä tehohoitoon joutuneiden (>15 %) osuudet pysyivät korkeina, mutta vastasyntyneiden matalat verensokeriarvot vähenivät. Riskitekijäanalyyseissä äidin ylipaino ennusti sikiön liikakasvua ja pre-eklampsiaa. Alku- ja loppuraskauden huono sokeritasapaino ennusti pre-eklampsiaa, synnytystä ennen 37. raskausviikkoa sekä vastasyntyneen liikakasvuisuutta ja tehohoidon tarvetta. Loppuraskauden huono sokeritasapaino ennusti myös vastasyntyneen alhaista napaveren pH-arvoa ja matalia verensokeritasoja. Yhteenvetona todetaan, että seuranta-aikana tyypin 1 diabeetikoilla raskautta edeltävä painoindeksi nousi, raskautta edeltävä ja toisen raskauspuoliskon sokeritasapaino huononi ja verenpainetasot kohosivat. Useimpien raskaus- ja synnytyskomplikaatioiden osuudet pysyivät korkeina tai lisääntyivät. Tyypin 1 diabeetikkojen raskauksien tulisi olla suunniteltuja, jotta mahdollisimman hyvä sokeritasapaino ja verenpainetaso saavutettaisiin jo ennen raskautta. Tyypin 1 diabetesta sairastavien naisten hoitoa tulisi tehostaa myös raskausaikana

Genetic Risk Factors and Gene–Lifestyle Interactions in Gestational Diabetes

Paralleling the increasing trends of maternal obesity, gestational diabetes (GDM) has become a global health challenge with significant public health repercussions. In addition to short-term adverse outcomes, such as hypertensive pregnancy disorders and fetal macrosomia, in the long term, GDM results in excess cardiometabolic morbidity in both the mother and child. Recent data suggest that women with GDM are characterized by notable phenotypic and genotypic heterogeneity and that frequencies of adverse obstetric and perinatal outcomes are different between physiologic GDM subtypes. However, as of yet, GDM treatment protocols do not differentiate between these subtypes. Mapping the genetic architecture of GDM, as well as accurate phenotypic and genotypic definitions of GDM, could potentially help in the individualization of GDM treatment and assessment of long-term prognoses. In this narrative review, we outline recent studies exploring genetic risk factors of GDM and later type 2 diabetes (T2D) in women with prior GDM. Further, we discuss the current evidence on gene–lifestyle interactions in the development of these diseases. In addition, we point out specific research gaps that still need to be addressed to better understand the complex genetic and metabolic crosstalk within the mother–placenta–fetus triad that contributes to hyperglycemia in pregnancy

Distinct Changes in Placental Ceramide Metabolism Characterize Type 1 and 2 Diabetic Pregnancies with Fetal Macrosomia or Preeclampsia

Disturbances of lipid metabolism are typical in diabetes. Our objective was to characterize and compare placental sphingolipid metabolism in type 1 (T1D) and 2 (T2D) diabetic pregnancies and in non-diabetic controls. Placental samples from T1D, T2D, and control pregnancies were processed for sphingolipid analysis using tandem mass spectrometry. Western blotting, enzyme activity, and immunofluorescence analyses were used to study sphingolipid regulatory enzymes. Placental ceramide levels were lower in T1D and T2D compared to controls, which was associated with an upregulation of the ceramide degrading enzyme acid ceramidase (ASAH1). Increased placental ceramide content was found in T1D complicated by preeclampsia. Similarly, elevated ceramides were observed in T1D and T2D pregnancies with poor glycemic control. The protein levels and activity of sphingosine kinases (SPHK) that produce sphingoid-1-phosphates (S1P) were highest in T2D. Furthermore, SPHK levels were upregulated in T1D and T2D pregnancies with fetal macrosomia. In vitro experiments using trophoblastic JEG3 cells demonstrated increased SPHK expression and activity following glucose and insulin treatments. Specific changes in the placental sphingolipidome characterize T1D and T2D placentae depending on the type of diabetes and feto-maternal complications. Increased exposure to insulin and glucose is a plausible contributor to the upregulation of the SPHK-S1P-axis in diabetic placentae

Raskaana olevien ylipaino ja lihavuus yleistyvät

English summaryPeer reviewe

Kaikkien äitien ja lasten terveydestä kannattaa huolehtia

Pääkirjoitu

Large maternal waist circumference in relation to height is associated with high glucose concentrations in an early-pregnancy oral glucose tolerance test : A population-based study

Publisher Copyright: © 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).Introduction: To explore the role of maternal anthropometric characteristics in early-pregnancy glycemia, we analyzed the associations and interactions of maternal early-pregnancy waist circumference (WC), height and pre-pregnancy body mass index (BMI) with plasma glucose concentrations in an oral glucose tolerance test (OGTT) at 12–16 weeks’ gestation. Material and Methods: A population-based cohort of 1361 pregnant women was recruited in South Karelia, Finland, from March 2013 to December 2016. All participants had their WC, weight, height, HbA1c, and blood pressure measured at 8–14 weeks’ gestation and subsequently underwent a 2-h 75-g OGTT, including assessment of fasting insulin concentrations, at 12–16 weeks’ gestation. BMI (kg/m2) was calculated using self-reported pre-pregnancy weight. Maternal WC ≥80 cm was defined as large. Maternal height ≥166 cm was defined as tall. Data on gestational diabetes treatment was extracted from hospital records. Results: In the total cohort, 901 (66%) of women had an early-pregnancy WC ≥80 cm, which was associated with higher early-pregnancy HbA1c, higher concentrations of fasting plasma glucose and serum insulin, higher post-load plasma glucose concentrations, higher HOMA-IR indices, higher blood pressure levels, and higher frequencies of pharmacologically treated gestational diabetes, than early-pregnancy WC 0.5 was positively associated with both fasting and post-load plasma glucose concentrations at 12–16 weeks’ gestation, even when adjusted for age, smoking, nulliparity, and family history of type 2 diabetes. The best cut-offs for WHtR (0.58 for 1-h plasma glucose, and 0.54 for 2-h plasma glucose) were better predictors of post-load glucose concentrations >90th percentile than the best cut-offs for BMI (28.1 kg/m2 for 1-h plasma glucose, and 26.6 kg/m2 for 2-h plasma glucose), with areas-under-the-curve (95% confidence interval) 0.73 (0.68–0.79) and 0.73 (0.69–0.77), respectively, for WHtR, and 0.68 (0.63–0.74) and 0.69 (0.65–0.74), respectively, for BMI. Conclusions: In our population-based cohort, early-pregnancy WHtR >0.5 was positively associated with both fasting and post-load glucose concentrations at 12–16 weeks’ gestation and performed better than BMI in the prediction of post-load glucose concentrations >90th percentile. Overall, our results underline the importance of evaluating maternal abdominal adiposity in gestational diabetes risk assessment.Peer reviewe

Macronutrient intake during pregnancy in women with a history of obesity or gestational diabetes and offspring adiposity at 5 years of age

Background/objectives The impact of maternal macronutrient intake during pregnancy on offspring childhood adiposity is unclear. We assessed the associations between maternal macronutrient intake during and after pregnancy with offspring adiposity at 5 years of age. Additionally, we investigated whether gestational diabetes (GDM), BMI, or breastfeeding modified these associations. Subjects/methods Altogether, 301 mother-child dyads with maternal prepregnancy BMI >= 30 and/or previous GDM participated in the Finnish Gestational Diabetes Prevention Study (RADIEL) and its 5 years follow-up. Macronutrient intakes (E%) were calculated from 3-day food records collected at 5-18 weeks' gestation, in the third trimester, and at 12 months and 5 years after pregnancy. Offspring body fat mass (BFM) and fat percentage (BF%) at 5 years were measured by bioimpedance. Statistical analyses were multivariate linear regression. Results Mean (SD) prepregnancy BMI was 33(4) kg/m(2). GDM was diagnosed in 47%. In normoglycemic women, higher first half of pregnancy n-3 PUFA intake was associated with lower offspring BFM (g) (ss -0.90; 95% CI -1.62, -0.18) and BF% (ss -3.45; 95% CI -6.17, -0.72). In women with GDM, higher first half of pregnancy n-3 PUFA intake was associated with higher offspring BFM (ss 0.94; 95% CI 0.14, 1.75) and BF% (ss 3.21; 95% CI 0.43, 5.99). Higher SFA intake in the third trimester and cumulative intake across pregnancy (mean of the first half and late pregnancy) was associated with higher BFM and BF% (across pregnancy: ss 0.12; 95% CI 0.03, 0.20 and ss 0.44; 95% CI 0.15, 0.73, respectively). Higher carbohydrate intake across pregnancy was associated with lower BFM (ss -0.044; 95% CI -0.086, -0.003), and borderline associated with BF% (ss -0.15; 95% CI -0.31, 0.00). Conclusions The macronutrient composition of maternal diet during pregnancy is associated with offspring BFM and BF% at 5 years. GDM modifies the association between prenatal n-3 PUFA intake and offspring anthropometrics.Peer reviewe