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Branched-chain amino acids (BCAAs) are known to be associated with cardiovascular disease risk in adults. The aim of this study is to investigate whether an increased cardiometabolic risk profile can be observed in the amino acid profile of young adult offspring of women with type 1 diabetes. This cross-sectional case-control study included 73 offspring born to women with type 1 diabetes (cases) and 82 control participants (controls). At the age of 18–23 years, they participated in a clinical assessment including laboratory tests and questionnaires. Amino acid levels were analyzed from venous serum samples after 10 h of fasting using nuclear magnetic resonance (NMR) spectroscopy. No differences in cardiovascular disease or cardiometabolic risk factors were observed between the cases and the controls. Circulating amino acid levels were similar in both groups. The glucogenic score (combined alanine, glycine) was higher in overweight case men (case versus controls adjusted p  = 0.015 (mean ratio 1.25 [95% CI 1.11 to 1.49]). The present findings do not support our hypothesis that serum amino acid profiles, determined in early adulthood, are associated with a more adverse cardiometabolic risk profile in offspring of women with type 1 diabetes. Further studies are warranted to clarify the potential role of amino acids in the development of cardiovascular disease in offspring of women with type 1 diabetes.

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 <80 cm. Maternal height ≥166 cm was negatively associated with 1‐ and 2‐h post‐load plasma glucose concentrations. Waist‐to‐height ratio (WHtR) >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. In a Finnish population‐based cohort, maternal early‐pregnancy waist‐to‐height ratio >0.5 correlated positively with both fasting and post‐load glucose concentrations at 12–16 weeks’ gestation and performed better than body mass index in the prediction of post‐load glucose concentrations >90th percentile. Overall, our results underline the importance of evaluating maternal abdominal adiposity in gestational diabetes mellitus risk assessment.

Background Early-onset GDM often requires pharmacological treatment and is associated with adverse perinatal outcomes, but data is insufficient regarding the best methods to identify high-risk women requiring early GDM screening. The aim of this study was to analyze the diagnostic accuracy of HbA 1c in the prediction of (1) plasma glucose concentrations > 90th percentile in an oral glucose tolerance test (OGTT) at 12–16 weeks’ gestation; and (2) pharmacologically treated early- or late-onset GDM. Methods HbA 1c was measured at 8—14 weeks’ gestation in a population-based cohort of 1394 Finnish women recruited for the Early Diagnosis of Diabetes in Pregnancy (EDDIE) study between 3/2013 and 12/2016. Information on maternal risk factors were collected at recruitment. Subsequently, a 2-hour 75 g OGTT was performed at 12—16 weeks’ gestation (OGTT1), and if normal, repeated at 24–28 weeks’ gestation (OGTT2). Early- and late-onset GDM were diagnosed using the same nationally endorsed cut-offs for fasting, 1 h- and 2 h-plasma glucose: ≥5.3, ≥ 10.0mmol/l, and/or ≥ 8.6mmol/l, respectively. In total, 52/1394 (3.7%) women required metformin or insulin treatment for GDM, including 39 women with early-onset GDM diagnosed at OGTT1 and 13 women with late-onset GDM diagnosed at OGTT2. Results Maternal early-pregnancy HbA 1c  ≥ 35mmol/mol (≥ 5.4%) was the best cut-off to predict fasting or post-load plasma glucose > 90th percentile in OGTT1, but its diagnostic accuracy was low [AUC (95% CI) 0.65 (0.62 to 0.69), sensitivity 0.55 (0.49 to 0.60) and specificity 0.67 (0.64 to 0.70)] both alone and in combination with other maternal risk factors. However, HbA 1c  ≥ 35mmol/mol correlated positively with plasma glucose concentrations at all time points of OGTT1 and predicted pharmacologically treated GDM diagnosed at OGTT1 or OGTT2; AUC (95% CI) 0.75 (0.68 to 0.81), sensitivity 0.75 (0.61 to 0.86), specificity 0.64 (0.61 to 0.66). Conclusions In our population-based cohort, early-pregnancy HbA 1c  ≥ 35mmol/mol was positively associated with fasting and post-load plasma glucose concentrations in an OGTT at 12—16 weeks’ gestation and predicted pharmacologically-treated early- and late-onset GDM, suggesting potential utility in first-trimester identification of women at high risk of severe GDM subtypes.

Objectives Our aim was to assess how pre-eclampsia, gestational hypertension, and chronic (pre-pregnancy) hypertension, compared to no hypertensive disorders during pregnancy, impact development of cardiovascular disease and all-cause mortality in type 1 diabetes (T1D). Methods We included 190 T1D women with median age of 29.4 (interquartile range 26.0–33.3) years at delivery between 1988 and 1994 at the Helsinki University Hospital, and who were later re-examined within the Finnish Diabetic Nephropathy Study. Of these, 43 (22.6%) had had pre-eclampsia, 32 (16.8%) gestational hypertension, 20 (10.5%) chronic hypertension, and 95 (50.0%) had remained normotensive during the index pregnancy. We retrieved follow-up data on cardiovascular events and mortality from national registries until the end of 2020. Results During a median 27.9 (25.4–30.7) years of follow-up, 46 (24.2%) experienced a composite cardiovascular event and 25 (13.2%) died from any cause. In Cox regression analysis, the risk of a cardiovascular event was increased for chronic hypertension [hazard ratio, HR 3.45 (95% CI 1.25–9.54)], gestational hypertension [HR 3.63 (1.55–8.51)], and pre-eclampsia [HR 5.07 (2.31–11.11)] compared with the non-hypertension group, after adjustment for delivery age and age at T1D onset. The corresponding risk of all-cause mortality was increased for chronic hypertension [HR 3.31 (1.06–10.35)] and pre-eclampsia [HR 2.92 (1.07–7.98)], but not for gestational hypertension [HR 1.26 (0.33–4.85)]. After further adjustment for diabetic kidney disease or diabetic retinopathy as a time-dependent covariate, the association with cardiovascular disease remained for pre-eclampsia and gestational hypertension, while for mortality, none of the associations were significant. Conclusion Hypertension during pregnancy is associated with increased risk of cardiovascular events during long-term follow-up in women with T1D, with pre-eclampsia conferring the highest risk. For all-cause mortality, chronic hypertension and pre-eclampsia, but not gestational hypertension, increases the risk of death, yet not independently of diabetic kidney disease. Graphical abstract

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.

Background Exposure to a hyperglycemic environment during prenatal life may result in an unfavorable metabolic profile later in adulthood. We aimed to assess whether fatty liver index, a non-invasive indicator of nonalcoholic fatty liver disease risk, differs in young adult offspring of women with type 1 diabetes from offspring of women without diabetes. Methods This cohort study was conducted within the hospital district of Helsinki and Uusimaa, Finland. Between 1996 and 2000, we identified 238 singleton offspring of women with type 1 diabetes, born at the Department of Obstetrics and Gynecology, Helsinki University Hospital, Helsinki, Finland. From the Finnish Medical Birth Register, we identified 476 singleton age- and region-matched offspring of women without diabetes. At 18–23 years of age, 70 offspring of women with type 1 diabetes and 83 offspring of women without diabetes participated in a clinical study, including laboratory tests, clinical assessments, and self-reported questionnaires. The noninvasive fatty liver index was used to estimate nonalcoholic fatty liver disease. Results Fatty liver index (FLI) was similar between offspring of women with type 1 diabetes and offspring of women without diabetes (p = 0.59). Additionally, no differences between the groups could be observed for FLI ≥ 60, i.e., to cut-off value for NAFLD. Likewise, we could not find any statistically significant differences between young adult offspring of women with type 1 diabetes (20.4 years [SD 1.6]) and young adult offspring of women without diabetes (20.6 years [SD 1.6]) regarding metabolic characteristics: BMI 24.5 kg/m 2 vs. 24.0 kg/m 2 , fasting plasma glucose 5.39 mmol/L vs. 5.40 mmol/L, fasting insulin 11.0 mU/L vs. 10.6 mU/L, total cholesterol 4.36 mmol/L vs. 4.30 mmol/L, systolic BP 117 mmHg vs. 119 mmHg, triglycerides 0.89 mmol/L vs. 0.96 mmol/L, and Waist-to-height ratio 0.41 vs. 0.42. Conclusions Our results suggest that fatty liver index is not elevated in young adult offspring of women with type 1 diabetes. Further research on whether pregestational type 1 diabetes in pregnancy affects offspring’s nonalcoholic fatty liver disease risk is warranted.

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.

Background Offspring of mothers with type 1 diabetes have an increased risk for acquiring early onset cardiovascular disease (CVD). Arterial stiffness, measured as pulse wave velocity (PWV), is a non-invasive biomarker for CVD risk assessment. Our aim is to determine whether PWV is increased in young adult offspring of mothers with type 1 diabetes. Methods This is a case–control study carried out in the hospital district of Helsinki and Uusimaa, Finland. 75 offspring of mothers with type 1 diabetes (cases) and 84 offspring of mothers without diabetes (controls), aged 18–23 years, were enrolled in this study. All participants attended clinical assessments, including questionnaires and laboratory tests. Carotid-femoral PWV (cfPWV), carotid-radial PWV (crPWV), and PWV ratio were measured from each participant using the Complior Analyse mechanotransducer (Alam Medical, France). Student’s t-test and chi-squared test were used to assess differences between the groups. Stata 17.0, StataCorp LP (College Station, TX, USA) statistical package was used for the analysis. Results We did not observe any differences in conventional CVD risk factors: systolic blood pressure, LDL, Hb A1c , and smoking between cases and controls. We detected higher cfPWV in cases 6.5 (SD ± 1.2) m/s than in controls 6.2 (SD ± 0.7) m/s, p = 0.049, after adjustments for BMI, smoking, mean arterial pressure, height, and pulse rate was made. We did not observe any difference between cases and controls regarding crPWV or PWV ratio. Additionally, we detected no sex differences. Conclusions We report a novel finding of signs of increased arterial stiffness already in young adult offspring of mothers with type 1 diabetes compared to matched offspring of mothers without diabetes. Our finding suggests that exposure to an adverse intrauterine environment of type 1 diabetes mothers may affect the vascular health of offspring already in young adulthood. Additional research within this topic is warranted.

Small‐for‐gestational age (SGA) neonates exhibit increased perinatal morbidity and mortality, and a greater risk of developing chronic diseases in adulthood. Currently, no effective maternal blood‐based screening methods for determining SGA risk are available. We used a high‐resolution MS/MSALL shotgun lipidomic approach to explore the lipid profiles of small extracellular vesicles (sEV) released from the placenta into the circulation of pregnant individuals. Samples were acquired from 195 normal and 41 SGA pregnancies. Lipid profiles were determined serially across pregnancy. We identified specific lipid signatures of placental sEVs that define the trajectory of a normal pregnancy and their changes occurring in relation to maternal characteristics (parity and ethnicity) and birthweight centile. We constructed a multivariate model demonstrating that specific lipid features of circulating placental sEVs, particularly during early gestation, are highly predictive of SGA infants. Lipidomic‐based biomarker development promises to improve the early detection of pregnancies at risk of developing SGA, an unmet clinical need in obstetrics. Distinct lipid signatures of circulating placenta‐derived sEVs define the trajectory of a healthy pregnancy and identify SGA risk in the first trimester of gestation.

Aims/hypothesis Our aim was to analyse possible changes in the glycaemic control, BP, markers of renal function, and obstetric and perinatal outcomes of parturients with diabetic nephropathy during 1988–2011. Methods The most recent childbirth of 108 consecutive type 1 diabetes patients with diabetic nephropathy and a singleton pregnancy were studied. Two periods, 1988–1999 and 2000–2011, were compared. Results The prepregnancy and the first trimester median HbA 1c values persisted at high levels (8.2% [66 mmol/mol] vs 8.5% [69 mmol/mol], p  = 0.16 and 8.3% [67 mmol/mol] vs 8.4% [68 mmol/mol], p  = 0.67, respectively), but decreased by mid-pregnancy (6.7% [50 mmol/mol] vs 6.9% [52 mmol/mol], p  = 0.11). Antihypertensive medication usage increased before pregnancy (34% vs 65%, p  = 0.002) and in the second and third trimesters of pregnancy (25% vs 47%, p  = 0.02, and 36% vs 60%, p  = 0.01, respectively). BP exceeded 130/80 mmHg in 62% and 61% ( p  = 0.87) of patients in the first trimester, and in 95% and 93% ( p  = 0.69) in the third trimester, respectively. No changes were observed in the markers of renal function. Pre-eclampsia (52% vs 42%, p  = 0.29) and preterm birth rates before 32 and 37 gestational weeks (14% vs 21%, p  = 0.33, and 71% vs 77%, p  = 0.49, respectively) remained high. The elective and emergency Caesarean section rates were 71% and 45% ( p  = 0.01) and 29% and 48% ( p  = 0.05), respectively. Neonatal intensive care unit admissions increased from 26% to 49% ( p  = 0.02). Conclusions/interpretation Early pregnancy glycaemic control and hypertension management were suboptimal in both time periods. Pre-eclampsia and preterm delivery rates remained high in patients with diabetic nephropathy.