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Background: Despite the significant personal and societal burden of tic disorders (TD), treatment outcomes remain modest, necessitating a deeper understanding of their etiology. Family history is the biggest known risk factor and identifying risk genes could accelerate progress in the field., Methods: Expanding upon previous sample size limitations, we added 4,800 new TD cases and 971,560 controls, conducting a GWAS meta-analysis with 9,619 cases and 981,048 controls of European ancestry. We attempted to replicate the results in an independent deCODE Genetics GWAS (885 TD cases and 310,367 controls). To characterize GWAS findings, we conducted several post-GWAS gene-based and enrichment analyses., Results: A genome-wide significant hit (rs79244681, p=2.27x10 -08 ) within MCHR2-AS1 was identified, though it was not replicated. Post-GWAS analyses revealed a 13.8% SNP-heritability and three significant genes: BCL11B, NDFIP2, and RBM26. Common variant risk for TD was enriched within genes preferentially expressed in the cortico-striato-thalamo-cortical circuit (including the putamen, caudate, nucleus accumbens, and Brodman area 9) and five brain cell types (excitatory and inhibitory telencephalon-, inhibitory- di- and mesencephalon, hindbrain-, and medium spiny neurons). TD polygenic risk was enriched within loss-of-function intolerant genes (p=0.0017) and high-confidence neurodevelopmental disorder genes (p=0.0108). Of 112 genetic correlations, 43 were statistically significant, showing high positive correlations with most psychiatric disorders. Of the two SNPs previously associated with TD, one (rs2453763) replicated in an independent sub-sample of our GWAS (p=0.00018)., Conclusions: This GWAS was still underpowered to identify high-confidence, replicable loci, but the results suggest imminent discovery of common genetic variants for TD., (Copyright © 2024. Published by Elsevier Inc.)

Background: Continuous glucose monitoring (CGM) can provide a comprehensive assessment of glycaemic control. This exploratory analysis of the ONWARDS 1 trial assessed CGM-based metrics and CGM-derived hypoglycaemia duration in insulin-naive individuals with type 2 diabetes treated with subcutaneous once-weekly insulin icodec (icodec) versus once-daily insulin glargine U100 (glargine U100)., Methods: ONWARDS 1 was a 78-week (52-week main treatment phase and a 26-week treatment extension phase plus a 5-week follow-up), randomised, open-label, treat-to-target, phase 3a trial done at 143 sites (outpatient clinics and hospital departments) across 12 countries. Adults (aged ≥18 years) with type 2 diabetes (HbA 1c : 7·0-11·0%) who had not previously received insulin were randomly assigned (1:1) via an interactive web-response system to once-weekly icodec or once-daily glargine U100. Double-masked CGM data were collected during treatment initiation (weeks 0-4), midtrial (weeks 22-26), end of main phase (weeks 48-52), end of extension phase (weeks 74-78), and follow-up (weeks 78-83). Secondary and exploratory outcomes were CGM-based metrics, including the mean percentages of time in glycaemic range (TIR; sensor glucose 3·9-10·0 mmol/L [70-180 mg/dL]), time in tight range (TITR; 3·9-7·8 mmol/L [70-140 mg/dL]), time above range (TAR; >10·0 mmol/L [>180 mg/dL]), and time below range (TBR; <3·9 mmol/L [<70 mg/dL] and <3·0 mmol/L [<54 mg/dL]), and CGM-derived hypoglycaemic episode durations (episodes defined by sensor glucose <3·9 mmol/L [<70 mg/dL for ≥15 consecutive minutes]). Analyses were done in the full analysis set (all randomly assigned participants). The ONWARDS 1 trial is registered with ClinicalTrials.gov, NCT04460885, and is complete., Findings: Participants were enrolled and randomly assigned in ONWARDS 1 between Nov 25, 2020, and Dec 1, 2022 (n=492 in each treatment group). During treatment initiation, we observed no statistically significant differences in the mean percentages of TIR, TITR, TAR, and TBR with icodec versus glargine U100. During the midtrial, end of main phase, and end of extension phase periods, the mean percentages of TIR and TITR were statistically significantly greater and the mean percentages of TAR statistically significantly lower with icodec versus glargine U100. The mean percentages of TIR met the internationally recommended CGM target (>70%) with icodec but not with glargine U100 during the three periods. TBR (<3·9 mmol/L [<70 mg/dL] and <3·0 mmol/L [<54 mg/dL]) was low and below recommended targets (<4% and <1%, respectively) across all study periods in both treatment groups, with no statistically significant differences between treatment groups for the lower threshold (<3·0 mmol/L [<54 mg/dL]). During the follow-up period, mean percentages of TIR, TITR, TAR, and TBR did not statistically significantly differ with icodec versus glargine U100. The duration of overall hypoglycaemic episodes was similar between treatment groups throughout the trial (median duration ≤35 min)., Interpretation: These CGM data support the long-term efficacy and safety of icodec versus glargine U100 during treatment and indicated no increase in the duration of individual hypoglycaemic episodes with icodec versus glargine U100 in insulin-naive individuals with type 2 diabetes., Funding: Novo Nordisk., Competing Interests: Declaration of interests RMB has received research support, consultant fees, or has served on advisory panels for Abbott Diabetes Care, Ascensia Diabetes Care, Bigfoot Biomedical, CeQur, Dexcom, Eli Lilly, Embecta, Hygieia, Insulet, Medtronic, Novo Nordisk, Onduo, Roche Diabetes Care, Sanofi, Tandem Diabetes Care, United Healthcare, Vertex Pharmaceuticals, and Zealand Pharma. RMB's employer, the nonprofit organisation HealthPartners Institute, contracts for his services and he receives no personal income from these activities. BÁ and SKW are employees of Novo Nordisk; TN is both an employee and shareholder of Novo Nordisk. IL has received research funding (paid to their institution) from Boehringer Ingelheim, Merck, Mylan, Novo Nordisk, Pfizer, and Sanofi; and has received advisory or consulting fees, travel support, or manuscript editorial support from AstraZeneca, Bayer, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly, Intercept Pharmaceuticals, Johnson & Johnson, Merck, Novo Nordisk, Pfizer, Sanofi, Shionogi, Structure Therapeutics, Target Pharma, Translational Medical Academy, Valeritas, WebMD, and Zealand Pharma. JKM has received speaker fees from Abbott Diabetes Care, A Menarini Diagnostics, BD and Embecta, Dexcom, Eli Lilly, Medtronic, Medtrust, Novo Nordisk, Roche Diabetes Care, Sanofi, Servier, Viatris, and Ypsomed; is a member of advisory boards for Abbott Diabetes Care, BD and Embecta, Boehringer Ingelheim, Eli Lilly, Medtronic, Novo Nordisk, Prediktor, Roche Diabetes Care, Sanofi, and Viatris; is a board member of the Austrian Diabetes Society and of the European Association for the Study of Diabetes; is a chair for the Postgraduate Education Committee of the European Association for the Study of Diabetes; has received materials provided by Menarini Diagnostics and Dexcom; is a shareholder of Decide Clinical Software and Elyte Diagnostics; and serves as the Chief Medical Officer at Elyte Diagnostics. JR reports clinical research grants from Applied Therapeutics, Biomea Fusion, Boehringer Ingelheim, Carmot, Corcept, Eli Lilly, Hanmi, Merck, Novartis, Novo Nordisk, Oramed, Regeneron, Pfizer, and Sanofi; has served on scientific advisory boards and received honorarium or consulting fees from Applied Therapeutics, Biomea Fusion, Boehringer Ingelheim, Eli Lilly, Hanmi, Novo Nordisk, Oramed, Regeneron, Roche, Sanofi, Structure Therapeutics, and Zealand Pharma; and has received honoraria for lectures from Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and Sanofi., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Aim: To explore the efficacy and safety of once-weekly insulin icodec (icodec) in Japanese adults (≥20 years old) with type 2 diabetes from the global ONWARDS 1, 2 and 4 trials., Materials and Methods: Insulin-naive (ONWARDS 1) and insulin-experienced (ONWARDS 2 and 4) individuals were randomized to icodec or a once-daily insulin comparator: insulin glargine U100 [ONWARDS 1 (basal insulin only) and 4 (basal-bolus regimen)] or insulin degludec [ONWARDS 2 (basal insulin only)]. The primary outcome was change in glycated haemoglobin from baseline to end of treatment (EOT) (ONWARDS 1: Week 52; ONWARDS 2 and 4: Week 26). Here, we present the Japanese subgroup results., Results: Similar reductions in glycated haemoglobin from baseline to EOT were observed in each trial for icodec and comparators. The proportion of time in range (blood glucose 3.9-10.0 mmol/L) at EOT was also comparable across treatment groups (time in range: 58%-68%), as was time spent with blood glucose below 3.0 mmol/L (<1.0%). Combined clinically significant (blood glucose <3.0 mmol/L) or severe (requiring external assistance for recovery) hypoglycaemia rates were low, with no severe events (ONWARDS 1 and 2) or a single severe event (ONWARDS 4; icodec group) reported. These results generally aligned with findings from the respective global populations. No new safety issues were identified., Conclusions: Icodec improved glycaemic control to a similar degree as once-daily basal insulin comparators while maintaining low levels of clinically significant or severe hypoglycaemia. The findings support icodec use in Japanese individuals with different levels of type 2 diabetes progression., (© 2024 Novo Nordisk and The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aim: To perform a participant-level post hoc meta-analysis of Phase 3a trials in type 2 diabetes (T2D) to characterize the hypoglycaemia safety and glycaemic efficacy of once-weekly insulin icodec (icodec)., Materials and Methods: All ONWARDS 1-5 randomized participants were pooled as overall T2D, insulin-naive, an insulin-experienced subgroups, and by once-daily trial comparator (degludec or glargine U100). The main outcomes included incidence and rates of clinically significant and severe hypoglycaemia. Additional endpoints included change in glycated haemoglobin (HbA1c) from baseline and HbA1c target achievement without clinically significant or severe hypoglycaemia., Results: The meta-analysis comprised 3765 participants (1882 icodec vs. 1883 comparators). In the overall T2D pool, clinically significant hypoglycaemia incidence was similar in the icodec group versus the comparator group (17.9% vs. 16.2%, odds ratio [OR] 1.14, 95% confidence interval [CI] 0.94, 1.38); however, rates were low but significantly higher in the icodec group (1.15 vs. 1.00 episodes/participant-year of exposure, estimated rate ratio 1.51 [95% CI 1.24, 1.85]). Fewer severe hypoglycaemic episodes occurred with icodec than with comparators (8 vs. 18). A greater reduction in HbA1c occurred with icodec versus comparators, irrespective of subgroup (estimated treatment difference range [-0.10 to -0.29%]; all p < 0.05). Across subgroups, except for the insulin-experienced subgroup, the odds of achieving HbA1c <53 mmol/mol (7.0%) without clinically significant or severe hypoglycaemia were greater with icodec than with comparators (OR range 1.30-1.55; all p < 0.05)., Conclusions: Icodec was associated with a similar incidence but higher rates of clinically significant hypoglycaemia (equating to one additional hypoglycaemic episode every 6 years) and fewer severe hypoglycaemic episodes versus comparators. Our findings also confirmed the greater efficacy of icodec that was demonstrated in the ONWARDS trial programme., (© 2024 Novo Nordisk A/S and The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Objective: This post hoc analysis assessed continuous glucose monitoring (CGM)-based metrics and hypoglycemia duration with once-weekly insulin icodec versus once-daily basal insulin analogs in insulin-experienced individuals with long-standing type 2 diabetes from two 26-week phase 3a trials (ONWARDS 2 and ONWARDS 4)., Research Design and Methods: Time in range (TIR) (3.9-10.0 mmol/L), time above range (TAR) (>10.0 mmol/L), and time below range (TBR) (<3.9 mmol/L and <3.0 mmol/L) were assessed during three CGM time periods (switch [weeks 0-4], end of treatment [weeks 22-26], and follow-up [weeks 27-31]) for icodec versus comparators (ONWARDS 2, insulin degludec [basal regimen]; ONWARDS 4, insulin glargine U100 [basal-bolus regimen]) using double-blind CGM data. CGM-derived hypoglycemic episode duration (<3.9 mmol/L) was assessed., Results: In both trials, there were no statistically significant differences in TIR, TAR, or TBR (<3.0 mmol/L) for icodec versus comparators across all time periods. In the end-of-treatment period, mean TIR was 63.1% (icodec) vs. 59.5% (degludec) in ONWARDS 2 and 66.9% (icodec) vs. 66.4% (glargine U100) in ONWARDS 4. Mean TBR <3.9 mmol/L and <3.0 mmol/L remained within recommended targets (<4% and <1%, respectively) across time periods and treatment arms. Hypoglycemic episode duration (<3.9 mmol/L) was comparable across time periods and treatment arms (median duration ≤40 min)., Conclusions: In insulin-experienced participants with long-standing type 2 diabetes, CGM-based TIR, TAR, and CGM-derived hypoglycemia duration (<3.9 mmol/L) were comparable for icodec and once-daily basal insulin analogs during all time periods. TBR remained within recommended targets., (© 2024 by the American Diabetes Association.)

Background: Insulin icodec (icodec) is a basal insulin analogue suitable for once-weekly dosing. ONWARDS 4 aimed to assess the efficacy and safety of once-weekly icodec compared with once-daily insulin glargine U100 (glargine U100) in individuals with long-standing type 2 diabetes on a basal-bolus regimen., Methods: In this 26-week, phase 3a, randomised, open-label, multicentre, treat-to-target, non-inferiority trial, adults from 80 sites (outpatient clinics and hospital departments) across nine countries (Belgium, India, Italy, Japan, Mexico, the Netherlands, Romania, Russia, and the USA) with type 2 diabetes (glycated haemoglobin [HbA 1c ] 7·0-10·0%) were randomly assigned (1:1) to receive once-weekly icodec or once-daily glargine U100 combined with 2-4 daily bolus insulin aspart injections. The primary outcome was change in HbA 1c from baseline to week 26 (non-inferiority margin of 0·3 percentage points). The primary outcome was evaluated in the full analysis set (ie, all randomly assigned participants). Safety outcomes were evaluated in the safety analysis set (ie, all participants randomly assigned who received at least one dose of trial product). This trial is registered with ClinicalTrials.gov, NCT04880850., Findings: Between May 14 and Oct 29, 2021, 746 participants were screened for eligibility, of whom 582 (78%) were randomly assigned (291 [50%] to icodec treatment and 291 [50%] to glargine U100 treatment). Participants had a mean duration of type 2 diabetes of 17·1 years (SD 8·4). At week 26, estimated mean change in HbA 1c was -1·16 percentage points in the icodec group (baseline 8·29%) and -1·18 percentage points in the glargine U100 group (baseline 8·31%), showing non-inferiority for icodec versus glargine U100 (estimated treatment difference 0·02 percentage points [95% CI -0·11 to 0·15], p<0·0001). Overall, 171 (59%) of 291 participants in the icodec group and 167 (57%) of 291 participants in the glargine U100 group had an adverse event. 35 serious adverse events were reported in 22 (8%) of 291 participants in the icodec group and 33 serious adverse events were reported in 25 (9%) of 291 participants receiving glargine U100. Overall, combined level 2 and level 3 hypoglycaemia rates were similar between treatment groups. No new safety concerns were identified for icodec., Interpretation: In people with long-standing type 2 diabetes on a basal-bolus regimen, once-weekly icodec showed similar improvements in glycaemic control, with fewer basal insulin injections, lower bolus insulin dose, and with no increase in hypoglycaemic rates compared with once-daily glargine U100. Key strengths of this trial include the use of masked continous glucose monitoring; the high trial completion rate; and the inclusion of a large, diverse, and multinational population. Limitations include the relatively short trial duration and the open-label design., Funding: Novo Nordisk., Competing Interests: Declaration of interests CM serves or has served on the advisory panel for Novo Nordisk, Sanofi, Merck Sharp & Dohme, Eli Lilly and Company, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, Medtronic, ActoBio Therapeutics, Pfizer, Imcyse, Insulet, Zealand Pharma, Avotres, MannKind, Sandoz, and Vertex. Financial compensation for these activities has been received by Katholieke Universiteit Leuven (Leuven, Belgium); Katholieke Universiteit Leuven has received research support for CM from Medtronic, Imcyse, Novo Nordisk, Sanofi, and ActoBio Therapeutics; CM serves or has served on the speakers' bureau for Novo Nordisk, Sanofi, Eli Lilly and Company, Boehringer Ingelheim, AstraZeneca, and Novartis. Financial compensation for these activities has been received by KU Leuven. BÁ, ALSAM, and KS are employees of Novo Nordisk and might hold stock in Novo Nordisk. HSB reports trial fees paid to his institution by Novo Nordisk during ONWARDS 3 and 5; and trial fees paid to his institution by Amgen, AstraZeneca, Boehringer Ingelheim, Ceapro, Eli Lilly and Company, Gilead, Janssen, Kowa Pharmaceuticals, Madrigal Pharmaceuticals, Merck, Novo Nordisk, Pfizer, Sanofi, and Tricida, outside the submitted work. WL has served on the speakers' bureau for Dexcom and Novo Nordisk and has served on advisory boards for Arecor and Novo Nordisk. SM has served on advisory councils for Novo Nordisk, Sanofi India, Sun Pharmaceutical Industries, Torrent Pharmaceuticals, and USV, and has been part of clinical trials for Boehringer Ingelheim, Eli Lilly and Company, Johnson & Johnson, Novo Nordisk, and Sanofi India. JR has served on advisory panels for Applied Therapeutics, Boehringer Ingelheim, Eli Lilly, Intarcia, Novo Nordisk, Oramed, Hanmi, Sanofi, and Zealand, and has received research support from Applied Therapeutics, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Genentech, Novartis, Intarcia, Merck, Novo Nordisk, Oramed, Pfizer, and Sanofi., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Once-daily and once-weekly injectable glucagon-like peptide-1 receptor agonist therapies (GLP-1 RAs) are established in obesity and type 2 diabetes mellitus (T2DM). In T2DM, both once-daily and once-weekly insulin are expected to be available. This study elicited utilities associated with these treatment regimens from members of the general public in the UK, Canada, and China, to quantify administration-related disutility of more-frequent injectable treatment, and allow economic modelling., Methods: Two anchor states (no pharmacological treatment), and seven treatment states (daily oral tablet and generic injectable regimens of variable frequency), with identical outcomes were tested A broadly representative sample of the general public in each country participated (excluding individuals with diabetes or pharmacologically treated obesity). An adapted Measurement and Valuation of Health protocol was administered 1:1 in web-enabled interviews by trained moderators: visual analogue scale (VAS) as a "warm-up", and time trade-off (TTO) using a 20-year time horizon for utility elicitation., Results: A total of 310 individuals participated. The average disutility of once-daily versus once-weekly GLP-1 RA was - 0.048 in obesity and - 0.033 in T2DM; the corresponding average disutility for insulin was - 0.064. Disutilities were substantially greater in China, relative to UK and Canada., Discussion: Within obesity and T2DM, more-frequent treatment health states had lower utility. Scores by VAS also followed a logical order. The generated utility values are suitable for use in modelling injectable therapy regimens in obesity and T2DM, due to the use of generic descriptions and assumption of equal efficacy. Future research could examine the reasons for greater administration-related disutility in China., (© 2022. The Author(s).)

Episodic ataxia type 1 and 2 (EA1 and EA2) are the most well-described of the episodic ataxias. They are autosomal dominantly inherited early-onset diseases characterized by attacks of cerebellar dysfunction. EA1 is clinically characterized by short episodes of ataxia with interictal myokymia, whereas EA2 is characterized by longer-lasting recurrent ataxia, slurred speech, and interictal nystagmus. We report on a patient with EA2 with interictal focal dystonia and also interictal myokymia, which is hitherto not reported as an interictal feature associated to EA2. The patient carries a previously described heterozygous pathogenic de novo frameshift variant in the CACNA1A gene, establishing the diagnosis of EA2. She had symptom onset at age 13 and from age 48 she developed interictal myokymia and focal dystonia as illustrated in Supplemental Movie S1. We conclude that interictal myokymia and focal dystonia may be interictal features associated to EA2 caused by the cerebellar pathophysiology of EA2. Episodes of ataxia were successfully treated with acetazolamide in low dose, whereas the interictal features were unresponsive to acetazolamide., (© 2022 Nielsen et al.; Published by Cold Spring Harbor Laboratory Press.)

Context: Outside of pregnancy, home blood pressure (BP) has been shown to be superior to office BP for predicting cardiovascular outcomes., Objective: This work aimed to evaluate home BP as a predictor of preeclampsia in comparison with office BP in pregnant women with preexisting diabetes., Methods: A prospective cohort study was conducted of 404 pregnant women with preexisting diabetes; home BP and office BP were measured in early (9 weeks) and late pregnancy (35 weeks). Discriminative performance of home BP and office BP for prediction of preeclampsia was assessed by area under the receiver operating characteristic curves (AUC)., Results: In total 12% (n = 49/404) developed preeclampsia. Both home BP and office BP in early pregnancy were positively associated with the development of preeclampsia (adjusted odds ratio (95% CI) per 5 mm Hg, systolic/diastolic): home BP 1.43 (1.21-1.70)/1.74 (1.34-2.25) and office BP 1.22 (1.06-1.40)/1.52 (1.23-1.87). The discriminative performance for prediction of preeclampsia was similar for early-pregnancy home BP and office BP (systolic, AUC 69.3 [61.3-77.2] vs 64.1 [55.5-72.8]; P = .21 and diastolic, AUC 68.6 [60.2-77.0] vs 66.6 [58.2-75.1]; P = .64). Similar results were seen when comparing AUCs in late pregnancy (n = 304). In early and late pregnancy home BP was lower than office BP (early pregnancy P < .0001 and late pregnancy P < .01 for both systolic and diastolic BP), and the difference was greater with increasing office BP., Conclusion: In women with preexisting diabetes, home BP and office BP were positively associated with the development of preeclampsia, and for the prediction of preeclampsia home BP and office BP were comparable., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: To evaluate the prevalence and severity of diabetic retinopathy including macular oedema in pregnant women with diabetes and to identify women in whom the frequency of retinal screening can be reduced to minimize the burden of health care visits., Methods: A cohort study of 348 women with pre-existing diabetes were routinely screened with retinal photo in early (12 weeks) and late pregnancy (27 weeks). Diabetic retinopathy was classified in five stages in accordance with National Danish Guidelines based on the eye with the highest retinopathy level. Sight-threatening retinopathy was defined as the presence of proliferative retinopathy and/or clinically significant macular oedema (CSMO)., Results: Retinopathy was present in 52% (116/223) vs. 14% (17/125), with sight-threatening retinopathy in 16% (35/223) vs. 6% (7/125) of women with type 1 and type 2, respectively. Women without retinopathy in early and late pregnancy were characterized by shorter diabetes duration (p < 0.0001 and p = 0.008) and predominance of type 2 diabetes. Amongst the 50% (175/348) of the cohort having no retinopathy in early pregnancy and HbA1c<53 mmol/mol (7.0%), none developed sight-threatening retinopathy and 94% (165/175) remained without any retinopathy during pregnancy. Development of sight-threatening retinopathy was mainly observed in women with retinopathy in early pregnancy. Treatment for sight-threatening retinopathy was given to a minority (2.7 and 2.4%, respectively)., Conclusion: Good glycaemic control and no retinopathy was seen in a large proportion of women in early pregnancy and none of these women developed sight-threatening retinopathy. The frequency of retinal screening can probably be safely reduced during pregnancy in these women., (© 2022 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Context: Falling insulin requirements often lead to considerations of whether a pregnancy can continue safely or if delivery is indicated., Objective: To evaluate prevalence and predictors of falling insulin requirements in pregnant women with preexisting diabetes delivering preterm and to explore the relationship to fetal asphyxia and neonatal morbidity., Methods: A prospective cohort study of 101 consecutive singleton pregnant women with preexisting diabetes delivering preterm < 37 weeks (68 type 1 and 33 type 2 diabetes) where the prevalence of falling insulin requirements (≥20%) before delivery was recorded., Results: In total, 27% (27/101) experienced falling insulin requirements of median 30% (interquartile range 24-40) before delivery. In all women with type 1 diabetes, the prevalence was 37% (25/68), whereas it was 43% (24/56) in those with indicated preterm delivery and 6% (2/33) among women with type 2 diabetes. In women with type 1 diabetes and indicated preterm delivery, falling insulin requirements were first identified at 34 + 5 (33 + 6-35 + 4) weeks + days and delivery occurred 3 (1-9) days later. Gestational age at delivery, prevalence of suspected fetal asphyxia, and neonatal morbidity were similar in women with and without falling insulin requirements. Neither glycemic control, nausea, or preeclampsia was associated with falling insulin requirement., Conclusion: Falling insulin requirements often preceded preterm delivery in women with type 1 diabetes, foremost when preterm delivery was indicated, but was not related to fetal asphyxia or neonatal morbidity. Whether falling insulin requirements in late pregnancy are a warning sign of placental insufficiency or mainly reflects variations in normal physiology needs further investigation., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To explore the impact of anti-hypertensive treatment of pregnancy-induced hypertension on foetal growth and hemodynamics in women with pre-existing diabetes., Methods: A prospective cohort study of 247 consecutive pregnant women with pre-existing diabetes (152 type 1 diabetes; 95 type 2 diabetes), where tight anti-hypertensive treatment was initiated and intensified (mainly with methyldopa) when office blood pressure (BP) ≥135/85 mmHg and home BP ≥130/80 mmHg. Foetal growth was assessed by ultrasound at 27, 33 and 36 weeks and foetal hemodynamics were assessed by ultrasound Doppler before and 1-2 weeks after initiation of anti-hypertensive treatment., Results: In 215 initially normotensive women, anti-hypertensive treatment for pregnancy-induced hypertensive disorders was initiated in 42 (20%), whilst 173 were left untreated. Chronic hypertension was present in 32 (13%). Anti-hypertensive treatment for pregnancy-induced hypertensive disorders was not associated with foetal growth deviation (linear mixed model, p = 0.681). At 27 weeks, mainly before initiation of anti-hypertensive treatment, the prevalence of small foetuses with an estimated foetal weight <10th percentile was 12% in women initiating anti-hypertensive treatment compared with 4% in untreated women (p = 0.054). These numbers were close to the prevalence of birth weight ≤10th percentile (small for gestational age (SGA)) (17% vs. 4%, p = 0.003). Pulsatility index in the umbilical and middle cerebral artery remained stable after the onset of anti-hypertensive treatment in a representative subgroup (n = 12, p = 0.941 and p = 0.799, respectively)., Conclusion: There is no clear indication that antihypertensive treatment causes harm in this particular at-high-risk group of pregnant women with diabetes, such that a larger well-designed study to determine the value of tight antihypertensive control would be worthwhile., (© 2021 Diabetes UK.)

Biallelic pathogenic variants in the ANO10 gene cause spinocerebellar ataxia recessive type 10. We report two patients, both compound heterozygous for ANO10 variants, including two novel variants. Both patients had onset of cerebellar ataxia in adulthood with slow progression and presented corticospinal tract signs, eye movement abnormalities and cognitive executive impairment. One of them had temporal lobe epilepsy and she also carried a heterozygous variant in CACNB4 , a potential risk gene for epilepsy. Both patients had pronounced cerebellar atrophy on cerebral magnetic resonance imaging (MRI) and reduced metabolic activity in cerebellum as well as in the frontal lobes on 2-deoxy-2-( 18 F)fluoro-D-glucose positron emission tomography (( 18 F)FDG PET) scans. We provide comprehensive clinical, radiological and genetic data on two patients carrying likely pathogenic ANO10 gene variants. Furthermore, we provide evidence for a cerebellar as well as a frontal involvement on brain ( 18 F)FDG PET scans which has not previously been reported., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims/hypothesis: We aimed to identify potentially modifiable risk factors and causes for preterm delivery in women with type 1 or type 2 (pre-existing) diabetes., Methods: A secondary analysis of a prospective cohort study of 203 women with pre-existing diabetes (117 type 1 and 86 type 2 diabetes) was performed. Consecutive singleton pregnancies were included at the first antenatal visit between September 2015 and February 2018., Results: In total, 27% (n = 55) of the 203 women delivered preterm at median 36 + 0 weeks. When stratified by diabetes type, 33% of women with type 1 diabetes delivered preterm compared with 20% in women with type 2 diabetes (p = 0.04). Women delivering preterm were characterised by a higher prevalence of pre-existing kidney involvement (microalbuminuria or diabetic nephropathy) (16% vs 3%, p = 0.002), preeclampsia (26% vs 5%, p < 0.001), higher positive ultrasound estimated fetal weight deviation at 27 gestational weeks (2.7% vs -1.6% from the mean, p = 0.008), higher gestational weight gain (399 g/week vs 329 g/week, p = 0.01) and similar HbA 1c levels in early pregnancy (51 mmol/mol [6.8%] vs 49 [6.6%], p = 0.22) when compared with women delivering at term. Independent risk factors for preterm delivery were pre-existing kidney involvement (OR 12.71 [95% CI 3.0, 53.79]), higher gestational weight gain (per 100 g/week, OR 1.25 [1.02, 1.54]), higher positive ultrasound estimated fetal weight deviation at 27 gestational weeks (% from the mean, OR 1.07 [1.03, 1.12]) and preeclampsia (OR 7.04 [2.34, 21.19]). Two-thirds of preterm deliveries were indicated and one-third were spontaneous. Several contributing factors to indicated preterm delivery were often present in each woman. The main indications were suspected fetal asphyxia (45%), hypertensive disorders (34%), fetal overgrowth (13%) and maternal indications (8%). Suspected fetal asphyxia mainly included falling insulin requirement and abnormal fetal haemodynamics., Conclusions/interpretations: Presence of preeclampsia, higher positive ultrasound estimated fetal weight deviation at 27 gestational weeks and higher gestational weight gain were independent potentially modifiable risk factors for preterm delivery in this cohort of women with pre-existing diabetes. Indicated preterm delivery was common with suspected fetal asphyxia or preeclampsia as the most prevalent causes. Prospective studies evaluating whether modifying these predictors will reduce the prevalence of preterm delivery are warranted., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To evaluate the prevalence of preeclampsia after implementation of prophylactic aspirin for all pregnant women with preexisting diabetes compared with the prevalence in a previous risk-based prophylaxis., Research Design and Methods: A prospective observational cohort study of 410 consecutive pregnant women with preexisting diabetes categorized according to aspirin prophylaxis strategy, with the prevalence of preeclampsia as primary outcome. In total, 207 women were included after implementation of prophylactic aspirin for all pregnant women with preexisting diabetes in February 2018 (all-cohort). The 203 women included before this date, where aspirin prophylaxis was risk based and only prescribed to selected women (selected-cohort), were studied for comparison., Results: Aspirin was prescribed at ∼10 gestational weeks for 88% (all-cohort) compared with 25% (selected-cohort). HbA 1c , parity, chronic hypertension, home blood pressure, microalbuminuria/diabetic nephropathy, and smoking were similar in the two cohorts in early pregnancy. In the all-cohort, fewer women had type 2 diabetes (32% vs. 42%, respectively; P = 0.04) and BMI tended to be lower ( P = 0.05). The prevalence of preeclampsia was similar (12% vs. 11%, P = 0.69) in the two cohorts, and this was also the case with stratification for diabetes type. Prevalence of preterm delivery <37 weeks (23% vs. 27%, P = 0.30), preterm preeclampsia (7% vs. 7%, P = 0.96), and infants large (40% vs. 32%, P = 0.07) and small (7% vs. 6%, P = 0.88) for gestational age was similar in the two cohorts., Conclusions: Implementation of prophylactic aspirin for all pregnant women with diabetes did not reduce the prevalence of preeclampsia compared with the previous risk-based prophylaxis in this cohort study., (© 2021 by the American Diabetes Association.)

Aims: To study the prevalence of anxiety and depression symptoms in pregnant women with type 2 diabetes compared with pregnant women without diabetes. Secondly, to explore whether anxiety and/or depression symptoms in early pregnancy have an impact on glycaemic control and gestational weight gain., Methods: A prospective cohort study of 90 consecutive singleton pregnant women with type 2 diabetes and 88 singleton pregnant women without diabetes. All women completed the Hospital Anxiety and Depression Scale questionnaire in early and late pregnancy. A score ≥8 in the anxiety or the depression scale was used to define anxiety and/or depression symptoms., Results: Anxiety and/or depression symptoms were present in 40% of women with type 2 diabetes and 7% of women without diabetes in early pregnancy (Relative Risk = 5.87 (95% Confidence Interval: 2.60-13.22)). The figures were similar in late pregnancy. In women with type 2 diabetes and anxiety and/or depression symptoms in early pregnancy, HbA 1c (mean ± SD) was 52 ± 14 vs. 49 ± 11 mmol/mol (6.9 ± 1.2 vs. 6.6 ± 1.0%), p = 0.31 in early pregnancy and 43 ± 8 vs. 40 ± 4 mmol/mol (6.1 ± 0.7 vs. 5.8 ± 0.4%), p = 0.04 in late pregnancy compared with women without symptoms. Gestational weight gain was similar in both groups., Conclusions: In women with type 2 diabetes, 40% had anxiety and/or depression symptoms in early pregnancy. Women with these symptoms obtained less optimal glycaemic control in late pregnancy but similar gestational weight gain as the remaining women., (© 2020 Diabetes UK.)

In pregnant women with type 1 diabetes, a low but sufficient, intake of carbohydrates is important to aim for near normal glycemic control. However, knowledge about the carbohydrate intake in this group is limited. To assess the average quantity and quality of carbohydrate intake in pregnant women with type 1diabetes compared to healthy pregnant women and current dietary reference intakes. A narrative literature search was performed in PubMed, Embase, and Cochrane Library and by using a snow-ball search technique to identify papers published on studies conducted in industrialized countries within the last 20 years. Intakes of carbohydrate were assessed qualitatively in relation to the Dietary Reference Intakes recommended by the American Diabetes Association and quantitatively as mean intake of dietary fiber. Five observational studies including 810 pregnant women with type 1 diabetes and 15 observational studies with a total of 118,246 healthy pregnant women were identified. The mean total carbohydrate intake was within the Acceptable Macronutrient Distribution Range (45%-64% of energy intake) in both groups. In pregnant women with type 1 diabetes, the average total intake was 218 ± 19 g/day, which was 20% (53 g/day) lower than in healthy pregnant women. Mean intake of dietary fiber in women with diabetes was lower than the recommended adequate intake for healthy women. With the limitations of pronounced heterogeneity across the included studies, pregnant women with type 1 diabetes reported a mean total carbohydrate intake, which was lower than in healthy pregnant women but still within the recommended range., Competing Interests: None of the authors had any conflict of interest., (© 2020 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Objective: Pregnancies complicated by maternal preexisting diabetes have a 4-5-fold increased risk of stillbirth, and consequently routine antenatal nonstress testing (NST) was implemented into clinical practice decades ago. Though, international guidelines lack consensus and recommend anything from twice weekly testing from 32 weeks to once weekly testing from 38 weeks. The objective of this study was to examine how routine antenatal NST was used in centers with specific interest and dedication in the care of pregnant women with preexisting diabetes., Study Design: An electronic survey concerning the routine use of antenatal NST was sent to members of the European Diabetic Pregnancy Study Group (DPSG) between October 2016 and January 2017, representing in total 55 centers in 26 countries taking care of pregnant women with diabetes., Results: Answers from 38 centers (69.1 % (38/55)) in 22 countries were received. Based on real world information from these primarily European centers, anything from avoiding routine antenatal NST to testing twice weekly from early in third trimester in women with preexisting diabetes was reported. NST was commonly used (71.1 % of centers) if insulin treatment was needed. NST was also used among diet treated women with type 2 diabetes in several places. The use varied markedly within and between countries. The most common practice was routine NST once weekly from 32 weeks., Conclusion: Among pregnant women with preexisting diabetes, routine antenatal testing practice with NST differs considerably both within and between countries. Studies examining the cost benefit of routine antenatal NST in pregnancies in women with the different types of diabetes are needed., Competing Interests: Declaration of Competing Interest The authors have no conflicts to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: Preexisting diabetes in pregnancy is associated with a high risk of emergency cesarean section (CS), which is associated with increased risk of maternal and neonatal complications. Thus, the aim of this study was to identify possible predictors of emergency CS in women with preexisting diabetes., Study Design: This is a secondary analysis of a prospective observational study of 204 women with preexisting diabetes (118 with type 1 diabetes and 86 with type 2) with singleton pregnancies recruited at Rigshospitalet, Copenhagen, Denmark from August 2015 to February 2018. Mode of delivery (trial of labor or planned CS) was individually planned in late pregnancy based on clinical variables reflecting maternal and fetal health including glycemic control and ultrasonically estimated fetal weight. Univariate and multivariable analyses were performed to identify possible predictors of in labor emergency CS., Results: Trial of labor was planned in 79 % (n = 162) of the women of whom 65 % (n = 105) were delivered vaginally and 35 % (n = 57) by an emergency CS, while the remaining 21 % (n = 42) were offered a planned CS. Nulliparity (adjusted odds ratio (aOR) 5.6 95 % CI 1.7-18.8), presence of a hypertensive disorder (aOR 2.8, 95 % CI 1.2-6.7) and previous CS (aOR 6.7, 95 % CI 1.5-28.9) were independently associated with an emergency CS. Maternal height was inversely associated with emergency CS (aOR 0.6 95 %, CI 0.5-0.9 per 5 cm decrease). Neither maternal HbA1c nor ultrasonically estimated fetal size in late pregnancy were associated with emergency CS. Women scheduled for a planned CS were characterized by poorer glycemic control and higher estimated fetal size than those offered a trial of labor., Conclusion: Nulliparity, presence of a hypertensive disorder, previous CS and shorter maternal height were predictors of emergency CS in women with a planned trial of labor, whereas this not was the case for late pregnancy maternal Hba1c or fetal size estimated by ultrasound., Competing Interests: Declaration of Competing Interest The authors have no conflicts to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aims: To explore the association between physical activity in early pregnancy and development of preeclampsia in women with preexisting diabetes., Methods: In a prospective cohort study of 189 women with preexisting diabetes (110 type 1 and 79 type 2 diabetes), physical activity during pregnancy including sedentary behavior was evaluated with the Pregnancy Physical Activity Questionnaire. Primary outcome was preeclampsia. Secondary outcomes were preterm delivery, large and small for gestational age infants., Results: Women developing preeclampsia (n = 23) had higher diastolic blood pressure in early pregnancy (mean 82 ± 9 SD vs. 77 ± 8, p = 0.004) and were more often nulliparous (91 vs. 52%, p < 0.001) compared with the remaining women (n = 166). Total physical activity in early pregnancy was similar between the groups (median 148 metabolic equivalent of task hours per week (MET-h/week) (interquartile range 118-227) versus 153 (121-205), p = 0.97). In early pregnancy, women developing preeclampsia reported a higher level of sedentary behavior (15 MET-h/week (7-18) versus 7 (4-15); p = 0.04); however, when adjusting for parity, diastolic blood pressure and smoking, the association attenuated (p = 0.13). Total physical activity and sedentary behavior in early pregnancy were not associated with preterm delivery, large or small for gestational age infants., Conclusions: Among women with diabetes, sedentary behavior was reported higher in early pregnancy in women developing preeclampsia compared with the remaining women, while total physical activity was similar. Sedentary behavior was a predictor of preeclampsia in the univariate analysis, but not in the multiple regression analysis, and larger studies are needed to evaluate this possible modifiable risk factor. Trial registration The study was registered at ClinicalTrials.gov (ID: NCT02890836).

Aims/hypothesis: Hypertensive disorders are prevalent among pregnant women with pre-existing diabetes, but the prevalence and impact of white coat hypertension are unknown. Measurement of home BP before initiation of antihypertensive treatment is necessary to identify white coat hypertension since international guidelines recommend that white coat hypertension is left untreated. The aim of this study, conducted among women with pre-existing diabetes, was therefore to examine the prevalence of white coat hypertension in early pregnancy, and pregnancy outcome in women with white coat hypertension in early pregnancy., Methods: A prospective cohort study was undertaken involving women with pre-existing diabetes from a geographically well-defined area. Based on office BP in early pregnancy and home BP measured for 3 days, women were categorised in three groups: (1) white coat hypertension, defined as office BP ≥ 135/85 mmHg and mean home BP < 130/80 mmHg; (2) chronic hypertension, defined as pre-pregnancy hypertension including newly detected office BP ≥ 135/85 mmHg with home BP ≥ 130/80 mmHg; and (3) normotension. Office BP was measured every 2 weeks and, if ≥ 135/85 mmHg, home BP measurements were performed. White coat hypertension was left untreated, and tight antihypertensive treatment was initiated when both office BP ≥ 135/85 mmHg and home BP ≥ 130/80 mmHg. Pregnancy-induced hypertensive disorders were defined as office BP ≥ 140/90 mmHg with home BP ≥ 130/80 mmHg when available, with onset after 20 weeks of gestation., Results: In total, 32 out of 222 women with pre-existing diabetes had newly detected office BP ≥ 135/85 mmHg in early pregnancy. White coat hypertension was present in 84% (27/32) of these women, representing 12% (95% CI 8%, 17%) of the whole cohort. Chronic hypertension was present in 14% (n = 32) and normotension in 74% (n = 163). Women with white coat hypertension were characterised by higher pre-pregnancy BMI (p = 0.011), higher home BP (p < 0.001) and higher prevalence of type 2 diabetes (p = 0.009), but similar HbA 1c (p = 0.409) compared to women with normotension. Regarding pregnancy outcome, pregnancy-induced hypertensive disorders developed in 44% (12/27) of women with white coat hypertension in comparison with 22% (36/163) among initially normotensive women (p = 0.013), while the prevalence of preterm delivery was comparable (p = 0.143). The adjusted analysis, performed post hoc, suggested approximately double the risk of developing pregnancy-induced hypertensive disorders (OR 2.43 [CI 0.98, 6.05]) if white coat hypertension was present in early pregnancy, independently of pre-pregnancy BMI and parity., Conclusions/interpretation: White coat hypertension is prevalent in women with pre-existing diabetes and may indicate a high risk of later development of pregnancy-induced hypertensive disorders. To distinguish between persistent white coat hypertension and onset of pregnancy-induced hypertension, repeated home BP monitoring is recommended when elevated office BP is detected. The study was registered at ClinicalTrials.gov (ID: NCT02890836).

Objective: To study how lifestyle coaching with motivational interviewing to improve adherence to healthy eating affects gestational weight gain and fetal growth in pregnant women with type 2 diabetes in a real-world setting., Research Design and Methods: A cohort study including a prospective intervention cohort of consecutive, singleton pregnant, Danish-speaking women with type 2 diabetes included between August 2015 and February 2018 and a historical reference cohort included between February 2013 and August 2015. The intervention consisted of a motivational interviewing to improve adherence to healthy eating in addition to routine care. The reference cohort received routine care only. The main outcomes were gestational weight gain and large for gestational age (LGA) infants., Results: Ninety-seven women were included in the intervention cohort and 92 in the reference cohort. Pre-pregnancy body mass index (32.8±6.9 kg/m 2 vs 32.4±7.4 kg/m 2 , p=0.70), gestational weight gain (9.2±5.8 kg vs 10.2±5.8 kg, p=0.25), HbA1c in early pregnancy (6.7%±1.1% vs 6.5%±1.3% (50±12 mmol/mol vs 48±14 mmol/mol), p=0.32) and late pregnancy (5.9%±0.5% vs 6.0%±0.6% (41±6 mmol/mol vs 42±7 mmol/mol), p=0.34) were comparable in the two cohorts. LGA infants occurred in 20% vs 31%, p=0.07, respectively, and after adjustment for maternal characteristics 14% vs 27% delivered LGA infants (p=0.04). Birth weight z-score was 0.24±1.36 vs 0.61±1.38, p=0.06., Conclusions: Motivational interviewing to improve adherence to healthy eating in addition to routine care in pregnant women with type 2 diabetes tended to reduce fetal overgrowth without major effect on gestational weight gain. Further studies investigating the cost-benefit of enhancing motivation are needed., Trial Registration Number: NCT02883127., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To investigate whether the upper home blood pressure reference limit in healthy pregnant women correspond to 135/85 mmHg as used when diagnosing white coat hypertension outside pregnancy., Methods: In this prospective observational study 103 healthy, singleton pregnant women with a mean age of 32 ± 4 (±SD) years and with a median pre-pregnancy body mass index of 21 (interquartile range 20-24) kg/m were included. Home blood pressure was measured with the device Microlife® BP 3A Plus twice daily for three days (18 measurements in total) in addition to routine office blood pressure measurements in early (median 12 (weeks)), mid (20) and late pregnancy (35). Upper blood pressure reference limits were calculated as mean +2 SD., Results: Office blood pressure versus home blood pressure were 115 ± 11/72 ± 7 versus 103 ± 7/64 ± 5 mmHg in early pregnancy, 112 ± 11/74 ± 7 versus 102 ± 7/63 ± 5 mmHg in mid pregnancy and 118 ± 11/75 ± 8 versus 107 ± 8/66 ± 6 mmHg in late pregnancy. The mean difference between office blood pressure and home blood pressure was 10 mmHg. In late pregnancy, the upper reference limit was 140/91 mmHg for office blood pressure and 123/78 mmHg for home blood pressure with slightly lower values in early and mid pregnancy, respectively., Conclusion: In late pregnancy, the upper home blood pressure reference limit in a population of healthy women was 123/78 mmHg. This value questions the generally proposed level of 135/85 mmHg to define white coat hypertension in pregnancy.

Aims: To secure adequate carbohydrate supply in pregnancy, the Institute of Medicine (IOM) recommends a minimum amount of carbohydrates of 175 g daily. Currently a low carbohydrate diet is a popular health trend in the general population and this might also be common among overweight and obese pregnant women with type 2 diabetes (T2D). Thus, we explored carbohydrate consumption among pregnant women with T2D including women with type 1 diabetes (T1D) for comparison., Methods: A retrospective cohort study of consecutive women with T2D (N = 96) and T1D (N = 108), where dietary records were collected at the first antenatal visit., Results: Among women with T2D and T1D, bodyweight at the first visit was 90.8 ± 22 (mean ± SD) and 75.5 ± 15 kg (P < 0.001) while HbA1c was 6.6 ± 1.2% (49 ± 13 mmol/mol) and 6.6 ± 0.8% (48 ± 8 mmol/mol), P = 0.8, respectively. The average daily carbohydrate consumption from the major carbohydrate sources was similar in the two groups (159 ± 56 and 167 ± 48 g, P = 0.3), as was the level of total daily physical activity (median (interquartile range)): 215 (174-289) and 210 (178-267) metabolic equivalent of task-hour/week (P = 0.9). A high proportion of women with T2D and T1D (52% and 40%, P = 0.08) consumed fewer carbohydrates than recommended by the IOM. The prevalence of ketonuria (≥4 mmol/L) was 1% in both groups., Conclusions: In early pregnancy, a lower daily carbohydrate consumption than recommended by the IOM was common among women with T2D. The results were quite similar to women with T1D, despite a markedly higher bodyweight in women with T2D. Reassuringly, ketonuria was rare in both groups., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aims: To identify early clinical, modifiable risk factors for preeclampsia present at first antenatal visit and assess the prevalence of pregnancy-related hypertensive disorders in women with pre-existing diabetes treated with tight glycemic and blood pressure (BP) control., Methods: A population-based cohort study of 494 women with pre-existing diabetes (307 and 187 women with type 1 and type 2 diabetes, respectively), included at their first antenatal visit from 2012 to 2016. The prevalence of chronic hypertension (without diabetic nephropathy or microalbuminuria), gestational hypertension and preeclampsia was recorded. Diabetic microangiopathy included presence of nephropathy, microalbuminuria and/or retinopathy. Treatment target was BP <135/85 mmHg., Results: HbA1c was 6.9 ± 2.4% (50 ± 12 mmol/mol) at first antenatal visit and 6.0 ± 0.6% (43 ± 6 mmol/mol) before delivery with no differences between women with type 1 and type 2 diabetes. At the first antenatal visit, the prevalence of microalbuminuria was 6% (6% vs. 6%), nephropathy 2% (1% vs. 2%) and chronic hypertension 6% (3% vs. 10%, p = 0.03). Gestational hypertension developed in 8% (9% vs. 6%) and preeclampsia developed in 8% (9% vs. 7%). Presence of diabetic microangiopathy (adjusted odds ratio (OR) 4.35 (confidence interval 2.12-8.93)) and diastolic BP (adjusted OR 1.72 per 10 mmHg (1.05-2.82)) at the first antenatal visit were independent risk factors for preeclampsia., Conclusions: At the first antenatal visit, diastolic BP was the only independent, potentially modifiable risk factor for preeclampsia in women with pre-existing diabetes in the context of tight glycemic and BP control. One out of four women had hypertensive disorders during pregnancy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aims: To study the influence of the quantity and the quality of carbohydrate consumption on glycemic control in early pregnancy among women with type 1 diabetes., Methods: A retrospective study of 107 women with type 1 diabetes who completed 1-3days of diet recording before first antenatal visit, as a part of routine care. The total daily carbohydrate consumption from the major sources (e.g. bread, potatoes, rice, pasta, dairy products, fruits, candy) was calculated. A dietician estimated the overall glycemic index score (scale 0-7)., Results: At least two days of diet recording were available in 75% of the 107 women at mean 64 (SD±14) gestational days. The quantity of carbohydrate consumption from major sources was 180 (±51)g/day. HbA1c was positively associated with the quantity of carbohydrate consumption (β=0.41; 95% CI 0.13-0.70, P=0.005), corresponding to an increase of 0.4% in HbA1c per 100g carbohydrates consumed daily, when adjusted for insulin dose/bodyweight and use of insulin pump treatment. The median (IQR) glycemic index score was 2 (0-3). An adjusted association between HbA1c and glycemic index score was not demonstrated. The women using carbohydrate counting daily (45%) had lower HbA1c compared to the remaining women (6.4 (±0.5) vs. 6.8 (±0.9)% (47±6 vs. 51±10mmol/mol), P=0.01)., Conclusions: HbA1c in early pregnancy was positively associated with the quantity of carbohydrate consumption regardless of insulin treatment. Carbohydrate counting is probably important for glycemic control in pregnant women with type 1 diabetes., (Copyright © 2017 Elsevier B.V. All rights reserved.)