Management of T1DM in Pregnancy: A Lancet Review PDF

Review Management of type 1 diabetes in pregnancy: update on lifestyle, pharmacological treatment, and novel technologies for achieving glycaemic targets...

Review Management of type 1 diabetes in pregnancy: update on lifestyle, pharmacological treatment, and novel technologies for achieving glycaemic targets Katrien Benhalima, Kaat Beunen, Sarah E Siegelaar, Rebecca Painter, Helen R Murphy, Denice S Feig, Lois E Donovan, Sarit Polsky, Elizabeth Buschur, Carol J Levy, Yogish C Kudva, Tadej Battelino, Lene Ringholm, Elisabeth R Mathiesen, Chantal Mathieu Lancet Diabetes Endocrinol Glucose concentrations within target, appropriate gestational weight gain, adequate lifestyle, and, if necessary, 2023; 11: 490–508 antihypertensive treatment and low-dose aspirin reduces the risk of pre-eclampsia, preterm delivery, and other Published Online adverse pregnancy and neonatal outcomes in pregnancies complicated by type 1 diabetes. Despite the increasing use June 5, 2023 of diabetes technology (ie, continuous glucose monitoring and insulin pumps), the target of more than 70% time in https://doi.org/10.1016/ S2213-8587(23)00116-X range in pregnancy (TIRp 3·5–7·8 mmol/L) is often reached only in the final weeks of pregnancy, which is too late This online publication has for beneficial effects on pregnancy outcomes. Hybrid closed-loop (HCL) insulin delivery systems are emerging as been corrected. The corrected promising treatment options in pregnancy. In this Review, we discuss the latest evidence on pre-pregnancy care, version first appeared at management of diabetes-related complications, lifestyle recommendations, gestational weight gain, antihypertensive thelancet.com/diabetes- treatment, aspirin prophylaxis, and the use of novel technologies for achieving and maintaining glycaemic targets endocrinology on August 7, 2023 during pregnancy in women with type 1 diabetes. In addition, the importance of effective clinical and psychosocial Endocrinology, University support for pregnant women with type 1 diabetes is also highlighted. We also discuss the contemporary studies Hospital Gasthuisberg, examining HCL systems in type 1 diabetes during pregnancies. Katholieke Universiteit Leuven, Leuven, Belgium (K Benhalima PhD MD, Introduction continuous glucose monitoring (CGM) and insulin K Beunen MBiomed, Pregnancy in women with type 1 diabetes is associated pumps, pregnant women with type 1 diabetes continue Prof C Mathieu PhD MD); with an increased risk of pregnancy complications, to spend on average 8 hours per day above target glucose Department of Endocrinology including congenital malformations, pre-eclampsia, concentrations.13,14 The 2019 Advanced Technologies and and Metabolism, Amsterdam preterm delivery, and perinatal mortality (appendix p 3). Treatments for Diabetes (ATTD) consensus on CGM UMC, University of Amsterdam, Amsterdam, In addition, approximately 50% of infants born to targets included the aims that a CGM time in range in Netherlands mothers with type 1 diabetes are large for gestational age pregnancy (TIRp) of 3·5–7·8 mmol/L (63–140 mg/dL) (S E Siegelaar PhD MD); (LGA).1–3 LGA can lead to problems during labour, should be achieved more than 70% of the time and time Amsterdam Gastroenterology including shoulder dystocia, which can result in neonatal below range in pregnancy (TBRp) of less than Endocrinology and Metabolism, Amsterdam, birth trauma and has been associated with a long-term 3·5 mmol/L (63 mg/dL) less than 4% of the time.15 Netherlands (S E Siegelaar); risk for type 2 diabetes in the offspring.4 Several A Swedish cohort study showed that mothers of LGA Department of Gynaecology population-based cohort studies have shown that, despite infants had lower TIRp during the second (52% vs 58%) and Obstetrics, Amsterdam new technologies for type 1 diabetes, birth outcomes have and third trimesters (58% vs 62%) than mothers of non- UMC, Vrije Universiteit, Netherlands barely improved over time.1,5,6 Although target glycaemia LGA infants, and a 5–6% lower TIRp was associated (Prof R Painter PhD MD); around the time of conception (HbA1c should be 0·050), but TBRp at night was higher with Flash (6·5% vs 0·0%, p=0·0030) and TIRp was lower with Flash (55·4% vs 68·8%, p=0·0050; primary outcomes). FreeStyle Libre 2 Flash glucose monitoring system ·· ·· European Conformity mark since Approved, 2018 Approved, (is-CGM with alarm function) 2018 and approved by FDA in 2020 2023 FreeStyle Libre 3 Flash glucose monitoring system ·· ·· European Conformity mark since Approved, 2020 Approved, (rt-CGM) 2020 and approved by FDA in 2022 2023 Dexcom G5 (rt-CGM; Dexcom, San Diego, CA, USA) Pilot prospective CGM quality improvement project in ·· European Conformity mark and Not approved Not approved pregnancy (NCT02556554). approved by FDA since 2015 Several prospective observational studies in which Dexcom G4 and G5 were used.90–92 Dexcom G6 (rt-CGM) Prospective observational study93 in 32 pregnant women in Three studies in type 1 diabetes: European Conformity mark and Approved, 2020 Not approved second or third trimester (type 1 diabetes n=20, type 2 AiDAPT RCT,94 LOIS-P study approved by FDA since 2018 diabetes n=3, and GDM n=9). Each wore two G6 sensors on (NCT04902378), and CIRCUIT the abdomen, upper buttock, posterior upper arm, or in RCT (NCT04492566). One study combination for 10 days and underwent a 6 h clinic session in type 2 diabetes with YSI Analyzer (Xylem, Yellow Springs, OH, USA) (NCT05370612). Five studies in reference blood glucose values obtained every 30 min. GDM (NCT05067075, Compared with the reference blood glucose values, NCT03981328, NCT04948112, 92·5% of CGM values were within ±20% of paired reference NCT05430204, NCT05037526, values >100 mg/dL or ±20 mg/dL of YSI values ≤100 mg/dL. NCT04605497). Three studies in The MARD on the abdomen was 11·5%, upper buttock was pregestational diabetes and 11·2%, and posterior upper arm was 8·7%. GDM: (NCT04605497, NCT04542148, NCT05492890). Dexcom G7 (rt-CGM) ·· ·· European Conformity mark and Approved, 2022 Approved, approved by FDA since 2022 2022 (Table 1 continues on next page) Review 495 496 Study results on pregnancy that are available Studies on pregnancy Approval outside pregnancy Specific approval Specific that are ongoing for pregnancy by approval European Conformity for pregnancy mark, year by FDA, year Review (Continued from previous page) Dexcom One (rt-CGM, no connectivity with insulin ·· ·· European Conformity mark since Approved, 2022 Not approved pump) 2022, but not approved by FDA Medtronic Guardian 3 (rt-CGM; Medtronic, ·· CRISTAL RCT (NCT04520971).95 European Conformity mark since Approved, 2017 Not approved Northridge, CA, USA) 2017 and approved by FDA in 2018 Medtronic Guardian 4 (rt-CGM) ·· CRISTAL RCT (NCT04520971).95 European Conformity mark since Approved, 2021 Not approved 2021, but not approved by FDA Pump Medtronic MiniMed 670G (by use of treat-to-target Case reports showed no safety events:96 automatic mode Pregnancy intervention with European Conformity mark since Not approved Not approved proportional integral derivative technology with started at 16 weeks gestation. TIRp increased from 46·8% a closed-loop system RCT 2018 and approved by FDA in insulin feedback with Guardian 3 CGM), non- to 51·3%.97 HCL therapy throughout gestation, but with (NCT03774186). 2016 customisable glucose target 6·7 mmol/L (120 mg/dL) inconsistent time in automatic mode. Glycaemic control improved with time at 0·050), respectively. Postprandial glucose control, glucose variability, insulin infusion rates, and CGM sensor accuracy were similar in early or late pregnancy, suggesting the MPC algorithm safely adapted insulin delivery for advancing gestational age. Murphy et al, 2011;21 UK FreeStyle Navigator CGM sensor with an Phase 1b randomised crossover trial with 12 pregnant Plasma glucose Plasma glucose TIRp was similar for HCL and conventional (ISRCTN50385583) intravenous sampling catheter and study women with type 1 diabetes, median TIRp 3·5–7·8 mmol/L CSII (81% vs 81%, p=0·75) with less time spent extreme pump (Animas 2020; Johnson and Johnson, HbA1c 46 mmol/mol (6·4%), comparing HCL with (63–140 mg/dL) from 1400 h hypoglycaemic