Insulin Use During Gestational and Pre-existing Diabetes in Pregnancy: A Systematic Review of Study Design.

INTRODUCTION: Insulin is the first-line pharmacologic therapy for women with diabetes in pregnancy. However, conducting well-designed randomized clinical trials (RCTs) and achieving recommended glycemic targets remains a challenge for this unique population. This systematic literature review (SLR) aimed to understand the evidence for insulin use in pregnancy and the outcome metrics most often used to characterize its effect on glycemic, maternal and fetal outcomes in gestational diabetes mellitus (GDM) and in pregnant women with diabetes. METHODS: An SLR was conducted using electronic databases in Medline, EMBASE via Ovid platform, evidence-based medicine reviews (2010-2020) and conference proceedings (2018-2019). Studies were included if they assessed the effect of insulin treatment on glycemic, maternal or fetal outcomes in women with diabetes in pregnancy. Studies on any type of diabetes other than gestational or pre-existing diabetes as well as non-human studies were excluded. RESULTS: In women diagnosed with GDM or pre-existing diabetes, most studies compared treatment of insulin with metformin (n = 35) followed by diet along with lifestyle intervention (n = 24) and glibenclamide (n = 12). Most studies reporting on glycemic outcomes compared insulin with metformin (n = 22) and glibenclamide (n = 4). Fasting blood glucose was the most reported clinical outcome of interest. Among the studies reporting maternal outcomes, method of delivery and delivery complications were most commonly reported. Large for gestational age, stillbirth and perinatal mortality were the most common fetal outcomes reported. CONCLUSION: This SLR included a total of 108 clinical trials and observational studies with diverse populations and treatment arms. Outcomes varied across the studies, and a lack of consistent outcome measures to manage diabetes in pregnant women was observed. This elucidates a need for global consensus on study design and standardized clinical, maternal and fetal outcomes metrics.

Performance of the Dexcom G7 Continuous Glucose Monitoring System in Pregnant Women with Diabetes.

Background: We evaluated accuracy and safety of a seventh-generation real-time continuous glucose monitoring (CGM) system during pregnancy. Materials and Methods: Evaluable data for accuracy analysis were obtained from 96 G7 sensors (Dexcom, Inc.) worn by 96 of 105 enrolled pregnant women with type 1 (n = 59), type 2 (n = 21), or gestational diabetes (n = 25). CGM values were compared with arterialized venous glucose values from the YSI comparator instrument during 6-h clinic sessions at different time points throughout the sensors' 10-day wear period. The primary endpoint was the proportion of CGM values in the 70-180 mg/dL range within 15% of comparator glucose values. Secondary endpoints included the proportion of CGM values within 20% or 20 mg/dL of comparator values ≥ or <100 mg/dL, respectively (the %20/20 agreement rate). Results: Of the 1739 pairs with CGM in the 70-180 mg/dL range, 83.2% were within 15% of comparator values. The lower bound of the 95% confidence interval was 79.8%. Of the 2102 pairs with CGM values in the 40-400 mg/dL range, the %20/20 agreement rate was 92.5%. Of the 1659 pairs with comparator values in the 63-140 mg/dL range, the %20/20 agreement rate was 92.3%. The %20/20 agreement rates on days 1, 4 and 7, and 10 were 78.6%, 96.3%, and 97.3%, respectively. Consensus error grid analysis showed 99.8% of pairs in the clinically acceptable A and B zones. There were no serious adverse events. The sensors' 10-day survival rate was 90.3%. Conclusion: The G7 system is accurate and safe during pregnancies complicated by diabetes and does not require confirmatory fingerstick testing. Clinical Trial Registration: clinicaltrials.gov NCT04905628.

Concordance of Blood Glucose and CGM During a Pilot Trial of Automated Insulin Delivery in Type 1 Diabetes Pregnancies.

Background: Customized and standard automated insulin delivery (AID) systems for use in pregnancies of women with preexisting type 1 diabetes (T1D) are being developed and tested to achieve pregnancy appropriate continuous glucose monitoring (CGM) targets. Guidance on the use of CGM for treatment decisions during pregnancy in the United States is limited. Methods: Ten pregnant women with preexisting T1D participated in a trial evaluating at-home use of a pregnancy-specific AID system. Seven-point self-monitoring of blood glucose (SMBG) was compared to the closest sensor glucose (Dexcom G6 CGM) value biweekly to assess safety and reliability based on the 20%/20 mg/dL criteria. Results: All participants completed the study with 7 participants satisfying the safety and reliability criteria with a mean absolute relative difference of 10.3%. Three participants did not fulfill the criteria, mainly because the frequency of SMBG did not meet the requirements. Conclusion: Dexcom G6 CGM is safe and accurate in the real-world setting for use in pregnant women with preexisting T1D with reduced SMBG testing as part of a pregnancy-specific AID system.

A Randomized Comparison of Postprandial Glucose Excursion Using Inhaled Insulin Versus Rapid-Acting Analog Insulin in Adults With Type 1 Diabetes Using Multiple Daily Injections of Insulin or Automated Insulin Delivery.

OBJECTIVE: To compare postprandial glucose excursions following a bolus with inhaled technosphere insulin (TI) or subcutaneous rapid-acting analog (RAA) insulin. RESEARCH DESIGN AND METHODS: A meal challenge was completed by 122 adults with type 1 diabetes who were using multiple daily injections (MDI), a nonautomated pump, or automated insulin delivery (AID) and who were randomized to bolus with their usual RAA insulin (n = 61) or TI (n = 61). RESULTS: The primary outcome, the treatment group difference in area under the curve for glucose >180 mg/dL over 2 h, was less with TI versus RAA (adjusted difference -12 mg/dL, 95% CI -22 to -2, P = 0.02). With TI, the glucose excursion was smaller (P = 0.01), peak glucose lower (P = 0.01), and time to peak glucose shorter (P = 0.006). Blood glucose <70 mg/dL occurred in one participant in each group. CONCLUSIONS: Postmeal glucose excursion was smaller with TI than with RAA insulin in a cohort that included both AID and MDI users.