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.

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.

A review of CONCEPTT study findings including subanalyses in pregnant women using continuous glucose monitoring with type 1 diabetes and their offspring.

The main objective of this article is to provide a comprehensive review of continuous glucose monitor (CGM) use in pregnant women with type 1 diabetes (T1D) from the CONCEPTT study including subanalyses. Literature search was accessed through MEDLINE (1966-September 2023) using the key terms: CONCEPTT, pregnancy, women, T1D, and CGM with limitations set to distinguish human subjects written in English. A total of 17 publications including one main clinical trial and 15 subanalyses have been published to date regarding the use of CGM in pregnant women with T1D which were conducted by a research group identified as the CONCEPTT Collaborative Group. While advances in maternal care have resulted in safer pregnancy for both the mother and child, women with preexisting T1D and pregnancy still experience higher rates of complications both in the short and long term. The use of CGM in pregnancy has not been studied extensively until more recently. The CONCEPTT clinical trial was a landmark study that involved several subanalyses. The main trial proved that CGM use in T1D pregnancy resulted in less hyperglycemia in the third trimester, reduced large for gestational age (LGA, >90th percentile), reduced neonatal intensive care unit admissions lasting longer than 24 h, and reduced neonatal hypoglycemia. Although subanalyses showed a variety of results including 'inconclusive' due to lack of prespecification, it is believed that CGM in T1D during pregnancy is to be recommended and used for overall improved outcomes.

At-Home Use of a Pregnancy-Specific Zone-MPC Closed-Loop System for Pregnancies Complicated by Type 1 Diabetes: A Single-Arm, Observational Multicenter Study.

OBJECTIVE: There are no commercially available hybrid closed-loop insulin delivery systems customized to achieve pregnancy-specific glucose targets in the U.S. This study aimed to evaluate the feasibility and performance of at-home use of a zone model predictive controller-based closed-loop insulin delivery system customized for pregnancies complicated by type 1 diabetes (CLC-P). RESEARCH DESIGN AND METHODS: Pregnant women with type 1 diabetes using insulin pumps were enrolled in the second or early third trimester. After study sensor wear collecting run-in data on personal pump therapy and 2 days of supervised training, participants used CLC-P targeting 80-110 mg/dL during the day and 80-100 mg/dL overnight running on an unlocked smartphone at home. Meals and activities were unrestricted throughout the trial. The primary outcome was the continuous glucose monitoring percentage of time in the target range 63-140 mg/dL versus run-in. RESULTS: Ten participants (HbA1c 5.8 ± 0.6%) used the system from mean gestational age of 23.7 ± 3.5 weeks. Mean percentage time in range increased 14.1 percentage points, equivalent to 3.4 h per day, compared with run-in (run-in 64.5 ± 16.3% versus CLC-P 78.6 ± 9.2%; P = 0.002). During CLC-P use, there was significant decrease in both time over 140 mg/dL (P = 0.033) and the hypoglycemic ranges of less than 63 mg/dL and 54 mg/dL (P = 0.037 for both). Nine participants exceeded consensus goals of above 70% time in range during CLC-P use. CONCLUSIONS: The results show that the extended use of CLC-P at home until delivery is feasible. Larger, randomized studies are needed to further evaluate system efficacy and pregnancy outcomes.

Accuracy of the Third Generation of a 14-Day Continuous Glucose Monitoring System.

INTRODUCTION: We have evaluated the performance of the FreeStyle Libre® 3 continuous glucose monitoring system (FSL3) compared to (1) the venous plasma reference for participants aged ≥ 6 years and (2) the fingerstick capillary blood glucose (BG) reference for pediatric participants aged 4 and 5 years. The analytical performance of the third-generation factory-calibrated FSL3 CGM system was compared to the plasma venous blood glucose reference using the YSI 2300 STAT PLUS Glucose and Lactate Analyzer (the YSI reference) and the self-monitoring blood glucose (SMBG) reference for participants aged ≥ 6 years and participants aged 4 and 5 years, respectively. METHODS: A total of 108 participants aged ≥ 4 years with type 1 or type 2 diabetes from four sites in the USA were enrolled in the study. The data of 100 participants were ultimately evaluated. Adult participants (aged ≥ 18 years) participated in three in-clinic sessions, and pediatric participants (aged 4-17 years) participated in up to two in-clinic sessions, all stratified to provide data for days 1, 2, 3, 7, 8, 9, 12, 13 or 14 of sensor wear. Performance evaluation included accuracy measures, such as proportion of CGM values that fell within ± 20% or ± 20 mg/dL (1.1 mmol/L) of the reference glucose values, and difference measures, such as the mean absolute relative difference (MARD) between the CGM and reference values. RESULTS: Data from the 100 study participants were analyzed. The overall MARD was 7.8%, and 93.4% of the CGM values were within ± 20% or ± 20 mg/dL of the YSI reference for participants aged ≥ 6 years, with 6845 CGM-YSI matched pairs. The performance was stable over the 14-day wear period. For participants aged 4-5 years, MARD was 10.0%, and 88.9% of the CGM values were within 20%/20 mg/dL compared to a SMBG reference. No serious adverse events were reported. CONCLUSIONS: The FSL3 CGM system demonstrated accurate performance across the dynamic glycemic range during the 14-day sensor wear period.

Randomized controlled trial of prepregnancy lifestyle intervention to reduce recurrence of gestational diabetes mellitus.

BACKGROUND: Preconception lifestyle intervention holds potential for reducing gestational diabetes mellitus, but clinical trial data are lacking. OBJECTIVE: This study aimed to determine the effects of a prepregnancy weight loss intervention on gestational diabetes mellitus recurrence in women with overweight/obesity and previous gestational diabetes mellitus. STUDY DESIGN: A 2-site, randomized controlled trial comparing a prepregnancy lifestyle intervention with educational control was conducted between December 2017 and February 2022. A total of 199 English- and Spanish-speaking adults with overweight/obesity and previous gestational diabetes mellitus were randomized to a 16-week prepregnancy lifestyle intervention with ongoing treatment until conception or educational control. The primary outcome was gestational diabetes mellitus recurrence. Analyses excluded 6 participants who conceived but did not have gestational diabetes mellitus ascertained by standard methods. RESULTS: In the 63 (33%) women who conceived and had gestational diabetes mellitus ascertained (Ns=38/102 [37%] intervention vs 25/91 [28.0%] control; P=.17), those in the intervention group had significantly greater weight loss at 16 weeks compared with controls (4.8 [3.4-6.0] vs 0.7 [-0.9 to 2.3] kg; P=.001) and a greater proportion lost ≥5% of body weight (50.0% [17/34] vs 13.6% [3/22]; P=.005). There was no significant difference in the incidence of gestational diabetes mellitus recurrence between the intervention (57.9% [ns=23/38]) and the control group (44.0% [ns=11/25]; odds ratio, 1.8 [0.59-5.8]). Independent of group, greater prepregnancy weight loss predicted 21% lower odds of gestational diabetes mellitus recurrence (odds ratio, 0.79 [0.66-0.94]; P=.008). A ≥5% weight loss before conception reduced the odds of gestational diabetes mellitus recurrence by 82% (odds ratio, 0.18 [0.04-0.88]; P=.03). CONCLUSION: Lifestyle intervention produced considerable prepregnancy weight loss but did not affect gestational diabetes mellitus rates. Given that the conception rate was 50% lower than expected, this study was underpowered.

Update on Measuring Ketones.

Ketone bodies are an energy substrate produced by the liver and used during states of low carbohydrate availability, such as fasting or prolonged exercise. High ketone concentrations can be present with insulin insufficiency and are a key finding in diabetic ketoacidosis (DKA). During states of insulin deficiency, lipolysis increases and a flood of circulating free fatty acids is converted in the liver into ketone bodies-mainly beta-hydroxybutyrate and acetoacetate. During DKA, beta-hydroxybutyrate is the predominant ketone in blood. As DKA resolves, beta-hydroxybutyrate is oxidized to acetoacetate, which is the predominant ketone in the urine. Because of this lag, a urine ketone test might be increasing even as DKA is resolving. Point-of-care tests are available for self-testing of blood ketones and urine ketones through measurement of beta-hydroxybutyrate and acetoacetate and are cleared by the US Food and Drug Administration (FDA). Acetone forms through spontaneous decarboxylation of acetoacetate and can be measured in exhaled breath, but currently no device is FDA-cleared for this purpose. Recently, technology has been announced for measuring beta-hydroxybutyrate in interstitial fluid. Measurement of ketones can be helpful to assess compliance with low carbohydrate diets; assessment of acidosis associated with alcohol use, in conjunction with SGLT2 inhibitors and immune checkpoint inhibitor therapy, both of which can increase the risk of DKA; and to identify DKA due to insulin deficiency. This article reviews the challenges and shortcomings of ketone testing in diabetes treatment and summarizes emerging trends in the measurement of ketones in the blood, urine, breath, and interstitial fluid.

Hypoglycemia in Prospective Multicenter Study of Pregnancies with Pre-Existing Type 1 Diabetes on Sensor-Augmented Pump Therapy: The LOIS-P Study.

Background: Pregnancies in type 1 diabetes are high risk, and data in the United States are limited regarding continuous glucose monitoring (CGM)-based hypoglycemia throughout pregnancy while on sensor-augmented insulin pump therapy. Materials and Methods: Pregnant women with type 1 diabetes in the LOIS-P Study (Longitudinal Observation of Insulin use and glucose Sensor metrics in Pregnant women with type 1 diabetes using continuous glucose monitors and insulin pumps) were enrolled before 17 weeks gestation at three U.S. centers and we used their personal insulin pump and a study Dexcom G6 CGM. We analyzed data of 25 pregnant women for CGM hypoglycemia based on international consensus guidelines for percentage time <63 and 54 mg/dL, hypoglycemic events and prolonged hypoglycemia events for 24-h, daytime, and overnight periods, and severe hypoglycemia (SH) episodes. Results: For a 24-h period, biweekly median percentage of time <63 mg/dL ranged from 0.8% at biweek 4-5 to 3.7% at biweek 14-15 with high variability throughout pregnancy. Median percentage of time <63 and 54 mg/dL was higher overnight than daytime (P < 0.01). Hypoglycemic events occurred throughout the pregnancy, ranged 1-4 events per 2 weeks, significantly decreased after the 20th week, and occurred predominantly during daytime (P < 0.01). For overnight period, hypoglycemia and events were more concentrated from 12 to 3 am. Seven prolonged hypoglycemia events without any associated SH occurred in four participants (16%), primarily overnight. Three participants experienced a single episode of SH. Conclusions: Our results suggest a higher overall risk of hypoglycemia throughout pregnancy during the overnight period with continued daytime risk of hypoglycemic events in pregnancies complicated by type 1 diabetes.

Feasibility of Closed-Loop Insulin Delivery with a Pregnancy-Specific Zone Model Predictive Control Algorithm.

Objective: Evaluating the feasibility of closed-loop insulin delivery with a zone model predictive control (zone-MPC) algorithm designed for pregnancy complicated by type 1 diabetes (T1D). Research Design and Methods: Pregnant women with T1D from 14 to 32 weeks gestation already using continuous glucose monitor (CGM) augmented pump therapy were enrolled in a 2-day multicenter supervised outpatient study evaluating pregnancy-specific zone-MPC based closed-loop control (CLC) with the interoperable artificial pancreas system (iAPS) running on an unlocked smartphone. Meals and activities were unrestricted. The primary outcome was the CGM percentage of time between 63 and 140 mg/dL compared with participants' 1-week run-in period. Early (2-h) postprandial glucose control was also evaluated. Results: Eleven participants completed the study (age: 30.6 ± 4.1 years; gestational age: 20.7 ± 3.5 weeks; weight: 76.5 ± 15.3 kg; hemoglobin A1c: 5.6% ± 0.5% at enrollment). No serious adverse events occurred. Compared with the 1-week run-in, there was an increased percentage of time in 63-140 mg/dL during supervised CLC (CLC: 81.5%, run-in: 64%, P = 0.007) with less time >140 mg/dL (CLC: 16.5%, run-in: 30.8%, P = 0.029) and time <63 mg/dL (CLC: 2.0%, run-in:5.2%, P = 0.039). There was also less time <54 mg/dL (CLC: 0.7%, run-in:1.6%, P = 0.030) and >180 mg/dL (CLC: 4.9%, run-in: 13.1%, P = 0.032). Overnight glucose control was comparable, except for less time >250 mg/dL (CLC: 0%, run-in:3.9%, P = 0.030) and lower glucose standard deviation (CLC: 23.8 mg/dL, run-in:42.8 mg/dL, P = 0.007) during CLC. Conclusion: In this pilot study, use of the pregnancy-specific zone-MPC was feasible in pregnant women with T1D. Although the duration of our study was short and the number of participants was small, our findings add to the limited data available on the use of CLC systems during pregnancy (NCT04492566).

Accuracy and Safety of Dexcom G7 Continuous Glucose Monitoring in Adults with Diabetes.

Background: We evaluated the accuracy and safety of a seventh generation (G7) Dexcom continuous glucose monitor (CGM) during 10.5 days of use in adults with diabetes. Methods: Adults with either type 1 or type 2 diabetes (on intensive insulin therapy or not) participated at 12 investigational sites in the United States. In-clinic visits were conducted on days 1 or 2, 4 or 7, and on the second half of day 10 or the first half of day 11 for frequent comparisons with comparator blood glucose measurements obtained with the YSI 2300 Stat Plus glucose analyzer. Participants wore sensors concurrently on the upper arm and abdomen. Accuracy evaluation included the proportion of CGM values within 15% of comparator glucose levels >100 mg/dL or within 15 mg/dL of comparator levels ≤100 mg/dL (%15/15), along with the %20/20 and %30/30 agreement rates. The mean absolute relative difference (MARD) between temporally matched CGM and comparator values was also calculated. Results: Data from 316 participants (619 sensors, 77,774 matched pairs) were analyzed. For arm- and abdomen-placed sensors, overall MARDs were 8.2% and 9.1%, respectively. Overall %15/15, %20/20, and %30/30 agreement rates were 89.6%, 95.3%, and 98.8% for arm-placed sensors and were 85.5%, 93.2%, and 98.1% for abdomen-placed sensors. Across days of wear, glucose concentration ranges, and rates of change, %20/20 agreement rates varied by no more than 9% from the overall %20/20. No serious adverse events were reported. Conclusions: The G7 CGM provides accurate glucose readings with single-digit MARD with arm or abdomen placement in adults with diabetes. Clinicaltrials.gov: NCT04794478.

Accuracy of a 14-Day Factory-Calibrated Continuous Glucose Monitoring System With Advanced Algorithm in Pediatric and Adult Population With Diabetes.

BACKGROUND: In this study, we evaluated the analytical performance of the second-generation factory-calibrated FreeStyle Libre Flash Glucose Monitoring (FreeStyle Libre 2) System compared to plasma venous blood glucose reference, Yellow Springs Instrument 2300 (YSI). METHODS: The study enrolled participants aged four and above with type 1 or type 2 diabetes at seven sites in the United States. Adult participants (18+ years) participated in three in-clinic sessions and pediatric participants (4-17 years) participated in up to two in-clinic sessions stratified to provide data for days 1, 2, 3, 7, 8, 9, 12, 13, or 14 of sensor wear. Participants aged 11+ underwent supervised glycemic manipulation during in-clinic sessions to achieve glucose levels across the measurement range of the System. Performance evaluation included accuracy measures such as the proportion of continuous glucose monitoring (CGM) values that were within ±20% or ±20 mg/dL of reference glucose values, and bias measures such as the mean absolute relative difference (MARD) between CGM and reference values. RESULTS: Data from the 144 adults and 129 pediatric participants were analyzed. Percent of sensor results within ±20%/20 mg/dL of YSI reference were 93.2% and 92.1%, and MARD was 9.2% and 9.7% for the adults and pediatric participants, respectively. The System performed well in the hypoglycemic range, with 94.3% of the results for the adult population and 96.1% of the data for pediatric population being within 15 mg/dL of the YSI reference. The time lag was 2.4 ± 4.6 minutes for adults and 2.1 ± 5.0 minutes for pediatrics. CONCLUSIONS: The System demonstrated improved analytical accuracy performance across the dynamic range during the 14-day sensor wear period as compared to the previous-generation device.NCT#: NCT03607448 and NCT03820050.

Traveling Across Time Zones With Type 1 Diabetes: A Pilot Study Comparing Insulin Degludec With Insulin Glargine U100.

OBJECTIVE: For people with type 1 diabetes, there are limited evidence-based resources to support self-management when traveling across multiple time zones. Here, we compared glycemic control on insulin degludec versus glargine U100 as the basal insulin for adults using multiple daily injections (MDI) while traveling across multiple time zones. RESEARCH DESIGN AND METHODS: This randomized crossover pilot study compared insulin degludec versus glargine U100 for adults with type 1 diabetes using MDI insulin during long-haul travel to and from Hawaii to New York. Insulin degludec was administered daily at the same time regardless of time zone, and glargine was administered per travel algorithm. Primary end point was the percentage of time in range (TIR) between 70 and 140 mg/dL during the initial 24 h after each direction of travel. Secondary end points included standard continuous glucose monitoring metrics, jet lag, fatigue, and sleep. RESULTS: The study enrolled 25 participants (56% women, mean ± SD age of 35 ± 14.5 years, HbA1c of 7.4 ± 1.2% [57 ± 13.1 mmol/mol], and diabetes duration of 20.6 ± 15 years). There was no significant difference in glycemic outcomes between the two arms of the study, including TIR, hypoglycemia, or hyperglycemia. Neither group achieved >70% TIR 70-180 mg/dL during travel. Jet lag was greater on glargine U100 in eastward travel but not westward. Fatigue was greater after westward travel on glargine. Sleep was not significantly different between basal insulins. CONCLUSIONS: In adults with type 1 diabetes using MDI of insulin and traveling across multiple time zones, glycemic outcomes were similar comparing insulin degludec and glargine U100.

Continuous Ketone Monitoring Consensus Report 2021.

This article is the work product of the Continuous Ketone Monitoring Consensus Panel, which was organized by Diabetes Technology Society and met virtually on April 20, 2021. The panel consisted of 20 US-based experts in the use of diabetes technology, representing adult endocrinology, pediatric endocrinology, advanced practice nursing, diabetes care and education, clinical chemistry, and bioengineering. The panelists were from universities, hospitals, freestanding research institutes, government, and private practice. Panelists reviewed the medical literature pertaining to ten topics: (1) physiology of ketone production, (2) measurement of ketones, (3) performance of the first continuous ketone monitor (CKM) reported to be used in human trials, (4) demographics and epidemiology of diabetic ketoacidosis (DKA), (5) atypical hyperketonemia, (6) prevention of DKA, (7) non-DKA states of fasting ketonemia and ketonuria, (8) potential integration of CKMs with pumps and automated insulin delivery systems to prevent DKA, (9) clinical trials of CKMs, and (10) the future of CKMs. The panelists summarized the medical literature for each of the ten topics in this report. They also developed 30 conclusions (amounting to three conclusions for each topic) about CKMs and voted unanimously to adopt the 30 conclusions. This report is intended to support the development of safe and effective continuous ketone monitoring and to apply this technology in ways that will benefit people with diabetes.

Longitudinal Observation of Insulin Use and Glucose Sensor Metrics in Pregnant Women with Type 1 Diabetes Using Continuous Glucose Monitors and Insulin Pumps: The LOIS-P Study.

Background: Suboptimal glycemic control is associated with maternal and neonatal morbidity and mortality in pregnancy complicated by type 1 diabetes (T1D). Prospective analysis of continuous glucose monitoring (CGM) metrics, insulin pump settings, and insulin delivery can better characterize the changes in glycemic levels and insulin use throughout pregnancy with T1D. Materials and Methods: Prescribed parameters, insulin delivery, carbohydrate intake, and CGM data for 25 pregnant women with T1D from three U.S. sites were collected. Participants enrolled before 17 weeks gestation and used personal insulin pumps and study CGM. Mean daily total, basal, and bolus insulin doses (units/kg), CGM time in range (TIR: 63-140 mg/dL), and pump-entered carbohydrates were analyzed for every 2-week gestational interval. Linear mixed-effects regression models were used to evaluate changes across gestational ages compared to 12-14 weeks. Results: Basal insulin was higher during weeks 6-12 and 24-40. Daily bolus and total insulin were higher during weeks 20-40. Pump parameters were adjusted to intensify insulin therapy from 22 weeks onward. Average TIR across pregnancy was 59% ± 14%. Between 18 and 30 weeks, TIR was significantly lower, and time above range was significantly higher compared to the reference biweek. Time below target was lower between 22 and 34 weeks. Seven participants achieved >70% recommended TIR for pregnancy. Participants with maternal complications or infant neonatal intensive care unit admissions had lower TIR. Conclusion: While insulin dosing changed significantly with advancing gestation, most participants did not achieve >70% TIR. Customized anticipatory pump setting adjustments and automated systems aimed toward the designated TIR are needed to improve outcomes for this population. NCT03761615.

Protocol for a randomized controlled trial of pre-pregnancy lifestyle intervention to reduce recurrence of gestational diabetes: Gestational Diabetes Prevention/Prevención de la Diabetes Gestacional.

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with several maternal complications in pregnancy, including preeclampsia, preterm labor, need for induction of labor, and cesarean delivery as well as increased long-term risks of type 2 diabetes, metabolic syndrome, and cardiovascular disease. Intrauterine exposure to GDM raises the risk for complications in offspring as well, including stillbirth, macrosomia, and birth trauma, and long-term risk of metabolic disease. One of the strongest risk factors for GDM is the occurrence of GDM in a prior pregnancy. Preliminary data from epidemiologic and bariatric surgery studies suggest that reducing body weight before pregnancy can prevent the development of GDM, but no adequately powered trial has tested the effects of a maternal lifestyle intervention before pregnancy to reduce body weight and prevent GDM recurrence. METHODS: The principal aim of the Gestational Diabetes Prevention/Prevención de la Diabetes Gestacional is to determine whether a lifestyle intervention to reduce body weight before pregnancy can reduce GDM recurrence. This two-site trial targets recruitment of 252 women with overweight and obesity who have previous histories of GDM and who plan to have another pregnancy in the next 1-3 years. Women are randomized within site to a comprehensive pre-pregnancy lifestyle intervention to promote weight loss with ongoing treatment until conception or an educational control group. Participants are assessed preconceptionally (at study entry, after 4 months, and at brief quarterly visits until conception), during pregnancy (at 26 weeks' gestation), and at 6 weeks postpartum. The primary outcome is GDM recurrence, and secondary outcomes include fasting glucose, biomarkers of cardiometabolic disease, prenatal and perinatal complications, and changes over time in weight, diet, physical activity, and psychosocial measures. DISCUSSION: The Gestational Diabetes Prevention /Prevención de la Diabetes Gestacional is the first randomized controlled trial to evaluate the effects of a lifestyle intervention delivered before pregnancy to prevent GDM recurrence. If found effective, the proposed lifestyle intervention could lay the groundwork for shifting current treatment practices towards the interconception period and provide evidence-based preconception counseling to optimize reproductive outcomes and prevent GDM and associated health risks. TRIAL REGISTRATION: ClinicalTrials.gov NCT02763150 . Registered on May 5, 2016.

Feasibility of Continuous Ketone Monitoring in Subcutaneous Tissue Using a Ketone Sensor.

BACKGROUND: The feasibility of measuring ß-hydroxybutyrate in ISF using a continuous ketone monitoring (CKM) sensor using a single calibration without further adjustments over 14 days is described. METHODS: A CKM sensor was developed using wired enzyme technology with ß-hydroxybutyrate dehydrogenase chemistry. In vitro characterization of the sensor was performed in phosphate buffered saline at 37°C. In vivo performance was evaluated in 12 healthy participants on low carbohydrate diets, who wore 3 ketone sensors on the back of their upper arms to continuously measure ketone levels over 14 days. Reference capillary ketone measurements were performed using Precision Xtra® test strips at least 8 times a day. RESULTS: The sensor is stable over 14 days and has a linear response over the 0-8 mM range. The operational stability of the sensor is very good with a 2.1% signal change over 14 days. The first human study of the CKM sensor demonstrated that the sensor can continuously track ketones well through the entire 14 days of wear. The performance with a single retrospective calibration of the sensor showed 82.4% of data pairs within 0.225 mM/20% and 91.4% within 0.3 mM/30% of the capillary ketone reference (presented as mM at <1.5 mM and as percentage at or above 1.5 mM). This suggests that the sensor can be used with a single calibration for the 14 days of use. CONCLUSIONS: Measuring ketones in ISF using a continuous ketone sensor is feasible. Additional studies are required to evaluate the performance in intended patient populations, including conditions of ketosis and diabetic ketoacidosis.

Performance of the Dexcom G6 Continuous Glucose Monitoring System in Pregnant Women with Diabetes.

Background: The aim of this study was to determine the performance of the Dexcom G6 continuous glucose monitoring (CGM) system across three sensor wear sites in pregnant women with diabetes in the second or third trimesters. Methods: Participants with type 1 (T1D), type 2 (T2D), or gestational (GDM) diabetes mellitus were enrolled at three sites. Each wore two G6 sensors on the abdomen, upper buttock, and/or posterior upper arm for 10 days and underwent a 6-h clinic session between days 3 and 7 of sensor wear, during which YSI reference blood glucose values were obtained every 30 min. No intentional glucose manipulations were performed. Accuracy metrics included the proportion of CGM values that were within ±20% of paired reference values >100 mg/dL or ±20 mg/dL of YSI values ≤100 mg/dL (hereafter referred to as %20/20), as well as the analogous %15/15, %30/30, and %40/40. The mean absolute relative difference (MARD) between CGM-YSI pairs was also calculated. Results: Thirty-two participants with T1D (n = 20), T2D (n = 3), or GDM (n = 9) were enrolled: 19 were in the second trimester and 13 were in the third trimester of pregnancy. Compared with the reference, 92.5% of CGM values were within ±20%/20 mg/dL. The overall MARD and that of sensors worn on the abdomen, upper buttock, and posterior upper arm was 10.3%, 11.5%, 11.2%, and 8.7%, respectively. There were no device-related adverse events. Skin reactions at the insertion sites were absent or minor. Conclusions: The Dexcom G6 CGM system is accurate and safe in pregnant women with diabetes.