Tandem T:Slim X2 Insulin Pump Use in Clinical Practice Among Pregnant Individuals With Type 1 Diabetes: A Retrospective Observational Cohort Study.

BACKGROUND: Insulin pump use is increasing in frequency among pregnant individuals with type 1 diabetes (T1D). Automated insulin delivery (AID) technologies have not been studied extensively in pregnancy. METHOD: We present a retrospective case series of eight individuals with T1D who used the Tandem t:slim X2 insulin pump (Tandem Diabetes Care, Inc., CA, USA) during pregnancy. Weekly continuous glucose monitor and insulin pump data were analyzed from electronic medical records and data-sharing portals. Safety, glycemic control, and pregnancy outcomes were examined with both the control IQ (CIQ) and basal IQ (BIQ) algorithms. RESULTS: Six CIQ and two BIQ users were studied. The mean glycated hemoglobin (A1C) during pregnancy was 6.1%, and the average time in pregnancy-recommended glycemic range (TIR; 63-140mg/dL) was 67.9%. There were no instances of diabetic ketoacidosis or severe hypoglycemia. CIQ users had a higher mean sensor glucose (127.6 mg/dL) compared to BIQ participants (118.4 mg/dL). However, the average time below range (<63 mg/dL) was 6.1% in BIQ participants compared to 1.5% in CIQ participants. CIQ participants used several strategies to achieve glycemic targets, including daytime use of sleep activity. An increased basal-to-bolus insulin ratio was negatively correlated with TIR (r=-0.415). CONCLUSIONS: Tandem t:slim X2 insulin pumps were safely used during pregnancy in eight individuals with T1D, with variable success in achieving recommended glycemic targets. Further research is needed to understand differences in CIQ and BIQ use in pregnancy. AID device manufacturers must additionally develop further methods to target lower glucose for pregnant users.

Expert Guidance on Off-Label Use of Hybrid Closed-Loop Therapy in Pregnancies Complicated by Diabetes.

Automated insulin delivery (AID) systems have established benefits in terms of glycemic control, health outcomes, and quality of life and are strongly recommended for people with type 1 diabetes outside of pregnancy. While evidence for use of investigational AID systems during pregnancy is promising, data and guidance are still needed regarding use of commercially available systems during pregnancy. Unfortunately, none of the hybrid closed-loop (HCL) systems that are currently available in the United States have glucose targets that are as aggressive as pregnancy glycemic targets, none have a pregnancy-specific algorithm, and none are approved for use during pregnancy. As such, any use of these systems during pregnancy is considered off-label in the United States and would be "assisted" by provider/user techniques. Despite these limitations, many women conceive while using clinically available HCL systems and may be hesitant to cease use during pregnancy. Achievement of strict pregnancy glycemic targets can be difficult, and it is conceivable that selective off-label use of clinically available HCL systems in some women could lead to improved glycemia. We herein offer expert guidance based on clinical experience and available case reports on how to identify appropriate candidates for HCL therapy in pregnancy, how to counsel pregnant women with diabetes on the potential risks and benefits of HCL therapy during pregnancy, and how to manage commercially available systems off-label throughout gestation in an assisted HCL approach.

Transition From Pediatric to Adult Care for Individuals With Type 1 Diabetes: Opportunities and Challenges.

OBJECTIVES: Type 1 diabetes (T1D) is a chronic disease with patients across the age spectrum that has high potential for morbidity and mortality. Unfortunately, patients transitioning from pediatric to adult care continue to demonstrate worsened glycemic control in part due to lack of understanding of transition of care best practices. METHODS: This review highlights the impact of existing transition of care interventions, assessment tools, and other recently published strategies for providers to consider to improve care of adolescent and young adult (AYA) patients with T1D in both hospital- and clinic-based settings. RESULTS: Many barriers impact patients with T1D during the transition period and disparities by race, sex, insurance status, and comorbid illness persist. As diabetic care continues to evolve and the prevalence of adolescents and young adults living with T1D increases, an intentional approach to transition of care is more pressing than ever. While current literature on transition of care models is limited, many show promise in improving clinic attendance and decreasing hospitalization. There are critical discussions that providers should lead with AYA patients to improve their outcomes and increase diabetes self-management, such as re-addressing carbohydrate counseling, sleep hygiene, and reproductive planning. CONCLUSION: While further research on transition of care is needed, many care models offer the promise of improved T1D outcomes, enhancements in our approach to care, and increased value for our health care system at large.

CGM in the Hospital: Is It Ready for Prime Time?

PURPOSE OF REVIEW: The use of continuous glucose monitoring (CGM) in the hospital setting is growing with more patients using these devices at home and when admitted to the hospital, especially during the COVID-19 pandemic. RECENT FINDINGS: Historically, most evidence for CGM use in the inpatient setting was limited to small studies utilizing outdated CGM technology and analyzing accuracy of sensor measurements. Previous studies have shown reduced sensor accuracy during extreme hypo- or hyperglycemia, rapid fluctuations of glucose, compression of the sensor itself, and in those who are critically ill. Studies that are more recent have shown CGM to have adequate accuracy and may be effective in reducing hypoglycemia in hospitalized patients; some studies have also showed improvement in time in target glycemic range. Furthermore, CGM may reduce nursing workload, cost of inpatient care, and use of personal protective equipment and face-to-face patient care especially for patients during the COVID-19 pandemic. This review will describe the evidence for use of CGM in hospitalized critically ill or non-critically ill patients, address accuracy and safety considerations, and outline paths for future implementation.

Exploratory Analysis of Glycemic Control and Variability Over Gestation Among Pregnant Women with Type 1 Diabetes.

In exploratory analyses, we evaluated glycemic variability (GV) and gestational outcomes in pregnant women (n = 28) with type 1 diabetes (T1D). Gestational age at delivery was higher for women with lower glycemic measures, including estimated HbA1c (eHbA1c) (0.14% decrease in HbA1c per 1-week greater gestational age, P = 0.0035), mean sensor glucose (-3.9 mg/dL P = 0.0039), time spent >140 mg/dL (-3.1%, P = 0.0029), and higher time in range (TIR) of 63-140 mg/dL (3.2%, P = 0.0029). Third trimester measured HbA1c was significantly associated with gestational age at delivery (P = 0.0081). Preeclampsia was associated with less TIR in first (50.5% vs. 69.9%, P = 0.0034) and second trimesters (47.1% vs. 66.7%, P = 0.0025), but not with measured HbA1c. There were significant differences in other markers of GV (continuous overall net glycemic action, high blood glucose index, J-index, mean amplitude of glycemic excursions) with infant birth weight and gestational age at delivery. Thus, multiple markers of glycemia and GV were associated with gestational health outcomes in T1D pregnancies in this pilot study. Clinical Trial Registration number: NCT02556554.

Type 1 Diabetes: Management in Women From Preconception to Postpartum.

CONTEXT: This review presents an up-to-date summary on management of type 1 diabetes mellitus (T1DM) among women of reproductive age and covers the following time periods: preconception, gestation, and postpartum. EVIDENCE ACQUISITION: A systematic search and review of the literature for randomized controlled trials and other studies evaluating management of T1DM before pregnancy, during pregnancy, and postpartum was performed. EVIDENCE SYNTHESIS: Preconception planning should begin early in the reproductive years for young women with T1DM. Preconception and during pregnancy, it is recommended to have near-normal glucose values to prevent adverse maternal and neonatal outcomes, including fetal demise, congenital anomaly, pre-eclampsia, macrosomia, neonatal respiratory distress, neonatal hyperbilirubinemia, and neonatal hypoglycemia. CONCLUSION: Women with T1DM can have healthy, safe pregnancies with preconception planning, optimal glycemic control, and multidisciplinary care.

The use of longitudinal hemoglobin A1c values to predict adverse obstetric and neonatal outcomes in pregnancies complicated by pregestational diabetes.

BACKGROUND: Although an elevated early pregnancy hemoglobin A1c has been associated with both spontaneous abortion and congenital anomalies, it is unclear whether A1c assessment is of value beyond the first trimester in pregnancies complicated by pregestational diabetes. OBJECTIVE: We sought to investigate the prognostic ability of longitudinal A1c assessment to predict obstetric and neonatal adverse outcomes based on degree of glycemic control in early and late pregnancy. MATERIALS AND METHODS: This was a retrospective cohort study of all pregnancies complicated by pregestational diabetes from January 2012 to December 2016 at The Ohio State University Wexner Medical Center with both an early A1c (<20 weeks' gestation) and late A1c (>26 weeks' gestation) available for analysis. Patients were categorized by good (early and late A1c <6.5%), improved (early A1c >6.5% and late A1c <6.5%) and poor (late A1c >6.5%) glycemic control. A multivariate regression model was used to calculate adjusted odds ratios (aOR) for each identified obstetric and neonatal outcome, controlling for maternal age, body mass index, race/ethnicity, type of diabetes, and gestational age at delivery compared to good control as the referent group. RESULTS: A total of 341 patients met inclusion criteria during the study period. The median A1c values improved from early to late gestation in the good (5.7% [interquartile range [IQR], 5.4-6.1%] versus 5.4%; [IQR 5.2-5.7%]), improved (7.5% [IQR, 6.7-8.5] versus 5.9% [IQR, 5.6-6.1%]) and poor (8.3% [IQR, 7.1-9.6%] versus 7.3% [IQR, 6.8-7.9%]) glycemic control groups. There were no statistically significant differences in the rate of adverse outcomes between the good and improved groups except for an increased rate of neonatal intensive care unit admissions in the improved group (aOR, 3.7; confidence interval [CI], 1.9-7.3). In contrast, the poor control group had an increased rate of shoulder dystocia (aOR, 6.8; CI, 1.4-34.0), preterm delivery (aOR, 3.9; CI, 2.1-7.3), neonatal intensive care unit admission (aOR, 2.8; CI, 1.4-5.3), respiratory distress syndrome (aOR, 3.0; CI, 1.1-8.0), hypoglycemia (aOR, 3.2; CI, 1.5-6.9), large for gestational age weight at birth (aOR, 2.7; CI, 1.5-4.9), neonatal length of stay >4 days (aOR, 3.1; CI, 1.6-6.0) and preeclampsia (aOR, 2.4; CI, 1.2-4.6). There were no differences in rates of cesarean delivery, umbilical artery pH <7.1, or Apgar score <7 at 5 minutes after regression analysis. CONCLUSION: Antenatal hemoglobin A1c values are useful for objective risk stratification of patients with pregestational diabetes. Strict glycemic control throughout pregnancy with a late pregnancy A1c target of <6.5% leads to reduced rates of obstetric and neonatal adverse outcomes independent of early pregnancy glucose control.

The Accuracy and Cost-Effectiveness of Selective Fetal Echocardiography for the Diagnosis of Congenital Heart Disease in Patients with Pregestational Diabetes Stratified by Hemoglobin A1c.

OBJECTIVE: To evaluate the accuracy of antenatal diagnosis of congenital heart disease (CHD) using screening methods including a combination of elevated hemoglobin A1c, detailed anatomy ultrasound, and fetal echocardiography. STUDY DESIGN: This is a retrospective cohort study of all pregnancies complicated by pregestational diabetes from January 2012 to December 2016. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated for each screening regimen. The incremental cost-effectiveness ratio (ICER) was calculated for each regimen with effectiveness defined as additional CHD diagnosed. RESULTS: A total of 378 patients met inclusion criteria with an overall prevalence of CHD of 4.0% (n = 15). When compared with a detailed ultrasound, fetal echocardiography had a higher sensitivity (73.3 vs. 40.0%). However, all cases of major CHD were detected by detailed ultrasound (n = 6). Using an elevated early A1c > 7.7% and a detailed ultrasound resulted in a sensitivity and specificity of 60.0 and 99.4%, respectively. The use of selective fetal echocardiography for an A1c > 7.7% or abnormal detailed anatomy ultrasound would result in a 63.3% reduction in cost per each additional minor CHD diagnosed (ICER: $18,290.52 vs. $28,875.67). CONCLUSION: Fetal echocardiography appears to have limited diagnostic value in women with pregestational diabetes. However, these results may not be generalizable outside of a high-volume academic setting.

Transition of care for patients with type 1 diabetes mellitus from pediatric to adult health care systems.

Planning for the transition from pediatric to adult healthcare is broadly understood to be beneficial to the quality of care of patients with chronic illness. Due to the level of self-care that is necessary in the maintenance of most chronic diseases, it is important that pediatric settings can offer support during a time when adolescents are beginning to take more responsibility in all areas of their lives. Lack of supportive resources for adolescents with chronic conditions often results in both decreased access to care and impaired health and function likely leading to increased medical costs later. Additionally, fundamental differences in health care delivery exist between pediatric and adult care settings. There is limited empiric data and information on best practices in transition care. In this article we address the importance of bridging pediatric and adult care settings and highlight the challenges and successes of the implementation of the young adult transition clinic program for patients with type 1 diabetes at our facility. We provide recommendations for further research and program implementation with the transition population.

Insulin Pump Malfunction During Hospitalization: Two Case Reports.

BACKGROUND: Insulin pump malfunctions and failures continue to occur; however, more severe malfunctions such as the "runaway pump" phenomenon are rarely reported. This article describes two cases of pump malfunction in which pump users appear to have received an unsolicited bolus of insulin resulting in severe episodes of hypoglycemia during hospitalization. MATERIALS AND METHODS: Both cases of insulin pump malfunction occurred in the inpatient setting at a large academic medical center in the United States. An analysis of the corresponding insulin pump downloads was performed. The Food and Drug Administration's (FDA's) Manufacturer and User Facility Device Experience (MAUDE) database was searched for similar cases involving Medtronic (Northridge, CA) insulin pumps using the terms "pump," "infusion," "insulin AND malfunction AND Medtronic." RESULTS: The two cases described show remarkable similarities, each demonstrating a severe hypoglycemic event preceded by an infusion site change followed by an alarm. In both cases a rapid spraying of insulin was reported. The insulin pump downloads validated much of the patients' and medical staff's descriptions of events. The FDA's MAUDE database search revealed 425 cases meeting our search term criteria. All cases were reviewed. Seven cases were identified involving independent movement of the reservoir piston. CONCLUSIONS: The cases detailed are the first to describe an insulin pump malfunction of this nature in the hospital setting involving unsolicited insulin boluses leading to severe hypoglycemia. The cases are particularly compelling in that they were witnessed by medical personnel. Providers and patients should receive instruction education on the recognition and management of insulin pump malfunction.

Euglycemic Diabetic Ketoacidosis: A Potential Complication of Treatment With Sodium-Glucose Cotransporter 2 Inhibition.

OBJECTIVE: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are the most recently approved antihyperglycemic medications. We sought to describe their association with euglycemic diabetic ketoacidosis (euDKA) in hopes that it will enhance recognition of this potentially life-threatening complication. RESEARCH DESIGN AND METHODS: Cases identified incidentally are described. RESULTS: We identified 13 episodes of SGLT-2 inhibitor-associated euDKA or ketosis in nine individuals, seven with type 1 diabetes and two with type 2 diabetes, from various practices across the U.S. The absence of significant hyperglycemia in these patients delayed recognition of the emergent nature of the problem by patients and providers. CONCLUSIONS: SGLT-2 inhibitors seem to be associated with euglycemic DKA and ketosis, perhaps as a consequence of their noninsulin-dependent glucose clearance, hyperglucagonemia, and volume depletion. Patients with type 1 or type 2 diabetes who experience nausea, vomiting, or malaise or develop a metabolic acidosis in the setting of SGLT-2 inhibitor therapy should be promptly evaluated for the presence of urine and/or serum ketones. SGLT-2 inhibitors should only be used with great caution, extensive counseling, and close monitoring in the setting of type 1 diabetes.

Abiraterone acetate to lower androgens in women with classic 21-hydroxylase deficiency.

CONTEXT: Chronic supraphysiological glucocorticoid therapy controls the androgen excess of 21-hydroxylase deficiency (21OHD) but contributes to the high prevalence of obesity, glucose intolerance, and reduced bone mass in these patients. Abiraterone acetate (AA) is a prodrug for abiraterone, a potent CYP17A1 inhibitor used to suppress androgens in the treatment of prostate cancer. OBJECTIVE: The objective of the study was to test the hypothesis that AA added to physiological hydrocortisone and 9α-fludrocortisone acetate corrects androgen excess in women with 21OHD without causing hypertension or hypokalemia. DESIGN: This was a phase 1 dose-escalation study. SETTING: The study was conducted at university clinical research centers. PARTICIPANTS: We screened 14 women with classic 21OHD taking hydrocortisone 12.5-20 mg/d to enroll six participants with serum androstenedione greater than 345 ng/dL (>12 nmol/L). INTERVENTION: AA was administered for 6 days at 100 or 250 mg every morning with 20 mg/d hydrocortisone and 9α-fludrocortisone acetate. MAIN OUTCOME MEASURE: The primary endpoint was normalization of mean predose androstenedione on days 6 and 7 (< 230 ng/dL [<8 nmol/L)] in greater than 80% of participants. Secondary end points included serum 17-hydroxyprogesterone and testosterone (T), electrolytes, plasma renin activity, and urine androsterone and etiocholanolone glucuronides. RESULTS: With 100 mg/d AA, mean predose androstenedione fell from 764 to 254 ng/dL (26.7-8.9 nmol/L). At 250 mg/d AA, mean androstenedione normalized in five participants (83%) and decreased from 664 to 126 ng/dL (23.2-4.4 nmol/L), meeting the primary end point. Mean androstenedione declined further during day 6 to 66 and 38 ng/dL (2.3 and 1.3 nmol/L) at 100 and 250 mg/d, respectively. Serum T and urinary metabolites declined similarly. Abiraterone exposure was strongly negatively correlated with mean androstenedione. Hypertension and hypokalemia were not observed. CONCLUSION: AA 100-250 mg/d added to replacement hydrocortisone normalized several measures of androgen excess in women with classic 21OHD and elevated serum androstenedione.