Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT): a multicentre international randomised controlled trial.

BACKGROUND: Pregnant women with type 1 diabetes are a high-risk population who are recommended to strive for optimal glucose control, but neonatal outcomes attributed to maternal hyperglycaemia remain suboptimal. Our aim was to examine the effectiveness of continuous glucose monitoring (CGM) on maternal glucose control and obstetric and neonatal health outcomes. METHODS: In this multicentre, open-label, randomised controlled trial, we recruited women aged 18-40 years with type 1 diabetes for a minimum of 12 months who were receiving intensive insulin therapy. Participants were pregnant (≤13 weeks and 6 days' gestation) or planning pregnancy from 31 hospitals in Canada, England, Scotland, Spain, Italy, Ireland, and the USA. We ran two trials in parallel for pregnant participants and for participants planning pregnancy. In both trials, participants were randomly assigned to either CGM in addition to capillary glucose monitoring or capillary glucose monitoring alone. Randomisation was stratified by insulin delivery (pump or injections) and baseline glycated haemoglobin (HbA1c). The primary outcome was change in HbA1c from randomisation to 34 weeks' gestation in pregnant women and to 24 weeks or conception in women planning pregnancy, and was assessed in all randomised participants with baseline assessments. Secondary outcomes included obstetric and neonatal health outcomes, assessed with all available data without imputation. This trial is registered with ClinicalTrials.gov, number NCT01788527. FINDINGS: Between March 25, 2013, and March 22, 2016, we randomly assigned 325 women (215 pregnant, 110 planning pregnancy) to capillary glucose monitoring with CGM (108 pregnant and 53 planning pregnancy) or without (107 pregnant and 57 planning pregnancy). We found a small difference in HbA1c in pregnant women using CGM (mean difference -0·19%; 95% CI -0·34 to -0·03; p=0·0207). Pregnant CGM users spent more time in target (68% vs 61%; p=0·0034) and less time hyperglycaemic (27% vs 32%; p=0·0279) than did pregnant control participants, with comparable severe hypoglycaemia episodes (18 CGM and 21 control) and time spent hypoglycaemic (3% vs 4%; p=0·10). Neonatal health outcomes were significantly improved, with lower incidence of large for gestational age (odds ratio 0·51, 95% CI 0·28 to 0·90; p=0·0210), fewer neonatal intensive care admissions lasting more than 24 h (0·48; 0·26 to 0·86; p=0·0157), fewer incidences of neonatal hypoglycaemia (0·45; 0·22 to 0·89; p=0·0250), and 1-day shorter length of hospital stay (p=0·0091). We found no apparent benefit of CGM in women planning pregnancy. Adverse events occurred in 51 (48%) of CGM participants and 43 (40%) of control participants in the pregnancy trial, and in 12 (27%) of CGM participants and 21 (37%) of control participants in the planning pregnancy trial. Serious adverse events occurred in 13 (6%) participants in the pregnancy trial (eight [7%] CGM, five [5%] control) and in three (3%) participants in the planning pregnancy trial (two [4%] CGM and one [2%] control). The most common adverse events were skin reactions occurring in 49 (48%) of 103 CGM participants and eight (8%) of 104 control participants during pregnancy and in 23 (44%) of 52 CGM participants and five (9%) of 57 control participants in the planning pregnancy trial. The most common serious adverse events were gastrointestinal (nausea and vomiting in four participants during pregnancy and three participants planning pregnancy). INTERPRETATION: Use of CGM during pregnancy in patients with type 1 diabetes is associated with improved neonatal outcomes, which are likely to be attributed to reduced exposure to maternal hyperglycaemia. CGM should be offered to all pregnant women with type 1 diabetes using intensive insulin therapy. This study is the first to indicate potential for improvements in non-glycaemic health outcomes from CGM use. FUNDING: Juvenile Diabetes Research Foundation, Canadian Clinical Trials Network, and National Institute for Health Research.

CONCEPTT: Continuous Glucose Monitoring in Women with Type 1 Diabetes in Pregnancy Trial: A multi-center, multi-national, randomized controlled trial - Study protocol.

BACKGROUND: Women with type 1 diabetes strive for optimal glycemic control before and during pregnancy to avoid adverse obstetric and perinatal outcomes. For most women, optimal glycemic control is challenging to achieve and maintain. The aim of this study is to determine whether the use of real-time continuous glucose monitoring (RT-CGM) will improve glycemic control in women with type 1 diabetes who are pregnant or planning pregnancy. METHODS/DESIGN: A multi-center, open label, randomized, controlled trial of women with type 1 diabetes who are either planning pregnancy with an HbA1c of 7.0 % to ≤10.0 % (53 to ≤ 86 mmol/mol) or are in early pregnancy (<13 weeks 6 days) with an HbA1c of 6.5 % to ≤10.0 % (48 to ≤ 86 mmol/mol). Participants will be randomized to either RT-CGM alongside conventional intermittent home glucose monitoring (HGM), or HGM alone. Eligible women will wear a CGM which does not display the glucose result for 6 days during the run-in phase. To be eligible for randomization, a minimum of 4 HGM measurements per day and a minimum of 96 hours total with 24 hours overnight (11 pm-7 am) of CGM glucose values are required. Those meeting these criteria are randomized to RT- CGM or HGM. A total of 324 women will be recruited (110 planning pregnancy, 214 pregnant). This takes into account 15 and 20 % attrition rates for the planning pregnancy and pregnant cohorts and will detect a clinically relevant 0.5 % difference between groups at 90 % power with 5 % significance. Randomization will stratify for type of insulin treatment (pump or multiple daily injections) and baseline HbA1c. Analyses will be performed according to intention to treat. The primary outcome is the change in glycemic control as measured by HbA1c from baseline to 24 weeks or conception in women planning pregnancy, and from baseline to 34 weeks gestation during pregnancy. Secondary outcomes include maternal hypoglycemia, CGM time in, above and below target (3.5-7.8 mmol/l), glucose variability measures, maternal and neonatal outcomes. DISCUSSION: This will be the first international multicenter randomized controlled trial to evaluate the impact of RT- CGM before and during pregnancy in women with type 1 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01788527 Registration Date: December 19, 2012.

Pregnancy snapshot: a retrospective, observational case-control study to evaluate the potential effects of maternal diabetes treatment during pregnancy on macrosomia.

OBJECTIVE: Pregnancy in women with diabetes is associated with increased incidence of macrosomia (high birth weight) versus women without diabetes. Macrosomia increases the risk of complications during delivery and neonatally. The potential effect on macrosomia incidence certain diabetes treatments may have is not fully established. This study aims to identify whether specific components of the prenatal care of mothers with diabetes are associated with increased macrosomia risk in a real-world U.S. RESEARCH DESIGN AND METHODS: Retrospective, observational case-controlled study of mothers either without diabetes, or with type 1 (T1D), type 2 (T2D), or gestational diabetes mellitus (G.D.M.), using data from a U.S. insurance claims database. Treatment selection was at physician discretion. MAIN OUTCOME MEASURE: Incidence of macrosomia. RESULTS: For mothers with T2D, use of neutral protamine Hagedorn (N.P.H.) insulin and glyburide increased during pregnancy, from 3.4% to 33.3%, and 3.7% to 16.5%, respectively. The most common G.D.M. treatments during pregnancy were glyburide (15.5%), N.P.H. (12.9%), basal-bolus therapy (10.0%), and metformin (8.1%). Endocrinologist care during pregnancy was associated with insulin use - but not glyburide use - for mothers with G.D.M., and with insulin use for mothers with T1D and T2D (compared with mothers not visiting an endocrinologist). Glyburide was associated with higher odds for macrosomia: G.D.M. (odds ratio [O.R.] 1.53, 95% confidence interval [C.I.] 1.38-1.69, p < 0.0001); T2D (O.R. 1.93, 95% C.I. 1.51-2.47, p < 0.0001). Endocrinologist care was associated with lower odds for macrosomia overall (O.R. 0.86, 95% C.I. 0.81-0.92) and for mothers with G.D.M. (O.R. 0.85, 95% C.I. 0.75-0.97, p = 0.0156) when the sub-populations were examined in separate models. CONCLUSIONS: Healthcare utilization and endocrinologist care were related to positive birth outcomes, especially with G.D.M. Further research into the safety and efficacy of glyburide in pregnancy is warranted. This study cannot infer causality and may not be representative of current U.S. healthcare practice.

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY 2016 OUTPATIENT GLUCOSE MONITORING CONSENSUS STATEMENT.

This document represents the official position of the American Association of Clinical Endocrinologists and American College of Endocrinology. Where there were no randomized controlled trials or specific U.S. FDA labeling for issues in clinical practice, the participating clinical experts utilized their judgment and experience. Every effort was made to achieve consensus among the committee members. Position statements are meant to provide guidance, but they are not to be considered prescriptive for any individual patient and cannot replace the judgment of a clinician.

Trends in the incidence of diabetes, its clinical sequelae, and associated costs in pregnancy.

BACKGROUND: Increasing diabetes prevalence affects a substantial number of pregnant women in the United States. Our aims were to evaluate health outcomes, medical costs, risks and types of complications associated with diabetes in pregnancy for mothers and newborns. METHODS: In this retrospective claims analysis, patients were identified from the Truven Health MarketScan(®) database (2004-2011 inclusive). Participants were aged 18-45 years, with ascertainable diabetes status [Yes/No], date of birth event >2005 and continuous health plan enrolment ≥21 months before and 3 months after the birth. RESULTS: In total, 839 792 pregnancies were identified, and 66 041 (7.86%) were associated with diabetes mellitus [type 1 (T1DM), 0.13%; type 2 (T2DM), 1.21%; gestational (GDM), 6.29%; and GDM progressing to T2DM (patients without prior diabetes who had a T2DM diagnosis after the birth event), 0.23%]. Relative risk (RR) of stillbirth (2.51), miscarriage (1.28) and Caesarean section (C-section) (1.77) was significantly greater with T2DM versus non-diabetes. Risk of C-section was also significantly greater for other diabetes types [RR 1.92 (T1DM); 1.37 (GDM); 1.63 (GDM progressing to T2DM)]. Risk of overall major congenital (RR ≥ 1.17), major congenital circulatory (RR ≥ 1.19) or major congenital heart (RR ≥ 1.18) complications was greater in newborns of mothers with diabetes versus without. Mothers with T2DM had significantly higher risk (RR ≥ 1.36) of anaemia, depression, hypertension, infection, migraine, or cardiac, obstetrical or respiratory complications than non-diabetes patients. Mean medical costs were higher with all diabetes types, particularly T1DM ($27 531), than non-diabetes ($14 355). CONCLUSIONS: Complications and costs of healthcare were greater with diabetes, highlighting the need to optimize diabetes management in pregnancy.

Artificial pancreas (AP) clinical trial participants' acceptance of future AP technology.

BACKGROUND: Artificial pancreas (AP) systems are currently an active field of diabetes research. This pilot study examined the attitudes of AP clinical trial participants toward future acceptance of the technology, having gained firsthand experience. SUBJECTS AND METHODS: After possible influencers of AP technology adoption were considered, a 34-question questionnaire was developed. The survey assessed current treatment satisfaction, dimensions of clinical trial participant motivation, and variables of the technology acceptance model (TAM). Forty-seven subjects were contacted to complete the survey. The reliability of the survey scales was tested using Cronbach's α. The relationship of the factors to the likelihood of AP technology adoption was explored using regression analysis. RESULTS: Thirty-six subjects (76.6%) completed the survey. Of the respondents, 86.1% were either highly likely or likely to adopt the technology once available. Reliability analysis of the survey dimensions revealed good internal consistency, with scores of >0.7 for current treatment satisfaction, convenience (motivation), personal health benefit (motivation), perceived ease of use (TAM), and perceived usefulness (TAM). Linear modeling showed that future acceptance of the AP was significantly associated with TAM and the motivation variables of convenience plus the individual item benefit to others (R(2)=0.26, P=0.05). When insulin pump and continuous glucose monitor use were added, the model significance improved (R(2)=0.37, P=0.02). CONCLUSIONS: This pilot study demonstrated that individuals with direct AP technology experience expressed high likelihood of future acceptance. Results support the factors of personal benefit, convenience, perceived usefulness, and perceived ease of use as reliable scales that suggest system adoption in this highly motivated patient population.

Clinical evaluation of an automated artificial pancreas using zone-model predictive control and health monitoring system.

BACKGROUND: This study was performed to evaluate the safety and efficacy of a fully automated artificial pancreas using zone-model predictive control (zone-MPC) with the health monitoring system (HMS) during unannounced meals and overnight and exercise periods. SUBJECTS AND METHODS: A fully automated closed-loop artificial pancreas was evaluated in 12 subjects (eight women, four men) with type 1 diabetes (mean±SD age, 49.4±10.4 years; diabetes duration, 32.7±16.0 years; glycosylated hemoglobin, 7.3±1.2%). The zone-MPC controller used an a priori model that was initialized using the subject's total daily insulin. The controller was designed to keep glucose levels between 80 and 140 mg/dL. A hypoglycemia prediction algorithm, a module of the HMS, was used in conjunction with the zone controller to alert the user to consume carbohydrates if the glucose level was predicted to fall below 70 mg/dL in the next 15 min. RESULTS: The average time spent in the 70-180 mg/dL range, measured by the YSI glucose and lactate analyzer (Yellow Springs Instruments, Yellow Springs, OH), was 80% for the entire session, 92% overnight from 12 a.m. to 7 a.m., and 69% and 61% for the 5-h period after dinner and breakfast, respectively. The time spent < 60 mg/dL for the entire session by YSI was 0%, with no safety events. The HMS sent appropriate warnings to prevent hypoglycemia via short and multimedia message services, at an average of 3.8 treatments per subject. CONCLUSIONS: The combination of the zone-MPC controller and the HMS hypoglycemia prevention algorithm was able to safely regulate glucose in a tight range with no adverse events despite the challenges of unannounced meals and moderate exercise.

Durability of glycemic control with insulin lispro mix 75/25 versus insulin glargine for older patients with type 2 diabetes.

BACKGROUND AND AIMS: Few studies have evaluated long-term durability of glycemic control in older patients. The aim of this study was to compare durability of glycemic control of twice-daily insulin lispro mix 75/25 (LM75/25; 75 % insulin lispro protamine suspension, 25 % insulin lispro) and once-daily insulin glargine (GL) added to oral antihyperglycemic medications in older patients (≥65 years of age). METHODS: Patients were participants in the maintenance phase of the DURABLE trial. During the initiation phase, patients with type 2 diabetes were randomized to LM75/25 or GL. After 6 months, patients with hemoglobin A1c (HbA1c) ≤7.0 % advanced to the 24-month maintenance phase. The primary objective was between-group comparison of duration of maintaining the HbA1c goal in older patients (≥65 years of age). A similar analysis was conducted for older patients achieving HbA1c ≤6.5 % in the initiation phase. RESULTS: Median time of maintaining HbA1c goal was longer in LM75/25 versus GL (19.6 versus 15.4 months, p = 0.007) and more LM75/25 patients maintained goal versus GL (49.2 versus 30.4 %; p = 0.003). HbA1c reduction from baseline was greater in LM75/25 versus GL (-1.56 ± 0.10 versus -1.24 ± 0.11 %; p = 0.003). Post-meal glucose was significantly lower in LM75/25 versus GL (158.86 ± 3.42 versus 171.67 ± 4.51 mg/dL; p = 0.017). No differences were observed in overall and severe hypoglycemia. LM75/25 patients had higher daily insulin doses (0.41 ± 0.02 versus 0.32 ± 0.02 units/kg/day; p < 0.001) and more weight gain (5.47 ± 0.49 versus 3.10 ± 0.53 kg; p = 0.001). Similar results were generally obtained in older patients with HbA1c ≤6.5 %. CONCLUSIONS: In our evaluation of older patients from a larger trial, LM75/25 appeared to provide longer durability of glycemic control, as well as a greater number of patients maintaining HbA1c goal versus GL.

A randomized trial comparing perinatal outcomes using insulin detemir or neutral protamine Hagedorn in type 1 diabetes.

OBJECTIVE: This randomized controlled trial aimed to compare the efficacy and safety of insulin detemir (IDet) with neutral protamine Hagedorn (NPH), both with insulin aspart, in pregnant women with type 1 diabetes. The perinatal and obstetric pregnancy outcomes are presented. METHODS: Subjects were randomized to IDet (n = 152) or NPH (n = 158) ≤12 months before pregnancy or at 8-12 gestational weeks. RESULTS: For IDet and NPH, there were 128 and 136 live births, 11 and 9 early fetal losses, and two and one perinatal deaths, respectively. Gestational age at delivery was greater for children from the IDet arm than the NPH arm (treatment difference: 0.49 weeks [95% CI 0.11;0.88], p = 0.012, linear regression). Sixteen children had a malformation (IDet: n = 8/142, 5.6%; NPH: n = 8/145, 5.5%). The incidence of adverse events was similar between treatments. CONCLUSION: IDet is as well tolerated as NPH as regards perinatal outcomes in pregnant women with type 1 diabetes and no safety issues were identified.

Diabetes and pregnancy: an endocrine society clinical practice guideline.

OBJECTIVE: Our objective was to formulate a clinical practice guideline for the management of the pregnant woman with diabetes. PARTICIPANTS: The Task Force was composed of a chair, selected by the Clinical Guidelines Subcommittee of The Endocrine Society, 5 additional experts, a methodologist, and a medical writer. EVIDENCE: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. CONSENSUS PROCESS: One group meeting, several conference calls, and innumerable e-mail communications enabled consensus for all recommendations save one with a majority decision being employed for this single exception. CONCLUSIONS: Using an evidence-based approach, this Diabetes and Pregnancy Clinical Practice Guideline addresses important clinical issues in the contemporary management of women with type 1 or type 2 diabetes preconceptionally, during pregnancy, and in the postpartum setting and in the diagnosis and management of women with gestational diabetes during and after pregnancy.

The postpartum management of women with gestational diabetes using a continuum model for health care.

Women with gestational diabetes mellitus require a continuum of care before, during, and after pregnancy for optimal management of hyperglycemia. Postpartum education and lifestyle modification should begin during pregnancy, and should continue during the postpartum period. Women should receive education on the long-term risk of type 2 diabetes mellitus, and should be encouraged to breastfeed, engage in regular physical activity, and select a highly effective contraceptive method in preparation for subsequent pregnancy. Postpartum women with gestational diabetes mellitus should be empowered to take ownership of their own health, including knowledge of health indicators such as weight, waist circumference hemoglobin A1C levels, and fasting and postprandial blood glucose levels.