Continuous glucose monitoring metrics and pregnancy outcomes in insulin-treated diabetes: A post-hoc analysis of the GlucoMOMS trial.

AIM: To investigate the association between continuous glucose monitoring (CGM) metrics and perinatal outcomes in insulin-treated diabetes mellitus in pregnancy. MATERIALS AND METHODS: In a post-hoc analysis of the GlucoMOMS randomized controlled trial, we investigated the association between the metrics of an offline, intermittent CGM, glycated haemoglobin (HbA1c) and perinatal outcomes per trimester in different types of diabetes (type 1, 2 or insulin-treated gestational diabetes mellitus [GDM]). Data were analysed using multivariable binary logistic regression. Outcomes of interest were neonatal hypoglycaemia, pre-eclampsia, preterm birth, large for gestational age (LGA) and Neonatal Intensive Care Unit (NICU) admission. The glucose target range was defined as 3.5-7.8 mmol/L (63-140 mg/dL). RESULTS: Of the 147 participants (N = 50 type 1 diabetes, N = 94 type 2 diabetes/insulin-treated GDM) randomized to the CGM group of the GlucoMOMS trial, 115 participants had CGM metrics available and were included in the current study. We found that, in pregnancies with type 1 diabetes, a higher second trimester mean glucose was associated with LGA (odds ratio 2.6 [95% confidence interval 1.1-6.2]). In type 2 and insulin-treated gestational diabetes, an increased area under the curve above limit was associated with LGA (odds ratio 10.0 [95% confidence interval 1.4-72.8]). None of the CGM metrics were associated with neonatal hypoglycaemia, pre-eclampsia, shoulder dystocia, preterm birth and NICU admission rates for pregnancies complicated by any type of diabetes. CONCLUSION: In this study, in type 2 diabetes or insulin-treated GDM, the glucose increased area under the curve above limit was associated with increased LGA. In type 1 diabetes, the mean glucose was the major determinant of LGA. Our study found no evidence that other CGM metrics determined adverse pregnancy outcomes.

SUGAR-DIP trial: oral medication strategy versus insulin for diabetes in pregnancy, study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial.

INTRODUCTION: In women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM. METHODS: The SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of the Utrecht University Medical Centre. Approval by the boards of management for all participating hospitals will be obtained. Trial results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NTR6134; Pre-results.

Continuous glucose monitoring during diabetic pregnancy (GlucoMOMS): A multicentre randomized controlled trial.

AIM: Diabetes is associated with a high risk of adverse pregnancy outcomes. Optimal glycaemic control is fundamental and is traditionally monitored with self-measured glucose profiles and periodic HbA1c measurements. We investigated the effectiveness of additional use of retrospective continuous glucose monitoring (CGM) in diabetic pregnancies. MATERIAL AND METHODS: We performed a nationwide multicentre, open label, randomized, controlled trial to study pregnant women with type 1 or type 2 diabetes who were undergoing insulin therapy at gestational age < 16 weeks, or women who were undergoing insulin treatment for gestational diabetes at gestational age < 30 weeks. Women were randomly allocated (1:1) to intermittent use of retrospective CGM or to standard treatment. Glycaemic control was assessed by CGM for 5-7 days every 6 weeks in the CGM group, while self-monitoring of blood glucose and HbA1c measurements were applied in both groups. Primary outcome was macrosomia, defined as birth weight above the 90th percentile. Secondary outcomes were glycaemic control and maternal and neonatal complications. RESULTS: Between July 2011 and September 2015, we randomized 300 pregnant women with type 1 (n = 109), type 2 (n = 82) or with gestational (n = 109) diabetes to either CGM (n = 147) or standard treatment (n = 153). The incidence of macrosomia was 31.0% in the CGM group and 28.4% in the standard treatment group (relative risk [RR], 1.06; 95% CI, 0.83-1.37). HbA1c levels were similar between treatment groups. CONCLUSIONS: In diabetic pregnancy, use of intermittent retrospective CGM did not reduce the risk of macrosomia. CGM provides detailed information concerning glycaemic fluctuations but, as a treatment strategy, does not translate into improved pregnancy outcome.

Neonatal Hypoglycemia Following Diet-Controlled and Insulin-Treated Gestational Diabetes Mellitus.

OBJECTIVE: To assess the risk of neonatal hypoglycemia following diet-controlled and insulin-treated gestational diabetes mellitus (GDM) and how it relates to birth weight. RESEARCH DESIGN AND METHODS: Prospective cohort study included term neonates born after GDM from January 2013 through December 2015 at the University Medical Center Utrecht (Utrecht, the Netherlands). Routine screening of neonatal blood glucose levels was performed at 1, 3, 6, 12, and 24 h after birth. Main outcome measures were neonatal hypoglycemia defined as blood glucose ≤36 mg/dL (severe) and ≤47 mg/dL (mild). RESULTS: A total of 506 neonates were included, born after pregnancies complicated by GDM treated either with insulin (22.5%) or without insulin (77.5%). The incidence of mild and severe hypoglycemia was similar in the insulin-treated and diet-controlled groups (33 vs. 35%, P = 0.66; and 20 vs. 21%, P = 0.79). A birth weight >90th centile was seen in 17.2% of all infants. Although children with a birth weight >90th centile had the highest risk for hypoglycemia, the vast majority of hypoglycemia (78.6%) was detected in those with a birth weight <90th centile. Over 95% of all hypoglycemia occurred within 12 h after birth. CONCLUSIONS: Routine screening for neonatal hypoglycemia following pregnancies complicated by GDM reveals high incidence of both mild and severe hypoglycemia for both diet-controlled and insulin-treated GDM and across the full range of birth weight centiles. We propose routine blood glucose screening for neonatal hypoglycemia within the first 12 h of life in all neonates after GDM, irrespective of maternal insulin use or birth weight.

Diagnostic Criteria and Treatment for Gestational Diabetes Mellitus.

The prevalence of gestational diabetes mellitus (GDM) is high, and the risks of maternal and perinatal complications with clear hyperglycemia are well recognized. The worldwide obesity epidemic and the consequent excess of hyperglycemia have resulted in a rising prevalence of GDM. Changing definitions and more intensive screening may also be contributing to an increased prevalence. Despite the recognized risks, much controversy surrounds the screening, diagnosis, and treatment of GDM. The more stringent diagnostic criteria, advocated in new guidelines, are based on observational studies and are not guided by interventional studies. Here, we review the evidence behind updated diagnostic criteria, stricter treatment targets, and current controversies and conclude that international consensus regarding diagnosis and treatment will only be achieved with further evidence from interventional studies.

[Increased risk of type II diabetes mellitus and cardiovascular disease after gestational diabetes mellitus: a systematic review]. / Verhoogd risico op diabetes mellitus type 2 en hart- en vaatziekten na diabetes gravidarum: een systematische review.

OBJECTIVE: To determine the long-term risk of developing type II diabetes (T2D) and cardiovascular disease (CVD) for women with a history of gestational diabetes mellitus. DESIGN: Systematic review and meta-analysis. METHOD: Two search strategies were used in PubMed and Embase to determine the long-term risks of developing T2D and CVD after a pregnancy complicated by gestational diabetes mellitus. After critical appraisal of the papers found, 11 papers were included, involving a total of 328,423 patients. Absolute and relative risks (RRs) were calculated. RESULTS: Eight studies (n=276,829) reported on the long-term risk of T2D and 4 (n=141,048) on the long-term risk of CVD. Follow-up ranged from 3.5 to 11.5 years for T2D and from 1.2 to 74.0 years for CVD. Women with gestational diabetes had a risk of T2D varying between 9.5% and 37.0% and a risk of CVD of between 0.28% and 15.5%. Women with gestational diabetes were at increased risk of T2D (weighted RR: 13.2; 95% CI: 8.5-20.7) and CVD (weighted RR: 2.0; 95% CI: 1.1-3.7) compared to women without gestational diabetes. CONCLUSION: Women with prior gestational diabetes mellitus have a significantly increased risk of developing T2D and CVD. It is very important that gestational diabetes is recognised as a cardiovascular risk factor in daily practice. It would be desirable to screen this group of women for the presence of hyperglycaemia and other cardiovascular risk factors. Further research is required to be able to specify the long-term risk of T2D and CVD and to demonstrate whether such screening is cost-effective.

The efficacy and effectiveness of continuous glucose monitoring during pregnancy: a systematic review.

OBJECTIVE: Diabetic pregnancies carry a high risk for both mother and child, especially when glycemic control is poor. A novel technique that aims to improve glycemic control is the continuous glucose monitor (CGM). This tool is already in use to improve pregnancy outcome. This review presents the available evidence on the efficacy of CGM use in pregnancy and the effectiveness on pregnancy outcome. METHODS: A systematic search was conducted using PubMed, EMBASE, and the Cochrane Libraries for articles on CGM in pregnancy. We evaluated the selected articles with particular attention for clinical and cost-effectiveness of CGM to improve pregnancy outcome. RESULTS: We retrieved 5032 articles, 11 of which remained as relevant after selection according to predefined criteria. Most studies were limited to the evaluation of the role of CGM on clinical decision making. Only 2 studies were randomized controlled trials (RCTs) evaluating the effect on pregnancy outcome. One small RCT on retrospective CGM showed a significant reduction in third-trimester HbA1c and a significant reduction in neonatal macrosomia. A second RCT on real-time CGM did not show any effect on either glycemic control or on pregnancy outcome. CONCLUSIONS: Current evidence on the efficacy of CGM on improving glycemic control during pregnancy as well as on the effectiveness on pregnancy outcome is limited to 2 RCTs with contradicting results. Evidence on the cost-effectiveness is lacking. Further proper RCTs on the effectiveness and cost-effectiveness of CGM in pregnancy are required before wide implementation in practice.

Effectiveness of continuous glucose monitoring during diabetic pregnancy (GlucoMOMS trial); a randomised controlled trial.

BACKGROUND: Hyperglycemia in pregnancy is associated with poor perinatal outcome. Even if pregnant women with diabetes are monitored according to current guidelines, they do much worse than their normoglycaemic counterparts, marked by increased risks of pre-eclampsia, macrosomia, and caesarean section amongst others. Continuous Glucose Monitoring (CGM) is a new method providing detailed information on daily fluctuations, used to optimize glucose control. Whether this tool improves pregnancy outcome remains unclear. In the present protocol, we aim to assess the effect of CGM use in diabetic pregnancies on pregnancy outcome. METHODS/DESIGN: The GlucoMOMS trial is a multicenter open label randomized clinical trial with a decision and cost-effectiveness study alongside. Pregnant women aged 18 and over with either diabetes mellitus type 1 or 2 on insulin therapy or with gestational diabetes requiring insulin therapy before 30 weeks of gestation will be asked to participate. Consenting women will be randomly allocated to either usual care or complementary CGM. All women will determine their glycaemic control by self-monitoring of blood glucose levels and HbA1c. In addition, women allocated to CGM will use it for 5-7 days every six weeks. Based on their CGM profiles they receive dietary advice and insulin therapy adjustments if necessary. The primary outcome measure is rate of macrosomia, defined as a birth weight above the 90th centile. Secondary outcome measures will be birth weight, composite neonatal morbidity, maternal outcome and costs. The analyses will be according to the intention to treat principle. DISCUSSION: With this trial we aim at clarifying whether the CGM improves pregnancy outcome when used during diabetic pregnancies. TRIAL REGISTRATION: Nederlands Trial Register: NTR2996.